FRONT COVER

SSP HANDBOOK OF STROKE

Guidelines for Prevention, Treatment, and Rehabilitation

Sixth
Edition

2014
Copyright © 2014 The Stroke Society of the Philippines. All rights reserved.

SSP Handbook of Stroke

Copyright No.: A2010-2696
ISBN: 978-971-94968-1-6

Published
1st Edition 1999 | 2nd Edition 2002 | 3rd Edition 2004 | 4th Edition 2006
5th Edition 2010 | 5th Revised Edition 2011 | 6th Edition 2014

Editor-in-Chief:
Artemio A. Roxas Jr., MD, FPNA

The Stroke Society of the Philippines

Rm.1403 North Tower, Cathedral Heights Building Complex
St. Luke's Medical Center, E. Rodriguez Sr. Avenue,
Quezon City, Philippines
www.strokesocietyphil.org

For inquries please contact:

SSP Secretariat
Telephone: (632)723-0101 local 5143
Telefax: (632)722-5877
Email: ssp_secretariat@yahoo.com

Printed in the Philippines

GoldenPages Publishing Company

Clinical practice guidelines are developed to provide evidence-based information

about a particular condition and guide practitioners in clinical decision-making
process. In no way should these recommendations be misconstrued as absolute
rules, since nuances and peculiarities in each individual patient, situation, or
communitiy may entail differences in specific approaches. While every reasonable
effort has been taken to ensure that the information contained herein is generally
in accordance with the state of knowledge at the time of publication, the authors,
editors, or the publisher make no warranty, expressed or implied, as to the accuracy,
currency, and completeness of this material.
 Table of Contents
Message from the Founding President ..................................................................................3
Message from the President and Editor-in-Chief ...............................................................4
SSP Mission and Vision ..................................................................................................................5
Guide to the Use of SSP Handbook of Stroke .....................................................................6

CHAPTER I
Overview of Stroke and Transient Ischemic Attack ..................................................................8

CHAPTER II
Guidelines for Primary and Secondary Prevention of Stroke ..........................................28
I. Hypertension and Stroke ...................................................................................................28
II. Diabetes Mellitus and Stroke .......................................................................................32
III. Dyslipidemia and Stroke ....................................................................................................36
IV. Cigarette Smoking and Stroke ........................................................................................41
V. Excessive Alcohol Intake and Stroke .............................................................................44
VI. Cardiac Risk Factors and Stroke ......................................................................................45
VII. Extracranial Carotid Stenosis and Stroke ....................................................................52
VIII. Intracranial Stenosis and Stroke .....................................................................................56
IX. Peripheral Arterial Disease and Stroke ........................................................................60
X. Physical Inactivity and Stroke ..........................................................................................63
XI. Obesity and Stroke ..............................................................................................................64
XII. Nutrition and Stroke ..........................................................................................................69

CHAPTER III
Guidelines for Treatment of Acute Stroke and Transient Ischemic Attack ...............72
I. SSP Classification of Acute Stroke Based on Clinical Severity ............................72
II. Guidelines for Management of Transient Ischemic Attack ...................................73
III. Guidelines for Management of Mild Stroke ...............................................................74
IV. Guidelines for Management of Moderate Stroke ....................................................75
V. Guidelines for Management of Severe Stroke...........................................................77
VI. Early Specific Treatment of Ischemic Stroke ..............................................................78
A. Antithrombotic Therapy in Acute Stroke ............................................................78
B. Neuroprotection ..........................................................................................................79
C. Anticoagulation in Acute Cardioembolic Stroke ..............................................84
D. Administration of rt-PA in Acute Ischemic Stroke ...........................................86
E. Blood Pressure Management in Acute Stroke ...................................................90
VII. Management of Increased Intracranial Pressure .........................................................95
VIII. Hemicraniectomy for Malignant Middle Cerebral Artery Infarction.................97

CHAPTER IV
Guidelines for Antiplatelet Therapy in Noncardioembolic Stroke
or Transient Ischemic Attack ..........................................................................................................104

CHAPTER V
Guidelines for Stroke Prevention in Nonvalvular Atrial Fibrillation .........................110

CHAPTER VI
Guidelines for the Management of Hemorrhagic Stroke ................................................124
I. Hypertensive Intracerebral Hemorrhage ......................................................................127
II. Aneurysmal Subarachnoid Hemorrhage........................................................................128
III. Cerebral Arteriovenous Malformation ..........................................................................133
1
 CHAPTER VII
Neuroimaging in Acute Stroke .....................................................................................................142

CHAPTER VIII
Complications of Stroke ..................................................................................................................158
I. Post-Stroke Pain ..................................................................................................................158
II. Post-Stroke Seizures............................................................................................................164
III. Post-Stroke Depression .....................................................................................................166
IV. Post-Stroke Dementia ........................................................................................................166

CHAPTER IX
Special Topics in Stroke Management........................................................................................170
I. Stroke in Infants and Children ........................................................................................174
II. Stroke in the Young ............................................................................................................175
III. Stroke in Pregnancy and the Puerperium ..................................................................182
IV. Movement Disorders in Stroke.......................................................................................187
V. Small Vessel Diseases: Lacunar Stroke and Microbleeds......................................189

CHAPTER X
Guidelines for Nursing Care of the Stroke Patient ..............................................................194

CHAPTER XI
Guidelines for Stroke Rehabilitation...........................................................................................200

CHAPTER XII
Post-Stroke Evaluation for Resuming Activities and Preoperative Assessment...212

CHAPTER XIII.
Guidelines on the Establishment and Operation of Stroke Units ...............................220
Directory of Stroke Units in the Philippines ........................................................................225

APPENDIX A
International Classification of Diseases (ICD) 10th Revision Codes for
Cerebrovascular Diseases ................................................................................................................229

APPENDIX B
Stroke Scales
1. Glasgow Coma Scale ............................................................................................................229
2. National Institutes of Health Stroke Scale (NIHSS) ...................................................230
3. Modified Rankin Scale (mRS) ............................................................................................233

APPENDIX C
International Headache Society (IHS) Diagnostic Criteria for Migrainous ............234
Infarction and Headache Attributable to TIA or Stroke ...................................................235

APPENDIX D
Gugging Swallowing Screen (GUSS) for Assessment of Dysphagia ...........................235

APPENDIX E
Braden Scale for Predicting Pressure Ulcer Risk ..................................................................237

Working Group and External Reviewers ..................................................................................238

SSP Officers, Board of Trustees, and Chapters .......................................................................239
SSP Corporate Members ..................................................................................................................240
2 List of Additional Topics available at the SSP Website ....................................................240
 MESSAGE from the FOUNDING PRESIDENT

We, the members of the Stroke Society of the Philippines, dedicate this sixth edition of the
Guidelines for the Prevention, Treatment and Rehabilitation of Stroke, to our beloved
countrymen!

For the past fifteen years, our members composed of neurologists, neurosurgeons, nurses,
physiatrists, physical therapists and lay people have worked tirelessly as STROKE
CHAMPIONS to help make a difference in reducing the mortality and morbidity from
stroke. We have small victories, but there is definitely more work to be done.

We can move towards our goal faster and more effectively with the concerted effort of the
government and the private sector. This is everyone's battle!

These guidelines, distilled from the researches of the recent past, is an instrument for
everyone to use, in the day-to-day encounter with this disease. More importantly,
prevention should be emphasized! Fortunately, many of the risk factors are modifiable.
Health education is therefore crucial!

We have advanced in the understanding in the pathophysiology of the disease, so that

quick diagnostic and therapeutic strategies appropriate to every case encountered must
be pursued. The setting of care is important and therefore more stroke centers all over the
country should be established.

We have a long way to go in our quest for a "stroke free" Philippines! The updated
knowledge contained in this handbook will surely help! Let us all use it!

Joven R. Cuanang, MD, FPNA

Founding President
Stroke Society of the Philippines

3
 MESSAGE from the PRESIDENT
and EDITOR-IN-CHIEF

Stroke remains to be the leading cause of disability and the second leading cause of
mortality in the Philippines. Many stroke cases in our country are underdiagnosed and/
or insufficiently treated because of inadequate knowledge among health care providers
and laymen. Furthermore, we have to acknowledge the limited health care resources and
coverage available today. The Stroke Society of the Philippines’ (SSP) mantra, “Stroke is
a brain attack; an emergency situation that is treatable and most of all preventable”, has
yet to reach far more areas. The imminent rise of stroke cases–explained by the emerging,
unchecked risk factors and ageing of population that is continually growing–underscores
the importance of educating our health care providers with up-to-date, effective, and
efficient strategies for both management and prevention of stroke.

It is our hope that this SSP Handbook of Stroke finds its way into the hands of many
physicians, nurses, physical therapists, health care administrators to help improve stroke
care; even to stroke patients, their loved ones and students who would like to learn more
about stroke. Since the release of the fifth edition in 2010, the availability of results from
meta-analyses and drug trials have resulted in changes in clinical guidelines. In this
latest edition, we have updated the contents of the regular sections and added ten new
topics to cover the other common important aspects of stroke management. This hand-
book has evolved from a simple compilation of guidelines into a more comprehensive
reference to cover almost all aspects of stroke care for different age groups and different
phases of stroke. As with the previous editions, the formulated statements and contents
are guided by the dictum, “Thinking Globally and Acting Locally“.

I would like to thank all the members of the multidisciplinary writing committee as well
as those who have reviewed the articles. To all our many collaborators who believe in the
noble cause of the SSP, our sincerest gratitude for your continued support. May the SSP
Handbook of Stroke be an instrument to help decrease, by any means, the occurrence,
deaths, and complications of stroke, and improve the quality of life of Filipino stroke
patients.

Always with the vision of SSP in mind,

Artemio A. Roxas Jr., MD, FPNA

President, Stroke Society of the Philippines
Chair, Stroke Council of the Philippine Neurological Association
Editor-in-Chief, SSP Guidelines, 5th and 6th Editions

4
 SSP Vision

By 2018, the Stroke Society of the Philippines will be the leading

multidisciplinary stroke organization of healthcare professionals in the
country, collaborating with partners working toward effective stroke
reduction in the Asia Pacific Region.

SSP MISSION

To empower people to take a proactive role towards a “culture of health”

through advocacy in stroke awareness and prevention
To disseminate and promote the practice of evidence-based stroke
management through continuing medical education
To create and utilize innovative strategies for optimum comprehensive
stroke care appropriate to the local setting
To promote and attain excellence in ethical and relevant stroke research
with local and international stroke care network
To take an active role in the international stroke care network
To organize stroke support groups and promote a “culture of help” by
supporting stroke survivors, their families and caregivers.
To institutionalize stroke prevention and intervention through legislative
advocacy and collaboration with government agencies

STROKE: THINK GLOBALLY, ACT LOCALLY

Principles:
1. Stroke is a "brain attack”
… needing emergency management, including specific treatment and
secondary and tertiary prevention.
2. Stroke is an emergency
… where virtually no allowances for worsening is tolerated.
3. Stroke is treatable
… optimally, through proven, affordable, culturally acceptable and ethical
means.
4. Stroke is preventable
… in a manner that could be implemented across all levels of society.

For anyone experiencing any

signs or symptoms suggestive of
an acute stroke, rush immediately to a
hospital with an organized stroke care
preferably one with a stroke unit.
Remember….
“TIME IS BRAIN”
5
 GUIDE TO THE USE OF THE SSP HANDBOOK OF STROKE
The SSP Handbook of Stroke consists of clinical practice guidelines (CPGs) and
consolidated information about stroke, intended to serve as a resource for healthcare
professionals in caring for stroke patients. This handbook, however, is not meant as a
substitute for comprehensive textbooks, but rather as a supplement and quick reference
material.

Although systematic appraisal of evidence is most ideal for guideline development,

adaptation of existing stroke guidelines considered to be applicable in the local setting
was implemented in this edition to make more efficient use of available resources
and avoid unnecessary duplication of guidelines. The previous SSP statements and
recommendations were reviewed and updated, together with the adopted statements
from foreign guidelines on cerebrovascular and cardiovascular care. These include
guidelines from the American Heart Association (AHA)/American Stroke Association
(ASA), European Stroke Organization (ESO), European Society of Cardiology (ESC),
European Heart Rhythm Association (EHRA), the United Kingdom National Institute
for Health and Care Excellence (NICE), and the National Stroke Foundation (NSF) of
Australia. External content experts reviewed the guidelines formulated by the different
working groups before the final version of the manuscript was made.

In the sections related to stroke prevention and care, the SSP adopted the evidence rating
system prescribed by the AHA/ASA for applying classifications of recommendations and
levels of evidence as follows:

Classification of Recommendations and Levels of Evidence

Size of Treatment Effect
Recommendation that the procedure/treatment is useful/effective; treatment
Class I
benefits clearly exceed risks
Conditions for which there is conflicting evidence or diverging opinion about the
Class II usefulness/efficacy of procedure/treatment
Evidence/expert opinion in favor of the procedure/treatment; treatment benefits
IIa exceed risk
Evidence/expert opinion about the usefulness/efficacy of procedure/treatment is
IIb less well-established; additional studies/data are needed
Recommendation that the procedure/treatment is not useful or effective and may
Class III be harmful; benefit does not exceed risk

Estimate of Certainty (Precision) of Treatment Effect

Level A Data derived from multiple, randomized clinical trials or meta-analyses

Level B Data derived from a single nonrandomized trial or nonrandomized studies

Level C Only consensus opinion of experts, case studies, or standard of care

When available or possible, the recommendations of the SSP are accompanied by a

specific class/level to reflect the importance of the recommendation and the strength
of the evidence.

Other topics available at the SSP website

http://www.strokesocietyphil.org
are indicated by this icon.
6
 CHAPTER I
Overview of Stroke and
Transient Ischemic Attack
I. The Burden Of Stroke
II. Stroke Awareness
III. The Evolving Definitions Of Stroke And Transient
Ichemic Attack
IV. Epidemiology Of Stroke Types
IV-A. Stroke Classifications
IV-B. Intracranial Versus Extracranial Stenosis
V. The Role Of Physicians In Acute Stroke Care
VI. Increasing The Yield For Correct Diagnosis Of Stroke
VII. Transient Ischemic Attack
VIII. Clinical Stroke Syndromes Based On Blood Vessel
Involvement
IX. Risk Factors For Stroke And Stroke Prevention
X. The Philippine Government And Stroke
Sixth
Edition
2014
Overview

Overview of Stroke and Transient Ischemic Attack

Stroke, also known as “brain attack” or cerebrovascular disease (CeVD), is the most
common neurological disorder in adults requiring emergency intervention. Although
stroke has fatal and debilitating complications, it is treatable and most of all preventable.
Despite the breakthroughs and sophistication in treatment over the years, the prevalence
of stroke and its sequelae continue to be a serious public health problem. There is a need
for widespread stroke awareness, organized stroke care, instituting a national stroke
program, and continuous research supported by substantial health resource allocation.

The Stroke Society of the Philippines (SSP), a multidisciplinary organization composed

of healthcare professionals and laymen, was established in 1995 with the aims of
reducing the stroke incidence, morbidity, and mortality in our country and improving
the quality of life of our stroke patients. Since 1999, the SSP has produced five editions
of clinical practice guidelines (CPGs) reflecting the dynamic research interests and latest
evidences on stroke. This handbook was developed to guide and provide our health
providers–clinicians, allied health professionals, and health service administrators–an
essential, practical, updated, evidence-based, and cost-effective management of stroke.

I. THE BURDEN OF STROKE

Stroke is the second leading cause of death following ischemic heart disease1 and
the third leading cause of disease burden worldwide.2 It is also a major cause of
acquired cognitive impairment, dementia, and long-term disability among adults.
The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study described a
trend of increase in stroke incidence and number of stroke-related deaths3, with the
bulk of disease burden borne by the low- and middle-income countries. The ageing
of populations, emergence of new risk factors, and young onset of stroke contribute
to the imminent rise in stroke prevalence in the succeeding years.

In the Philippines, the age-standardized mortality for CeVD is 82.8 per 100,000
person-years.4 It is the second leading cause of death (after cardiac diseases)5 and
ranks fifth among specific diseases with greatest burden.6 Based on regional data, in
general, there is a decreasing trend in stroke mortality congruent with an increase in
geographic distance from the National Capital Region (NCR).7 It appears however,
that underdiagnosis of stroke or low registration (especially in rural areas) contribute
to this trend, which is a direct result of shortage in available health resources and
unequal distribution of stroke care providers. As of the second quarter of 2014, there
are 309 board-certified adult neurologists and over a hundred neurosurgeons serving
a population of about 99 million; this translates to 1 neurologist for every ~320,000
Filipinos (in contrast to the World Health Organization [WHO] recommendation of 1
neurologist per 100,000). About 67% of neurologists practice in urban centers8, where
diagnostic imaging facilities are mostly accessible. It was reported that only 1.16
computerized tomography (CT) and 0.33 magnetic resonance imaging (MRI) units are
available for every 1 million population in the Philippines.9

1 Stroke ranks third if neoplastic diseases are grouped together.

2 Disease burden is measured by disability-adjusted life years (DALYs) lost.
3 Approximately 5.9 million (or 11%) of over 52 million deaths in 2010 are due to stroke.
4 Stroke mortality rate has increased for both sexes, although a greater proportion comes from the male population
(irrespective of life expectancy).
8
 Overview
Although previous community-based studies have determined the prevalence of
stroke in the country (Table 1), comprehensive estimates of incidence remains in lack.
The wide variation in stroke prevalence was due to different age groups surveyed,
different methods of sample collection, and case ascertainment. However, all three
studies utilized the validated questionnaires for stroke prevalence of the Philippine
Neurological Association (PNA).

Table 1. Prevalence of Stroke in the Philippines10-13

Stroke
Study Population N
Questionnaire Question on Previous
History of Stroke
FNRI - National
Nutrition and Health Ages 20 and 4,753 1.9% 1.4%
Survey I (NNHeS I)(2005) above
FNRI – NNHeS II (2008) Ages 20 and 1.2%
above 7,700 -
PNA Community Stroke
Prevalence Study, All age groups 19,113 0.5% -
Morong, Rizal (2005)
SSP Currimao Stroke Ages 40 and 1.6% 1.9%
Prevalence Study (2009) above 1,400
FNRI: Food and Nutrition Research Institute; PNA: Philippine Neurological Association; SSP: Stroke Society
of the Philippines

II. STROKE AWARENESS

A key strategy to reduce the disease burden from stroke (or any illness) is the
promotion of public awareness. Results from a community survey entitled “Stroke
Awareness Gap In the Philippines” (SAGIP) study among 750 adults in Currimao, Ilocos
Norte, show that only 34.4% of the respondents demonstrated some knowledge
about stroke. Twenty-one percent (21%) confused stroke with heart attack, while 27%
had no knowledge about stroke. Additionally, more than half of the respondents
incorrectly attributed chest pain and shortness of breath to stroke. The findings
imply that in general, there was poor public knowledge about stroke and its risk
factors14, underscoring the need to educate more people and expand public access
to information to help reduce the knowledge gap.

The SSP through its Committee On BRain Attack (COBRA) develops educational
materials using diverse formats (e.g., multimedia campaigns) and organizes lay fora
to increase public knowledge and understanding of stroke. Topics include sign and
symptom recognition (Panel 1) and taking proper courses of action.

Panel 1. Common Signs and Symptoms of Stroke

1. Sudden numbness or weakness of the face, arm or leg, especially on

one side of the body.
2. Sudden confusion, trouble speaking or understanding.
3. Sudden trouble seeing in one or both eyes.
4. Sudden trouble walking, dizziness, loss of balance or coordination.
5. Sudden, severe headache with no known cause.

Various stroke recognition tools have been developed for both pre-hospital and in-
hospital assessment. For easy recall, the SSP promotes the use of the “FAST” slogan
(Panel 2) and our local versions, “KAMBIO” (Panel 3), “UTAK” (Panel 4), and “DALI”
9
Overview
(Panel 5) slogans. These tools assess the three common presentations of stroke: facial
weakness, arm weakness, and speech disturbance. Should any of these signs and
symptoms be present, the public is advised to seek immediate medical consult.

Panel 2. The F.A.S.T. Slogan (Cincinnati Pre-hospital Stroke Recognition Tool)

Facial asymmetry
Have the person smile or show his or her teeth. If one side doesn't move as
well as the other or it seems to droop, that could be sign of a stroke.

Arm drift
Have the person close his or her eyes and hold his or her arms straight out in
front for about 10 seconds. Look for weakness or drift.

Slurred speech
Have the person say, "You can't teach an old dog new tricks," or some other
simple, familiar saying. If the person slurs the words, gets some words wrong,
or is unable to speak, that could be sign of stroke.

Time
If any of the above 3 is present, then patients are advised to seek immediate
hospital consultation.

Panel 3. KAMBIO Slogan (The Medical City)

Tandaan: “KAMBIO– Sambitin at Gawin Upang Stroke ay Alamin”

KAmay: Itaas ang kamay at obserbahan kung may panghihina o “drift”.

Mukha: Ipakita ang ngipin o mag-smile. Tingnan kung may kaibahan ang
kaliwa at kanang bahagi ng mukha.

BIgkas: Bigkasin at ulitin “Kumukutikutitap ang lampara”. Obserbahan kung

may mali sa pananalita.

Oras: Kung may mali sa kamay, mukha, o bigkas, pumunta agad sa ospital!

A local study revealed the underlying reasons for delays in care provision to acute
stroke, which included poor public knowledge about stroke symptoms and its
severity (i.e. failure to recognize symptoms as serious and/or stroke-related). The
longer delays resulted from healthcare-related factors, such as delayed referral to
specialist and/or delayed neuroradiologic diagnosis. The median delay time from
presentation to neurological evaluation was 7.5 hours, while the median time from
presentation to brain imaging ranged from 2 hours (in CT-equipped hospitals) to
11.5 hours (where there is a need to transfer patients to another institution with
neuroimaging facilities).15 As the majority of stroke cases (about 97%) are seen and
initially managed by non-neurologists, it is crucial for physicians in the emergency
and primary care to be knowledgeable and skillful with neurologic examination and
acute stroke management. To potentially eliminate barriers to treatment within the
therapeutic window, early neurologic evaluation and referral to a specialist (or if
unavailable, to a trained health provider) is a must. Whenever possible, admission
to a hospital equipped and capable of providing acute stroke care (i.e. hospital with
stroke unit) is optimal.
10
 Overview
Panel 4. UTAK Slogan (SSP 2009 Lay Education Campaign Winner)
Tandaan: “UTAK”

Utal, bulol o di makapagsalita

Bigkasin at ulitin “Kumukutikutitap ang lampara”. Obserbahan kung may mali
sa pananalita.

Tabingi ang mukha or lakas ng kanan o kaliwang bahagi ng katawan

Ipakita ang ngipin o mag-smile. Tingnan kung may kaibahan ang kaliwa sa
kanang mukha; Itaas ang kamay at obserbahan kung may panghihina o “drift”

Angal nang angal ng biglaang matinding sakit

Pakinggan ang daing ng pasyente.

Kumilos kaagad at kumonsulta

Huwag magpatumpik-tumpik at humarurot sa ospital!

Panel 5. DALI Slogan (SSP Northern Mindanao Chapter Campaign)

Kun ikaw nagsuspetsa sa Strokea, "Lihok DALI"
Dali nga pagkaluya sa dagway o nawong
Isugyot sa pasyente sa pagpakita sa iyang ngipon un tan-awa kun adunay
kahalhinan o pagkahiwi sa iyang nawong

Adunay pagpanghoyhoy sa kamot

Isugyot sa pasyente sa pagpataas sa duha ka kamot un tag-awa ang
pagpanghoyhoy o pagkahulog sa usa niya ka kamot

Lisud sa pag-istorya o pagkasalapid sa dila

Ipasulti sa pasyente, “sa kalisod ug kalipay basta naghinigugmaay”

Idali: kun kinsa sa imong kaila, kauban, o higala nga anaa nii-ni nga sintomas, ayaw
dugaya pagdala sa pinakaduol na Hospital (Emergency Room)

a
Stroke: barado o pagbuto sa agianan sa dugo padulong sa utok

III. THE EVOLVING DEFINITIONS OF STROKE AND TRANSIENT ICHEMIC ATTACK

Before setting the stage for disease management, it is important to know and
understand the terms used in stroke, as well as the reasons for the changing definitions.
In academic medicine, knowing the difference between the terms cerebrovascular
disease (CeVD) and stroke is crucial.

Cerebrovascular disease is the umbrella term for any abnormality in the brain
resulting from a vascular pathologic process such as occlusion (by embolus or
thrombus), alteration in blood flow, or vessel rupture; stroke, on the other hand, is
specifically the type caused by cerebrovascular disease.16 Cerebrovascular accident
(CVA) has been commonly used, however the use of such term is inaccurate. Stroke
is “not an accident” because the risk factors and pathogenesis are both established
and preventable. “Brain attack” is coined to signify the urgency of the condition just
like “heart attack”.

Stroke is traditionally defined by the WHO as a "neurological deficit of cerebrovascular

cause that persists beyond 24 hours, or is interrupted by death within 24 hours".
This may be attributed to ischemic or hemorrhagic stroke, or cerebrovascular
anomalies such as intracranial aneurysms and arteriovenous malformations (AVMs).
11
Overview
This definition reflects the reversibility of tissue damage, within the 24-hour time
frame (defined arbitrarily). Thus, a person is diagnosed with stroke if the neurological
symptoms persisted for more than 24 hours. A focal neurological deficit lasting <24
hours was defined as a Transient Ischemic Attack (TIA).

However, several studies have demonstrated that this arbitrary time threshold was
too broad because in 30% to 50% of cases with this TIA definition, brain injury is
evident on diffusion-weighted MRI. With the emergence of approved therapy for
acute ischemic stroke, where treatment is given within the golden time frame of
three (3) hours to reduce stroke severity and mortality, many have preferred the use
of alternative terms “brain attack” and “acute ischemic cerebrovascular syndrome”–
modeled after “heart attack” and “acute coronary syndrome” respectively–which
indicate the prompt need for medical management.

Since most TIAs resolve within 15-20 minutes, a combined time- and tissue-based
definition for TIA was proposed by Albers et al. (2002) as:

a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with
clinical symptoms typically lasting less than one hour, and without evidence of acute
infarction.17

Subsequently, studies have shown that the use of time in the definition does not
accurately distinguish between patients with and without acute cerebral infarction.
However, it is impossible to define–with high sensitivity and specificity–a specific
time cut-off to determine whether a symptomatic ischemic event will result to brain
injury. Therefore, relying mainly on time-based definitions may unproductively
focus diagnostic attention on the temporal course rather than on the underlying
pathophysiology.

Based on these above reasons, in 2009 the American Heart Association (AHA) revised
the definition of TIA as:
a transient episode of neurological dysfunction caused by focal brain, spinal cord, or
retinal ischemia, without acute infarction.

Using this definition, ischemic stroke is then defined as “an infarction of central
nervous system tissue”. Similar to TIAs, this definition of ischemic stroke does not
have an arbitrary requirement for duration.

In September 2010, the SSP and the Stroke Council of the PNA convened to discuss
the changes in the definition of stroke and TIA. Aware that this handbook will be used
by local physicians practicing in places with limited access to neuroimaging facilities,
as well as of the arguments for and against the latest definitions, the working
definitions of TIA and Stroke (Panel 6) are as follows:

Panel 6. Definition of Transient Ischemic Attack and Stroke

Transient Ischemic Attack – a transient episode of neurological dysfunction caused by focal

brain, spinal, or retinal ischemia, without evidence of acute infarction in which clinical
symptoms typically last less than an hour

Stroke – a sudden onset of focal (or global) neurologic deficit due to an underlying vascular
pathology

12
 Overview
Stroke is mainly classified on the basis of pathological background: ischemic or
hemorrhagic. Ischemic stroke is defined as an episode of neurological dysfunction
caused by focal cerebral, spinal, or retinal infarction18 (it was agreed that no specific
time is included in the definition). The committee was unanimous on the importance
of underscoring that, in acute ischemic stroke there exists an area of penumbra around
the core of infarcted tissue that is potentially salvageable. A silent CNS infarction
is a documented CNS infarction (by imaging or pathologic evidence) that was
asymptomatic, but without a history of acute neurological dysfunction attributable
to the lesion. On the other hand, hemorrhagic stroke results from rupture of a blood
vessel or an abnormal vascular structure directly into and around the brain.

For patients with relatively brief symptom duration (e.g., symptoms that lasted for
several hours but less than a day) who did not receive detailed diagnostic evaluation,
it may be difficult to determine whether stroke or TIA is the appropriate diagnosis. For
these patients, it is reasonable to use terms such as ischemic cerebrovascular disease,
analogous to the terminology used in cardiology. This term may be appropriate for
patients who have just developed acute cerebrovascular symptoms in whom it is
not yet known whether deficits will resolve or persist, and in whom neurodiagnostic
testing has not been performed.

IV. EPIDEMIOLOGY OF STROKE TYPES

Based on western data, in general about 80% of stroke cases is ischemic and the
remaining 20% is hemorrhagic. However, recent data show that there is a relatively
higher proportion of hemorrhagic strokes among Asians. Notwithstanding the higher
global incidence of ischemic strokes, the majority of disease burden is actually due to
hemorrhagic stroke rather than the ischemic type.19 In the Philippines, the reported
age-standardized death rate is also higher for hemorrhagic (62.84 per 100,000 person-
years) compared to that of ischemic stroke (46.72 per 100,000 person-years).20 Based
on the stroke registries of selected NCR hospitals (Table 2), the prevalence ratios of
ischemic versus hemorrhagic cases are 68.2% and 31.8% respectively.

Table 2. Stroke Subtype Distribution (Hospital-based Registry, 2011)

Hemorrhagic
Ischemic
Hospitals Number Stroke
Stroke
(ICH + SAH)
Philippine General Hospital 1656 54% 46 %
St. Luke’s Medical Center-Quezon City 413 76% 24%
The Medical City 665 83% 17%
Makati Medical Center 543 70% 30%
University of Santo Tomas Hospital 514 67% 33%
Jose Reyes Memorial Medical Center 1,056 59% 41%

Because of the heterogeneity of mechanisms underlying stroke, classification

schemes (see Section IV-A) have been developed based on the aspect of stroke
being considered: pathophysiology, initial presentation, timing, and severity. The
classifications are both utilized in clinical practice and research.

The urgency and extent of treatment is influenced by the time or phase of stroke with
which the patient is initially seen. Based on the ictus (time from stroke onset), stroke
can be arbitrarily labeled as hyperacute (0-6 hours), acute (6-72 hours), subacute (3
13
Overview
Overview
Storke

days to <3 weeks) and chronic (>3 weeks). Differentiating hyperacute from acute
stroke is important as the treatment may vary depending on the number of hours
from the ictus, considering the existence of penumbra and the potential for salvaging
threatened tissues.

Unique to this handbook and acting on the dictum, “Thinking Globally and Acting
Locally”, the SSP classifies stroke into mild, moderate, or severe based on the severity
of neurologic deficit/s at the onset (see Chapter 3). Although no formal studies have
been done to show its impact, this classification was found to be useful, practical,
and cost-effective.

IV-A. STROKE CLASSIFICATIONS

Simply putting a diagnosis of ischemic stroke may not capture the pathophysiology
and the extent of cerebrovascular insult. Ischemic strokes are further classified
not only to establish a more specific diagnosis, but also to tailor management
and predict risks for subtypes with certain discrete features. The most common
classification schemes for ischemic stroke are the Oxfordshire Community
Stroke Project (OCSP) and the Trial of ORG 10172 in Acute Stroke Treatment
(TOAST) system (1993).

The Oxfordshire classification (OCSP) (Table 3) is a simple bedside classification

scheme based on clinical syndromes alone or in combination with cranial
CT findings. This classification can predict the size of stroke territory on CT, its
outcome and severity, but it does not address a particular etiology or potential risk
factor/s. The use of this classification is generally reliable in patients with larger
strokes since it poorly discriminates between lacunar and small-volume cortical
infarcts (especially when only clinical criteria are used).

Table 3. The Oxfordshire Classification of Stroke

Subtype Criteria
Total Anterior Circulation (TAC_) Triad of unilateral motor and/or sensory deficit, higher
cortical dysfunction (e.g. dysphasia, dyspraxia, dyscalculia,
visuo-spatial disorder), and homonymous hemianopia.
Partial Anterior Circulation (PAC_) At least two of the TAC features including isolated higher
cortical dysfunction or isolated motor or sensory deficits,
which are anatomically less extensive than lacunar
syndromes (see below).
Lacunar (LAC_) Pure motor or pure sensory deficit, sensorimotor deficit,
ataxic hemiparesis, or dysarthria-clumsy hand syndrome
Posterior Circulation (POC_) Isolated homonymous hemianopia, brain stem or cerebellar
syndromes
Note: A fourth code or letter is added on the subtype based on the following etiology: ischemic (I),
hemorrhagic (H), or syndromic (S) if the pathogenesis is indeterminate or prior to imaging.

This classification was used by Navarro et al. in determining the frequency of stroke
complications in Asian countries including the Philippines. The study generated
data on the stroke subtypes as shown in Table 4. More recently, the use of the
OCSP classification was noted to improve the prediction of post-thrombolysis
symptomatic intracerebral hemorrhage.21
14
 Overview
Overview
Storke
Table 4. Stroke Subtype Distribution in 10 Asian Countries22
Stroke Subtype Prevalence
All Infarcts 895 (74%)
Partial Anterior Circulation Infarct (PACI) 274 (27%)
Total Anterior Circulation Infarct (TACI) 115 (12%)
Lacunar Infarct (LACI) 247 (25%)
Posterior Circulation Infarct (POCI) 99 (10%)
Parenchymal Intracerebral Hemorrhage 258 (26%)

The TOAST classification (Table 5), which is the widest accepted stroke subtyping
system at present, is based on the likely pathophysiology using more extensive/
advanced diagnostics (i.e. neuroimaging, echocardiography, neurosonography,
and cerebral angiography). This classification was originally devised for the
purpose of investigating the potential efficacy of an anticoagulant drug for various
types of ischemic strokes. It is composed of five major subtypes, namely: large
artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO),
stroke of other determined cause (OC), and stroke of undetermined cause (UND).

In an attempt to improve its validity, this classification was modified to Stop Stroke
Study-TOAST (SSS-TOAST), which included a degree of certainty for a probable
mechanism of stroke by the weight of evidence in each evaluated risk factor. The
SSS-TOAST re-classified “aortic” causes of embolism under cardiac (CE) category
because of the overlap in clinical findings. On the other hand, cryptogenic stroke
was classified under the undetermined (UND) etiology.

Table 5. TOAST Classification for Ischemic Stroke

Category Criteria indicative of diagnosis23, 24

1. Large Artery Atherosclerosis • significant stenosis (>50%), occlusion, or an ulcerated plaque

(LAA) (>2mm thick) in intracranial artery as demonstrated by
Doppler or angiographic study;
• absence of cardiogenic embolism;
• imaging (CT/MR): cortical or subcortical infarcts >1.5 cm;
• others: presence of murmur(s) ipsilateral to the infarct;
history of ischemic heart disease, intermittent claudication
of lower extremities, or TIA where symptoms are ipsilateral
to the infarct
2. Cardioembolism (CE) • cardiac source of emboli (other possible etiologies must be
ruled out)
• imaging (CT/MR): cortical or subcortical infarcts >1.5 cm
• others: sudden maximum neurologic deficit; history or
coexistence of systemic emboli; other clinical findings
suggestive of embolism (see Chapter 3)
3. Small Artery Occlusion • clinical course is one of classic lacunar syndromes (see OCSP
(SAO) criteria for lacunar infarcts in Table 3); no potential cardiac
source of embolism or stenosis >50% in ipsilateral extracranial
arteries; history of hypertension or diabetes mellitus supports
the diagnosis
• imaging (CT/MR): subcortical or brainstem infarct < 1.5cm
4. Other determined Causes e.g., non-atherosclerotic vascular diseases (inflammatory, non-
(OC) inflammatory, infectious, hereditary); hypercoagulability states,
hematologic disorders, migraine-infarction, vasopasm, other
hereditary and metabolic diseases (presence of cardioembolic
source/s and atherosclerotic extracranial vessels must be ruled
out)
15
continued on next page
Overview TABLE 5 continued
Category Criteria indicative of diagnosis23, 24
5. Undetermined cause (UND) one of two explanations is needed:
• no cause was found despite extensive evaluation, or;
• a most likely cause could not be determined because
more than one plausible cause was found

Despite the emergence of various classification systems, the SSP considers

Oxfordshire classification acceptable and most applicable in general practice
because of its simplicity (based on clinical data and basic neuroimaging). On the
other hand, the TOAST classification, which requires more extensive work-up to
determine the pathophysiologic mechanism of stroke, is utilized in major stroke
trials and in fully-equipped health facilities.

IV-B. INTRACRANIAL VERSUS EXTRACRANIAL STENOSIS

Ischemic strokes can result from stenosis of the blood vessels located either
extracranially or intracranially. Extracranial carotid stenosis was found to be more
frequent among Caucasians, whereas intracranial vascular lesions are predominant
among Hispanics, Blacks, and Asians. A local study among stroke patients with
atherosclerosis diagnosed by transcranial duplex scans show that majority (26%)
had intracranial stenosis alone, while less than 4% each had a significant extracranial
carotid disease or concomitant intra- and extra-cranial occlusive diseases.25 Several
prospective studies have confirmed that intracranial stenosis is an independent
predictor for poor outcomes (i.e. recurrent vascular events and death) despite the
use of antiplatelets, with an event rate of approximately 15% per year.

V. THE ROLE OF PHYSICIANS IN ACUTE STROKE CARE

Upon initial health care contact, the first challenge is to make a correct clinical
diagnosis (and type) of stroke. Prompt medical care and neuroprotection during the
acute phase of stroke can significantly reduce the risk of death, disability, as well as
complications. Another role of the physician is to determine the need and eligibility
for tissue reperfusion. However, the use of thrombolytic agents is not simple as
with the limited experience locally, hence it is reserved only for centers completely
equipped and capable of performing thrombolysis and monitoring. As previously
mentioned, an early referral to a neurologist (or physician with training in acute stroke
care) and admission/transfer to a hospital with a stroke unit is recommended. Among
the programs of the SSP is to assist tertiary hospitals establish its own stroke unit
(see Chapter 13) and conduct training/workshops on administering thrombolytics in
eligible acute ischemic stroke patients.

Panel 7. The Role of Physicians in Acute Stroke Care:

1. Confirm that the diagnosis is STROKE and not mimics (see section VI); that the
stroke is ischemic and not hemorrhagic, or vice-versa.
2. Determine if acute treatment with thrombolytic agent is advisable.
3. Do diagnostics to screen for acute medical or neurologic complications of stroke.
4. Determine vascular distributions of the stroke and provide clues on likely
pathophysiology/etiology.

16
 Overview
VI. INCREASING THE YIELD FOR CORRECT DIAGNOSIS OF STROKE

All health providers who see patients acutely need to know how to recognize and
assess individuals with a suspected stroke. Details in the history particularly at the
symptom onset are crucial in arriving at the diagnosis to allow for an early and
appropriate intervention. Important points in the patient’s history should include the
following:

• At exactly what time did the ictus of stroke occur?

• Where and what was the patient doing at the time of stroke?
• What part/s of the body was/were initially affected? Did it progress to involve
the other parts?
• Was the progression of neurologic deficit rapid or slow? Was the deficit maximal
at onset?
• What are the accompanying signs and symptoms?
• What was the interval (duration) from the time of onset to arrival at the
emergency department?
• Has the symptom or event ever occurred in the past?
• If the vital signs were taken prior to arrival, what was the blood pressure of the
patient?
• What are the past and present illnesses of the patient (e.g., hypertension,
diabetes, MI)?
• What were the interventions done or medicines taken (if any)? What was the
response of the patient?

To increase the accuracy of the diagnosis, the use of stroke recognition tools
is recommended. One validated example is the Recognition of Stroke in the
Emergency Room (ROSIER) tool (Table 6), which include assessment of blood sugar,
visual field, history of seizures or loss of consciousness, focal neurological weakness,
and speech disturbance.

Table 6. ROSIER Scale Stroke Assessment

Glasgow Coma Scale: E__ V__ M__
Blood Pressure: ___ /___ mm Hg
Blood Sugar: ___ (if <3.5 mmol, treat urgently and reassess once blood glucose is normal)

Questions YES NO
Has there been loss of consciousness or syncope? -1 0

Has there been seizure activity? -1 0

Is there a NEW ACUTE onset (or on awakening from sleep)?
• Asymmetric facial weakness +1 0
• Asymmetric arm weakness +1 0
• Asymmetric leg weakness +1 0
• Speech disturbance +1 0
• Visual field defect +1 0
Total score (-2 to +5)

Note: Stroke is likely if the total score is >0. There is a low possibility of stroke if the score is
</= 0, however it should not be completely excluded. The ROSIER scale only serves as adjunct
to clinical judgment in making provisional diagnosis of stroke or in differentiating from stroke
mimics. Furthermore, this scale is not suitable for suspected TIA patients without neurologic
signs; instead use the ABCD2 assessment (see Section VII).
17
 Overview

The presence of the following should alert one to consider a condition other than
stroke:

• Gradual progressive course and insidious onset

• Pure hemi-facial weakness including forehead (Bell’s palsy)
Ischemic Attack

• Trauma
Transient

• Fever prior to onset of symptoms

• Recurrent seizures
• Weakness with atrophy
• Recurrent headaches (migraine, tension-type headache)
• Isolated dizziness or vertigo
• No vascular risk factor

There are other medical and neurologic diseases that can mimic stroke, therefore it is
important for healthcare providers to be familiar with these conditions. The following
are some of the stroke mimics in adults presenting in the emergency department26:

1. Seizures 10. Herpes encephalitis

2. Systemic infection 11. Transient global amnesia
3. Brain tumor 12. Dementia
4. Toxic-metabolic 13. Demyelinating disease
5. Positional vertigo 14. Cervical spine fracture
6. Cardiac 15. Myasthenia gravis
7. Syncope 16. Parkinsonism
8. Trauma 17. Hypertensive encephalopathy
9. Subdural hematoma 18. Conversion disorder

Although the diagnosis of stroke is clinical, differentiating between ischemic and

hemorrhagic stroke still requires neuroimaging. More so, an imaging confirmation of
stroke is required prior to initiating thrombolysis in otherwise eligible patients. The
SSP recommends that major municipalities each should have at least a CT scan unit
to be utilized in all stroke cases. Neuroimaging for stroke is discussed in Chapter 7.

VII. TRANSIENT ISCHEMIC ATTACK

There is a significant overlap between ischemic stroke and transient ischemic attack
because of the similarities in risk factors, treatment approach, and prevention.
Furthermore, the clinical features and mimicking conditions for both are almost
the same. This section covers only basic information and diagnosis of TIA at the
emergency department. The management for TIA is discussed in the corresponding
section in Chapter 3.

A. Epidemiology Of Transient Ischemic Attack

The precise estimates on the incidence and prevalence of TIAs are difficult to
determine mainly because of the varying criteria used by epidemiological studies
for diagnosis of TIA. The reported early stroke risks associated with TIA are 3.1% at
2 days, 5.2% at 7 days, 8.0% at 30 days, and 9.2% at 90 days.27
18
 Overview
B. Assessment Of Patients With Suspected Transient Ischemic Attack Or Minor
Stroke
All patients with suspected TIA or minor stroke should have immediate clinical
evaluation and diagnostic investigations to establish the diagnosis, rule out
mimics and other conditions (Table 7), and develop an immediate plan of care.
The use of a standardized risk stratification tool is recommended to guide the
triaging process. To date, the ABCD2 score (Table 8) appears to be the best clinical

Ischemic Attack
tool available for stratifying TIA patients in making recommendations for hospital

Transient
admission (Table 9).

Table 7. Differential Diagnoses of TIA28

Migraine with aura

Neurological disorders Focal epileptic seizure
Other

Metabolic disorders (particularly hypoglycemia)

Vertigo of ENT origin (e.g., Ménière’s disease, benign
paroxysmal positional vertigo [BPPV], vestibular neuritis)
Syncope
Non-neurological disorders
Orthostatic hypotension
Hyperventilation syndrome
Hysteria, simulation
Psychosomatic disorders

Amaurosis related to malignant hypertension

Acute glaucoma
Intracranial hypertension
In case of amaurosis fugax
Central retinal vein thrombosis
(blindness)
Retrobulbar optic neuritis
Retinal detachment
Temporal arteritis

It should be kept in mind that the ABCD2 score (Table 8) is not an absolute
determinant for hospitalization. However, it may be reasonable to hospitalize a
TIA patient if: the symptom presented within 48 hours; symptoms are multiple
and increasing (crescendo TIAs); patient has an ABCD2 score >3 or has high risk
cardiac source of embolism; hypercoagulable state, or symptomatic internal
carotid artery (ICA) stenosis; or if the evaluation cannot be rapidly completed in
an out-patient basis. Close observation during hospitalization has the potential
to allow more rapid and frequent administration of t-PA should a stroke occur.30,31

Routine emergent diagnostic tests for patients with suspected TIA or minor strokes
include blood count, glucose levels, coagulation studies, electrocardiography,
and neurovascular imaging. The imaging should be done as early as possible,
not beyond 24 hours for emergent patients (i.e. those classified to be at highest
risk of recurrent stroke) or 7 days for those classified as urgent. Patients who may
be candidates for carotid revascularization should have a CT Angiography (CTA),
MR Angiography (MRA), or a carotid duplex ultrasound (CDS) within 24 hours for
emergent patients or 7 days for urgent patients.

19
 Table 8. Actual Scoring System using the ABCD2 Rule
Risk Factor Points
Age >60 years 1
Blood pressure >140/90 mm Hg 1
Clinical features
Unilateral weakness 2
Language disturbance without weakness 1
overview

Diabetes 2
Durations >60 min 2
Duration 10-59 min 1
Duration <10 min 0
ABCD2 score (Total)

Table 9. Recommendations for Hospital observation using the ABCD2 score29

ABCD2 2-day stroke
Comment
score risk
Hospital observation may be unnecessary without another indication,
0-3 1
e.g. new AF

4-5 4.1 Hospitalization justified in most situations

6-7 8.1 Hospital observation worthwhile

VIII. CLINICAL STROKE SYNDROMES BASED ON BLOOD VESSEL INVOLVEMENT

Physicians encountering neurological cases are asked to answer several questions such
as: “Is there a lesion?”, “Where is the lesion?”, and “Can anything be done about the
lesion?” It is therefore crucial to get a thorough history and perform a goal-directed
physical and neurological examination to localize the region that is affected. This can
help the clinician decide which neuroimaging test to use and which particular area to
focus on. Table 10 presents the common clinical stroke syndromes based on vascular
involvement.

IX. RISK FACTORS FOR STROKE AND STROKE PREVENTION

Different strategies can be implemented for circumventing the occurrence of strokes

and minimizing disability from it. These can be divided into primordial prevention
(preventing occurrence of risk factors), primary prevention (preventing a first stroke),
secondary prevention (preventing recurrence), and tertiary prevention (preventing
or reducing complications of stroke). The SSP recommendations for the primary and
secondary prevention of common stroke risk factors are presented in Chapter 2.

As with most non-communicable diseases, the risk factors for stroke are classified into
modifiable or non-modifiable. The non-modifiable factors include older age, male sex,
ethnicity (i.e., non-white), and familial history of stroke or TIA. The modifiable stroke risk
factors are presented in Tables 11 and 12.
20
 Table 10. Common Clinical Stroke Syndromes Based on Blood Vessel Involvement16,32-34
Blood Vessel Involvement Signs and Symptoms
Contralateral weakness of leg & foot > arm
(cerebral paraplegia, if bilateral ACA occlusion)
Cortical sensory loss over toes, foot, & leg
Urinary incontinence
Contralateral grasp reflex, paratonia (gegenhalten)
Frontal lobe release signs, abulia (akinetic mutism), amnesia with apathy
Dyspraxia; tactile aphasia of left limbs
Others: postural/gait disorders, mental impairment, transcortical motor
Anterior Cerebral Artery (ACA) aphasia, whispering, etc.
Contralateral weakness of face & arm > leg
Preferential gaze looking away from the weakness
Contralateral hemineglect
Contralateral hemisensory impairment over face, arm, & leg
Global aphasia (if dominant hemisphere is affected)
Middle Cerebral Artery (MCA) Homonymous hemianopia (often superior quadrantanopia)
Proximal Segment
Contralateral weakness of face & arm > leg
Contralateral hemisensory loss of face & arm > leg
Preferential gaze looking away from the weakness
Expressive (Broca’s) aphasia (if dominant hemisphere is affected)
Anatomical location/structure involved
Motor leg (and arm) area
Sensory area for foot & leg
Superior frontal gyrus (bilateral)
Posterior frontal lobe
Mesiofrontal region (bilateral)
Corpus callosum
Somatic motor area supplied by MCA in frontal lobe
Opposite frontal eye field or projecting fibers
Non-dominant parietal lobe
Somatosensory area supplied by MCA in parietal lobe
Central language area & dominant parietooccipital cortex
Optic radiation deep to second temporal convolution
Somatic motor area (face & arm) in frontal lobe
Somatic sensory area (face & arm) in parietal lobe
Opposite frontal eye field or projecting fibers
Broca’s area in frontal suprasylvian area

MCA Superior Division

Contralateral weakness of face & arm Somatic motor area for face & arm
Contralateral hemisensory loss of face & arm Somatic sensory area for face & arm
Conduction aphasia (if dominant) Parietal operculum
Agraphia, acalculia, finger agnosia, right-left confusion (Gerstmann) Dominant parietal cortex
Constructional dyspraxia (if non-dominant) Non-dominant parietal lobe
MCA Parasylvian region
Homonymous hemianopia (often superior quadrantanopia) Optic tracts as it courses towards the brainstem
Contralateral constructional dyspraxia; left visual neglect Non-dominant parietal lobe
(if non-dominant) Dominant temporal lobe, incl. angular & supramarginal
Receptive (Wernicke’s) aphasia (if dominant hemisphere) gyri

MCA Inferior Division

Contralateral hemiplegia (primarily upper extremity) Motor area (incl. descending fibers in corona radiata
Contralateral hemisensory loss & int. capsule); sensory area (incl. thalamoparietal
Transcortical motor and/or sensory aphasia projections)
(if dominant hemisphere is affected)
Cortical abnormalities (apraxia, neglect); less frequent: pure motor
MCA Deep territory hemiparesis with cortical signs, dyarthria, clumsy hand
Illustrations adapted from Misulis K and Head T (2007). Netter's Concise Neurology. Philadelphia: Elsevier.
21

overview

22
Table 10. (continued)
Vascular territory involved
Posterior cerebral artery (PCA)
unilateral
PCA, bilateral
(Anton’s syndrome)
PCA
(Weber syndrome)
PCA-MCA border zone
(Balint syndrome)
Anterior inferior cerebellar artery (AICA) Ipsilateral dysmetria, hearing loss, Horner’s syndrome, choreiform
Lateral Pontine Syndrome
Superior cerebellar artery
(SCA)
Superior cerebellar artery syndrome
Posterior inferior cerebellar artery
(PICA)
(Wallenburg syndrome)
Basilar artery
(Top of the basilar syndrome)
Basilar artery
(Locked-in syndrome)
Vertebral artery (VA)
(Dejerine syndrome)
Anterior spinal artery
overview
Signs and Symptoms Anatomical location/structure involved
Signs and symptoms Occipital lobe
Homonymous hemianopia with macular sparing Ventral occipital cortex; infracalcarine
Contralateral achromatopsia (loss of color differentiation) Myers loop (temporal lobe) or infracalcarine
Superior quadrantanopsia Optic radiation; supracalcarine
Inferior quadrananopsia
Bilateral visual loss with denial of blindness and confabulations or Bilateral occipital lobes, visual association areas
visual hallucinations
Contralateral weakness of extremities; ipsilateral oculomotor palsy
with parasympathetic involvement Issuing third nerve and cerebral peduncle
Optic ataxia (inability to reach targets with optic guidance),
Bilateral occipital-parietal border zones
oculomotor apraxia, simultagnosia
Lateral pons
dyskinesia, contralateral thermoanalgesia
Dorsolateral upper brainstem, cerebellum, superior
Ipsilateral limb ataxia, vertigo nystagmus, dysarthria, gait ataxia
cerebellar peduncle
Vertigo, nausea, vomiting, ipsilateral facial numbness and Lateral medulla
dysmetria, Horner’s syndrome, choreiform dyskinesia,
contralateral thermoanalgesia
Somnolence, peduncular hallucinosis, convergence nystagmus, Midbrain, thalamus, mesial temporal lobes, and
skew deviation, oscillatory eye movements, Colliers sign
(retraction and elevation of eyelids), vertical gaza paralysis occipital lobes
Quadriplegia, horizontal gaze paralysis, bifacial paralysis, tongue Lower pons
and mandibular weakness; awareness is spared
Contralateral weakness of leg and arm, hemisensory loss; Medulla and cervical spinal cord
ipsilateral tongue paralysis
Quadriparesis, bilateral pain and temperature loss, decreased
sphincter tone, autonomic instability, and hyperreflexia;
proprioception spared
 Table 11. Risk Factors for Stroke in 22 countries including the Philippines:
the INTERSTROKE Study35
Population-attributable
Risk Factor risk (PAR) % (99% CI)
Hypertension 34.6 (30.4-39.1)

Smoking 18.9 (15.3-23.1)

overview
Waist-to-hip ratio 26.5 (18.8-36.0)

Dietary risk score 18.8 (11.2-29.7)

Regular physical activity 28.5 (14.5-48.5)

Diabetes mellitus 5.0 (2.6-9.5)

Alcohol intake 3.8 (0.9-14.4)

Cardiac causes 6.7 (4.8-9.1)

Ratio of apolipoprotein B to A1 24.9 (15.7-37.1)

Stress 4.6 (2.1-9.6)

Depression 5.2 (2.7-9.8)

Table 12. Risk Factors for Stroke among Filipinos: the PNA-DOH RIFASAF Study36

Risk Factor Odds Ratio (OR) (95% CI)

Hypertension 6.01 (4.48-8.05)
Diabetes 1.60 (1.10-2.32)
Atrial Fibrillation 1.91 (0.51-7.19)
Myocardial Infarction 4.67 (1.18-18.52)
Rheumatic Heart Disease 3.69 (1.05-12.99)
Smoking 1.36 (1.00-1.86)
Snoring 3.37 (2.49-4.58)
Stress 1.69 (1.25-2.29)
Frequent Alcohol Intake 1.75 (1.14-2.70)

There are other emerging risk factors for stroke which are not covered in this handbook.
Although the focus is on the individual risk factors, the appropriate approach in
prevention of a first-ever stroke (FES) or recurrence is to perform total risk assessment
and to address each individual risk. The use of validated risk assessment tools such as
the Framingham Risk Score (for estimating the risk of cardiovascular events, including
stroke) has not been a practice of many physicians. Making patients aware of their risk
for developing heart attacks or stroke within 5 to 10 years’ time will urge them to focus
on the risk and protective factors, as well as initiate healthier lifestyle practices.

It has been established that atherosclerosis is the underlying condition of most cases
of myocardial infarction, stroke, and vascular deaths, hence the awareness of the
atherosclerotic risk factors can help direct attention and efforts on the more prevalent
ones. The prevalence of the atherosclerosis-related risk factors and diseases is shown
in Table 13.
23
 Table 13. Prevalence of Atherosclerosis-Related Risk Factors and Diseases (>20 years old),
Philippines (2003 & 2008 FNRI National Nutrition Survey)10,13
2003 2008
Risk Factor
% (95% CI) % (95% CI)
Hypertension, single visit 22.5 25.3
Hypertension, true prevalence 17.4 25.7
Diabetes by FBG 3.4 4.8
overview

Diabetes by FBG and/or History 4.6 6.2

Diabetes by FBG and/or History and/or 2HrPG load NA 7.2
Dyslipidemia 62.5 73.1
Smoking 35.2 31
Obesity by BMI (≥30) 4.8 5.2
Coronary Artery Disease 1.8 1.3
Cerebrovascular (Stroke) 1.4 1.2
Peripheral Arterial Disease 0.4 1.2

X. THE PHILIPPINE GOVERNMENT AND STROKE

Through SSP’s effort to promote awareness on stroke, former President Gloria

Macapagal-Arroyo signed Proclamation Number 92 in 2001, which declared every
third week of August as “Brain Attack Awareness Week”. The SSP also holds its annual
convention and stroke awareness programs during this month.

Since 2011, the Philippine Health Insurance Corporation (PhilHealth) under the
Department of Health (DOH), started implementing its policy of fixed deductions to
accredited hospitals and clinics initially for 11 medical and 11 surgical cases including
stroke. Under its reimbursement scheme called Case Rates Payment, the allotted
payment for patients admitted for cerebral infarction of any cause (designated
as Cerebrovascular Accident I, or CVA I) is Php 28,000, while those admitted for
hemorrhagic stroke (designated as Cerebrovascular Accident II, or CVA II) is Php
38,000. As previously discussed, the use of the term “CVA” is not accurate, although
it is still used by local health agencies in conformity with the previous International
Classification of Diseases (ICD) codes for cerebrovascular diseases. (See Appendix A
for ICD-10-CM codes for cerebrovascular diseases).

For patients admitted to government hospitals, a “No Balance Billing Policy” is

applied, thus patients need not pay anything regardless of the length of hospital
stay or presence of any complication from stroke. On the other hand, for private
patients, the PhilHealth member is required to pay the balance beyond the stated
reimbursement schedule.

Any individual with residual deficit/s from stroke may avail of the benefits in “Persons
with Disability (PWD) Program” of the Department of Social Welfare and Development
(DSWD). Patients issued with PWD identification card are entitled to a 20% discount
on medications, some basic groceries, recreational activities, and transportation,
among others. Patients can apply for such benefits in their respective Municipal or
City Halls.
24
Stroke remains a global public health concern. To decrease the incidence of stroke,
population-based strategies for stroke prevention must be implemented. These include
increasing public awareness and prevention/control of risk factors. To help improve
geographic variations in practice patterns within and across regions, clinical practice
guidelines have become available for use by healthcare providers. Minimizing the
impact of stroke in the society entails implementing all known strategies at the national
level. However, there is a continuing challenge in exploring new solutions to decrease
the overall stroke burden.

overview
References

1. World Health Organization. Top 10 Causes of Death, Fact Sheet 310, updated July 2013. http://www.who.
int/mediacentre/factsheets/fs310/en/index.html. Accessed February 11, 2014.
2. Murray CJ, Vos T, Lozano R, Naghavi M, et al. Disability-adjusted life years (DALYs) for 291 diseases and
injuries in 21 regions, 1990—2010: a systematic analysis for the Global Burden of Disease Study 2010.
Lancet. 2012; 380: 2197-2223.
3. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age
groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012
Dec 15;380(9859):2095-128.
4. Mendis S, Puska P, Norrving B. eds. Global Atlas on Cardiovascular Disease Prevention and Control.
Geneva: World Health Organization, 2011.
5. National Statistical Office, Republic of the Philippines. Philippines in figures 2014. Available at http://
www.census.gov.ph/. Accessed March 10 2014.
6. Global Burden of Disease Study 2010. Philippines Global Burden of Disease Study 2010 (GBD 2010)
Results 1990-2010. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2013.
7. Loo KW, Gan SH. Burden of Stroke in the Philippines. Int J Stroke. 2013 Feb;8(2):131-4.
8. Navarro JC, Baroque AC, Lokin JK, et al. The real stroke burden in the Philippines. Int J Stroke. 2014
Jul;9(5):640-1.
9. World Health Organization. Baseline country survey on medical devices. Geneva: World Health
Organization, 2010.
10. Dans AL, Morales DD, Abola TB, Roxas A, et al.; for NNHeS 2003 Group. National Nutrition and Health
Survey (NNHeS): Atherosclerosis-related diseases and risk factors. Phil J Int Med. 2005;43;103-115.
11. Navarro J. Prevalence of stroke: a community survey. Phil J Neuro. 2005; 9:11-15.
12. Collantes E, for the SSP. The SSP SICAP (Stroke in Currimao – Philippines) Study. Presented during the
10th SSP Annual Convention - The Philippine Stroke Agenda. Holiday Inn, Clark Field Pampanga, August
20-22, 2009.
13. Sy RG, Morales D, Dans A, et al. Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the
Philippines. J Epidemiol. 2012; 22(5): 440–447.
14. Roxas A., for SSP. The SSP SAGIP (Stroke Awareness Gap in the Philippines) Study. Presented at the 10th
SSP Annual Convention, Pampanga, 20-22 August 2009.
15. Yu R, San Jose MC, Gan R. et al. Sources and reasons for delays in the care of acute stroke patients. J Neurol
Sci. 2002 Jul 15;199(1-2):49-54.
16. Ropper A, Samuels MA. Adams and Victor's Principles of Neurology, 9th ed. Philadelphia: McGraw-Hill,
2009.
17. Albers DW, Caplan LR, Easton JD, et al. for the TIA Working Group. Transient Ischemic Attack: proposal
for a new definition. N Engl J Med. 2002; 347:1713-1716.
18. Sacco RL, Kasner SE, Broderick JP, et al. An Updated Definition of Stroke for the 21st Century: A Statement
for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke.
2013; 44:2064-4089.
19. Hankey GJ. The global and regional burden of stroke. Lancet Global Health. 1 November 2013; 1(5):239-
240.
20. Krishnamuthi R, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during
1990–2010: findings from the Global Burden of Disease Study 2010. Lancet Global Health. 1 November
2013; 1(5);259-281.
25
 21. Sung et al. Oxfordshire community stroke project classification improves prediction of post-thrombolysis
symptomatic intracerebral hemorrhage. BMC Neurology. 2014, 14:39.
22. Navarro J, Bitanga E, Suwanwela N, et al. Complication of acute stroke: A study in ten Asian countries.
Neurology Asia. 2008;13:33-39.
23. Ustrell-Roig X, Serena-Leal J. Stroke: Diagnosis and Management of Cerebrovascular Disease. Rev Esp
Cardiol. 2007;60(7):753-69.
24. Ay H, Benner T, Arsava EM, et al. A Computerized Algorithm for Etiologic Classification of Ischemic
Stroke; The Causative Classification System. Stroke. 2007;38:2979-2984.
25. De Guzman V, Yu R, San Jose MC. Risk factors and outcome among Filipino stroke patients with
intracranial stenosis. Presented during the PNA Annual Convention.
26. Libman RB, Wirkowski E, Alvir J, et al. Conditions that mimic stroke in the emergency department.
Implications for acute stroke trials. Arch Neurol. 1995 Nov;52(11):1119-22.
27. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-
analysis. Lancet Neurol. 2007; 6: 1063–1072.
28. Calvet D, Mas JL. Clinical features of transient ischemic attacks. In: Norrving B (ed). Oxford Textbook of
Stroke and Cerebrovascular Disease. New York: Oxford University Press, 2014. 82p.
29. Johnston SC, Rothwell PM, Huynh-Huynh MN, et al. Validation and refinement of scores to predict very
early stroke risk after transient ischemic attack. Lancet. 369:283-292, 2007.
30. Nguyen-Huynh MN, Johnston SC. Is hospitalization after TIA cost-effective on the basis of treatment with
tPA? Neurology. 2005; 65:1799–1801.
31. Hacke W, Donnan G, Fieschi C, et al. for the ATLANTIS Trials Investigators, ECASS Trials Investigators,
NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled
analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6;363(9411):768-74.
32. Brazis PW, Masdeu JC, Biller J. Localization in Clinical Neurology. 6th ed. Philadelphia: Lippincott,
Williams & Wilkins, 2011.
33. Misulis KE, Head TC. Netter's Concise Neurology. Philadelphia, Elsevier, 2007.
34. Nouh A, Remke J, Ruland S. Ischemic posterior circulation stroke: a review of anatomy, clinical
presentations, diagnosis, and current management. Front Neurol. 2014 Apr 7;5:30.
35. O'Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in
22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010 Jul 10;376(9735):112-23.
36. Roxas A, for the PNA-DOH RIFASAF Collaborators. The RIFASAF Project: a case-control study on risk
factors for stroke among Filipinos. Phil J Neuro. 2002; 6:1:1-7.

26
 CHAPTER II
Guidelines for Primary and Secondary
Prevention of Stroke

I. Hypertension and Stroke

II. Diabetes Mellitus and Stroke
III. Dyslipidemia and Stroke
IV. Cigarette Smoking and Stroke
V. Excessive Alcohol Intake and Stroke
VI. Cardiac Risk Factors and Stroke
I. Nonvalvular Atrial Fibrillation
II. Acute Myocardial Infarction
III. Cardiomyopathy
IV. Valvular Heart Diseases
IV.A. Rheumatic Mitral Valve Disease
IV.B. Mitral Valve Prolapse and Mitral Annular
Calcification
IV.C. Aortic Valve Disease
V. Prosthetic Heart Valves
VII. Extracranial Carotid Stenosis and Stroke
VIII. Intracranial Stenosis and Stroke
IX. Peripheral Arterial Disease and Stroke
X. Physical Inactivity and Stroke Sixth
Edition
2014
XI. Obesity and Stroke
XII. Nutrition and Stroke
 Guidelines for Primary and Secondary Prevention of Stroke
The relative contribution of each risk factor to stroke varies with each stroke subtype.
In this chapter, the significant associations between stroke and its main modifiable risk
factors are highlighted, including epidemiology and the findings of studies or clinical
trials. The recommendations presented herein are based on several evidence-based
guidelines and consensus of the members of the Stroke Society of the Philippines.
Where applicable, the classes of recommendations and levels of evidence (see Guide to
the Use of SSP Handbook) are included. Because cerebral infarcts comprise the majority
of stroke cases, the focus is primarily on the prevention of ischemic stroke and transient
ischemic attack. There are other less well-documented or emerging risk factors for
stroke but are beyond the scope of this chapter. These include metabolic syndrome,
illicit drug abuse, oral contraceptive use, sleep disorders (e.g., sleep-disordered
breathing, insomnia), migraine headache, hyperhomocysteinemia, hypercoagulable
states (including pregnancy), sickle cell disease, inflammation, and infection. Some of
these risk factors are discussed under the sections of Stroke in the Young and Stroke in
Prevention

Pregnancy (Chapter 9). Although the primary outcome of interest is the prevention of
stroke, the recommendations also reflect evidences for the prevention or reduction of
risks for other cardiovascular outcomes.

I. HYPERTENSION AND STROKE

There is overwhelming evidence substantiating hypertension as the major independent
risk factor for stroke and stroke-related mortality. Hypertensive individuals are 3-4
times more likely to develop stroke than individuals with normal blood pressures (BP).1
Both systolic and diastolic hypertension (defined as >140 mm Hg and >90 mm Hg,
respectively) have a continuous association with the risk of ischemic stroke. Likewise, the
risk for hemorrhagic stroke is also significant in untreated cases of hypertension (odds
ratio [OR]=3.5; 95% confidence interval [CI], 2.3-5.2).2 Studies have shown that there is a
higher risk of fatal vascular events with every 20 mm Hg increase in SBP (or 10 mm Hg
increase in DBP) over the range of 115/75 mm Hg.3,4

The risk factors (and markers) for hypertension include age, ethnicity, genetic factors
(e.g., family history of hypertension), metabolic syndrome, cigarette smoking, physical
inactivity, obesity, dietary factors (i.e. high sodium intake, lower potassium intake,
excessive dietary fats and high alcohol intake), psychosocial stressors, and sleep-
disordered breathing. The most frequently affected are the elderly–usually with higher
systolic BP5–because of the normal effects of ageing in the cardiovascular system and
buildup of risk factors through time.

A. Epidemiology
The population-attributable fraction (PAF) of hypertension for stroke is 34.6% (95%
C.I., 30.4-39.1).6 In the Asia-Pacific region, the fraction of ischemic stroke linked
to hypertension ranged from 8% to 44% in men and 12% to 45% in women. The
corresponding range for hemorrhagic stroke is 18% to 66% in men and 15% to
49% in women.7 In the Philippines, the age-adjusted prevalence of hypertension is
20.6%.8 In the hospital-based population, hypertension-related stroke is the most
common cause of death, which is attributed to uncontrolled BP and poor compliance
to treatment.9

B. Risk Modification
It is well-established that the control or treatment of hypertension–as well as
risk factor prevention–substantially reduce the risk of a first or recurrent stroke,
myocardial infarction, vascular events, and its equivalents. Furthermore, it improves
the risk of all-cause and stroke-related mortalities as well as patient outcomes. The
28
Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC 8) provides a comprehensive, evidence-
based approach to the classification and treatment of hypertension.10 It stresses the
importance of lifestyle modifications in the overall management of hypertension.
Despite data showing that the first and recurrent stroke can be prevented by
hypertension awareness and BP control, the treatment and control remain low.

B.1. Primary Stroke Prevention

There is strong evidence showing that pharmacologic lowering of BP prevents
stroke and other BP-related target organ damage such as coronary heart diseases,
heart failure, and kidney failure.11 Relative to no treatment, pharmacologic
therapy reduces the risk of stroke by 32% (95% CI, 24-39%).12 Several classes of
antihypertensive agents (e.g., thiazide diuretics [TZD], angiotensin-converting
enzyme inhibitors [ACEI], angiotensin receptor blockers [ARB], calcium channel
blockers [CCB], and ß-blockers [BB]) are widely used for the treatment of
hypertension and as a means to prevent a first stroke. The risk ratios (RR, at 95% CI)

Prevention
for each drug class, when compared with placebo or no treatment, are 0.63 (0.57-
0.71) for TZD, 0.65 (0.52-0.82) for ACEIs, 0.58 (0.41-0.84) for CCB, and 0.83 (0.72-
0.97) for BB.13 In a meta-analysis of trials which compared the impact of treatment
with ACEI and ARB, the latter was inferior in reducing stroke risk among high-risk
patients (although both drugs are interchangeable in the case of heart failure).14
Nonetheless, there is no definitive evidence that any drug class provides special
protection against first stroke, hence the choice of antihypertensive medication/s
should be individualized.

Studies have shown that BP reduction is generally more important than the
choice of medication for primary prevention. While it is well-established that
pharmacologic therapy confers significant benefit, a comprehensive approach is
recommended to help keep the BP under control. Strategies should include diet
modification (e.g., low salt and high potassium content [i.e. DASH diet]), regular
aerobic exercise, gradual weight loss, and smoking cessation. The epidemiologically
expected benefit of BP control can be achieved within a few years even for the
very elderly. A meta-analysis of randomized trials show that BP lowering results
in 30% to 40% primary stroke risk reduction, while a greater risk reduction has
been observed with each larger decreases in BP.15 Epidemiological studies show
that SBP reductions of 1 mm Hg decreases stroke risk by 5%.16 Whereas, a 10
mm Hg lower SBP, in individuals aged <60 years, 60-69 years, and ≥70 years, is
associated with approximately 40%-50%, 30%-40%, and 20%-30% lower stroke
risks respectively.17 Control of isolated systolic hypertension (i.e. SBP >160 mm
Hg and DBP < 90mm Hg) in the elderly can decrease stroke risk by 36%.18 Even a
small reduction in diastolic BP to as low as 2 mm Hg is also associated with 14%
fewer strokes.18 Furthermore, there is a potential effect of BP lowering in improving
stroke mortality; SBP declines of 2 mm Hg, 3 mm Hg, and 5 mm Hg reduce deaths
due to stroke by 6%, 8%, and 14% respectively.19

Despite the ease of diagnosis and efficacy of antihypertensive regimens,

hypertension remains prevalent or undertreated in the community. Population-
based approaches aimed at targeting the risk factors and downward shift in BP
distribution, as well as improved compliance to treatment, are needed.

B.2. Secondary Stroke Prevention

A systematic review showed that pharmacologic treatment of hypertension is
associated with a significant reduction in recurrent stroke (RR=0.78; 95% CI, 0.68-
0.90).20 A greater decline in recurrence rate was observed with larger reductions
in SBP. In contrast to primary prevention, antihypertensive therapy for secondary
prevention among individuals with “compelling indications” (e.g.,
29
 recurrent stroke, ischemic heart disease, chronic kidney disease) is limited to certain
antihypertensive agents, as not all drug classes have proved to confer benefit.

The Post-Stroke Antihypertensive Treatment Study (PATS), the first major trial
to investigate the effect of BP treatment for secondary stroke prevention,
demonstrated a higher risk reduction (relative risk reduction [RRR] = 30%; 95%
CI, 14-43%) with diuretic use (i.e. indapamIde) compared to placebo. Another
trial, named Perindopril Protection Against Recurrent Stroke Study (PROGRESS),
confirmed the benefit of an ACE inhibitor–based regimen in reducing the incidence
of secondary stroke as well as myocardial infarction. In addition, combination
therapy with perindopril and indapamide resulted to larger reductions in stroke
and hypertensive risks than with perindopril monotherapy. On the other hand,
ß–blockers, calcium channel blockers, or renin-angiotensin system inhibitors alone
were not shown to have significant benefit in secondary prevention.20,21 Although
a number of meta-analyses have shown a significant reduction in recurrent stroke
with the use of diuretics (alone or in combination with angiotensin-converting
enzyme inhibitors [ACEIs]), it remains uncertain whether a particular drug class or
Prevention

a specific drug confers special protection after ischemic stroke.

There is limited data on the optimal BP target for secondary stroke prevention.
Results of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, which
randomized patients to target SBP levels of <150 mm Hg versus <130 mm Hg,
showed that there was no difference between the target groups with regard to the
composite outcome of stroke, MI, and vascular death (hazard rate [HR]=0.84; 95%
CI, 0.68-1.04). The management of BP during acute stroke is discussed in Chapter 3.

C. Recommendation
C.1. Primary Stroke Prevention
Regular screening for hypertension (i.e. at least every 2 years in most adults
and more frequently in minority populations and the elderly) and appropriate
management (Class I, level A), including dietary changes, lifestyle modification
and pharmacological therapy as summarized in the JNC 8 and the ESH/ESC
guidelines (Table 1), are recommended.

C.2. Secondary Stroke Prevention

1. Antihypertensive treatment is recommended for both prevention of recurrent
stroke and other vascular events in patients who have had an ischemic stroke
or TIA and are beyond the hyperacute period (Class I, level A). Because
this benefit extends to people with or without a history of hypertension,
this recommendation should be considered for all ischemic stroke and TIA
patients (Class IIa, level B).
2. The absolute target BP level and reduction are uncertain and should be
individualized, but benefit has been associated with an average reduction
of 10/5 mm Hg. BP levels of <140/90 mm Hg are acceptable targets, even in
diabetic patients (Class IIa, level B).
3. BP should be adequately controlled in patients with hypertension. Physicians
should check the BP of all patients at every visit. Patients with hypertension
should be advised to monitor their BP at home.
4. Several lifestyle modifications have been associated with BP reductions and
should be included as part of a comprehensive antihypertensive therapy
(Class I, level B).
5. The optimal drug regimen remains uncertain. However, available data support
the use of thiazide diuretics, CCBs, ACEIs, ARBs, or their combinations (Class I,
level A). The choice of specific drugs and targets should be individualized on
the basis of reviewed data and consideration of specific patient characteristics
30
 (e.g., extracranial cerebrovascular occlusive disease, renal impairment, cardiac
disease, diabetes) (Class IIb, level C).
6. The SSP supports the guidelines set forth by the Philippine Society of
Hypertension.
Table 1. Possible combinations of classes of antihypertensive drugs22
Preferred combinations • Thiazide diuretics + ACE inhibitors
• Thiazide diuretics + CCB
• Thiazide diuretics + ARB
• CCB + ARB
• CCB + ACE inhibitors
Useful combinations (with some
limitations) • Thiazide diuretics + Beta blockers
Possible combinations but less • Beta blockers + ARB
well-tested combinations • Beta blockers + CCBa
• Beta blockers + ACE inhibitors
• Beta blockers + other antihypertensives
• CCB + other antihypertives

Prevention
• ACE inhibitors + other antihypertensives
• ARB + other antihypertensives
• Thiazide diuretics + other
antihypertensives
Not recommended • ACE inhibitors + ARB
• ACE inhibitors + other antihypertensives
• ARB + other antihypertensives
• Thiazide diuretics + other
antihypertensives
modified from: Mancia et al. J Hypertens. 2013 Jul;31(7):1281-357.

References
1. Lawes CM, Vander Hoorn S, Rodgers A. International Society of Hypertension. Global burden of blood-
pressure-related disease, 2001. Lancet. 2008;371:1513–8.
2. Woo D, Haverbusch M, Sekar P, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke.
2004 Jul;35(7):1703-8.
3. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular
mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Prospective
Studies Collaboration. Lancet. 2002;360:1903–1913.
4. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management
of ischemic heart disease: a scientific statement from the American Heart Association Council for High
Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention.
Circulation. 2007 May 29;115(21):2761-88.
5. SHEP Cooperative Research Group. Prevalence of stroke by antihypertensive drug treatment in older
persons with isolated systolic hypertension. Final result of the Systolic Hypertension in the Elderly
Program (SHEP). JAMA. 1991;265:3255-3264.
6. O'Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in
22 countries (the INTERSTROKE study): a case–control study. Lancet. 2010;376:112-123.
7. Martiniuk AL, Lee CM, Lawes CM, et al. Hypertension: its prevalence and population-attributable fraction
for mortality from cardiovascular disease in the Asia-Pacific region. J Hypertens. 2007 Jan;25(1):73-9.
8. Sy RG, Morales D, Dans A, et al. Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the
Philippines. J Epidemiol. 2012; 22(5): 440–447.
9. Sison J, Arceo LP, Trinidad E, et al. Philippine Heart Association-Council on Hypertension Report on
Survey of Hypertension and Target Organ Damage (PRESYON 2-TOD): A Report on Prevalence of
Hypertension, Awareness, Treatment Profile and Control Rate. Phil J Cardiol. 2007;35:1–9.
10. James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood
Pressure in Adults: Report from the Panel Members appointed to the Eighth Joint National Committee
(JNC 8). JAMA. 2014 Feb 5;311(5):507-20.
11. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline
for heath professionals from the American Heart Association/American Stroke Association. Stroke.
2011;42:517-584.
12. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive
31
 therapies used as first-line agents: a network meta-analysis. JAMA. 2003;289:2534 –2544.
13. Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database Syst Rev. 2009:CD001841.
14. Ong HT, Ong LM, Ho JJ. Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor
Blockers (ARBs) in Patients at High Risk of Cardiovascular Events: A Meta-Analysis of 10 Randomised
Placebo-Controlled Trials. ISRN Cardiol. 2013 Nov 6;2013:478597.
15. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45:000-000.
16. Grossman E. Blood Pressure: The lower, the better. Diabetes Care. May 2011;34:2;S308-S312.
17. Lawes CMM, Bennett DA, Feigin VL, et al. (2004). Blood pressure and stroke. An overview of published
reviews. Stroke. 2004;35:1024–1033.
18. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease, part 1: prolonged
differences in blood pressure: prospective observation studies corrected for the regression dilution bias.
Lancet. 1990;335:765–774.
19. Stamler J, Rose G, Stamler R, et al. INTERSALT study findings. Public health and medical care implications.
Hypertension. 1989;14:570-577.
20. Liu L, Wang Z, Gong L, et al. Blood pressure reduction for the secondary prevention of stroke: a Chinese
trial and a systematic review of the literature. Hypertens Res. 2009;32:1032–1040.
Prevention

21. Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other
vascular events: a systematic review. Stroke. 2003;34:2741-2748.
22. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial
hypertension: the Task Force for the management of arterial hypertension of the European Society of
Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013 Jul;31(7):1281-
357.

II. DIABETES MELLITUS AND STROKE

The principal disorders of glucose metabolism (i.e. Type 1 diabetes mellitus (DM), Type
2 DM, and pre-DM) predispose individuals to a higher risk of atherosclerosis and earlier
onset of vascular events. The criteria for the diagnosis of DM and pre-DM (Table 2) are
based from the clinical symptoms of hyperglycemia and measures of plasma glucose
(PG) and glycosylated hemoglobin (A1c).

Table 2. Criteria for Diagnosis of Diabetes Mellitus and Prediabetes1

DIABETES MELLITUS (4 options)* PREDIABETES
• A1c ≥6.5%a • Impaired Fasting Glucose (IFG): FPG 100 mg/dL–125
• FPG ≥126 mg/dL (7.0 mmol/L)b mg/dL (5.6 mmol/L–6.9 mmol/L)
• 2-hour PG ≥200 mg/dL (11.1 mmol/L) • Impaired Glucose Tolerance (IGT): 2-hour PG in
during an OGTTc the 75-g OGTT 140 mg/dL–199 mg/dL (7.8 mmol/L–11
• Random PG ≥200 mg/dL (11.1 mmol/L)d mmol/L)
• A1c 5.7–6.4%
A1c: glycosylated hemoglobin; FPG: fasting plasma glucose; OGTT: oral glucose tolerance test; PG:
plasma glucose
a
The test should be performed in a laboratory using a method that is NGSP-certified and
standardized to the Diabetes Control and Complications Trial (DCCT) assay.
b
Fasting is defined as no caloric intake for at least 8 hours
c
The test should be performed as described by the WHO, using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water.
d
In persons with classic symptoms of hyperglycemia or hyperglycemic crisis
* In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing.

A. Epidemiology
The global prevalence of DM is estimated to be 8.3% (about 382 million people) of
adult population.2 In the Philippines, the prevalence of DM (based on fasting blood
sugar [FBG]) remains high at 3.9%.3

A.1 Prediabetes and Stroke

In a meta-analysis of 15 prospective cohort studies4, eight (8) studies which
32
 analyzed prediabetes (at FPG 100-125 mg/dL) did not show an increased risk of
stroke after adjustment for cardiovascular risk factors (1.08, 95% CI, 0.94-1.23). On
the other hand, five studies on prediabetes (at FPG 110-125 mg/dL) showed an
increased risk of stroke after adjustment for established risk factors (1.21, 95%CI,
1.02-1.44). It was concluded that prediabetes may be associated with a higher
future risk of stroke.

A.2. Diabetes and Ischemic stroke

Studies have shown that diabetes independently increases the risk of ischemic
stroke, with an adjusted relative risk (RR) ranging from 1.5 to 3.7.5 Among
Filipinos, there is a 1.6-fold higher risk for stroke in diabetic patients compared to
normoglycemic individuals.6 DM is often a co-morbid condition seen in persons
with established cerebrovascular disease; up to 28% of ischemic stroke patients
have pre-diabetes, while 25%-45% have overt DM.5

The increased risk for ischemic stroke can be explained by the increased
atherogenic risk in the intra- and extracranial vessels attributable to dyslipidemia,

Prevention
hypertension, and hyperglycemia. Hyperinsulinemia and insulin resistance also
lead to atherosclerotic changes independent of the hyperglycemic state or other
attendant cardiovascular (CV) risk factors. This is particularly true in the small
cerebral vessels, hence the increased incidence of both overt and silent lacunar
infarcts.

A.3. Diabetes and Intracerebral Hemorrhage

Although case control studies were inconclusive of whether DM is an independent
risk factor for intracerebral hemorrhage (ICH), one meta-analysis suggested that
diabetes is a weaker cause of ICH (RR=1.30; 95% CI, 1.02-1.67) as compared to
chronic hypertension.7 DM was not found to be independently associated with
aneurysmal subarachnoid hemorrhage (SAH). However, recent studies have
established a correlation between type 1 DM and the incidence of non-aneurysmal
SAH.8

In a study of 138 rt-PA-treated ischemic stroke patients, DM was associated with

a 25% (8/32) symptomatic hemorrhage rate (compared with the 5% symptomatic
hemorrhage rate [5/106] in non-diabetic subjects), thus independently predicting
ICH in thrombolytic therapy (odds ratio [OR]=6.73; 95% CI 2.20-22.4).9

A.4. Diabetes, Stroke Recurrence, and Outcomes

DM is a consistent predictor of recurrence following stroke and is associated with
a significantly higher neurologic and functional impairment and longer hospital
stay. The increased risk of secondary stroke ranges from 2.1 to 5.6 times that of
the nondiabetics, which is independent of glycemic control during the interstroke
period.10 DM is also associated with reduced survival after the initial stroke. There is
doubling of mortality rate within the first year, while the 5-year survival rate is 20%.
The risk of stroke-related dementia is more than tripled with the presence of DM.11

B. Risk Modification
B.1. Primary Stroke Prevention
In normal nonpregnant adults, maintaining a glycosylated hemoglobin (A1c) level
below or around 7% has been shown to reduce microvascular complications of
DM (i.e. retinopathy, nephropathy, neuropathy) as well as macrovascular diseases
(e.g., stroke).1
In patients with recent-onset type 1 DM, intensive insulin therapy (IIT) (versus
conventional therapy) was associated with 42% risk reduction of macrovascular
events.12 In patients with type 2 DM, intensive treatment with either sulfonylureas
(SU) or insulin (versus conventional treatment) substantially reduced the risk
of microvascular and renal events, but not macrovascular diseases.13 Although
33
 intensive glycemic control delays the onset and/or progression of microvascular
complications, as well as decreases the burden of CV diseases, there is limited
benefit in reducing all-cause mortality or stroke risk (OR=0.93, 95% CI, 0.81-1.06).14

The studies on pharmacologic agents for DM have focused on the effect of

treatment on macrovascular events. The United Kingdom Prospective Diabetes
Study (UKPDS) found that using metformin as first-line therapy for overweight type
2 DM patients appears to decrease diabetes-related end points as such as stroke.13
A meta-analysis of RCTs using pioglitazone demonstrated a significantly lower risk
of death, stroke, or MI in a diverse population of diabetic patients15; its efficacy
in preventing stroke recurrence is still being examined in the Insulin Resistance
Intervention After Stroke (IRIS) trial (ClinicalTrials.gov, identifier: NCT00091949).

Approximately 20%-60% of DM patients are hypertensive. They have approximately

twice the risk of hypertensive nondiabetic patients for CV disease and an increased
risk for DM-specific complications.1 The primary prevention guidelines for stroke
have been revised with a target BP of <140/90 mm Hg in both types of DM, as
Prevention

no additional benefits were seen with lower target BP (i.e. ≤130/80 mm Hg) in
preventing major adverse CV events.16 For both types of DM, ACEI and ARB proved
efficacious in delaying disease progression, however there is no evidence that
these drugs are effective in primary prevention of diabetic nephropathy (DN).17
Although combination therapy with these two drugs further reduces proteinuria
than monotherapy, some studies have shown that ACEI/ARB combination causes
clinically significant decrease in the renal function (GFR).

DM is frequently accompanied by serum lipid and lipoprotein abnormalities which

predispose patients to CV events. Diabetic dyslipidemia should be recognized as
part of metabolic syndrome–another risk factor for stroke–which is extremely
common among T2DM patients. The American Diabetes Association (ADA) and
the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III)
recommends reduction of LDL-cholesterol level to less than 100 mg/dL among
diabetics, or even up to 70 mg/dL in the very high-risk groups.18 Addition of a
statin to existing DM treatments reduces stroke risk by 24% (95% CI, 6%-39%).19
T2DM patients with at least one additional risk factor (i.e. hypertension, retinopathy,
albuminuria, current smoking) and LDL less than 160 mg/dL without a prior history
of CVD would benefit from statin therapy with 48% stroke risk reduction (95%
CI, 11%-69%).20 In another trial using gemfibrozil, there was a 40% stroke risk
reduction (versus placebo) among DM patients, although it did not have an effect
in the nondiabetic group.21 Fenofibrates alone or in addition to a statin did not
show benefit in lowering CV events.22

B.2. Secondary Stroke Prevention

In one sub-study involving elderly patients with ischemic stroke, the presence of
diabetes was associated with 60% increased risk of recurrence (RR=1.59, 95% CI,
1.07-2.37).23 Diabetic patients with TIA also have an increased stroke risk during
the first week post-TIA. Although there are no major trials for secondary stroke
prevention that specifically examined interventions for pre-diabetes and DM,
glycemic control and preventive care are recommended for both primary and
secondary prevention. The ADA recommends a multifactorial approach; this
includes behavioral measures and the use of a statin, ACEI, ARB, and antiplatelet
drugs, as appropriate. The beneficial role of antiplatelets among stroke patients
with or without diabetes has been proven in many trials.

Although no single hypoglycemic drug has been proven to reduce macrovascular

events, there are studies suggesting possible advantages of pharmacotherapy.
Metformin potentially reduces the incidence of stroke by 31% (95% CI, 17-43%),
whereas other drugs are either more effective (i.e. rosiglitazone and pioglitazone)
34
 or about as effective (i.e. acarbose), but have greater adverse effects that may
compromise compliance.5 As mentioned previously, the effectiveness of
pioglitazone for secondary prevention is under investigation in the ongoing IRIS
trial.

Among patients with a history of stroke or TIA who are at high-risk for CV event,
aggressive lowering to HbA1c <6.5% has not been shown to be better than
standard treatment in reducing macrovascular events.24-26

Regardless of the pre-treatment LDL-cholesterol, the ADA recommends statin

therapy for diabetic patients with existing CVD, with an LDL goal of <100 mg/dL
(or <70 mg/dL [optional]). A meta-analysis of RCTs utilizing statin in DM patients
showed a higher risk reduction of stroke among diabetic patients (21%; 95% CI,
7–33%) than in the non-diabetic group (16%; 95% CI 7–24%).27

C. Recommendations
C.1. Primary Stroke Prevention

Prevention
1. Control of prediabetes (FPG=110-125 mg/dL) and DM, which includes behavioral
and pharmacological modification to prevent microvascular and macrovascular
complications, is recommended.
2. For prevention of microvascular complications, the HbA1c goal for the non-
pregnant adult in general is <7% (Class I, level A). The same HbA1c target of
<7% appears reasonable for many adults for macrovascular risk reduction
including stroke prevention (Class I, level B).
3. Rigorous BP and lipid control should be considered in patients with DM (Class
IIa, level B).
4. A target BP of <140/90 mm Hg (Class I, level A) is recommended as part of
a comprehensive risk-reduction program. An ACEI or ARB is preferred for DM
patients.
5. Adults with DM, especially those with additional risk factors, should be treated
with a statin to lower the risk of a first stroke (Class I, level A).
6. Aspirin is not recommended for primary stroke prevention in diabetic patients
without evidence of atherosclerotic disease (Class III, level A).
C.2. Secondary Stroke Prevention
1. Among diabetic patients with TIA or stroke, glucose control is recommended to
near-normoglycemic levels to reduce microvascular complications (Class I, level
A) and possibly macrovascular complications (Class IIb, level B). The HbA1c goal
should be <7% (Class IIa, level B).
2. Among patients with cardiovascular disease or in the presence of other vascular
risk factors, HBA1c should not be lowered to <6.5%.
3. Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in
patients with diabetes with a history of CVD (Class I, level A).
4. After ischemic stroke or TIA, all patients should probably be screened for
DM. The choice of test and timing should be guided by clinical judgment and
recognition, such that an acute illness may perturb plasma glucose values.
HbA1c, in general, may be more accurate than other screening tests in the
immediate postevent period (Class IIa, level C).

References
1. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(suppl
1):S14-S80.
2. International Diabetes Federation. IDF Diabetes Atlas, 6th ed. Brussels, Belgium: International Diabetes
Federation, 2013.
3. Sy RG, Morales D, Dans A, et al. Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the
Philippines. J Epidemiol. 2012; 22(5): 440–447.
4. Lee M, Saver J, Hong K, et al. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ. 2012;344:2-11.
5. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke
and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/
35
 American Stroke Association. Stroke. 2014;45:00-00.
6. Roxas A. The RIFASAF project: A case control study on risk factors for stroke among Filipinos. Phil J Neuro.
2002; 6: 1-7
7. Ariesen MJ, Claus SP, Rinkel GJE, Algra A. Risk factors for intracerebral hemorrhage in the general population:
a systemic review. Stroke. 2003;34(8):2060-2065.
8. Korja M, Thorn LM, Hägg S, et al. Subarachnoid hemorrhage in type 1 diabetes: a prospective cohort study of
4,083 patients with diabetes. Diabetes Care. 2013 Nov;36(11):3754-8.
9. Demchuk A, Morgenstern L, Krieger DW, et al. Serum glucose level and diabetes predict tPA-related
intracerebral hemorrhage in acute ischemic stroke. Stroke. 1999;30:34-39.
10. Air EL, Kissela BM. Diabetes, the metabolic syndrome, and ischemic stroke: Epidemiology and possible
mechanisms. Diabetes Care. 2007;30:3131-40.
11. Luchsinger JA, Tang MX, Stern Y, et al. Diabetes mellitus and risk of Alzheimer’s disease and dementia with
stroke in a multiethnic cohort. Am J Epidemiol. 2001;154:635-41.
12. Diabetes Control and Complications Trial (DCCT) Research Group: Effect of intensive diabetes management
on macrovascular events and risk factors in the diabetes control and complications trial. Am J. Cardiol.
1995;75:894-903.
13. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or
insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes
(UKPDS 33). Lancet. 1998; 352:837-53.
14. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and
Prevention

death in patients with diabetes mellitus: a metaanalysis of RCT. Lancet. 2009;373:1765–1772.

15. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with
type 2 diabetes mellitus: a metaanalysis of randomized trials. JAMA. 2007;298:1180-8.
16. Cushman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure
control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–1585.
17. Ma TKW, Kam KKH, Yan BP, Lam Y-Y. Renin-angiotensin-aldosterone system blockade for cardiovascular
diseases: current status. Br J Pharmacol. Jul 2010;160(6):1273–1292.
18. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel
on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
JAMA. 2001;285:2486-2497.
19. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for
heath professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:517-
584.
20. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with
atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre
randomised placebo-controlled trial. Lancet. 2004;364:685-696.
21. Rubins H, Robins S, Collins D, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis
from the Department of Veterans Affairs HDL intervention trial (VA-HIT). Arch Int Med. 2002;162:2597-
2604.
22. Ginsberg HN, Elam MB, Lovato LC, et al. ACCORD Study Group. Effects of combination lipid therapy in
T2DM. N Engl J Med. 2010;362:1563–1574.
23. Kaplan RC, Tirschwell DL, Longstreth WT Jr, et al. Vascular events, mortality, and preventive therapy following
ischemic stroke in the elderly. Neurology. 2005; 65: 835–842.
24. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group. Effects of intensive glucose
lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59.
25. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with
type 2 diabetes. N Engl J Med. 2008; 358:2560 –2572.
26. Duckworth WC, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2
diabetes. N Engl J Med. 2009 Jan 8;360(2):129-39.
27. Collaborators CTTC, Kearney PM, Blackwell L, et al. Efficacy of cholesterol-lowering therapy in 18,686 people
with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008; 371:117-25.

III. DYSLIPIDEMIA AND STROKE

Dyslipidemia is a well-established risk factor for atherosclerotic cardiovascular diseases
(ASCVD) and other comorbid conditions. Although epidemiologic and observational
studies found no definite correlation between dyslipidemia and overall stroke risk,
it does play an important role in intra- and extracranial atherothromboembolism,
another independent risk factor for both first and recurrent strokes. The effect of high
blood cholesterol concentration on stroke, however, is complex; high levels have a
stronger positive association with ischemic stroke but a weaker negative association
with hemorrhagic stroke.1 One possible explanation is that cholesterol, being a major
component of the cell membrane, is essential in maintaining vascular integrity including
that of the brain. Depletion of cholesterol therefore potentially increases the risk of
bleeding. This is also common in individuals with alcohol use disorders or those with
36 severe or chronic illness, which may be confounding factors for the demonstrated trend
between hemorrhagic stroke and low cholesterol levels.

Over a wide range of lipid indices, epidemiological data suggest that there is a modest
link between high low-density lipoprotein cholesterol (LDL-C) levels and the risk of
ischemic stroke. Also, a low HDL cholesterol (HDL-C) and high lipoprotein (a) levels
are associated with increased risk of stroke.2,3 On the other hand, hypertriglyceridemia
has been correlated with both ischemic stroke and large-artery atherosclerotic (LAA)
subtype.4,5 Nonetheless, all these are implicated in all-cause and cardiovascular
mortalities.

A. Epidemiology
The prevalence of dyslipidemia in the Philippines is 72.0% (95% CI, 70.7-73.3%).6 The
percent distributions of “high” total cholesterol, LDL-C, and triglyceride levels are
10.2%, 11.8%, and 14.6% respectively.7 On the other hand, the prevalence of isolated
low HDL-C is 28.8%.8 Among type 2 diabetic patients, approximately 60% to 75%
have a high total cholesterol; 70% have high LDL-C; 50% to 60% have low HDL-C; and
40% to 50% have hypertriglyceridemia.9,10

Prevention
Studies have shown that dyslipidemia, especially hypercholesterolemia, contributes
to the increased incidence and higher rates of mortality from ischemic strokes. In
the Asia-Pacific region, the population-attributable risk (PAR) of ischemic stroke
secondary to non-optimal levels of serum cholesterol was estimated to be as high
as 45%.11

B. Risk Modification
Dietary intake of saturated fats, physical inactivity, obesity, and diabetes all contribute
to raising of blood cholesterol levels. As such, lifestyle modification is most crucial
in risk modification. There is a compelling body of evidence that lipid-lowering,
especially LDL-C, reduces major cardiovascular events including primary and
secondary stroke. Current evidences show that lipid-lowering agents, particularly
statins, can halt or reverse atherosclerotic progression in a dose-dependent manner.

Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors)

are commonly used as the first-line agent for the treatment of hypercholesterolemia.
Not only that this drug class effectively lowers blood cholesterol levels, but it can
also reduce inflammation, promote angiogenesis and neurogenesis, and upregulate
endogenous tissue plasminogen activator (tPA). Statins have proved efficacious in
reducing primary stroke risk without a statistically significant increase in ICH.12

Other lipid-modifying agents include niacin, fibrates, cholesterol absorption

inhibitors, and omega-3 fatty acids. Niacin increases HDL-C levels and lowers plasma
lipoprotein (a) levels.13 Fibric acid derivatives such as gemfibrozil and fenofibrate also
increase HDL-C and lower triglyceride levels. Ezetimibe, a cholesterol absorption
inhibitor, has been suggested as an add-on to statins particularly in patients who
do not reach LDL-C targets.14 In general, however, supporting data regarding the use
of non-statin agents for stroke prevention are less certain. Thus, the use of these
medications should be carefully considered on the basis of safety and efficacy.

B.1. Primary Stroke Prevention

Major statin trials have demonstrated significant reductions in ischemic stroke
rates. In a meta-analysis of 42 trials, statin therapy was associated with reduction of
all stroke types (RR=0.84; 95% CI, 0.79-0.91), all-cause mortality (RR=0.88; 95% CI,
0.83-0.93), and nonhemorrhagic strokes (RR=0.81; 95% CI, 0.69-0.94).15 It conferred
an important and large relative reduction in cardiovascular events (including stroke)
among hypertensive patients who are not conventionally deemed dyslipidemic.16
Pretreatment with statins seems to reduce clinical severity in patients with stroke,
especially among diabetics.17 In this subset of patients, statin use was associated
37
 with a significant relative risk reduction of major cardiovascular or cerebrovascular
events (RR=9.75, 95% CI, 0.670.85), strokes (RR=0.69, 95% CI, 0.51-0.92), and a
non-significant RR reduction in all-cause mortality.18 Even in patients with mild
to moderate renal disease, statin therapy resulted in 30% reduction in the risk of
stroke (RR = 0.70; 95% CI, 0.57-0.85), 24% reduction in the risk of cardiovascular
disease (RR = 0.76; 95% CI, 0.72- 0.80), and a 21% reduction in the risk of total
mortality (RR = 0.79; 95% CI, 0.72-0.86).19 Although the protective effect against
stroke has been demonstrated in high-risk patients, it remains uncertain whether
statins are effective for primary prevention among individuals without CHD or
additional vascular risk factors. Current recommendations of the American College
of Cardiology/American Heart Association (ACC/AHA) regarding indications
for statin treatment primarily include: those having clinical atherosclerotic
cardiovascular disease (ASCVD); individuals with LDL-C ≥190 mg/dL; patients aged
40-75 years with LDL-C of 70-189 mg/dL and history of diabetes (regardless of
concomitant clinical ASCVD); and otherwise having a 10-year predicted risk of
vascular events (ASCVD risk) ≥7.5%. Individuals who do not fall under these groups
may be considered for treatment on the basis of other factors (e.g., ankle brachial
Prevention

index, C-reactive protein level).

On the other hand, treatment with niacin was shown to reduce the risk of stroke
by 24%, however the overall estimate cannot be computed.20 Pooled estimates
from the Veterans Administration HDL Intervention Trial (VA-HIT) showed a trend
toward a reduction of stroke (primarily ischemic) with gemfibrozil (hazard ratio,
0.75; 95% CI, 0.53−1.06; p=0.10) among patients with CHD and low HDL-C levels.21
However, the effect of agents other than statins on the risk of ischemic stroke is not
established and awaits further studies.

B.2. Secondary Stroke Prevention

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
study, by far the only trial dedicated to the evaluation of secondary stroke risk,
demonstrated a significant 16% risk reduction in recurrent stroke with high-
dose statins (i.e. atorvastatin 80 mg/day) relative to placebo.22 The effect is
consistent in both men and women, young and elderly, and across subtypes of
noncardioembolic ischemic stroke.23-25 A subgroup of the Heart Protection Study
(HPS) trial also demonstrated a significant reduction of secondary cerebrovascular
events. Post-hoc analysis of SPARCL revealed an increase in incident hemorrhagic
strokes with statin treatment, although subsequent meta-analysis did not find
significant difference in the incidence of ICH among controls and statin-treated
patients (OR=1.08, 95% CI, 0.88-1.32).26 Thus, the preventive effect of statin
therapy against ischemic events outweighs any possible excess of hemorrhagic
stroke. However, a very recent trial suggested no clinical benefit with statins in the
case of subarachnoid hemorrhage (SAH).27

It was found that lowering LDL-C (by about 1 mmol/L) with statins reduces the
risk of recurrent stroke by ~12% and all strokes by ~21% (95% CI, 6-33%), with
greater risk reductions for even lower LDL-C levels.12,28 However, the optimum
target LDL-C concentration is uncertain. The ongoing Treat Stroke to Target (TST)
trial (ClinicalTrials.gov identifier NCT01252875) is testing the effects of targeting
LDL-C concentration on reducing recurrent atherosclerotic stroke risk.

C. Recommendations
C.1. Primary Stroke Prevention
1. In addition to lifestyle changes such as smoking cessation, weight management,
and regular physical activity, adults ≥21 years of age with primary LDL
cholesterol ≥190 mg/dL (>4.91 mmol/L) should be treated with high-intensity
statin therapy, unless contraindicated.
2. For patients at any level of cardiovascular risk, especially those with established
38
 atherosclerosis, a low-fat cholesterol diet is recommended for life.
3. Patients without DM or clinical atherosclerotic cardiovascular disease (ASCVD)
aged 40-75 years but with LDL cholesterol of 80-189 mg/dL (2.07-4.89 mmol/L)
should receive high-intensity statin therapy.
4. Patients <70 years old with clinical ASCVD should be treated with lifestyle
measures and high-intensity statin therapy, unless contraindicated (Class I,
level A).
5. Diabetic patients without clinical ASCVD aged 40-75 years should receive
moderate-intensity statin therapy (Class I, level A), or high-intensity statin
therapy if high risk (i.e. ≥7.5% 10-year ASCVD risk) (Class II, level A).
6. Patients with coronary artery disease and low HDL may be treated with weight
reduction, increased physical activity, smoking cessation, and possibly niacin or
fibrates (Class IIa, level B).

C.2. Secondary Stroke Prevention29

1. Patients <70 years old with clinical atherosclerotic cardiovascular disease
(ASCVD), including ischemic stroke or TIA, should be managed with lifestyle

Prevention
modification, dietary guidelines, and high-intensity statin therapy, unless
contraindicated, thus placed on moderate-intensity statin therapy (Class I, level
A).
2. Patients >70 years old with clinical atherosclerotic cardiovascular disease
(ASCVD) should be treated with lifestyle measures and placed on either
moderate- or high-intensity statin therapy depending on risk stratification,
adverse drug reactions, and patient preferences (Class II, level A).

Table 3. High- Moderate- and Low-intensity Statin Therapya

STATIN THERAPY Average lowering effect on Examples (daily dose)
LDL-C with daily dose
Atorvastatin 40-80 mg
High-intensity > 50%
Rosuvastatin 20 (40) mg
Atorvastatin 10 (20) mg
Rosuvastatin (5) 10 mg
Simvastatin 20-40 mg
Moderate-intensity 30% to <50%
Pravastatin 40 (80) mg
Lovastatin 40 mg
Fluvastatin 40 mg bid
Pravastatin 10-20 mg
Lovastatin 20 mg
Low-intensity <30 % Simvastatin 10 mg
Fluvastatin 20-40 mg
Pitavastatin 1 mg+
a
modified from Stone N, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to
Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines. Circulation. 2013;00:000–000.
+
not available in the Philippines; drugs or doses in italics are approved by the US FDA but not
included in RCTs; individual responses to therapy may vary; simvastatin 80 mg is not recommended
due to increased risk of myopathy, including rhabdomyolysis.

References

1. Woodward M, Martiniuk A. Asia Pacific Cohort Studies Collaboration. Elevated total cholesterol; its
prevalence and population attributable fraction for mortality and coronary heart disease and ischemic
stroke in the Asia Pacific region. Eur J Cardiovasc Prev Rehabil. 2008;15;397-401.
2. Amarenco P, Labreuche J, Touboul PJ. High-density lipoprotein-cholesterol and risk of stroke and carotid
atherosclerosis: a systematic review. Atherosclerosis. 2008;196:489–496.
3. Smolders B, Lemmens R, Thijs V. Lipoprotein (a) and stroke: a metaanalysis of observational studies.
Stroke. 2007;38:1959–1966.
39
 4. Bang OY, Saver JL, Liebeskind DS, et al. Association of serum lipid indices with large artery atherosclerotic
stroke. Neurology. 2008;70:841–847.
5. Labreuche J, Touboul PJ, Amarenco P. Plasma triglyceride levels and risk of stroke and carotid
atherosclerosis: a systematic review of the epidemiological studies. Atherosclerosis. 2009;203:331–345.
6. Sy RG, Morales D, Dans A, et al. Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the
Philippines. J Epidemiol. 2012; 22(5): 440–447.
7. The Seventh National Nutrition Survey: Philippines, 2008: Initial Results. Taguig: Food and Nutrition
Research Institute.
8. Rutherford J, McDade T, Feranil A, et al. High prevalence of low HDL-c in the Philippines compared to the
U.S.: population differences in associations with diet and BMI. Asia Pac J Clin Nutr. 2010;19(1):57–67.
9. The Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines: Executive
Summary. Manila: Philippine Heart Association/Philippine College of Cardiology, 2005.
10. Ho H, Gatbonton P, Batongbacal M, et al. The Lipid Profile of Diabetic Patients at the Diabetes Clinic of
the Philippine General Hospital. Phil J Int Med. 2000;38:16-20.
11. Graeme J. Hankey. Ka S, L. Wong et al. Management of cholesterol to reduce the burden of stroke in Asia:
consensus statement. Int J Stroke. 2010; 1-8.
12. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-
analysis of statins for stroke prevention. Lancet Neurol. 2009;8:453–463.
Prevention

13. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline
for health professionals from the American Heart Association/American Stroke Association. Stroke.
2011;42:517-584.
14. Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin
monotherapy and identification of factors associated with treatment response: a pooled analysis of over
21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223: 251–61.
15. O'Regan C, Wu P, Arora P, et al. Statin Therapy in Stroke Prevention: A Meta-analysis Involving 121,000
Patients. Am J Med. 2008 Jan;121(1):24-33.
16. Sever PS, Dahlof B, Poulter NR, et al. ASCOT investigators. Prevention of coronary and stroke events with
atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations,
in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LEA): a multicentre
randomised controlled trial. Lancet. 2003;361:1149-1158.
17. Greisenegger S, Mullner M, Tentschert S, et al. Effect of pretreatment with statins on the severity of acute
ischemic cerebrovascular events. J Neurol Sci. 2004,221:5-10.
18. de Vries FM, Denig P, Pouwels KB, Postma MJ, Hak E. Primary prevention of major cardiovascular and
cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. 2012; 72(18): 2365-2373.
19. Zhang X, Xiang C, Zhou YH, et al. Effect of statins on cardiovascular events in patients with mild to
moderate chronic kidney disease: a systematic review and meta-analysis of randomized clinical trials.
BMC Cardiovasc Disord. 2014 Feb 17;14:19.
20. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231:360–81.
21. Bloomfield Rubins H, Davenport J, Babikian V, et al. Study Group. Reduction in stroke with gemfibrozil
in men with coronary heart disease and low HDL cholesterol: the Veterans Affairs HDL Intervention Trial
(VA-HIT). Circulation. 2001;103:2828–33.
22. Amarenco P, Goldstein LB, Szarek M, et al. Effects of intense low-density lipoprotein cholesterol reduction
in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in
Cholesterol Levels (SPARCL) trial. Stroke. 2007;38:3198–204.
23. Amarenco P, Benavente O, Goldstein LB, et al, and the Stroke Prevention by Aggressive Reduction in
Cholesterol Levels Investigators. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol
Levels (SPARCL) trial by stroke subtypes. Stroke. 2009; 40: 1405–09.
24. Goldstein LB, Amarenco P, Lamonte M, et al. Relative effects of statin therapy on stroke and cardiovascular
events in men and women: secondary analysis of the Stroke Prevention by Aggressive Reduction in
Cholesterol Levels (SPARCL) Study. Stroke. 2008;39:2444–2448.
25. Chaturvedi S, Zivin J, Breazna A, et al. Effect of atorvastatin in elderly patients with a recent stroke or
transient ischemic attack. Neurology. 2009;72:688–694.
26. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31
randomized controlled trials. Stroke. 2012; 43: 2149–56.
27. Kirkpatrick PJ, Turner CL, Smith C, et al. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH):
a multicentre randomised phase 3 trial. Lancet Neurol. 2014 May 15.
28. Baigent C, Blackwell L, Emberson J, et al, and the Cholesterol Treatment Trialists’ (CTT) Collaboration.
Effi cacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000
participants in 26 randomised trials. Lancet. 2010;376: 1670–81.
29. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College
of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;00:000–
000.
40
IV. CIGARETTE SMOKING AND STROKE
A. Epidemiology
The 2009 Philippine Global Adult Tobacco Survey (GATS) revealed that 28.3% (17.3
million) of Filipinos aged 15 years old and above smoke tobacco; 47.7% (14.6 million)
are men and 9.0% (2.8 million) are women.1 Eighty percent of them smoke on a daily
basis, consuming an average of 11.3 and 7 cigarette sticks/day in men and women
respectively. In the same survey, it was found that overall, 2.8% of men and 1.2% of
women currently use smokeless tobacco. Exposure to second-hand smoke (SHS) is
experienced/allowed at home (48.8%), at work (36.9%), in public transport (55.3%),
restaurants (33.6%), government buildings (25.5%), and health care facilities (7.6%). In
a separate survey, it was observed that from 1994 to 2013, there has been a decreased
proportion of adolescent smokers (less than 1 out of 5 individuals), with a higher
percentage of smokers in males than in females (37.3% and 6.3% respectively).2

A.1. Cigarette Smoking and Risk of Stroke and its Subtypes

Numerous studies have shown that cigarette smoking is an independent

Prevention
predictor for first ischemic stroke in both men and women. A meta-analysis of 22
studies showed that the relative risk (RR) of cerebral infarction among smokers
approximately doubles that of the non-smokers.3 In the Japan Public Health Center
(JPHC 1) prospective cohort study, the RR for a first stroke among current smokers,
after adjustment for cardiovascular risk factors, were 1.27 (95% CI, 1.05-1.54)
for total stroke, 0.72 (95% CI, 0.49-1.07) for intraparenchymal hemorrhage, 3.60
(95% CI, 1.62-8.01) for subarachnoid hemorrhage, and 1.66 (95% CI, 1.25-2.20) for
ischemic stroke.4 Similarly, a positive association was observed between smoking
and the risks of lacunar infarction and large-artery occlusive infarction, but not
embolic infarction. Male smokers were observed to have a greater risk of ischemic
stroke (lacunar or large-artery occlusive infarct) than female smokers, although
both sexes have increased risks of total and hemorrhagic (ICH and SAH) strokes.
Women who smoke ≥15 cigarettes per day have RRs for total hemorrhagic stroke,
ICH, and SAH of 3.29 (95% CI, 1.72-6.29), 2.67 (95% CI, 1.04-6.90), and 4.02 (95%
CI, 1.63-9.89) respectively. Males who smoke ≥20 cigarettes daily have RRs for total
hemorrhagic stroke, ICH, and SAH of 2.36 (95% CI, 1.38-4.02), 2.06 (95% CI, 1.08-
3.96), and 3.22 (95% CI, 1.26-8.18) respectively.5

A.2. Dose-dependent effect of Smoking

Studies have shown that there is a dose-response relationship between stroke and
cigarette smoking. A large cohort study involving U.S. male physicians showed
that heavy smokers (>20 cigarettes/day) have relative risks of 2.7 and 1.46 for
total nonfatal and fatal strokes respectively.6 The RRs among heavier smokers (<40
cigarettes/day) was twice as that of the less-heavy smokers (<10 cigarettes/day).7
The quantitative effects of cigarettes were also demonstrated in carotid intimal
and medial wall thickness, which is another important independent risk factor for
stroke.8

A.3. Secondhand Smoke and Risk of Stroke

Environmental/passive/secondhand smoke (SHS) also exert detrimental effects on
vascular homeostasis. In a cohort study, the prevalence of stroke was higher among
non-smoking women living with husbands who smoked, compared with non-
smoking women whose spouses do not smoke.9 This effect is also influenced by
the duration and quantity of exposure to SHS by the non-smoker. In a population-
based cross-sectional study of 1,209 non-smoking women, those who were
exposed to SHS, after adjustment of 13 potential risk factors, had a significantly
higher risks of coronary heart disease (OR=1.69, 95% CI, 1.31-2.18) and ischemic
stroke (OR=1.56, 95% CI, 1.03-2.35) than unexposed individuals.10 Current smokers
exposed to SHS, on the other hand, have a six-fold increased risk of stroke when
compared with nonsmokers who were never exposed to environmental smoke.11
41
 A.4. Smokeless Tobacco and Risk of Stroke
Smokeless tobacco products, including oral snuff and chewing tobacco, have
been associated with the risk of oral leukoplakic lesions and cancers. In a meta-
analysis of 11 studies, there is an increased risk of fatal stroke among users of
smokeless tobacco products (RR=1.19, 95% CI, 0.97-1.47) compared with the non-
users, although the studies are heterogenous.12 Only one study included in this
meta-analysis indicated the relative risks for each subtype, which is higher for fatal
ischemic stroke (1.63, 95% CI, 1.02-2.62) than for hemorrhagic stroke (1.05, 95% CI
0.61 to 1.80).13

B. Risk Modification
In most cases, the risk of stroke can reach the level of a non-smoker after 5 years
from smoking cessation.7 The risk reduction, however, is dependent on the quantity
of cigarettes smoked before stopping. It was found that the risk of stroke among light
smokers (<20 cigarettes/day) revert back to baseline, but heavy smokers retain twice
the incidence of stroke as that of the non-smokers.14 Given the strong association
Prevention

between the risk of stroke and smoking, the need for abstention from smoking
(or complete cessation) cannot be overemphasized. However, there is no trial to
date which have examined the effectiveness of smoking cessation for secondary
prevention among individuals with a history of stroke or TIA.

B.1. Nicotine Dependence Treatment

Several behavioral and pharmacologic interventions are used (usually in
combination) for the treatment of nicotine dependence. These include nicotine
replacement products (e.g., patch, gum, lozenge, nasal spray, inhaler), non-nicotine
medications (e.g., antidepressants, varenicline [Chantix], clonidine), counseling,
rehabilitation, social support groups, and smoking cessation programs.

B.2. Smoke-free Initiatives

The Philippines has a number of legislations and programs under its national
smoking infrastructure to reduce the consumption and effects of tobacco. These
include Republic Act (RA) 9211 (also known as Tobacco Regulations Act of 2003) and
Administrative Order No. 2007-0004, which mandated the creation of the National
Tobacco Prevention and Control Program (NTCP). In June 2005, the Philippines
ratified the WHO’s Framework Convention on Tobacco Control (WHO-FCTC), which
included policies and regulations on tobacco marketing, prohibition of smoking in
public places and transportation, youth sales restrictions, and enclosure of graphic
warning labels. The more recent R.A. No. 10351 (also known as Sin Tax Law) is
being implemented with the goal of reducing tobacco use as well as collect more
revenues for the administration’s universal health care program.

B.3 Electronic Cigarettes

The use of electronic cigarettes (e-cigarettes) as an alternative to smoking is
controversial. Although a recent review suggests e-cigarettes as potentially “harm
reduction” (thus possible means for smoking cessation)15, other studies have shown
possible increased risk of cardiovascular events.16 Further studies are needed to
establish its safety and effectiveness as a smoking cessation method.

C. Recommendations

C.1. Primary Stroke Prevention

1. Smoking cessation for all current smokers is recommended (Class II, level B).
2. Smoking should be banned in public places since second hand smoke is
associated with increased risk of CVD (Class II, level B).
3. Effective behavioral and pharmacological treatments should be advised and
encouraged for nicotine dependence (Class IIa, level B).
42
 4. Tobacco Regulation Act of 2003 should be implemented to protect the populace
from hazardous products, promote the right to health and instill health
consciousness.

C.2. Secondary Stroke Prevention17

1. Patients with stroke or TIA who have smoked in the past year should be strongly
advised to quit smoking (Class I, level C).
2. Counseling, nicotine products, and oral smoking cessation medications are
effective for helping smokers to quit (Class I, level A).
3. It is reasonable to advise patients after TIA or ischemic stroke to avoid
environmental (passive) tobacco smoke (Class IIa, level B).

References

1. Global Tobacco Surveillance System. 2009 Philippines’ GATS > Global Adult Tobacco Survey - Country

Prevention
Report. Atlanta GA: U.S. Department of Health and Human Services, Public Health Service, Centers for
Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion,
Office on Smoking and Health. 2010b.
2. UP Population Institute. YAFS 4 (Young Adult Fertility and Sexuality Study). 2013
3. Shinton R. Beevers G. Meta-analysis of relation between cigarette smoking and stroke. Br Med J. 1989;
298-789-794.
4. Mannami T, Iso H, Baba S, et al. Cigarette smoking and risk of stroke and its subtypes among middle-aged
Japanese men and women: the JPHC Study Cohort I. Stroke. 2004;35:1248–1253.
5. Kurth T, Kase CS, Berger K, Schaeffner ES, Buring JE, Gaziano JM. Smoking and the risk of hemorrhagic
stroke in men. Stroke. 2003;34:1151–1155.
6. Robbins AS, Manson JE, Lee I, et al. Cigarette smoking and stroke in a cohort of US male physicians. Ann
Intern Med. 1994;120:458-62.
7. Wolf PA, D’Agostino RB, Kannet WB, et al. Cigarette smoking as a risk factor for stroke. The Framingham
Study. JAMA. 1988;259:1025-9.
8. Howard G, Burke GL, Szklo M, et al. Active and passive smoking are associated with increased carotid wall
thickness. The atherosclerotic risk in community study. Arch Intern Med. 1994;154:1277-82.
9. Zhan X, Shu XO, Yang G, Li HL, Xiang YB, GaoYT, Li Q, Zeng W. Association of passive smoking by
husbands with prevalence of stroke among Chinese women nonsmokers. Am J Epid. 2005;161:213-218.
10. He Y, Lam T. Passive smoking and risk of peripheral arterial disease and ischemic stroke in chinese women
who never smoked. Circulation. 2008;118:1535-1540.
11. Bonita R, Duncan J, Truelsen T, Jackson RT, Beaglehole R. Passive smoking as well as active smoking
increases the risk of acute stroke. Tob Control. 1999;8:156–160.
12. Boffetta P, Straif K. Use of smokeless tobacco and risk of myocardial infarction and stroke: systematic
review with meta-analysis. BMJ. 2009;339:b3060.
13. Hergens MP, Lambe M, Pershagen G, et al. Smokeless tobacco and the risk of stroke. Epidemiology. 2008
Nov; 19(6):794-9.
14. Tell GS, Polak JF, Ward BJ, et al. Relation of smoking with carotid artery wall thickness and stenosis in
older adults. The cardiovascular health study. Circulation. 1994;902905-9.
15. Palazzolo DL. Electronic Cigarettes and vaping: a new challenge in clinical medicine and public health. A
literature review. Front Public Health. 2013; 1:56.
16. Lippi G, Favaloro EJ, Meschi T, et al. E-cigarettes and cardiovascular risk: beyond science and mysticism.
Semin Thromb Hemost. 2014; 40:60-5.
17. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45:000-000.

43
 V. EXCESSIVE ALCOHOL INTAKE AND STROKE
A. Epidemiology
The WHO 2014 Global status report on alcohol and health revealed that the
prevalence of heavy episodic drinkinga in the Philippines is 1.9% of the total
population (aged ≥15 years) and 4.2% of drinking population.1 The total alcohol
per capita consumption combined for both male and female drinkers is 12.3 liters
of pure alcohol (16.7 in males, 5.2 in females) generally comprised of spirits (73%),
beer (27%), and wine (<1%). Furthermore, the prevalence of alcohol use disorders
(AUD) and alcohol dependence (including harmful use of alcohol) is 4.6% and 2.3%
respectively.

Studies have shown that alcohol consumption has a direct, dose-dependent effect
on the risk of hemorrhagic stroke.2,3 Whereas for ischemic stroke, the risk varies as
demonstrated by a J-shaped association. In one meta-analysis, alcohol consumption
at 60 grams per day was associated with a 64% increased risk of stroke (RR=1.64;
95% CI, 1.39-1.93), 69% increase in ischemic stroke (RR=1.69; 95% CI, 1.34-2.15), and
Prevention

more than doubled risk for hemorrhagic stroke (RR=2.18; 95% CI, 1.48-3.20).4 Among
Filipinos, the odds ratio (OR) for stroke due to frequent alcohol intake is 1.75 (95%
CI, 1.14-2.70).5

B. Risk Modification
In general, light to moderate alcohol consumption is associated with a reduced risk
of first-ever stroke, although the effect of alcohol differs according to stroke subtype.6
Light to moderate consumption (up to 1 drink per day for nonpregnant women and up
to 2 drinks per day in men) appears to decrease the risk of ischemic stroke, or at least
does not increase the risk of both ischemic and hemorrhagic stroke.7,8 This protective
effect may be related to the increased levels of HDL cholesterol, apolipoprotein
A1, and adiponectin, as well as reduced platelet aggregation and lower fibrinogen
levels.9,10 On the other hand, heavy alcohol use, either daily or in binges, is related to
increased stroke risk regardless of sex and ethnicity.11

For patients with a history of stroke or TIA, however, only few studies have directly
examined the association of alcohol with the risk of recurrence.6 The high risk of
recurrence was associated with heavy alcohol consumption.12 As for AUDs and alcohol
dependence, a multimodal approach is preferred, which includes pharmacologic
treatment, psychotherapy, and rehabilitation.

C. Recommendation
1. Nondrinkers should not be counseled by their healthcare providers to start
drinking (Class IIb, level B).
2. Patients with ischemic stroke, TIA, or hemorrhagic stroke who are heavy drinkers
should eliminate or reduce their consumption of alcohol (Class I, level A).
3. For patients who choose to drink alcohol, consumption must be limited to 2
drinksb per day for men and one drink per day for nonpregnant women (Class
IIb, level B).
References
1. World Health Organization. Global Status Report on Alcohol and Health. Geneva, Switzerland: WHO; 2014.
Available at: http://www.who.int/substance_abuse/publications/global_alcohol_report/msb_gsr_2014_2.
pdf?ua=1 (Accessed 16 June 2014)
2. Klatsky AL, Armstrong MA, Friedman GD, et al. Alcohol drinking and risk of hemorrhagic stroke.
Neuroepidemiology. 2002;21:115–122.
3. Feigin VL, Rinkel GJ, Lawes CM, et al. Risk factors for subarachnoid hemorrhage: an updated systematic
review of epidemiological studies. Stroke. 2005;36:2773–2780.
a
Heavy episodic drinking is defined as consumption of at least 60 grams of pure alcohol on at least one occasion in
the past 30 days.
b
The U.S. Dietary Guidelines define one “drink” as 12 ounces of regular beer (5% alcohol), 5 ounces of wine (12%
44 alcohol), or 1.5 ounces of 80 proof (40% alcohol) distilled spirits. One drink contains 0.6 ounces of alcohol.
4. Reynolds K, Lewis B, Nolen JD, et al. Alcohol consumption and risk of stroke: a meta-analysis. JAMA.
2003;289:579–588.
5. Roxas A, for the PNA-DOH RIFASAF Collaborators. The RIFASAF Project: a case-control study on risk
factors for stroke among Filipinos. Phil J Neuro. 2002; 6:1:1-7.
6. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and
transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2014;45:000-000.
7. Iso H, Baba S, Mannami T, et al. JPHC Study Group. Alcohol consumption and risk of stroke among
middle-aged men: the JPHC Study Cohort I. Stroke. 2004;35:1124-9.
8. Elkind MSV, Sciacca R, Boden-Albal B, et al. Moderate alcohol consumption reduces risk of ischemic
stroke. The Northern Manhattan Study. Stroke. 2006; 37: 13-19.
9. Brien SE, Ronksley PE, Turner BJ, et al. Effect of alcohol consumption on biological markers associated
with risk of coronary heart disease: a systemic review and meta-analysis of interventional studies. BMJ.
2011;342:d636
10. Mukamal KJ, Massaro JM, Ault KA, et al. Alchol consumption and platelet activation and aggregation
among women and men: the Framingham Offspring Study. Alcohol Clin Exp Res. 2005;29:1906-1912.
11. Patra J, Taylor B, Irving H, et al. Alcohol consumption and the risk of morbidity and mortality for different
stroke types - a systematic review and meta-analysis. BMC Public Health. 2010;10:258.

Prevention
12. Ois A, Gomis M, Rodríguez-Campello A, et al. Factors associated with a high risk of recurrence in patients
with transient ischemic attack or minor stroke. Stroke. 2008;39:1717–1721.

VI. CARDIAC RISK FACTORS AND STROKE

I. NONVALVULAR ATRIAL FIBRILLATION (NVAF) AND STROKE
See Chapter 5: Guidelines for Stroke Prevention in Nonvalvular Atrial Fibrillation

II. ACUTE MYOCARDIAL INFARCTION (AMI) AND STROKE

A. Epidemiology
Acute Myocardial Infarction (MI) is associated with up to 5% increased risk of
ischemic stroke within 2 weeks from an event. The rate is higher among persons
with infarcts of the anterior wall than that of the inferior wall, and may reach to as
high as 20% among persons with large antero-apical infarcts.1 Patients with large
anterior wall MI associated with an LV ejection fraction (LVEF) <40% and antero-
apical wall motion abnormalities are at increased risk of developing LV mural
thrombus because of the stasis of blood in the ventricular cavity and endocardial
injury with associated inflammation. The duration of risk of thrombus formation
and embolization after a large MI is uncertain, but the risk appears to be highest
during the first 1 to 2 weeks, then subsequently declines over a period of up to
3 months. After 3 months, the risk of embolization diminishes as the residual
thrombus becomes organized, fibrotic, and adherent to the LV wall.

Patients with persistent myocardial dysfunction, congestive heart failure (CHF),

atrial fibrillation (AF), as well as those with persistent mobile or protruding
thrombus (as visualized by echocardiography or another imaging modality) may
remain at an increased risk of stroke and other embolic events beyond 3 months. In
the absence of systemic anticoagulation, the risk of embolization within 3 months
among patients with MI complicated by a mural thrombus is 10% to 20%.

B. Risk Modification
There are no randomized controlled trials (RCTs) which assessed the value of
antithrombotic therapy for the prevention of mural thrombus and stroke in patients
with ST segment-elevation MI (STEMI). However, in a randomized open-label trial
which compared the effects of antithrombotic agents (warfarin, aspirin, or its
combination) in 3,630 patients with AMI (mean follow-up period of 4 years)2, the
primary composite outcome (i.e. death, nonfatal re-infarction, or thromboembolic
stroke) was observed in 20% (241 of 1206 participants) assigned to aspirin, 16.7%
(203 of 1216 participants) assigned to warfarin, and 15% (181 of 1208 participants)
45
 assigned to combination therapy. As compared with those who received aspirin
monotherapy, the primary outcome was significantly reduced by 19% in patients
treated with warfarin, and by 29% in patients who received combination therapy.
Furthermore, there was a 48% reduction in the risk of thromboembolic stroke in
both warfarin groups relative to aspirin. Major nonfatal bleeding was four-fold
higher in patients receiving warfarin (0.62% per year) than in those receiving
aspirin (0.17% per year). In a meta-analysis of 11 studies on post-MI patients with
mural thrombus3, it was reported that treatment with vitamin K antagonists (VKAs)
significantly decreased the risk of both LV thrombus formation and embolization.
The overall risk of embolization in patients with LV thrombus was 11% compared
with 2% in patients without thrombus.

C. Recommendation
1. Oral anticoagulation for MI patients is recommended if they have one or more
of the following conditions: persistent AF, decreased LV function (e.g., EF ≤28%),
or when LV thrombi are detected within several months after MI.
2. Treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0) for 3 months may be
Prevention

considered in patients with ischemic stroke or TIA in the setting of acute anterior
STEMI without demonstrable LV mural thrombus formation but with anterior
apical akinesis or dyskinesis identified by echocardiography or other imaging
modality (Class IIb, level C).
3. In patients with ischemic stroke or TIA in the setting of acute MI complicated by LV
mural thrombus formation or anterior or apical wall-motion abnormalities with
an LVEF <40%, who are intolerant to VKA therapy because of nonhemorrhagic
adverse events, treatment with a LMWH, dabigatran, rivaroxaban, or apixaban for
3 months may be considered as an alternative to VKA therapy for the prevention
of recurrent stroke or TIA (Class IIb, level C).

III. CARDIOMYOPATHY AND STROKE

A. Epidemiology
Patients with ischemic or non-ischemic dilated cardiomyopathy have an increased risk
of stroke. Results of two large studies show that the incidence of stroke is inversely
proportional to ejection fraction (EF).4,5 In the Survival and Ventricular Enlargement
(SAVE) study, patients with EF of 29% to 35% (mean: 32%) had a stroke rate of 0.8%
per year, whereas the yearly rate among those with EF of <28% (mean: 23%) was
higher at 1.7%.6 There was an 18% incremental increase in stroke risk for every 5%
decline in EF. A retrospective analysis of data from the Studies of Left Ventricular
Dysfunction (SOLVD) trial, which excluded patients with AF, found a 58% increase in
the risk of thromboembolic events for every 10% decrease in EF in women.6 However,
there was no noted increased risk in men. In patients with a non-ischemic dilated
cardiomyopathy, the rate of stroke appeared similar to that of cardiomyopathy
resulting from ischemic heart disease.
B. Risk Modification
Warfarin is sometimes prescribed to prevent cardioembolic events in patients
with cardiomyopathy. However, no RCT to date has demonstrated the efficacy of
anticoagulation in this case. A considerable controversy surrounds the use of warfarin
in patients with cardiac failure or reduced LVEF.
There have been at least 4 published randomized trials that evaluated the effects
of antithrombotic therapy on clinical outcomes (including strokes) in patients with
heart failure and reduced LVEF. Based on the results of the Warfarin versus Aspirin
in Reduced Cardiac Ejection Fraction (WARCEF) trial, which is the largest of these
4 studies, there was no difference in the event rates of primary outcome between
aspirin and warfarin (7.93 and 7.47 per 100 patient-years respectively) after a mean
follow-up period of 3.5 years.7 The rates of intracranial hemorrhage did not differ
46
 between groups, but the risk of major bleeding was higher with warfarin.
The main findings of the WARCEF were confirmed in a meta-analysis of 4 randomized
trials involving 3,681 patients.8 Analysis of data showed that warfarin was significantly
associated with a 41% reduction in the risk of stroke (pooled relative risk [RR], 0.59;
95% CI, 0.41–0.85; p=0.004; number needed to treat [NNT], 61) and a nearly 2-fold
increase in the risk of major hemorrhage (RR, 1.95; 95% CI, 1.37–2.76; p=0.0001;
number needed to harm, 34).9 There were more than twice as many intracranial
hemorrhages among warfarin-treated patients (pooled risk ratio, 2.17), but this
difference was not statistically significant. There was no difference between warfarin
and aspirin with respect to mortality, MI, or heart failure exacerbation. The findings
were confirmed in a second meta-analysis that adopted death or stroke as its primary
end point.9,10
Restrictive cardiomyopathies (e.g., amyloid heart disease and hypereosinophilic
syndrome with endocardial fibrosis [Loeffler syndrome])–although less common
than dilated cardiomyopathies–are also associated with increased risk of stroke
and arterial embolization attributable to left atrial (LA) appendage thrombus or LV

Prevention
mural thrombus. In the absence of contraindications, systemic anticoagulation is
recommended in patients with restrictive cardiomyopathy and those with evidence
of thrombus in the left atrium or ventricle or history of arterial embolization.
As with acute MI, no data are available on the use of newer anticoagulant drugs for the
prevention of stroke in patients with cardiomyopathy or mechanical assistive devices.
Thus, VKA therapy is recommended for patients in whom systemic anticoagulation
is indicated.
C. Recommendation
1. In patients with ischemic stroke or TIA in sinus rhythm with either dilated
cardiomyopathy (LVEF ≤35%) or restrictive cardiomyopathy without evidence of
LA or LV thrombus, the effectiveness of anticoagulation compared with antiplatelet
therapy is uncertain, and the choice should be individualized (Class IIb, level B).
2. In patients with ischemic stroke or TIA in sinus rhythm with dilated cardiomyopathy
(LVEF ≤35%), restrictive cardiomyopathy, or a mechanical left ventricular assistive
device (LVAD) who are intolerant to VKA therapy because of nonhemorrhagic
adverse events, the effectiveness of treatment with dabigatran, rivaroxaban, or
apixaban is uncertain compared with VKA therapy for the prevention of recurrent
stroke (Class IIb, level C).

IV. VALVULAR HEART DISEASES AND STROKE

A. Epidemiology
Patients with valvular heart disease (VHD) (e.g., mitral stenosis) and paroxysmal or
persistent AF are at highest risk for future embolic events. The annual incidence rates
of systemic thromboembolism (TE) in different VHDs are shown in Table 4.

Table 4. Incidence of Systemic Thromboembolism in Valvular Heart Disease11-14

With AF
Condition Alone (i.e. no AF)
(versus without AF)
1. Prosthetic valve 20% Increased
2. Rheumatic mitral regurgitation 7.7% 22%
3. Rheumatic mitral stenosis 1.5% - 4.0% Increased by 7x
4. Mitral valve prolapse <2% - 18x
5. Aortic valve Not increased Increased

47
 B. Risk Modification
Antithrombotic therapy can reduce the likelihood of stroke and systemic embolism in
patients with VHD. The rate of TE in patients with mechanical heart valves is 4.4 per
100 patient-years (PY) without antithrombotic therapy; 2.2 per 100 PY with antiplatelet
drugs; and 1 per 100 PY with warfarin.15 With or without AF, all patients with
mechanical heart valves require anticoagulation. However, the target anticoagulant
levels vary according to the type and position of the valve and the presence of other
risk factors. The risk of TE in patients with native VHD or mechanical or biological
heart valve prostheses must be balanced with the risk of bleeding. Nevertheless,
because the frequency and the permanency of consequences of TE events are usually
greater than the outcome of hemorrhagic complications, anticoagulant therapy is
generally recommended, particularly when associated with AF.

IV.A. RHEUMATIC MITRAL VALVE DISEASE AND STROKE

A. Epidemiology
The annual TE rates in rheumatic mitral regurgitation (MR) and mitral stenosis (MS)
Prevention

without AF are 7.7% and 1.5% to 4.7% respectively.16 The presence of AF increases
TE events by 22% in patients with MR and by 7- to 18-fold in patients with MS.17,18
Recurrent embolism occurs in 30% to 65% of patients with rheumatic mitral
valve disease who have a history of embolic event. About 60% to 65% of these
recurrences develop within the first year, most within 6 months.

B. Risk Modification
Several observational studies have shown that long-term anticoagulant therapy
effectively reduces the risk of systemic embolism in patients with rheumatic mitral
valve disease, although this was not evaluated in randomized trials. In patients
with MS and LA thrombus detected by transesophageal echocardiography (TEE),
long-term anticoagulant therapy can result in the disappearance of the thrombus.

C. Recommendation
1. For patients with rheumatic mitral valve disease or prosthetic valve without
a prior stroke or TIA, oral anticoagulation with VKA is recommended unless
contraindicated.
2. Antiplatelet agents should not be routinely added to warfarin to avoid any
additional bleeding risk (Class III, level C).
3. For patients with ischemic stroke or TIA who have rheumatic mitral valve disease
and AF, long-term VKA therapy with an INR target of 2.5 (range, 2.0– 3.0) is
recommended (Class I, level A).
4. For patients with ischemic stroke or TIA who have rheumatic mitral valve disease
without AF or another likely cause for their symptoms (e.g., carotid stenosis),
long-term VKA therapy with an INR target of 2.5 (range, 2.0–3.0) may be
considered instead of antiplatelet therapy (Class IIb, level C).
5. For patients with rheumatic mitral valve disease who are prescribed with VKA
therapy after an ischemic stroke or TIA, antiplatelet therapy should not be
routinely added (Class III, level C).
6. For patients with rheumatic mitral valve disease who have an ischemic stroke
or TIA while being treated with adequate VKA therapy, the addition of aspirin
might be considered (Class IIb, level C).

IV.B. MITRAL VALVE PROLAPSE (MVP), MITRAL ANNULAR CALCIFICATION, AND

STROKE

A. Epidemiology
Mitral valve prolapse (MVP) is the most common form of valve disease in adults.
Thromboembolic (TE) phenomena have been reported in patients with MVP in
whom no other source could be found.16 The annual rate of TE in patients with MVP
48
 without AF is less than 2%, while the risk increases in the presence of AF. Recent
observational cohort and case-control studies have not confirmed an association
between MVP and risk of ischemic stroke. In the midst of some lingering uncertainty
in this area, observational studies provide reassuring information that the risk of
stroke in persons with MVP is low (<1% annually).

In the Framingham Heart Study, mitral annular calcification was associated with
increased risk of all stroke types during 8 years of observation (adjusted RR, 2.10;
95% CI, 1.24-3.57). however only 14 of 22 stroke outcomes were embolic and some
were associated with development of AF during follow-up.

B. Risk Modification
No randomized trials have addressed the efficacy of selected antithrombotic
therapies for this subgroup of stroke or TIA patients. The evidence on the efficacy
of antiplatelet agents for all stroke and TIA patients was used to reach these
recommendations.

Prevention
C. Recommendation
1. For patients with MVP who have an ischemic stroke or TIA and who do not
have AF or another indication for anticoagulation, antiplatelet therapy is
recommended as it would be without MVP (Class I, level C).
2. For patients with mitral annular calcification who have an ischemic stroke or
TIA, and do not have AF or another indication for anticoagulation, antiplatelet
therapy is recommended as it would be without the mitral annular calcification
(Class I, level C).

IV.C. AORTIC VALVE DISEASE AND STROKE

A. Epidemiology
Clinically detectable systemic embolism in isolated aortic valve disease is
increasingly recognized because of microthrombi or calcific emboli.19 In an autopsy
study of 165 patients with calcific aortic stenosis, systemic embolism was found
in 31 patients (19%).20 In the absence of associated mitral valve disease or AF,
systemic embolism in patients with aortic valve disease is uncommon.

Aortic valvular diseases include aortic regurgitation (AR) and aortic stenosis
(AS). Neither of these is known to be associated with an increased risk of first or
recurrent stroke in patients without concomitant AF or mitral valve disease. Studies
on lesser degrees of aortic diseases, including aortic valve sclerosis and aortic
annular calcification, have also not established an association with the risk for
stroke. Pathological studies have demonstrated microthrombi on damaged aortic
valves suggesting a possible source of emboli, however the clinical significance is
uncertain.

B. Risk Modification
There is no existing randomized trial of patients with stroke and aortic valve disease,
thus the recommendations are based on the evidence from larger antiplatelet trials
of stroke and TIA patients.

C. Recommendation
For patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral
valve disease who do not have AF or another indication for anticoagulation,
antiplatelet therapy is recommended (Class I, level C).

49
 V. PROSTHETIC HEART VALVES AND STROKE
A. Epidemiology
All patients with mechanical heart valves have an increased risk of thromboembolic
(TE) event/s, but the risk can be reduced with use of oral VKAs. The recommended
international normalized ratio (INR) intensity varies depending on the valve type,
location, and other factors that may influence the risk for embolism including
previous or recent embolic events. The annual risk percentage of systemic TE
among persons with prosthetic heart valves is 20%. The risk increases in the
presence of AF.

B. Risk Modification
A variety of mechanical heart valve prostheses are available for clinical use, all
of which require antithrombotic prophylaxis. The most convincing evidence that
oral anticoagulants are effective in patients with prosthetic heart valves comes
from the study of patients randomized to warfarin of uncertain intensity or one
of two aspirin-containing platelet inhibitor regimens over a period of 6 months.21
Prevention

In another trial involving 148 subjects with prosthetic heart valves randomized
to warfarin monotherapy or combination of aspirin 1.0 gram/day and warfarin,
a significant reduction of embolic events was observed in the aspirin-treated
group.22 Another trial showed that the addition of aspirin 100 mg/day to warfarin
(INR 3.0-4.5) improved efficacy compared with warfarin alone.23

The European Society of Cardiology (ESC) guidelines recommend anticoagulant

intensities proportionate to the TE risk associated with specific types of prosthetic
heart valves.24 For first generation valves, an INR of 3.0 to 4.5 is recommended.
An INR of 3.0 to 3.5 is recommended for second-generation valves in the mitral
position, while an INR of 2.5 to 3.0 is recommended for second-generation valves
in the aortic position.

In 2004, the American College of Chest Physicians (ACCP) recommended an

INR of 2.5 to 3.5 for patients with mechanical prosthetic valves, and INR of 2.0
to 3.0 for patients with bioprosthetic valves and for low-risk patients with bi-
leaflet mechanical valves (e.g., St. Jude Medical device) in the aortic position.25
Both ACC/AHA and ACCP guidelines suggest more intensive therapy (i.e. INR
2.5–3.5) for patients with mechanical valves in the mitral position compared with
the aortic position, regardless of prior embolism.26,27 Furthermore, both guidelines
recommend addition of aspirin therapy to all patients with mechanical valves who
are at low-risk for bleeding.

Bioprosthetic valves are associated with a lower TE rate than mechanical valves;
however, the risk for TE is not uniform and is affected by specific patient features
such as AF. The ACCP guidelines recommend antiplatelet therapy alone for long-
term protection in patients with sinus rhythm. This is consistent with the ACC/
AHA guidelines, however it recommends VKA therapy in the presence of other
thromboembolic risk factors besides AF (i.e. previous thromboembolism, severe
LV dysfunction, and hypercoagulable condition). Patients who have had a
thromboembolic stroke after bioprosthetic valve placement may be at increased
risk for recurrence. Limited data suggest that the annual risk for a second event
is ≈5%.

C. Recommendation
1. For patients with a mechanical aortic valve and a history of ischemic stroke or
TIA before its insertion, VKA therapy is recommended with an INR target of 2.5
(2.0–3.0) (Class I, level B).
2. For patients with a mechanical mitral valve and a history of ischemic stroke or
TIA before its insertion, VKA therapy is recommended with an INR target of 3.0
50 (2.5–3.5) (Class I, level C).
 3. For patients with a mechanical mitral or aortic valve who have a history of
ischemic stroke or TIA before its insertion and who are at low risk for bleeding,
the addition of aspirin 75 mg to 100 mg/day to VKA therapy is recommended
(Class I, level B).
4. For patients with a mechanical heart valve who have an ischemic stroke or
systemic embolism despite adequate antithrombotic therapy, it is reasonable
to intensify therapy by increasing the dose of aspirin to 325 mg/day or
increasing the target INR, depending on the bleeding risk (Class IIa, level C).
5. For patients with a bioprosthetic aortic or mitral valve, history of ischemic
stroke or TIA before its insertion, and no other indication for anticoagulation
therapy beyond 3 to 6 months from the valve placement, long-term therapy
with aspirin 75 to 100 mg/day is recommended in preference to long-term
anticoagulation (Class I, level C).
6. For patients with a bioprosthetic aortic or mitral valve who have a TIA, ischemic
stroke, or systemic embolism despite adequate antiplatelet therapy, the
addition of VKA therapy with an INR target of 2.5 (2.0–3.0) may be considered
(Class IIb, level C).

Prevention
References

1. Visser CA, Kan G, Meltzer RS, et al. Long-term follow-up of left ventricular thrombus after acute myocardial
infarction: a two-dimensional echocardiographic study in 96 patients. Chest. 1984;86:532-536.
2. Hurlen M, Abdelnoor M, Smith P , et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J
Med. 2002 Sep 26;347(13):969-74.
3. Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating
anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993 Oct;22(4):1004-9.
4. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left
ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial:
the SAVE Investigators. N Engl J Med. 1992; 327: 669–677.
5. Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction.
N Engl J Med. 1997;336:251-257.
6. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or
transient ischemic attack: a statement for healthcare professionals from the American Heart Association/
American Stroke Association Council on Stroke. Stroke. 2006 Feb;37(2):577-617.
7. Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus
rhythm. N Engl J Med. 2012 May 17;366(20):1859-69.
8. Kumar G, Goyal MK. Warfarin versus aspirin for prevention of stroke in heart failure: a meta-analysis of
randomized controlled clinical trials. J Stroke Cerebrovasc Dis. 2013;22:1279–1287.
9. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and
transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2014;45:000-000.
10. Lee M, Saver JL, Hong KS, et al. Risk-benefit profile of warfarin versus aspirin in patients with heart failure
and sinus rhythm: a meta-analysis. Circ Heart Fail. 2013;6:287–292.
11. Israel DH, Sharma SK, Fuster V. Antithrombotic therapy in prosthetic heart valve replacement. Am Heart J.
1994;127:400-411.
12. Israel DH, Fuster V, Ip JH, et al. Intracardiac thrombosis and systemic embolization. In: Colman RW, Hirsh
J, Marder V, Salzman EW, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed.
Philadelphia: JB Lippincott; 1994:1452–1468.
13. Coulshed N, Epstein EJ, McKendrick CS, et al. Systemic embolism in mitral valve disease. Br Heart J.
1970;32:26-34.
14. Wood JC, Conn HL Jr. Prevention of Systemic Arterial Embolism in Chronic Rheumatic Heart Disease by
Means of Protracted Anticoagulant Therapy. Circulation. 1954;10:517-523.
15. Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with
mechanical heart valve prostheses. Circulation. 1994;89:635–41.
16. Salem DN, Daudelin HD, Levine HJ, et al. Antithrombotic therapy in Valvular Heart Disease. Chest. 2001
Jan;119(1 Suppl):207S-219S.
17. Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation
and risk of stroke: the Framingham study. Neurology. 1978;28:973-7.
18. Braunwald E. Heart disease. Textbook of Cardiovascular Medicine. 5th ed. Philadelphia: WB Saunders;
51
 1997.
19. Brockmeier LB, Adolph RJ, Gustin BW, Holmes JC, Sacks JG. Calcium emboli to the retinal artery in calcific
aortic stenosis. Am Heart J. 1981;101:32–37.
20. Holley KE, Bahn RC, McGoon DC, Mankin HT. Spontaneous calcific embolization associated with calcific
aortic stenosis. Circulation. 1963; 27: 197–202.
21. Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the
prevention of prosthetic heart valve thromboembolism: a prospective clinical trial. Circulation. 1985; 72:
1059–1063.
22. Dale J, Myhre E, Storstein O, et al. Prevention of arterial thromboembolism with acetylsalicylic acid. A
controlled clinical study in patients with aortic ball valves. Am Heart J. 1977 Jul;94(1):101-11.
23. Turpie AG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with
warfarin after heart-valve replacement. N Engl J Med. 1993 Aug 19;329(8):524-9.
24. Gohlke-Barwolf C, Acar J, Oakley C, et al. Guidelines for prevention of thromboembolic events in valvular
heart disease. Study Group of the Working Group on Valvular Heart Disease of the European Society of
Cardiology. Eur Heart J. 1995;16(10):1320–30.
25. Proceedings of the Seventh ACCP Conference on antithrombotic and thrombolytic therapy: evidence-
based guidelines. Chest. 2004;126 (3 Suppl):172S-696S.
26. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With
Prevention

Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation. 2014 Jun 10;129(23):2440-92.
27. Vandvik PO, Lincoff AM, Gore JM, et al. American College of Chest Physicians. Primary and secondary
prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed.
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:
e637S–668S.

VII. EXTRACRANIAL CAROTID STENOSIS AND STROKE

A. Epidemiology
Extracranial carotid stenosis of ≥50% is present in over 5% of individuals above
the age of 65.1 The prevalence of clinically significant carotid artery stenosis varies
significantly by race; the highest frequency was noted among the native Americans,
while the lowest rates were seen among African American males and Asian females.2
Individuals with carotid stenosis often have a widespread atherosclerotic disease and
higher prevalence of coronary heart disease and claudication.3 The risk of coronary
events is higher among patients with carotid atherosclerosis (RR=22%; 95% CI, 14%–
30%) than among those without the condition.4

Carotid artery disease accounts for 15% to 20% of all ischemic strokes.5 Individuals
with symptomatic severe carotid stenosis have a higher annual stroke risk (13% to
15%) as compared with persons with asymptomatic lesions or no history of stroke or
TIA (1% to 2%).6-8 Factors associated with increased risk of neurological events include
echolucent ulcerated plaques, plaque hemorrhages, hypertension, and progressive
stenotic lesions.9

B. Risk Modification
B.1. Primary Stroke Prevention
Carotid endarterectomy (CEA) in asymptomatic cases showed modest benefit in
two large randomized controlled trials (RCTs), with 1%-2% reduction of annual
stroke risk. Results of the Asymptomatic Carotid Artery Stenosis (ACAS) trial
show that, among patients with asymptomatic carotid stenosis (60%-99%), CEA
combined with best medical treatment reduced the 5-year ipsilateral stroke risk
from 11% to 5.1% (relative risk reduction [RRR], 5.3%).7 Similar finding was noted
in the Asymptomatic Carotid Surgery Trial (ACST), which demonstrated a small but
definite reduction of stroke risk with surgery among patients with ≥60% stenosis
(5-year stroke risk: 11.8% in the medical arm versus 6.4% in the combined CEA and
medical treatment arm).8 For an asymptomatic patient to benefit from surgery, there
should be an exceptionally low perioperative complication rate (i.e. <3%).7,8 Within
the stenosis range of 60%-99%, neither of the trials showed a progressive increase
52
in surgical benefit with each increasing degree of asymptomatic stenosis.7,8,10

Over the last two decades, there have been substantial improvements in the
primary prevention of atherosclerosis by medical means than in reduction of
perioperative risks in carotid revascularization procedures.11,12 The benefits of CEA
or carotid artery stenting (CAS), when added to best medical management, may be
marginal at present than in the past. This hypothesis is currently investigated in the
second European Carotid Surgery Trial (ECST-2) (ISRCTN 97744893).13,14

B.2. Secondary Stroke Prevention

Among symptomatic patients with ≥70% stenosis but without near-occlusion,
the combined CEA and medical treatment provides greater risk reduction (over 5
years) in ipsilateral and perioperative stroke (absolute risk reduction [ARR]=16%;
RRR=61%) than medical treatment alone.6,15-17 There was a trend toward benefit
with surgical treatment at 2 years (ARR 5.6%) among patients with near-total
carotid occlusion, although this was seen only in the short term (-1.7% over 5
years).15

Prevention
CEA was marginally beneficial among patients with 50%-69% stenosis. Greater
benefit was seen in males, the elderly (age >75 years), those with hemispheric
symptoms (compared with those having transient monocular blindness), and those
treated within 2 weeks of a TIA or non-disabling ischemic stroke.6,15-17 CEA was
harmful for symptomatic patients with less than 30% stenosis. It also had no effect
among patients with 30%-49% stenosis. CEA in symptomatic patients is effective in
preventing future ischemic events, provided that the perioperative combined risk
of stroke and death is not higher than 6%.

Pooled analysis of data from RCTs of CEA for symptomatic stenosis showed that
surgical benefit is greatest among patients subjected to treatment within 2 weeks
after the ischemic event, whereas the degree of benefit decreases rapidly with the
increasing delay in treatment.18 Among stable patients, there was no difference in
the operative risks between early surgery (i.e. first 3 weeks) and late surgery (11
studies, OR 1.13; 95% CI 0.79-1.62; p=0.62).19

Carotid angioplasty and stenting have emerged as an alternative treatment for

carotid stenosis. Results of meta-analyses of RCTs (completed and terminated)
comparing endovascular treatment and CEA showed no difference in the odds
of mortality or stroke between the two groups in 2-3 years.20-24 However, a
consistent trend towards less periprocedural stroke at 30 days was seen in the
CEA group (albeit more MI), while a trend towards less periprocedural MI was
seen in the carotid angioplasty/stenting group (albeit more strokes). The Carotid
Revascularization Endarterectomy versus Stent Trial (CREST), which compared
the outcomes of CAS and CEA among symptomatic and asymptomatic patients,
yielded similar medium-term results for both procedures (i.e. composite endpoint
of stroke/MI/death at 4 years: 6.8% with CEA; 7.2% with CAS). Likewise, the 30-day
periprocedural risks for stroke and MI were high for CAS and CEA respectively.25
An intriguing finding of the CREST is the interaction of age and the efficacy of
therapy. CAS appeared to have a greater efficacy among younger patients (<70
years), while endartectomy was slightly superior than CAS when used in the older
patients.25,26

In 2012, the Cochrane Stroke Group conducted a systematic review of RCTs

comparing CAS and CEA (16 trials, 7572 patients). Similar to CREST, it was shown
that endovascular treatment is associated with increased risk of periprocedural
stroke or death compared with endarterectomy. However, this excess risk appears
to be limited to older patients. Among patients aged ≥70 years, the risk was
elevated for CAS (OR=2.20; 95% CI, 1.47–3.29), while in patients <70 years, the risk
53
 was similar (OR for CAS, 1.16; 95% CI, 0.80–1.67).27,28

C. Recommendation
1. Mass screening for carotid stenosis is not cost-effective.
2. Thorough history taking and physical and neurological examinations aid in
distinguishing between symptomatic and asymptomatic carotid stenosis (Good
Clinical Practice, GCP).
3. It is reasonable to screen, using readily available and reliable non-invasive
carotid duplex ultrasonography (CDUS), asymptomatic patients at risk for
significant carotid disease (e.g., those who survived a stroke or those who have
carotid bruit, peripheral vascular disease, and/or coronary artery disease) (Class
IIa, level C).
4. CDUS is recommended to detect carotid stenosis in symptomatic patients (i.e.
those who had a recent hemispheric or retinal stroke or TIA) (Class I, level C).
5. CDUS is not recommended for routine screening of asymptomatic patients with
no vascular risk factors (Class III, level C).
6. All patients with carotid artery disease (symptomatic or asymptomatic) should
Prevention

be advised on lifestyle modification, focusing on smoking cessation and

maintaining normal body mass index (BMI), adequate daily exercise, and healthy
balanced diet. Optimal medical management to reduce atherosclerotic risk
factors is recommended and should include long-term antiplatelet and statin
therapy11,29 (Class I, level A).
7. When CDUS is inconclusive in revascularization candidates, the use of MRA or
CTA is reasonable (Class IIa, level C). When noninvasive imaging studies are
discordant, it is reasonable to perform catheter-based contrast angiography
(Class IIa, level C).
8. When considering carotid revascularization procedures (i.e. carotid
endarterectomy [CEA] and carotid artery stenting [CAS]), it is imperative
to stratify patients by the degree of carotid stenosis (e.g., NASCET method);
whether symptomatic or asymptomatic; and into low- or high-surgical risk
groups.
9. It is reasonable to perform CEA in patients with asymptomatic carotid stenosis
of ≥70%, provided the perioperative risk of stroke, MI, and death can be reliably
documented to be <3% and that the patient’s life expectancy exceeds 5 years
(Class IIa, level A).
10. CEA is recommended for patients with recent TIA or non-disabling stroke and
ipsilateral severe carotid artery stenosis (70%-99%) if perioperative risk of <6%
can be attained (Class I, level A).
11. For symptomatic patients with 50% to 69% stenosis, CEA is recommended
depending on patient-specific factors such as age, gender, co-morbidities, and
severity of initial symptoms (Class I, level A).
12. When the degree of stenosis is <50%, CEA is not recommended (Class III, level
A).
13. CEA is not recommended for chronic total carotid occlusion (Class III, level C).
14. CEA is not recommended for patients with severe stroke disability that precludes
preservation of useful function7,30,31 (Class III, level C).
15. It is reasonable to perform CEA within 2 weeks of the TIA or minor stroke, rather
than delay the procedure, in patients who are clinically stable and with imaging
evidence of minimal infarction or mass effect18,32 (Class IIa, level B).
16. While CEA remains as the preferred treatment in most average-surgical risk
patients with symptomatic severe (>70%) stenosis, the endovascular approach
is reasonable in patients with high-surgical risk or in those with unfavorable
technical or anatomical conditions, such as surgically inaccessible stenosis,
irradiated neck, and restenosis after CEA (Class IIa, level B). CAS is reasonable
when performed by operators with established periprocedural stroke and
mortality rates of <6%24,26,28 (Class I, level B).
17. In deciding between CEA and CAS, it is reasonable to consider the patient’s
54
 age. For patients aged ≥70 years, CEA may be more appropriate. For patients
aged <70 years, CAS is as safe as CEA with regards to risk of periprocedural
complications and long-term risk for ipsilateral stroke33 (Class I, level B).
18. In patients with concomitant symptomatic carotid stenosis and coronary artery
disease, present data is insufficient to declare superiority of the timing of CEA
(either before or concurrent with myocardial revascularization). In patients with
asymptomatic carotid stenosis undergoing coronary artery bypass graft (CABG)
surgery, the safety and benefit of carotid revascularization prior to or concurrent
with myocardial revascularization is not convincingly established34,35 (Class IIb,
level C).

References
1. de Weerd M, Greving JP, de Jong AW, et al. Prevalence of asymptomatic carotid artery stenosis according
to age and sex: systematic review and metaregression analysis. Stroke. 2009; 40: 1105–13.
2. Rockman CB, Hoang H, Guo Y, et al. The prevalence of carotid artery stenosis varies significantly by race.

Prevention
J Vasc Surg. 2013 Feb;57(2):327-37.
3. Hertzner HR, Young JR, Beven EG, et al. Coronary angiography in 506 patients with extracranial
cerebrovascular disease. Arch Intern Med. 1985;145:849-852.
4. Sirimarco G, Amarenco P, Labreuche J, et al., on behalf of the REACH Registry Investigators. Carotid
Atherosclerosis and Risk of Subsequent Coronary Event in Outpatients With Atherothrombosis. Stroke.
2013;44:373-379.
5. Sacco RL, Ellenberg JA, Mohr JP, et al. Infarcts of undetermined cause: the NINDS stroke Data Bank. Ann
Neuro. 1989;25;382-390.
6. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic
moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
N EngI J Med. 1998;339:1415-1425.
7. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for
asymptomatic carotid arterectomy stenosis. JAMA. 1995;273:1421-1428.
8. MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and
fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms:
randomized controlled trial. Lancet. 2004;363:1491-1502.
9. Liapis C, Kakisis J, Kostakis, A. Carotid stenosis: Factors affecting symptomatology. Stroke. 2001; 32:2782-
2786.
10. Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: Asymptomatic
carotid surgery trial. Stroke. 2004;35:2425-2427.
11. Amarenco P, Labreuche J, Lavallee P, Touboul PJ: Statins in stroke prevention and carotid atherosclerosis:
systematic review and uptodate meta-analysis. Stroke. 2004; 35: 2902–9.
12. Naylor AR: What is the current status of invasive treatment of extracranial carotid artery disease? Stroke.
2011; 42: 2080–5.
13. Chaturvedi S. Aggressive medical therapy alone is adequate in certain patients with severe symptomatic
carotid stenosis. Stroke. 2013;44: 2955–56.
14. Hankey GJ. Secondary stroke prevention. Lancet Neurol. 2014; 13: 178–94
15. Rothwell PM, Eliasziw M. Gutnikov SA for the Carotid Endarterectomy Trialists’ Collaboration. Analysis
of pooled data from the randomized controlled trials of endarterectomy for symptomatic carotid stenosis.
Lancet. 2003;361:107-116.
16. Farrel B, Fraser A, Sandercock P, et al. Randomized trial of endarterectomy for recently symptomatic
carotid stenosis. Final results of MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351:1379-
1387.
17. Mayberg MR, Wilson E, Yatsu F, et al. Carotid endarterectomy and prevention of cerebral ischemia in
symptomatic carotid stenosis. JAMA. 1991;226:3289-3294.
18. Rothwell PM. Eliasziw M, Gutnikov SA for the Carotid Endarterectomy Trialists’ Collaboration. Effect of
endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and to timing of surgery.
Lancet. 2004:363;915-924.
19. Bond, R, Rerkasem K, Cuffe R, et al. A systematic review of the risk of carotid endarterectomy in relation
to the clinical indication and the timing of surgery. Stroke. 2003;34:2290-2301.
20. Murad MH, Flynn DN, Elamin MB, et al. Endarterectomy vs stenting for carotid artery stenosis: A
systematic review and meta-analysis. J Vasc Surg. 2008;48(2):pp487-493.
21. Brahmanandam S, Ding EL, Conte MS, et al. Clinical Results of carotid artery stenting compared with
55
 carotid endarterectomy. J Vasc Surg. 2008;47:343-9.
22. Ringleb PA, Chatellier G, Hacke W, et al. Safety of endovascular treatment of carotid artery stenosis
compared with surgical treatment: A meta-analysis. J Vasc Surg. 2008;47:350-5.
23. Jeng JS, Lui HM, Tu TK. Carotid angioplasty with or without stenting versus carotid endarterectomy for
carotid artery stenosis: A meta-analysis. J Neurol Sci. 2008 Jul 15;270(1-2):40-7.
24. Ederle J, Feathersone R, Brown M. Randomized controlled trials comparing endarterectomy and
endovascular treatment for carotid artery stenosis: A Cochrane systematic review. Stroke. 2009;40:1373-
1380.
25. Brott TG, Hobson RW II, Howard G et al. Stenting versus endarterectomy for treatment of carotid artery
stenosis. N Engl J Med. 2010 Jul 1;363(1):11-23.
26. Voeks JH, Howard G, Roubin GS, et al.; for the CREST Investigators. Age and outcomes after carotid
stenting and endarterectomy: the Carotid Revascularization Endarterectomy Versus Stenting Trial. Stroke.
2011;42:3484–3490.
27. Rerkasem K, Rothwell PM. Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database
Syst Rev. 2011; 4: CD001081.
28. Bonati LH, Lyrer P, Ederle J, Featherstone R, Brown MM. Percutaneous transluminal balloon angioplasty
and stenting for carotid artery stenosis. Cochrane Database Syst Rev. 2012;9:CD000515.
29. Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of
Prevention

stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39:1647-52.
30. National Institute of Neurological Disorders and Stroke Stroke and Trauma Division. North American
Symptomatic Carotid Endarterectomy Trial (NASCET) Investigators. Clinical alert: benefit of carotid
endarterectomy for patients with high-grade stenosis of the internal carotid artery. Stroke. 1991;22:816-7.
31. Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-
risk patients. N Engl J Med. 2008;358:1572–9.
32. Kittipan Rerkasem, MD, PhD; Peter M. Rothwell, MD, PhD, FRCP, FMedSci. A Systematic Review of
Randomized Controlled Trials of Carotid Endarterectomy for Symptomatic Carotid Stenosis. Stroke.
2011;42:e543-e544.
33. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With
Stroke and Transient Ischemic Attack A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke. 2014;45:00-00.
34. Naylor AR, Mehta Z, Rothwell PM. A systematic review and meta-analysis of 30-day outcomes following
staged carotid artery stenting and coronary bypass. Eur J Vasc Endovasc Surg. 2009;37:379–387.
35. Naylor AR, Bown MJ. Stroke after cardiac surgery and its association with asymptomatic carotid disease:
an updated systematic review and meta-analysis. Eur J Vasc Endovasc Surg. 2011 May;41(5):607-24.

VIII. INTRACRANIAL STENOSIS AND STROKE

A. Epidemiology
Intracranial atherosclerotic disease (ICAD) is responsible for ischemic strokes in
approximately 5% to 10% of the Caucasian population, 15% to 17% of Hispanic
and African populations, and 33% to 37% of Chinese and Asian populations.1-9 In
addition to racial/ethnic influences, other risk factors for intracranial atherosclerosis
include age, hypertension, cigarette smoking, diabetes, dyslipidemia, and metabolic
syndrome.10-17
The annual risk of stroke among patients with symptomatic intracranial stenosis
ranges from 3% to 15% (approximate annual values: 7.6% for the carotid siphon, 7.8%
for middle cerebral artery [MCA], 2% to 7% for vertebral artery, and 11% for basilar
artery).18-23 The risk of recurrent ipsilateral stroke is highest among persons with 70%–
99% intracranial stenosis (annual risk, 19%) and those with recent symptoms (i.e.
within 2 weeks of the initial event).24

In contrast, asymptomatic ICAD appears to have a benign prognosis based on

preliminary data. The annual risk of ipsilateral stroke in asymptomatic MCA stenosis is
1.4% among medically-treated Caucasian patients.25,26 Among patients enrolled in the
Warfarin-Aspirin in Symptomatic Intracranial Disease (WASID) study, the 1-year stroke
rate in the territory of asymptomatic stenosis was 3.5%.21,27 Impaired vasoreactivity on
CT or MR perfusion studies may have a role in predicting future stroke risk among
patients with asymptomatic intracranial stenosis.28-30
56
B. Risk Modification

B1. Primary Stroke Prevention

There is no data available at present.

B2. Secondary Stroke Prevention

Among patients with stroke or TIA caused by 50% to 99% stenosis of a major
intracranial artery, the WASID study showed that: (1) aspirin is safer and as effective
as warfarin for stroke prevention [2-year ischemic stroke rate: 19.7% for aspirin
versus 17.2% for warfarin]; and (2) the rate of ischemic events was high regardless
of antiplatelet or anticoagulant therapy.21

There have been three antiplatelet trials with outcomes related to neuroimaging
and transcranial Doppler (TCD) findings. In the Trial of Cilostazol in Symptomatic
Intracranial Arterial Stenosis (TOSS), adding cilostazol 100 mg BID to aspirin
was superior to aspirin monotherapy in preventing progression of intracranial
arterial stenosis as detected by MR angiography (MRA) at 6 months.33 In the

Prevention
TOSS-2, a non-significant trend towards less ICAD progression was observed in
patients who received, in addition to standard aspirin 75-150 mg, cilostazol 100
mg BID compared with clopidogrel 75 mg OD (9.9% versus 15.46%, respectively;
p=0.49).32 In an open-labeled CLopidogrel plus Aspirin for Infarction Reduction
(CLAIR) study involving 70 patients with stroke/TIA related to intracranial stenosis,
the combination of clopidogrel and aspirin was associated with significantly
fewer microembolic signals on TCD (at day 2 and day 7) compared with aspirin
monotherapy. Continued trials are warranted to confirm the role and efficacy of
antiplatelets in preventing progression and further vascular events among patients
with symptomatic intracranial arterial stenosis.33

The Extracranial-Intracranial (EC-IC) Bypass Trial failed to show clinical benefit with
revascularization procedure (extracranial-intracranial anastomosis) in patients with
atherosclerotic disease of the carotid artery and MCA.22 The bypass patency rate
was 96%, but fatal and non-fatal strokes occurred earlier and more frequently
among those randomized to surgery.

Single-center experiences suggest that intracranial angioplasty and/or stenting

can be performed with a high degree of technical success.34-40 Acceptable
anatomical outcomes were obtained in medically refractory patients with
strokes attributable to intracranial stenosis enrolled in Phase I trials of Stenting
of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries
(SSYLVIA) study and the National Institutes of Health (NIH) Multi-center Wingspan
Intracranial Stent Registry Study. Only 1 RCT, however, has been performed which
compared endovascular therapy and best medical therapy alone. The Stenting
and Aggressive Medical Management for the Prevention of Recurrent Stroke in
Intracranial Stenosis (SAMMPRIS) trial was prematurely terminated in 2011 after
randomization of 451 patients with recent stroke/TIA attributed to ≥70% stenosis
of major intracranial artery. The rate of early stroke or death within 30 days was
significantly higher among those randomized to percutaneous transluminal
angioplasty and stenting (PTAS) using the Wingspan system (14.7% in the PTAS
group versus 5.8% in the medical group, p=0.002). One-year event rates referable
to the qualified artery also differed significantly between the treatment groups
(20% in PTAS group versus 12.2% in the medical group, p=0.009).41 The early
benefit of aggressive medical treatment over stenting persisted for an extended
follow-up period (median, 32 months).42

The rate of primary endpoint among patients enrolled in the medical arm of the
SAMMPRIS trial was substantially lower than those randomized in the medical arm
of the WASID trial (30-day and 1-year primary outcome rates: 5.8% and 12.2%
57
 respectively in SAMMPRIS, versus 10.7% and 25% respectively in WASID).21,41
Although there are known limitations of using historical controls, aggressive
medical therapy with dual antiplatelets, intensive control of BP and LDL-cholesterol,
and adherence to a lifestyle program maybe more effective than aspirin alone and
usual management of vascular risk factors.43

C. Recommendation
1. In patients with ischemic stroke or TIA, screening for intracranial arterial stenosis
by vascular studies is recommended.
2. Non-invasive tests such as transcranial Doppler (TCD), CT angiography (CTA),
and MR angiography (MRA) are important in the evaluation and exclusion of
ICAD. Digital subtraction angiography (DSA) is recommended for accurate
categorization of lesion detected on non-invasive tests and for distinguishing
between atherosclerotic and non-atherosclerotic vasculopathies.
3. Best medical management must be targeted to plaque regression and
stabilization, global atherosclerotic risk management, and antithrombotic
treatment. Aspirin is recommended in most patients to prevent recurrent
Prevention
Prevention

ischemic events because it has a better safety profile than anticoagulation. The
Stroke

addition of cilostazol or clopidogrel to aspirin therapy may be reasonable.

4. Management of cardiovascular risk factors such as hypertension, dyslipidemia,
and diabetes mellitus is strongly advised. Maintaining the systolic BP to less than
140 mm Hg and high-intensity statin therapy are recommended in patients with
symptomatic intracranial stenosis.
5. For patients with stroke or TIA attributed to significant intracranial stenosis
>70% of diameter, stenting with the Wingspan system is not recommended as
an initial treatment even among patients who are already on antithrombotic
therapy at the time of stroke or TIA.
6. The usefulness of angioplasty alone or with stenting for patients with recurrent
events despite institution of aggressive medical therapy including dual
antiplatelets and high intensity statin therapy is unknown and is considered
investigational.
7. For patients with stroke or TIA attributed to moderate intracranial stenosis 50%
to 69% of diameter, angioplasty with or without stenting is not recommended
given the low risk of stroke with best medical management and inherent
procedural risk with endovascular therapy.43

References

1. Gorelick PB. Distribution of atherosclerotic cerebrovascular lesions. Effects of age, race, and sex. Stroke.
1993;24 (12 Suppl):I16-I19.
2. Sacco, RL, Kargman DE, Gu Q, Zamanillo MC. Race-ethnicity and determinants of intracranial
atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke. 1995;26:14-20.
3. Wityk RJ, Lehman D, Klag M, et al. Race and sex differences in the distribution of cerebral atherosclerosis.
Stroke. 1996;27:1974-1980.
4. Wong, KS, Huan L. Racial distribution of intracranial and extracranial atherosclerosis. J Clin Neurosc.
2003;10:30-34.
5. Leung SY, Ng TH, Yuen ST, et al. Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in
intracranial and extracranial vessels. Stroke. 1993;24:779-786.
6. Suh DC, Lee SH, Kim KR, et al. Pattern of atherosclerotic carotid stenosis in Korean Patients with stroke:
different involvement of intracranial versus extracranial vessels. Am J Neuroradiol. 2003;24:239-244.
7. Wong KS, Huang YN, Gao S, et al. Intracranial stenosis in Chinese patients with acute stroke. Neurology.
1998; 50: 812-813.
8. Wong KS. Li H, Chan YL, et al. Use of transcranial Doppler to predict outcome in patients with intracranial
large artery occlusive disease. Stroke. 2000; 31:2641-2647.
9. Wong KL. Global burden of intracranial atherosclerosis. Int J Stroke. 2006; 1: 158-159.
10. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: a review: Stroke.
1986;17:648-655.
11. Cho, SJ, Sohn YH, Kim JH. Blood flow velocity changes in the middle cerebral artery as an index of
chronicity of hypertension. J Neuro Sci. 1997;150:77-80.
58
12. Ingall TJ, Homer D, Baker HL Jr, et al. Predictors of intracranial carotid artery atherosclerosis. Duration of
cigarette smoking and hypertension are more powerful than serum lipid levels. Arch Neurol. 1991;48:687-
691.
13. Inzitari D, Hachinski VC, Taylor DW, Barnett HJ. Racial differences in the anterior circulation in
cerebrovascular disease. How much can be explained by risk factors. Arch Neurol.1990;47:1080-1084.
14. Arenillas JF, Molina CA, Chacon P, et al. High lipoprotein, diabetes and the extent of symptomatic
intracranial stenosis. Neurology. 2004;63:27-32.
15. Bang Oy, Kim JW, Lee JH, et al. Association of the metabolic syndrome with intracranial atherosclerotic
stroke. Neurology. 2005;65:296-298.
16. Bae, HJ, Lee J, Park JM, et al. Risk factors of intracranial stenosis among asymptomatics. Cerebrovascular
Dis. 2007; 24: 355-360.
17. Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebral arteries.:intracranial
versus extracranial. Neuroepidemiology. 2003; 22: 37-40.
18. Thijs VN, Albers GW. Symptomatic intracranial atherosclerosis: Outcome of patients who fail
antithrombotic therapy. Neurology. 2000;55:490-497.
19. Rundek T, Elkind MS, Chen X. Increased early stroke recurrence among patients with extracranial and
intracranial atherosclerosis: Northern Manhattan Stroke Study. Neurology. 1998;50 (Suppl 4):A75.
20. The WASID Study Group. Prognosis of patients with symptomatic vertebral or basilar artery stenosis.

Prevention
Prevention
Stroke. 1998;29:1389-1392.
21. Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Warfarin-Aspirin Symptomatic Intracranial Disease

Stroke
Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N
Engl J Med. 2005;352:1305-1316.
22. The EC-IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of
ischemic stroke. Results of an international randomized trial. N Eng J Med. 1985;313:1191-1200.
23. Wechler LR. Kristler JP, David KR. Kaminsky MJ. The prognosis of carotid siphon stenosis. Stroke.
1986;17:714-718.
24. Kasner, SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of of a symptomatic
intracranial arterial stenosis. Circulation. 2006; 113: 555-563.
25. Kremer C, Schaettin T, Giorgiadis D, Baumgartner R. Prognosis of asymptomatic stenosis of the middle
cerebral artery. J Neurol Neurosurg Psychiatry. 2004;75:1300-1303.
26. Kern R, Steinke W, Daffertshofer M, et al. Stroke recurrence in patients with symptomatic versus
asymptomatic middle cerebral artery disease. Neurology. 2005;65:859-864.
27. Nahab, F. Cotsonis G, Lynn M. et al. Prevalence and prognosis of co-existent asymptomatic intracranial
stenosis. Stroke. 2008; 39: 1039-1041.
28. Chen A, Shyr MH, Chen TY. et al. Dynamic CT perfusion imaging with acetazolamide challenge for the
evaluation of patient with unilateral cerebrovascular steno-occlusive disease. Am J Neuroradiol. 2006; 27:
1876-1881.
29. Ma J, Mehrkens JH, Holtmannspoetter M. et al. Perfusion MRI before and after acetazolamide
administration for asessement of cerebrovascular reserve capacity in patients with symptomatic ICA
occlusion: comparison with 99mTC-ECD SPECT. Neuroradiology. 2007; 49: 317 – 326.
30. Grubb RL. Jr, Derdeyn CP, Fritsch SM et al. Importance of hemodynamic factors in the prognosis of
symptomatic carotid occlusion. JAMA. 1998; 280. 1055 – 1060.
31. Kwon S, Cho YJ, Koo JS et al. Cilostazol prevents the progression of symptomatic intracranial stenosis.
Stroke. 2005;36:782-786.
32. Kwon SU, Hong, KS, Kong DB, et al. Efficacy and safety of combination therapies among patients with
symptomatic intracranial atherosclerotic stenosis. Stroke. 2011; 42: 2883-2890.
33. Wang X, Lin WH, Zhao YD et al.; CLAIR Study Investigators. The effectiveness of dual antiplatelet
treatment in acute ischemic stroke with intracranial arterial stenosis: a subgroup analysis of CLAIR study.
Int J Stroke. 2013; 8: 663-668.
34. Higashida R, Meyers PM, Connors J, et al. Intracranial angioplasty and stenting for cerebral atherosclerosis:
A Position Statement of the American Society of Interventional and Therapeutic Neuroradiology,
Society of Interventional Radiology, and the American Society of Neuroradiology. J Vasc Interv Radiol.
2005;16:1281-1285.
35. Jiang WJ, Xu XT, Jin M, et al. Apollo stent for symptomatic atherosclerotic intracranial stenosis study
results. Neuroradiology. 2007; 28: 830-834.
36. 36. Kurre W, Berkefeld J, Sitzer M et al. Treatment of symptomatic high grade intracranial stenosis with
the balloon-expandable Pharos stent. initial experience. Neuroradiology. 2008; 50: 701 – 708.
37. SSLYVIA Study Investigators. Stenting of symptomatic atherosclerotic lesions in the vertebral or
intracranial arteries (SSYLVIA). Stroke. 2004;35:1388-1392.
38. Henkes H, Miloslavski E, Lowens S, et al. Treatment of intracranial atherosclerotic stenosis with balloon
dilatation and self-expanding stent deployment (WingSpan). Neuroradiology. 2005;47:222-228.
59
 39. Fiorella D, Levy EI, Turk AS et al. US multicenter experience with the wingspan stent system for the
treatment of intracranial atheromatous disease: periprocedural results. Stroke. 2007; 38: 881-887.
40. Zaidat OO, Klucznic R, Alexander MJ. et al. NIH Multicenter Wingspan Intracranial Stent Registry
Study Group. The NIH registry on the use of Wingspan stent for 70–99% intracranial arterial stenosis.
Neurology. 2008; 70:1518-1524.
41. Chimowitz MI, Lynn MJ, Derdyn CP et al for the SAMMPRIS Trial Investigators. Stenting vs aggressive
medical therapy for intracranial arterial stenosis. N Eng J Med. 2011; 361: 993-1003.

IX. PERIPHERAL ARTERIAL DISEASE AND STROKE

Peripheral arterial disease (PAD) is characterized by arterial stenosis and occlusion of the
peripheral arterial bed. Regardless of the presence or absence of symptoms, PAD is an
indicator of a diffuse systemic atherosclerosis. Symptomatic lower extremity PAD ranges
from intermittent claudication (IC) to chronic limb ischemia (CLI). A simple and objective
test for detecting presence of PAD is the ankle-brachial index (ABI), computed as the
Prevention
Prevention

systolic BP at the ankle divided by the systolic BP at the arm. An ABI <0.9 indicates a
lower extremity arterial obstructive disease. PAD can be classified into 7 stages (Table 5):
Stroke

Table 5. Rutherford Classification of Peripheral Arterial Disease1

Stage Clinical feature
0 Asymptomatic
1 mild intermittent claudication
2 moderate intermittent claudication
3 severe intermittent claudication
4 presence of ischemic rest pain
5 loss of minor tissue loss
6 presence of ulceration or gangrene

A. Epidemiology
Up to one-third of persons aged >70 years and diabetics in the 50-to-69 age group
have a lower extremity PAD.2 The prevalence increases with age and with the presence
of risk factors. In the Philippines, the prevalence of PAD is 1.6% in adults aged 20 years
and above.3 About 2% of Filipinos aged 55 years and older have IC, and approximately
5% have PAD on ABI confirmation. In a local study of adults (≥40 years) admitted to
an intensive care unit for heart attack, stroke, or type 2 DM, approximately 30% were
found to have a silent PAD.

The risk factors for PAD include smoking, diabetes mellitus (DM), dyslipidemia,
and hyperhomocysteinemia. Often, these risk factors overlap and may coexist with
coronary and cerebrovascular disease. Studies have shown that patients with PAD
have an increased risk of myocardial infarction (MI) by 20% to 60%, stroke by 40%,
and a two- to six- fold mortality risk due to coronary events.4-8

In the Atherosclerosis Risk in Communities (ARIC) study, men with PAD have four
to five times higher risk of stroke and TIA than those without PAD.9 In addition,
the all-cause mortality rate after 10 years was 61.8% in men with PAD and 16.9%
in unaffected men. Among women, the corresponding mortality rates were 33.3%
and 11.6% respectively. The increase in total mortality was due to a sharp increase
in cardiovascular mortality which persisted even after adjusting for pre-existing
coronary artery disease (CAD) and cerebrovascular disease at baseline. In general,
the risk was proportional to the severity of PAD.

60
B. Risk Modification
In lower-extremity PAD, adverse cardiovascular events may be reduced with lifestyle
modification or elimination/control of risk factors such as cigarette smoking, diabetes
mellitus, dyslipidemia, and hypertension. Exercise and non-atherogenic diet are
strongly advised.

B.1. Smoking and PAD

Cigarette smoking is an important, dose-dependent risk factor for lower extremity
PAD.10 Observational studies have shown that the risk of death, MI, and limb loss
is greater among individuals who continue to smoke than persons who have
discontinued.11,12 In a prospective epidemiological study among Icelandic men,
smoking cessation and cholesterol lowering resulted in the sharp decline in
prevalence and incidence of intermittent claudication.13

B.2. Diabetes Mellitus and PAD

It is unclear whether blood glucose control decreases the risk of adverse
cardiovascular events among patients with lower-extremity PAD. Analysis of

Prevention
Prevention
the Diabetes Control and Complication Trial (DCCT) showed that intensive

Stroke
insulin therapy among type 1 DM patients decreased the risk of IC, peripheral
revascularization, and amputation by 22%, however this reduction was not
statistically significant.14

High glycosylated hemoglobin (A1c) levels in patients with DM and PAD correlate
with higher prevalence of severe PAD.15 In the elderly, the incidence of coronary
events is 1.5 times higher among those with DM and PAD (without coexistent
coronary artery disease) than among nondiabetics with PAD and prior MI.16

B.3. Dyslipidemia and PAD

Treatment of dyslipidemia in patients with systemic atherosclerosis can reduce
future cardiovascular events. In the Heart Protection Study (HPS) which included
6,748 patients with PAD, treatment with simvastatin caused a 6.3% absolute
reduction in major cardiovascular events, independent of age, gender, or serum
lipid levels.17

B.4. Hypertension and PAD

Antihypertensive treatment in patients with PAD was believed to diminish perfusion
of the limbs and exacerbate symptoms of limb ischemia. However, most patients
do not experience worsening of symptoms with an appropriate antihypertensive
regimen. Treatment with beta-blockers has been controversial in PAD. However, in
a meta-analysis of 11 placebo-controlled studies of patients with PAD, the use of
beta-blockers did not have an adverse effect in ambulation.18

In the Heart Outcomes Prevention Evaluation (HOPE) study which included 4,051
patients with PAD, treatment with ramipril 10 mg daily (versus placebo) among
patients with symptomatic PAD and asymptomatic PAD significantly reduced
cardiovascular events by 25% and 5.9% respectively.19

C. Recommendation 4,20
1. A history of walking impairment, claudication, ischemic rest pain, and/or non-
healing wounds is recommended as a required component of a standard review of
system for adults 50 years and older who have atherosclerosis risk factors and for
adults 70 years and older (Class I, level C).
2. Individuals with asymptomatic lower extremity PAD should be identified by
examination and/or measurement of the ABI so that therapeutic interventions
known to diminish the risk of MI, stroke, and death may be offered (Class I, level B).
3. Smoking cessation, lipid lowering, and treatment of diabetes and hypertension
according to current national treatment guidelines are recommended for
61
 individuals with asymptomatic lower extremity PAD (Class I, level B).
4. Antiplatelet therapy is indicated for individuals with asymptomatic lower extremity
PAD to reduce the risk of adverse cardiovascular ischemic events (Class I, level C).
5. The resting ABI should be used to establish diagnosis of lower extremity PAD in
patients with suspected lower extremity PAD, defined as having ≥1 of the following:
leg symptoms on exertion, non-healing wounds, age ≥65 years, or age ≥50 years
with a history of smoking or diabetes (Class I, level B).
6. Patients who are smokers or former smokers should be asked about status of
tobacco use at every visit (Class I, level A).
7. Patients should be assisted with counselling and developing a plan for quitting,
which may include pharmacotherapy and/or referral to a smoking cessation
program (Class I, level A).
8. Individuals with lower extremity PAD who smoke cigarettes or use other forms
of tobacco should be advised to stop smoking and be offered behavioral and
pharmacological treatment (Class I, level C).
9. A program of supervised exercise training is recommended as an initial treatment
modality for patients with intermittent claudication (Class I, level A).
Prevention

10. Supervised exercise training should be performed for a minimum of 30 to 45

minutes per session, at least 3 times per week for a minimum of 12 weeks (Class
I, level A).
11. Cilostazol 100 mg orally 2 times per day is recommended to improve symptoms
and increase walking distance in patients with lower extremity PAD and intermittent
claudication (in the absence of heart failure) (Class I, level A).
12. A therapeutic trial of cilostazol should be considered in all patients with lifestyle-
limiting claudication (in the absence of heart failure) (Class I, level A).

References

1. Dormandy JA, Rutherford RB, for the TASC Working Group. TransAtlantic Inter-Society Consensus
(TASC) Management of peripheral arterial disease (PAD). J Vasc Surg. 2000;31:S1–S296.
2. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and
treatment in primary care. JAMA. 2001;286(11):1317-1324.
3. Dans AL, Morales DD, Abola TB, et al.; for NNHeS 2003 Group. National Nutrition and Health Survey
(NNHeS): Atherosclerosis-related disease and risk factors. Phil J Int Med. 2005;43:103-115.
4. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of
patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic)
[truncated]. Circulation. 2006;113:e463-e654.
5. Criqui MH, Denenberg JO, Langer RD, et al. The epidemiology of peripheral arterial disease: importance
of identifying the population at risk. Vasc Med. 1997;2:221-226
6. Steg G, et al., for the REACH Registry Investigators. One-year cardiovascular event rates in outpatients
with atherothrombosis. JAMA. 2007;297:1197-1206
7. O’Hare AM, Katz R, Shlipak MG, et al. Mortality and cardiovascular risk across the ankle-arm index
spectrum: results from the Cardiovascular Health Study. Circulation. 2006;113:388-393.
8. McDermott MM, Liu K, Criqui MH, et al. Ankle brachial index and subclinical cardiac and carotid
disease: the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol. 2005;162(1):33-41006;113(3):388-393
9. Saito I, Folsom AR, Brancati FL. Nontraditional risk factors for coronary heart disease incidence
among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Ann Intern Med.
2000;133:81–91.
10. Fowkes FG, Housley E, Riemersma RA, et al. Smoking, lipids, glucose intolerance, and blood pressure as
risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery
Study. Am J Epidemiol. 1992;135:331–340.
11. ZhengZJ, Sharrett AR, Chambless LE, et al. Associations of ankle/brachial index with clinical coronary
heart disease, stroke and preclinical carotid and popliteal Atherosclerosis Risk in communities (ARIC)
Study. Atherosclerosis. 1997;131:115-125
12. Abola MT, Dans A; for the Council of Stroke and Peripheral Vascular Diseases, Philippine Heart
Association. The Philippine Peripheral Arterial Disease (PHILPAD) Study. Phil J Int Med. 2003;41:71-74.
13. Ingolfsson IO, Sigurdsson G, Sigvaldason H, et al. A marked decline in the prevalence and incidence
of intermittent claudication in Icelandic men 1968–1986: a strong relationship to smoking and serum
62
 cholesterol-the Reykjavik Study. J Clin Epidemiol. 1994; 47:1237–1243.
14. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control
and Complications Trial. Am J Cardiol. 1995;75:894-903.
15. Aronow WS, Ahn C, Weiss MB, et al. Relation of increased hemoglobin A1c levels to severity of peripheral
arterial disease in patients with diabetes mellitus. Am J Cardiol. 2007;99:1468–9.
16. Aronow WS, Ahn C. Elderly diabetics with peripheral arterial disease and no coronary artery disease have
a higher incidence of new coronary events than elderly nondiabetics with peripheral arterial disease and
prior myocardial infarction treated with statins and with no lipid-lowering drug. J Gerontol A Biol Sci
Med Sci. 2003;58:M573–5.
17. Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering
with simvastatin in 20,536 high-risk individuals:a randomised placebo-controlled trial. Lancet.
2002;360:7–22.
18. Radack K, Deck C. Beta adrenergic blocker therapy does not worsen intermittent claudiacation in subjects
with peripheral arterial disease: a meta-analysis of randomized controlled trials. Arch Intern Med.
1996;151:1769-1776.
19. Ostergren J, Sleight P, Dagenais G, et al. Impact of ramipril in patients with evidence of clinical or
subclinical peripheral arterial disease. Eur Heart J. 2004;25:17–24.
20. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA Focused Update of the Guideline for the

Prevention
Management of Patients With Peripheral Artery Disease (Updating the 2005 Guideline). A Report of
the American College of Cardiology Foundation / American Heart Association Task Force on Practice
Guidelines. J Vasc Surg. 2011 Nov;54(5):e32-58.

X. PHYSICAL INACTIVITY AND STROKE

A. Epidemiology
Physical inactivity is a global health concern accounting for about 6% of deaths
globally. The prevalence of physical inactivity among Filipino adults (>20 years) is
high in the domains of work (67%-76.3%), non-work (72.3%-81.5%), leisure (89.1% to
95.5%), and travel (91.0%-95.2%).1

Physical inactivity is a risk factor for stroke, diabetes mellitus (DM), obesity,
hypertension, and depression. The relative risk (RR) of cardiovascular diseases
(including stroke) associated with physical inactivity ranges from 1.5 to 2.4, similar
to that observed with high cholesterol, hypertension, or cigarette smoking.2 When
cohort and case-control studies are combined, highly active individuals have a 27%
lower risk of stroke incidence or mortality than do low-active individuals (RR=0.73;
95% CI, 0.67 to 0.79; P<0.001).3 Among Filipinos, the odds ratio (OR) for stroke
associated with physical inactivity is 1.23.4

B. Risk Modification
B.1. Primary Stroke Prevention
Physical activity red ces the risk of stroke in both males and females, and across
all age and racial/ethnic groups (OR, 0.37).5 Physical activity in the form of sports,
leisure time, or work also reduced the risk of stroke, particularly the ischemic type.6
Several studies have shown the protective effect of physical activity among men. In
the Physicians’ Health Study (PHS), a lower total stroke risk (RR=0.86) was associated
with vigorous exercise (≥5 times a week) in males.7 Among females, there seems
to be a graded linear relation between the volume of physical inactivity and total
stroke.8 The Nurses’ Health Study and the Copenhagen City Heart Study showed
an inverse association between the level of physical activity and stroke incidence.9

The protective effect of physical activity may be partly mediated by BP reduction,

improvement of lipid indices (i.e. reduction in triglyceride, increase in HDL
cholesterol, decrease in LDL;HDL ratios), improvement of glucose homeostasis
and insulin sensitivity, and improvement in body composition and weight. Other
benefits include reduction in blood coagulability, improvement of coronary blood
flow, augmentation of cardiac function, enhancement of endothelial function,
improvement of autonomic tone, and reduction of systemic inflammation.
63
 B.2. Secondary Stroke Prevention
Activity intolerance is common among stroke survivors. Approximately, 14%
achieve full recovery in physical functions; between 25%-50% require at least
some assistance with activities of daily living (ADL), and about half experience
severe long-term effects such as partial paralysis.10 Often, stroke survivors are
deconditioned, thus they are predisposed to a sedentary lifestyle, which then
limits the performance of ADL, increases the risk for falls, and may contribute to a
heightened risk for recurrent stroke and cardiovascular diseases.

Cardiorespiratory response to acute exercise in stroke survivors

Many physiologic changes occur in stroke survivors, especially in patients with
moderate or severe deficits. The cardiac response of stroke survivors to acute
exercise has been documented in some studies. During progressive exercise
testing, patients achieve significantly lower maximal workloads, heart rate, and
BP responses than do normal subjects.11 In general, oxygen uptake at a given
submaximal workload is greater in stroke patients than in healthy subjects, possibly
Prevention

because of reduced mechanical efficiency, effects of spasticity, or both. Another

physiologic change in stroke patients is the reduction in peak oxygen uptake.

Traditionally, physical rehabilitation of stroke survivors typically ends within several

months after stroke, because it was believed that most of the functional recovery
occur during this interval. Recent studies have shown that aggressive rehabilitation
(including treadmill and aerobic exercise) beyond this time period is beneficial
especially for increasing strength, timing of muscle activations, cardiorespiratory
fitness, and aerobic capacity.12

One of the major goals of stroke rehabilitation is to increase aerobic fitness of

patients. Stroke survivors can improve their cardiovascular health with regular
aerobic exercise. In a randomized controlled trial (RCT) of 42 hemiparetic stroke
survivors, vigorous aerobic exercise training three times weekly for 10 weeks
significantly improved peak oxygen consumption and workload, submaximal
exercise BP response, exercise time, and sensorimotor function.13 In a study of 35
stroke patients with multiple comorbidities who underwent an exercise program
(one-hour, thrice per week sessions for 12 weeks) of combined cardiovascular,
strength, and flexibility training, the exercise group gained significantly in peak
oxygen uptake, strength, and improvements in body composition as compared
with controls.14 In another RCT involving 88 disabled men with coronary artery
disease (CAD), two-thirds of whom were stroke survivors, a 6-month-home
exercise training program significantly increased the peak left ventricular ejection
fraction (LVEF) and HDL-cholesterol, as well as decreased resting heart rate and
total serum cholesterol.15

Given these evidences, the importance of physical fitness and exercise cannot
be overemphasized. The recommendation that stroke survivors participate in
an exercise program is based on the premise that the benefits outweigh the
risks. The major potential health hazards of exercise for stroke survivors include
musculoskeletal injury and sudden cardiac death. A summary of exercise programs
for stroke survivors is presented in Table 6.

C. Recommendation
1. Increased physical activity is recommended because it improves stroke risk
factors and reduces risk of stroke16 (Class I, level B).
2. The SSP adopts the 2010 Philippine National Guidelines on Physical Activitya
for general health for the safe implementation of the recommended levels of
physical activity based on FIT (frequency, intensity, and time) principle across
all age groups: children (5-12 years), adolescents to young adults (13-21 years),
64
 adults (22-45 years), older adults (46-59 years), and elderly (≥60 years). The
prescriptions for physical activity include different forms of activities under the
headings: 1) activities for daily living; 2) programmed physical activity; 3) high
impact play/unstructured spontaneous play or recreational activities; 4) muscle
strengthening and flexibility activities; 5) activities in the workplace; and 6)
balance and coordination activities.17
3. The SSP adopts the 2014 AHA/ASA recommendations for Physical Inactivity
among patients with stroke and TIA as follows18:
a. For patients with ischemic stroke or TIA, who are capable of engaging in
physical activity, at least 3 to 4 sessions per week of moderate- to vigorous-
intensity aerobic physical exercise are reasonable to reduce stroke risk
factors. Sessions should last an average of 40 minutes (Class IIa, level C).
b. For patients who are able and willing to initiate increased physical activity,
referral to a comprehensive, behaviorally oriented program is reasonable
(Class IIa, level C).
c. For individuals with disability after ischemic stroke, supervision by a
healthcare professional such as a physical therapist or cardiac rehabilitation

Prevention
professional, at least on initiation of an exercise regimen, may be considered
(Class IIb, level C).

References

1. The Seventh National Nutrition Survey: Philippines, 2008: Initial Results. Taguig: Food and Nutrition
Research Institute.
2. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health: a recommendation from the Centers
for Disease Control and Prevention and the American College of Sports Medicine. JAMA. 1995;273:402-
407.
3. Lee CD1, Folsom AR, Blair SN. Physical activity and stroke risk: a meta-analysis. Stroke. 2003
Oct;34(10):2475-81.
4. Roxas A; The RIFASAF Project: Risk factors for stroke among Filipinos. Phil J Neuro. 2002;6:1-7.
5. Thom T, Hasee N, Rosamond W, et al. Heart Disease and Stroke Statistics 2006 Update: A report from
the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation.
2006;113:e85-e151.
6. Sacco, RL, Gan R, Boden-Albala, et al. Leisure-time physical activity and ischemic stroke risk; the Northern
Manhattan Stroke Study. Stroke. 1998;24:1484-189.
7. Lee IM, Hennekens CH, Berger K, et al. Exercise and risk of stroke in male physicians. Stroke. 1999;30:1-6.
8. Hu FB, Stampfer MJ, Colditz GA, et al. Physical activity and risk of stroke in women. JAMA. 2000;283:2961-
2967.
9. Lindenstrom E, Boysen G, Nyboe J. Lifestyle factors and risk of cerebrovascular disease in women. The
Copenhagen City Heart Study. Stroke. 1993;24:1468-1472.
10. Roth EJ, Harvey RL. Rehabilitation of stroke syndromes. In: Braddom RL, ed. Physical Medicine and
Rehabilitation. 2nd ed. Philadelphia, PA: WB Saunders; 2000: 1117-1163.
11. Monga TN, Deforge DA, Williams J, et al. Cardiovascular responses to acute exercise I patients with
cerebrovascular accidents. Arch Phys Med Rehabil. 1998;69:937-940.
12. Macko RF, Smith GV, Dobrovolny CL, et al. Treadmill training improves fitness reserve in chronic stroke
patients. Arch Phys Med Rehabil. 2001;82:879-884.
13. Potempa K, Lopez M, Braun LT, et al. Physiological outcomes of aerobic exercise training in hemiparetic
stroke patients. Stroke. 1995;26:101-105
14. Rimmer JH, Riley B, Creviston T, et al. Exercise training in a predominantly African-American group of
stroke survivors. Med Sci Sports Exerc. 2000;32:1990-1996
15. Fletcher BJ, Dunbar SB, Felner JM, et al. Exercise testing and training in physically disabled men with
clinical evidence of coronary artery disease. Am J Cardiol. 1994;73:170-174.
16. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the Primary Prevention of Stroke: A Guideline
for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke.
2011;42:517-584.
17. Philippine Guidelines on Physical Activity. Healthbeat. March-April 2010;58:6-13.

2010 Philippine National Guidelines on Physical Activity

Available at http://www.strokesocietyphil.org
65
 18. Kernan WN, Ovbiagele B, et. al.,on behalf of the American Heart Association Stroke Council, Council
on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral
Vascular Disease. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic
Attack A Guideline for Healthcare Professionals From the American Heart Association/American Stroke
Association. Stroke. 2014;45:000-000.

Table 6. Summary of Exercise Programming Recommendations for Stroke Survivors

Mode of Exercise Major goals Intensity, frequency, duration

Aerobic
Large-muscle activities
(e.g, walking, treadmill,
stationary cycle,
combined arm-leg
ergometry, arm
ergometry, seated
stepper
Prevention
Increase independence in ADLs
Increase walking speed/efficiency
Improve tolerance for prolonged
physical activity
Reduced risk of cardiovascular
disease
40-70% peak oxygen uptake;
40-70% heart rate reserve;
50%-80% maximal heart rate;
RPE 11-14 (6-20 scale)
3-7 days/week
20-60 min/session (or multiple
10-min sessions)

Strength
Circuit training
Weight machines
Free weights
Isometric exercise
Increase independence in ADLs 1-3 sets of 10-15 repetitions of 8-10
exercises involving the major
muscle groups
2-3 days/week

Flexibility
Stretching Increase ROM of involved 2-3 days/week (before or after
extremities aerobic or strength training)
Prevent contractures Hold each stretch for 10-30
seconds
Neuromuscular
Coordination and balance Improve level of safety during ADLs 2-3 days/week (consider
activities performing on same day as
strength activities)

ADL, activities of daily living; RPE, rating of perceived exertion; ROM, range of motion
Recommended intensity, frequency, and duration of exercise depending on each individual
patient’s level of fitness. Intermittent training sessions may be indicated during the initial weeks of
rehabilitation.

XI. OBESITY AND STROKE

Obesity is defined as a body mass index (BMI) of ≥30 kg/m2 or a waist-hip ratio (WHR) of
≥1.0 for men or ≥0.85 for women. The cut-off BMI for overweight is 25 kg/m2.

A. Epidemiology
In the Philippines, the prevalence of obesity by BMI is 4.9%.1 By WHR, the prevalence
is 10.2% in men and 65.6% in women.1 The Seventh National Nutrition Survey (7th
NNS) showed an increasing trend of overweight and obesity among Filipino adults
(≥20 years) from 2003 to 2008.2 This was mainly attributed to sedentary lifestyle
and changing dietary patterns, which have become increasingly heavy in fats, salt,
additives, and other artificial ingredients.

Obesity is a recognized modifiable risk factor for cardiovascular diseases and stroke.3
Studies have shown that an elevated BMI is associated with an increased risk of stroke
66
regardless of sex.4,5 In a prospective cohort study of approximately 170,000 Chinese
men and women aged ≥40 years (mean follow-up, 8.3 years), the relative hazard of
incident stroke for overweight and obesity, after adjustment for risk factors, was 1.43
(95% CI, 1.36-1.52) and 1.72 (95% CI, 1.55-1.91) respectively.4

Several studies suggest that abdominal obesity is more positively associated with
stroke risk than is general obesity.6,7 In a case-control study of 1,137 participants
matched for age and sex, the markers of abdominal obesity (i.e. waist circumference
and WHR) were strongly associated with the risk of stroke/TIA independent of other
vascular risk factors.6

In addition to stroke, epidemiologic studies show that increased body weight and
abdominal fat are directly associated with risk for other vascular risk factors such as
insulin resistance, atherogenic dyslipidemia, diabetes mellitus, and hypertension.7,8

B. Risk Modification
B.1. Primary Stroke Prevention

Prevention
Weight reduction is recommended for primary prevention because it lowers the
blood pressure (Class I, level A) thus reduces the risk of stroke. Recommended
options include diet modification, exercise, weight loss counseling, and lifestyle
intervention.9

There is no randomized controlled trial (RCT) to date which directly examined

the effect of bariatric surgery on stroke risk. However, results of a large RCT (the
Swedish Obese Subjects [SOS] trial) of bariatric surgery reported a reduction in
the incidence of myocardial infarction (MI) (adjusted HR, 0.71; 95% CI, 0.54–0.94;
P=0.02) and stroke (adjusted HR, 0.66; 95% CI, 0.49–0.90; P=0.008).10 Foreign
guideline suggests that bariatric surgery may be an option in patients with BMI
≥40 kg/m2 or BMI ≥35 kg/m2 with obesity-related co-morbid conditions.9

Results of recent trials of anti-obesity drugs such as sibutramine and rimonabant

have raised concerns regarding cardiovascular complications, hence its marketing
has been discontinued in the United States and Europe.11-15

B.2. Secondary Stroke Prevention

Although no study has demonstrated a decline in risk of recurrence with weight
reduction among patients who have had a stroke or transient ischemic attack,
some recent studies done in Western populations suggest that weight loss after
stroke is associated with an increased stroke mortality, hence the term “obesity
paradox”.16,17 However, this association was not found in studies among Asians.4,18
Because weight reduction significantly improves blood pressure, fasting glucose
values, serum lipid indices, and physical endurance19 of both overweight and
obese individuals, weight loss and maintenance of a healthy weight should be
given utmost importance. Regular exercise and diet rich in fruits and vegetables
can help with weight control; this has been shown to reduce the risk of stroke,
myocardial infarction, and death.20,21

C. Recommendation
1. All patients with TIA or stroke should be screened for obesity with measurement
of Body Mass Index (BMI) (Class I, level C).
2. Although the usefulness of weight loss among patients with a recent TIA or
ischemic stroke and obesity is uncertain (Class IIb, level C), weight reduction
should be considered for all overweight patients to maintain the following
goals:
a. BMI between 18.5 kg/m2 to 24.9 kg/m2
b. Waist-Hip Ratio (WHR) not greater than 1.0 in men or 0.85 in women
c. Waist circumference not greater than 35 inches in men or 31 inches in women
67
 3. Clinicians should encourage weight management through an appropriate
balance of diet, exercise, and behavioral counseling.
4. Established comprehensive lifestyle intervention and weight loss programs and/
or bariatric surgery may be appropriate in some select patients.

References
1. Sy RG, Morales D, Dans A, et al. Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the
Philippines. J Epidemiol. 2012; 22(5): 440–447.
2. The Seventh National Nutrition Survey: Philippines, 2008: Initial Results. Taguig: Food and Nutrition
Research Institute.
3. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45:000-000.
4. Bazzano LA, Gu D, Whelton MR, et al. Body mass index and risk of stroke among Chinese men and
women. Ann Neurol. 2010;67:11–20.
5. Saito I, Iso H, Kokubo Y, et al. Body mass index, weight change and risk of stroke and stroke subtypes: the
Prevention

Japan Public Health Center-based prospective (JPHC) study. Int J Obes (Lond). 2011;35:283–291.
6. Winter Y, Rohrmann S, Linseisen J, et al. Contribution of obesity and abdominal fat mass to risk of stroke
and transient ischemic attacks. Stroke. 2008;39:3145–3151.
7. Kernan WN, Inzucchi SE, Sawan C, et al. Obesity: a stubbornly obvious target for stroke prevention.
Stroke. 2013;44:278–286.
8. Cornier MA, Després JP, Davis N, et al. Assessing adiposity: a scientific statement from the American
Heart Association. Circulation. 2011;124:1996–2019.
9. Jensen MD, Ryan DH. New obesity guidelines: promise and potential. JAMA. 2014;311:23-4
10. Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA.
2012;307:56–65.
11. Caterson ID, Finer N, Coutinho W, et al.; SCOUT Investigators. Maintained intentional weight loss
reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT)
trial. Diabetes Obes Metab. 2012;14:523–530.
12. Cheung BM. Drug treatment for obesity in the post-sibutramine era. Drug Saf. 2011;34:641–650.
13. James WP, Caterson ID, Coutinho W, et al.; SCOUT Investigators. Effect of sibutramine on cardiovascular
outcomes in overweight and obese subjects. N Engl J Med. 2010;363:905–917.
14. Topol EJ, Bousser MG, Fox KA, et al.; CRESCENDO Investigators. Rimonabant for prevention of
cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet.
2010;376:517–523.
15. European Medicines Agency (EMA). European Medicines Agency recommends suspension of marketing
authorisations for sibutramine. Press Release, January 21, 2010. http: http://www.ema.europa.eu/docs/
en_GB/document_library/Press_release/2010/01/WC500069995.pdf. Accessed June 20 2014.
16. Ovbiagele B, Bath PM, Cotton D, et al. Obesity and recurrent vascular risk after a recent ischemic stroke.
Stroke. 2011;42:3397–3402.
17. Doehner W, Schenkel J, Anker SD, et al. Overweight and obesity are associated with improved survival,
functional outcome, and stroke recurrence after acute stroke or transient ischaemic attack: observations
from the TEMPiS trial. Eur Heart J. 2013;34:268–277.
18. Yi SW, Odongua N, Nam CM, et al. Body mass index and stroke mortality by smoking and age at
menopause among Korean postmenopausal women. Stroke. 2009;40:3428 –3435.
19. Anderson JW, Knoz EC. Obesity and disease management: effects of weight loss on co-morbid conditions.
Obes Res. 2001:9 suppl 4;326S-334S.
20. Renaud S, Lorgeril M, Delaye J, et al. Cretan Mediterranean diet for prevention of coronary heart disease.
Am J Clin Nutr. 1995: 61 (suppl): 1360S-1367S.
21. Singh RB, Dubnov G, Niaz MA, et al. Effects of an Indo-Mediterranean diet on progression of coronary
artery disease in high risk patiens (Indo-Mediterranean Diet Heart Study : a randomized single-blind trial.
Lancet. 2002:360;1455-1461.

68
XII. NUTRITION AND STROKE
A. Epidemiology
Although nutrition is a potential risk factor for stroke, its role is poorly defined. In
a systematic review of 18 studies, the frequency of malnutrition in stroke ranged
from 6.1% to 62%1, however this variation may be attributed to the heterogeneity of
nutritional assessment methods. An excess or deficiency of specific micronutrients
appear to contribute to changes in the vasculature and increase the risk of stroke.
Case-control studies show that excessive homocysteine levels and deficiency of
folate and vitamins B6 and B12 may be associated with an increased risk for stroke.2
Likewise, a higher level of sodium intake3 and possibly calcium supplementation4 may
be associated with an increased risk for stroke. In a recent meta-analysis on the effect
of potassium to cardiovascular risks, a higher level of intake was associated with a
24% lower risk of stroke.5

B. Risk Modification
Prospective studies show that increased consumption of fruit and vegetable is

Prevention
associated with a dose-related reduction of stroke risk. Fruits and vegetables may
contribute to stroke prevention through antioxidant mechanisms or elevation
of potassium levels.6,7 Increased sodium intake is associated with hypertension,
thus reduced consumption of salt may significantly lower BP and reduce the risk
and mortality from stroke. Studies on the use of omega-3 fatty acids and fish oils,
although promising, is yet to show a definitive risk reduction.8 No clinical trial so far
has examined the effectiveness of specific diets for secondary prevention.9

The American Heart Association/American Stroke Association (AHA/ASA) Guidelines

recommend consumption of a diet with reduced sodium that is rich in fruits and
vegetables, such as the Dietary Approaches to Stop Hypertension (DASH)-style diet,
to reduce stroke risk.10 The DASH diet is composed mainly of fruits, vegetables, and
low-fat dairy products, and contains reduced total and saturated fat. On the other
hand, Mediterranean-type diets (i.e. rich in fish, fruit, vegetables, nuts, and olive oil)
have been found to have favorable effects on cardiovascular risk factors and all-cause
mortality.9,11

C. Recommendation
The SSP adopts the 2013 AHA/ACC Guideline on Lifestyle Management to reduce
cardiovascular risk and the 2014 AHA/ASA recommendations for nutrition of patients
with stroke/TIA.9

1. It is reasonable to conduct a nutritional assessment of patients with a history of

stroke/TIA to look for signs of overnutrition or undernutrition (Class IIa, level C).
2. Patients with a history of ischemic stroke/TIA should be referred for individualized
nutritional counseling (Class I, level B).
3. Routine supplementation with a single- or multi-vitamins is not recommended
(Class III, level A).
4. It is reasonable to recommend that patients with a history of stroke or TIA to
reduce their sodium intake to less than 2.4 g/day. Further reduction to <1.5 g/
day is also reasonable and is associated with even greater BP reduction (Class
IIa, level C).
5. It is reasonable to counsel patients to follow a Mediterranean-type diet instead
of a low-fat diet. The Mediterranean-type diet emphasizes vegetables, fruits,
and whole grains and includes low-fat dairy products, poultry, fish, legumes,
olive oil, and nuts. It limits intake of sweets and red meats (Class IIa, level C).

69
 References

1. Foley NC, Salter KL, Robertson J, et al. Which reported estimate of the prevalence of malnutrition after
stroke is valid? Stroke. 2009 Mar;40(3):e66-74.
2. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk
factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA. 1995;247:1049-1057.
3. Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-
analysis of prospective studies. BMJ. 2009;339:b4567.
4. Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of
cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis.
BMJ. 2011;342:d2040.
5. Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potassium intake on cardiovascular risk factors
and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378.
6. Ascherio A, Rimm EB, Hernan MA, et al. Intake of potassium, magnesium, calcium, and fiber and risk of
stroke among US men. Circulation. 1998;98:1198-1204.
7. Gillman MW, Cupples LA, Gagnon D et al. Protective effect of fruits and vegetables on development of
stroke in men. JAMA. 1995;273:1113-1117.
Prevention

8. Poppitt SD, Howe CA, Lithander FE, et al. Effects of moderate-dose omega-3 fish oil on cardiovascular risk
factors and mood after ischemic stroke: a randomized, controlled trial. Stroke. 2009 Nov;40(11):3485-92.
9. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and
transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2014;45:000-000.
10. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline
for heath professionals from the American Heart Association/American Stroke Association. Stroke.
2011;42:517-584.
11. Hankey GJ. Nutrition and the risk of stroke. Lancet Neurol. 2012 Jan;11(1):66-81.

Food Selection Guide by the Philippine Society of Parenteral and Enteral Nutrition (PHILSPEN)
Available at http://www.strokesocietyphil.org

70
 CHAPTER III
Guidelines for Treatment of Acute Stroke and
Transient Ischemic Attack

I. SSP Classification of Acute Stroke Based on Clinical

Severity
II. Guidelines for Management of Transient Ischemic
Attack
III. Guidelines for Management of Mild Stroke
IV. Guidelines for Management of Moderate Stroke
V. Guidelines for Management of Severe Stroke
VI. Early Specific Treatment of Ischemic Stroke
A. Antithrombotic Therapy in Acute Stroke
B. Neuroprotection
C. Anticoagulation in Acute Cardioembolic Stroke
D. Administration of rt-PA in Acute Ischemic Stroke
E. Blood Pressure Management in Acute Stroke
VII. Management of Increased Intracranial Pressure
VIII. Hemicraniectomy for Malignant Middle Cerebral
Artery Infarction
Sixth
Edition
2014
 Guidelines for Treatment of Acute Stroke and Transient Ischemic Attack

I. SSP CLASSIFICATION OF ACUTE STROKE BASED ON CLINICAL SEVERITY

Background and Rationale for the Simplified Initial Classification
The use of standardized stroke classification schemes such as those based on stroke type,
localization or brain/vascular territory involvement, pathologic mechanism, and time
course may be difficult and time-consuming especially for non-neuroscience specialists
in acute care setting. The working committee of the first edition of SSP Stroke Guidelines
(1999) has developed a practical and locally relevant initial classification scheme (Table 1),
which is based simply on the observed severity of patient’s neurologic deficits including
level of sensorium and response to pain. The present working committee still finds this
format useful particularly in emergency situations, and advocates its continuous use to
help both medical and paramedical professionals regarding decisions and crucial actions
at the emergency room.

After stabilization and initial management of the patient, additional diagnostic work-ups
are recommended for determining and further classifying stroke based on underlying
pathologic mechanism, which is necessary for selection of appropriate secondary
prevention strategies.
Table 1. SSP Definition of Stroke Severity
MILD Stroke MODERATE Stroke SEVERE Stroke
Alert patients with any (or Awake patient with significant Deep stupor or comatose
combination) of the following: motor and/or sensory and/or patient with non-purposeful
Treatment

1. Mild pure motor weakness language and/or visual deficit. response, decorticate, or
of one side of the body, decerebrate posturing to
acute

defined as: can raise arm or painful stimuli.

above shoulder, has clumsy
hand, or can ambulate Disoriented, drowsy or light or
without assistance. stupor with purposeful response
2. Pure sensory deficit to painful stimuli. Comatose patient with no
3. Slurred but intelligible response to painful stimuli.
speech
4. Vertigo with incoordination
(e.g., gait disturbance,
unsteadiness, or
clumsy hand)
5. Visual field defects alone
or or or
NIHSS score: 0 – 5 NIHSS score: 6 – 21 NIHSS score: > 22
See Guidelines for Mild Stroke See Guidelines for Moderate Stroke See Guidelines for Severe Stroke
NIHSS: National Institutes of Health Stroke Scale (see Appendix B)

Table 2. Recommended Place of Treatment According to Stroke Severity

Transient a. Outpatient if TIA occurred >2 weeks prior (work-up should be done within 24-48 h)
Ischemic Attack b. Hospital (acute stroke unit [ASU]) if:
• TIA within 48 hours
• Crescendo TIAs (multiple & increasing symptoms)
• TIA with known high-risk cardiac source of embolism
• known hypercoagulable state or symptomatic ICA stenosis
• ABCD2 score > 3
Mild Stroke Hospital (ASU/regular room)
Moderate Stroke Hospital (ASU/intensive care unit [ICU])
Severe Stroke Hospital (ICU)
72
II. Guidelines for Management of Transient Ischemic Attack

MANAGEMENT PRIORITIES • Ascertain clinical diagnosis of TIA (history, P.E. and neurologic exam are very
important).
• Exclude common TIA mimics (see Chapter 1).
• Identify comorbidities (e.g., cardiac disease, DM, liver disease, gastric ulcer).
• Provide basic emergent supportive care (ABCs of resuscitation).
• Monitor neuro-vital signs (NVS) including pupil size, blood pressure (BP), mean
arterial pressure (MAP), respiratory rate (RR), temperature, O2 saturation.
• Perform stroke scales (i.e. NIHSS, GCS; see Appendix B) and risk stratification using
ABCD2 scale (see Chapter 1)
• Treat BP if MAP >130. Precaution: Avoid precipitous drop (not > 15% of baseline MAP)
within 24 hours. Do not use rapid-acting sublingual (SL) agents; when needed, use
easily titratable intravenous (IV) or short-acting oral antihypertensive medication.
• Ensure appropriate hydration. Recommended IVF (if needed): 0.9% NaCl.
• Complete blood count (CBC)
DIAGNOSTICS
EMERGENT

• Blood glucose (CBG or RBS)

• Coagulation studies: Prothrombin time (PT), activated partial thromboplastin time
(aPTT)
• Electrocardiogram (ECG)
• Cranial MRI–diffusion weighted imaging (DWI) is preferred; may do non-contrast
Cranial CT (NCCT) scan if MRI is not available/possible.
CARDIOEMBOLISM NOT SUSPECTED CARDIOEMBOLISM SUSPECTED
EARLY SPECIFIC TREATMENT

• Start Aspirin (ASA) 160-325 mg/day as • Consider careful anticoagulation

early as possible and continue for 14 with intravenous (IV) heparin or
days. The combination of ASA 80 mg + subcutaneous (SQ) low-molecular-
clopidogrel 75 mg may be considered weight heparin (LMWH) for individuals
for short-term treatment. at high risk of early recurrence (e.g., AF

Treatment
• Ensure neuroprotection* with thrombus, valvular heart disease,
or myocardial infarction) or ASA 160-

acute
325 mg/day (if anticoagulation is not
possible or is contraindicated)
• Ensure neuroprotection*
• If infective endocarditis (IE) is
suspected, give antibiotics and DO NOT
anticoagulate.
• Give antiplatelets (e.g., ASA, • Request echocardiography and/or refer
DELAYED MANAGEMENT AND SECONDARY PREVENTION

clopidogrel, cilostazol, triflusal, to cardiologist.

dipyridamole, extended-release • Novel oral anticoagulants (NOACs) are
dipyridamole + ASA combination) (see preferred over dose-adjusted warfarin
Chapter 4) (see Chapter 5).
• Control/treat risk factors • If anticoagulation is contraindicated,
• Recommend carotid ultrasound (UTZ) give ASA 160-325 mg/day. The addition of
to document extracranial stenosis; clopidogrel to ASA therapy is reasonable.
if UTZ reveals >70% stenosis, refer
to a neurologist/neurosurgeon/
vascular surgeon for decision-making
regarding carotid endarterectomy
(CEA) or stenting.
• Recommend transcranial Doppler
(TCD) studies or CT or MR angiography
(CTA/MRA) to document intracranial
stenosis.
Others:
• Specialized tests: screening for hypercoagulable states (e.g., protein C, protein
S, antithrombin III, fibrinogen, homocysteine) and drug/toxicology tests (e.g.,
metamphetamine, cocaine) may be considered for young patients with TIA/stroke
especially when no vascular risk factors exist and no underlying cause is identified
(see Chapter 9).
• If vasculitis is suspected, may do erythrocyte sedimentation rate (ESR), antinuclear
antibody (ANA), and lupus anticoagulant tests.
• Trans-esophageal echocardiography (TEE) to rule out PFO in cryptogenic strokes.
*see section on Neuroprotection
73
 III. GUIDELINES FOR MANAGEMENT OF MILD STROKE (NIHSS score: 0–5)

• Ascertain clinical diagnosis of stroke (history, P.E. and neurologic exam are very
MANAGEMENT PRIORITIES
important).
• Exclude common stroke mimics (see Chapter 1).
• Identify comorbidities (e.g., cardiac disease, DM, liver disease, gastric ulcer).
• Provide basic emergent supportive care (ABCs of resuscitation).
• Monitor neuro-vital signs (NVS) including pupil size, blood pressure (BP), mean
arterial pressure (MAP), respiratory rate (RR), temperature, O2 saturation (SaO2).
• Perform and monitor stroke scales (i.e. NIHSS, GCS; see Appendix B).
• Provide O2 support to maintain SaO2 > 94%.
• Treat BP if MAP >130. Precaution: Avoid precipitous drop (not > 15% of baseline MAP)
within 24 hours. Do not use rapid-acting sublingual (SL) agents; when needed, use
easily titratable intravenous (IV) or short-acting oral antihypertensive medication.
• Ensure appropriate hydration. Recommended IVF: 0.9% NaCl.
• Complete blood count (CBC)
DIAGNOSTICS
EMERGENT

• Blood glucose (CBG or RBS)

• Coagulation studies: PT, aPTT
• Electrocardiogram (ECG)
• Cranial NCCT scan or MRI-DWI as soon as possible. If intracranial hemorrhage (ICH)
is evident, compute for the hematoma volume (see Chapter 7).

ISCHEMIC
CARDIOEMBOLISM NOT CARDIOEMBOLISM HEMORRHAGIC
SUSPECTED SUSPECTED
(Thrombotic, Lacunar)
Treatment

• Start Aspirin (ASA) 160-325 • Consider careful • Early neurology and/or

acute

mg/day as early as possible anticoagulation with neurosurgery consult

and continue for 14 days. intravenous (IV) heparin for all ICH cases.
(treatment requires neuroimaging confirmation)

The combination of ASA or subcutaneous (SQ) • Monitor and maintain

80 mg + clopidogrel 75
mg may be considered for
short-term treatment.
EARLY SPECIFIC TREATMENT
low-molecular-weight target SBP ≈140 mm Hg
heparin (LMWH) during the first week.
for individuals at
• Ensure neuroprotection*

• Ensure neuroprotection* high risk of early

recurrence (e.g., AF • Early rehabilitation once
with thrombus, valvular stable within 72 hours
heart disease, or • Give antiepileptic
myocardial infarction) drugs (AEDs) for
or ASA 160-325 mg/ clinical seizures and
day (if anticoagulation proven subclinical or
is not possible or is electrographic seizures.
contraindicated)
• Prophylactic AEDs and
• Ensure neuroprotection* steroids are generally
• If infective endocarditis not recommended.
(IE) is suspected, give • Monitor/correct for
antibiotics and DO NOT metabolic parameters
anticoagulate. and coagulation/
bleeding abnormalities
• Follow
recommendations
for neurosurgical
intervention
• For specific details on
ICH and treatment of
aneurysmal SAH, see
Chapter 6.
*see section on Neuroprotection

74
GUIDELINES FOR MANAGEMENT OF MILD STROKE (continued)

ISCHEMIC
DELAYED MANAGEMENT AND SECONDARY PREVENTION
CARDIOEMBOLISM NOT
SUSPECTED
(Thrombotic, Lacunar)
• Give antiplatelets (e.g.,
ASA, clopidogrel, cilostazol,
triflusal, dipyridamole,
extended-release
dipyridamole + ASA
combination) (see Chapter 4)
• Control/treat risk factors
• Recommend carotid
ultrasound (UTZ) to
document extracranial
stenosis; if UTZ reveals
>70% stenosis, refer to a
neurologist/neurosurgeon/
vascular surgeon for
decision-making regarding
carotid endarterectomy
(CEA) or stenting.
• Recommend transcranial
Doppler (TCD) studies or
CT or MR angiography
(CTA/MRA) to document
intracranial stenosis.
CARDIOEMBOLISM HEMORRHAGIC
SUSPECTED
• Request • Long-term strict
echocardiography and/or BP control and
refer to cardiologist monitoring
• Novel oral anticoagulants • Consider contrast CT
(NOACs) are preferred scan, 4-vessel cerebral
over dose-adjusted angiogram, MRA or
warfarin. CTA if the patient is:
• If anticoagulation is a. < 45 years old
contraindicated, give ASA b. normotensive
160-325 mg. The addition c. has lobar ICH
of clopidogrel to ASA d. has uncertain cause
therapy is reasonable. of ICH
e. suspected to have
aneurysm, AVM, or
vasculitis

Treatment
acute
III. GUIDELINES FOR MANAGEMENT OF MODERATE STROKE (NIHSS score: 6-21)

• Ascertain clinical diagnosis of stroke (history, P.E. and neurologic exam are very
important).
• Exclude common stroke mimics (see Chapter 1).
MANAGEMENT PRIORITIES

• Identify comorbidities (e.g., cardiac disease, DM, liver disease, gastric ulcer).
• Provide basic emergent supportive care (ABCs of resuscitation).
• Monitor neuro-vital signs (NVS) including pupil size, blood pressure (BP), mean
arterial pressure (MAP), respiratory rate (RR), temperature, O2 saturation (SaO2).
• Perform and monitor stroke scales (i.e. NIHSS, GCS; see Appendix B).
• Provide O2 support to maintain SaO2 > 94%.
• Treat BP if MAP >130. Precaution: Avoid precipitous drop (not > 15% of baseline MAP)
within 24 hours. Do not use rapid-acting sublingual (SL) agents; when needed, use
easily titratable intravenous (IV) or short-acting oral antihypertensive medication.
• Recognize and treat for early signs and symptoms of increased ICP (see Management
of Increased ICP).
• Ensure appropriate hydration. Recommended IVF: 0.9% NaCl.

• Complete blood count (CBC)

DIAGNOSTICS

• Blood glucose (CBG or RBS)

EMERGENT

• Coagulation studies: PT, aPTT

• Serum Na+ and K+
• Electrocardiogram (ECG)
• Cranial NCCT scan or MRI-DWI as soon as possible. If ICH is evident, compute for
hematoma volume (see Chapter 7).

(continued on next page)

75
 GUIDELINES FOR MANAGEMENT OF MODERATE STROKE (continued)

ISCHEMIC
HEMORRHAGIC
CARDIOEMBOLISM CARDIOEMBOLISM
NOT SUSPECTED SUSPECTED
• Refer to neurologist • Refer to a neurologist for • Early neurology and/or
for evaluation and evaluation and decision. neurosurgery consult
decision. • If the patient presents for all ICH cases.
• If the patient presents within 3 hours of stroke • Monitor and maintain
within 3 hours of onset, consider IV target SBP: ≈140 mm
(treatment requires neuroimaging confirmation)

stroke onset, consider thrombolysis with rt-PA. Hg during the first

IV thrombolysis with • Selected patients within 3 week.
recombinant tissue to 4.5 hour-time window • Ensure
plasminogen activator may benefit with IV rt-PA neuroprotection*
EARLY SPECIFIC TREATMENT

(rt-PA) . • If the stroke onset is • Early rehabilitation

• Selected patients
within 3 to 4.5 hour-
time window may
benefit with IV rt-PA • If the patient is ineligible
• If the stroke onset
is within 6 hours,
consider intra-arterial
(IA) thrombolysis
(only in specialized
centers).
• Start ASA 160-325 mg/
Treatment
within 6 hours, consider
IA thrombolysis (only in
specialized centers).
for thrombolytic
therapy, or 24 hours
post-rt-PA treatment,
consider careful
anticoagulation with IV
heparin or SQ LMWH
for individuals at high
once stable within 72
hours
• Give AEDs for
clinical seizures and
proven subclinical or
electrographic seizures.
• Prophylactic AEDs and
steroids are generally
not recommended.
• Monitor/correct for
metabolic parameters

day 24 hours after IV risk of early recurrence; and coagulation/

rt-PA treatment and or ASA 160-325 mg/ bleeding abnormalities
acute

continue for 14 days. day if anticoagulation • Follow

• Ensure is not possible or is
neuroprotection* contraindicated.
• Early rehabilitation • Ensure neuroprotection*
once stable within 72 • If infective endocarditis
hours. (IE) is suspected, give
antibiotics and DO NOT
anticoagulate
• Early rehabilitation once
stable within 72 hours.
recommendations
for neurosurgical
intervention
• For specific details on
ICH and treatment of
aneurysmal SAH, see
Chapter 6.

• Give antiplatelets (ASA, • Request • Long-term strict BP

clopidogrel, cilostazol, echocardiography and/or control and monitoring
triflusal, dipyridamole,
DELAYED MANAGEMENT AND

refer to cardiologist • Consider contrast CT

SECONDARY PREVENTION

extended-release • Novel oral anticoagulants scan, 4-vessel cerebral

dipyridamole) (see
Chapter 4).
• Control/treat identified
risk factors.
• If carotid UTZ reveals • If anticoagulation is
>70% stenosis, refer
to a neurologist/
neurosurgeon/
vascular surgeon
for decision-making
regarding carotid
endarterectomy (CEA)
or stenting.
(NOACs) are preferred
over dose-adjusted
warfarin.
contraindicated, give ASA
160-325 mg. The addition
of clopidogrel to ASA
therapy is reasonable.
angiogram, MRA or CTA
if the patient is:
a. < 45 years old
b. normotensive
c. has lobar ICH
d. has uncertain cause
of ICH
e. suspected to have
aneurysm, AVM, or
vasculitis

76
V. GUIDELINES FOR MANAGEMENT OF SEVERE STROKE (NIHSS score: >22)
• Ascertain clinical diagnosis of stroke (history, P.E. and neurologic exam are very
important).
• Exclude common stroke mimics (see Chapter 1).
MANAGEMENT PRIORITIES

• Identify comorbidities (e.g., cardiac disease, DM, liver disease, gastric ulcer).
• Provide basic emergent supportive care (ABCs of resuscitation).
• Monitor neuro-vital signs (NVS) including pupil size, blood pressure (BP), mean
arterial pressure (MAP), respiratory rate (RR), temperature, O2 saturation (SaO2).
• Perform and monitor stroke scales (i.e. NIHSS, GCS; see Appendix B).
• Provide O2 support to maintain SaO2 > 94%.
• Treat BP if MAP >130. Precaution: Avoid precipitous drop (not > 15% of baseline MAP)
within 24 hours. Do not use rapid-acting sublingual (SL) agents; when needed, use
easily titratable intravenous (IV) or short-acting oral antihypertensive medication.
• Recognize and treat for early signs and symptoms of increased ICP (see Management
of Increased ICP).
• Ensure appropriate hydration. Recommended IVF: 0.9% NaCl.

• Complete blood count (CBC)

DIAGNOSTICS

• Blood glucose (CBG or RBS)

EMERGENT

• PT, aPTT
• Serum Na+ and K+
• Electrocardiogram (ECG)
• Cranial NCCT scan or MRI-DWI as soon as possible. If ICH is evident, compute for
hematoma volume (see Chapter 7).

ISCHEMIC
HEMORRHAGIC
CARDIOEMBOLISM CARDIOEMBOLISM

Treatment
NOT SUSPECTED SUSPECTED

acute
• May give ASA 160-325 • May give ASA 160-325 • Supportive treatment:
mg/day. mg/day. Mannitol 20% 0.5-1 g/kg BW
• Ensure • Ensure every 4-6 hours for 3-7 days
(treatment requires neuroimaging confirmation)

neuroprotection* neuroprotection* • Ensure neuroprotection*

• Refer to a neurologist • Refer to a neurologist • Give antiepileptic drugs
for cases of posterior for cases of posterior (AEDs) for clinical seizures
circulation strokes circulation strokes and proven subclinical
or electrographic
EARLY SPECIFIC TREATMENT

within 12 hours of (see Chapter 1) within

seizures. Prophylactic
onset for evaluation 12 hours of onset AEDs are generally not
and decision regarding for evaluation and recommended.
thrombolytic therapy. decision regarding • Neurosurgical consult if:
• For cases of cerebellar thrombolytic therapy. - the patient is not
infarct, refer to a • For cases of cerebellar herniated
neurosurgeon as soon infarct, refer to a - the location of bleed
as possible. neurosurgeon as soon is lobar, putamen,
• Early supportive as possible. pallidum, or cerebellum
rehabilitation. • Early supportive - the patient’s family
rehabilitation. is willing to accept
consequences of
irreversible coma or
persistent vegetative
state
- ICP monitoring is
contemplated and
salvage surgery is
considered
• Early supportive
rehabilitation
• Goal is reduction of
mortality
Discuss the prognosis of the patient with family/relatives in the most compassionate manner
*see section on Neuroprotection (continued on next page)
77
 GUIDELINES FOR MANAGEMENT OF SEVERE STROKE (continued)

• Give antiplatelets • Request • Long-term strict BP

(ASA, clopidogrel, echocardiography and/
DELAYED MANAGEMENT AND
SECONDARY PREVENTION
cilostazol, triflusal, or refer to cardiologist
dipyridamole, • Novel oral
extended-release anticoagulants (NOACs)
dipyridamole + ASA are preferred over dose-
combination). adjusted warfarin.
• Control/treat risk • If anticoagulation is
factors. contraindicated, give
ASA 160-325 mg. The
addition of clopidogrel
to ASA therapy is
reasonable.
control and monitoring
• Consider contrast CT
scan, 4-vessel cerebral
angiogram, MRA or CTA if
the patient is:
a. < 45 years old
b. normotensive
c. has lobar ICH
d. has uncertain cause
of ICH
e. suspected to have
aneurysm, AVM, or
vasculitis

VI. EARLY SPECIFIC TREATMENT FOR ISCHEMIC STROKE

A. Antithrombotic Therapy In Acute Stroke
DRUG TRIAL STUDY DESIGN RESULT
Aspirin (ASA) IST: 19,435 patients with ASA-treated patients had
International acute ischemic stroke slightly fewer deaths at 14
Stroke Trial within 48 hours were days, significantly fewer
randomized to either recurrent ischemic strokes
Treatment

(Lancet 1997; ASA 300 mg/day, at 14 days, and no excess of

349: 1569 – subcutaneous heparin hemorrhagic strokes.
acute

1581) 5000 units BID or 12,500

units BID, ASA plus In heparin-treated patients,
heparin or neither. there were fewer deaths
or recurrent strokes;
however, there were
more hemorrhagic strokes
& serious extracranial
hemorrhage, mostly in the
higher-dose heparin group,
resulting in no net benefit.
ASA CAST: Chinese 21,106 patients with Aspirin significantly reduced
Acute Stroke acute ischemic stroke the risk of recurrent stroke
Trial within 48 hours were or vascular death.
randomized to ASA 160
(Lancet 1997; mg OD or placebo for up
449: 1641 – to 4 weeks.
1649)
[Clopidogrel + ASA] FASTER: Fast 392 patients with TIA or This trial was prematurely
versus ASA alone Assessment minor stroke within 24 terminated because of failure
of Stroke and hours were randomized to recruit patients at the
Transient to Clopidogrel (300 mg pre-specified recruitment
Ischemic loading dose then 75 rate due to increased use of
Attack to mg/day plus ASA 81 mg statins.
Prevent Early or ASA 75 mg alone, with
Recurrence or without Simvastatin Recurrent stroke at 90 days
(in factorial design) and were as follows: Clopidogrel-
(Lancet Neurol followed up for 90 days. ASA (7.1%), ASA alone (10.1%);
2007; 6: 961- absolute risk reduction of 3.8
969) % (p =0.19).
Hemorrhagic events were
higher with the combination
treatment.
78
Antithrombotic Therapy In Acute Stroke (continued)

DRUG TRIAL STUDY DESIGN RESULT

Clopidogrel- CHANCE: 5170 patients within 24 The rate of recurrent stroke
ASA versus Clopidogrel in hours of minor ischemic at 90 days were: Clopidogrel-
ASA alone High-risk Patients stroke or high-risk TIA ASA (8.2%), ASA alone (11.7%),
with Acute were randomized either hazard ratio=0.68 (p<0.001).
Non-Disabling to Clopidogrel 300 mg
Cerebrovascular loading dose then 75 mg There was no increase in
Event OD plus ASA 75 mg OD rate of moderate-severe
for 21 days, followed by bleeding and hemorrhagic
(N Eng J Med 2013; Clopidogrel alone vs. ASA stroke with the combination
369:11-19) alone 75 mg OD for 90 treatment.
days.
Cilostazol CAIST: Cilostazol 458 patients with acute The primary endpoint of
versus ASA in Acute Ischemic ischemic stroke with modified Rankin Score
Stroke Treatment NIHSS score < 15 within (mRS) 0-2 was achieved in
48 hours were randomly 76% of patients randomized
(Cerebrovasc Dse assigned to Cilostazol to Cilostazol and 75% of
2011; 32:65-71) 200mg/day or ASA 300 mg/ patients randomized to
day for 90 days. Aspirin, supporting the pre-
specified non-inferiority
outcome.
LMWH Meta-analysis Ten trials involving 2,885 The use of LMWH/
of randomized patients with acute heparinoids was associated

Treatment
controlled trials ischemic stroke given with significant reduction in

acute
on low molecular LMWH or heparinoids venous thromboembolism
weight heparins within 7 days of stroke. (i.e. DVT and PE). However,
and heparins in it did not have significant
acute ischemic effect on reducing death and
stroke. disability at 6 months.

(Stroke 2000; 31:31:

1770-1778)

B. Neuroprotection

The Five “H” Principle:

AVOID hypotension, hypoxemia, hyperglycemia, hypoglycemia, and
hyperthermia during acute stroke in an effort to “salvage” the ischemic
penumbra.

1. Neuroprotective Interventions:
a) Avoid hypotension and allow permissive hypertension during the first
seven (7) days
Aggressive BP lowering is detrimental in acute stroke. Manage hypertension
as per recommendation (see Management of BP in Acute Stroke).
b) Avoid hypoxemia
• Routine oxygen supplementation is not warranted for all stroke patients.
Only give supplemental O2 if with evidence of hypoxemia or desaturation.
• Monitor oxygenation via pulse oximetry and/or determine arterial blood
gases (ABG).
• Maintain adequate tissue oxygenation (target SaO2 >94%).
• Provide ventilatory support if the upper airway is threatened, sensorium is
impaired, or ICP is increased.
79
 c) Avoid hyperglycemia or hypoglycemia
• Hyperglycemia can increase the severity of ischemic injury (i.e. causes
lactic acidosis, increases free radical production, worsens cerebral
edema, and weakens blood vessels), whereas hypoglycemia can mimic a
stroke.
• Prompt determination of blood glucose should be done in all stroke
patients.
• In a meta-analysis of 11 trials involving 1,583 subjects, keeping the
blood glucose level within a tight range (4-7.5 mmol/L) immediately
after a stroke did not improve the outcomes of neurological deficit and
dependency, and significantly increased the risk of hypoglycemia, which
can be harmful and may cause further brain damage and death. Thus,
there is no benefit with intensive glycemic control after stroke.
• Treat acute ischemic stroke patients according to the American Diabetes
Association (ADA) inpatient glycemic control guidelines. Initiate therapy
to achieve glucose targets of 140 to 180 mg/dL if the fasting glucose is
greater than 140 mg/dL or random glucose is consistently higher than
180 mg/dL.
• Use an established and standardized IV insulin protocol for patients who
present with extreme or persistent hyperglycemia, are critically ill, or who
have received thrombolytic therapy for at least the first 24 to 48 hours of
hospitalization. Patients should then be transitioned to a subcutaneous
insulin regimen which includes a basal long-acting insulin, along with
rapid-acting insulin for corre cting deranged glucose levels.
• For patients who are feeding, add prandial (meal) insulin, preferably a
rapid-acting insulin which can be administered immediately before or
Treatment

after a meal.
• Avoid glucose-containing (D5) IV fluids. Use isotonic saline (0.9% NaCl).
acute

• Closely monitor and address hypoglycemia especially in patients with

type 1 DM, hepatic or renal impairment, or with complicated feeding
regimens.

d) Avoid hyperthermia
Fever in acute stroke is associated with poor outcome possibly related to
increased metabolic demand, increased free radical production, and enhanced
neurotransmitter release. Hyperthermia increases the relative risk (RR) of
1-year mortality by 3.4 times. For every 1°C increase in the body temperature,
the RR of death or disability increases by 2. On the other hand, hypothermia
can reduce the infarct size by 44% in animal studies.
• Maintain normothermia for all stroke patients.
• Treat fever with antipyretics and cooling blankets. Investigate for the
source of fever (e.g., infection).

2. Neuroprotective and Neurorestorative Drugs

Drugs with neurovascular protective properties:

• Protect against excitotoxins and help prolong neuronal survival.
• Block the release of glutamate and inflammatory cytokines and inhibit free
radical formation and apoptosis.

Drugs with neurotrophic/neurorestorative properties:

• Stimulate endogenous repair mechanisms such as angiogenesis,
neurogenesis, and synaptic plasticity.
• Help in the production of new sprouts and dendritic spines in surviving
neurons, as well as formation of new synapses.

80
Over fifty (50) neuroprotective agents including glutamate, NMDA/AMPA
antagonists, calcium channel blockers, and free radical scavengers have undergone
Phase III clinical trials, but all failed to show statistically significant benefit.
Several reasons have been raised to explain this apparent failure: animal models
were wrong, and that human trials were not done optimally (e.g., time-window
determination, patient heterogeneity, “targeted” neuroprotection which addresses
single mechanism of neuronal injury at a time, exclusion of concomitant treatment
with thrombolytic agents).

Cytidine 5’-diphosphate (CDP)-choline (citicoline) is one of the most well-

studied neuroprotective agent. It has multimodal effects on the ischemic and
reperfusion cascade. It helps increase synthesis of phosphatidylcholine for
membrane stabilization and repair. It inhibits the activation of phospholipase A2
and reduces oxygen free radicals and inflammatory cytokines within the injured
brain during ischemia. Citicoline has been shown to reduce caspase activation
products inhibiting apoptosis. Citicoline favors synthesis of nucleic acids, proteins,
acetylcholine, and other neurotransmitters.

Experimental studies have shown consistent improved functional outcome and

reduced infarct size in animal models of stroke. Several trials in ischemic and
hemorrhagic strokes conducted worldwide have documented its excellent safety
profile. In individual patient data pooling analysis (4 trials, 1652 patients), oral
citicoline given within the first 24 hours of moderate to severe ischemic stroke
significantly increased the probability of global recovery by 30% at 3 months. A
similar positive result in reduction of death and disability from acute stroke was
obtained in a meta-analysis in 2010 (10 trials, 2279 patients). The International
Citicoline Trial on Acute Stroke (ICTUS) was designed to confirm the encouraging

Treatment
results of the data pooling analyses and replicate trends. Global recovery at 90 days

acute
was similar in patients who received citicoline and in those who received placebo.
Some important characteristics in the ICTUS trial which may have influenced
the neutral results include randomization of more severe stroke and substantial
number of patients receiving thrombolytic therapy (47%), which may have resulted
in ceiling effect from maximum improvement due to rt-PA effect.

In addition to neuroprotective properties, citicoline also possesses

neuroregenerative properties which may explain the long-term beneficial effects
in post-stroke patients. In an open-label randomized trial among 347 patients with
first-ever ischemic stroke, the citicoline-treated group (at 1 g/day for 12 months)
had better outcome in attention-executive functions and temporal orientation at
6 and 12 months.

The two other pharmacologic agents with putative neuroprotective and

neurorestorative properties which have recently completed phase III clinical trials
are Cerebrolysin® and NeuroAiDTM.

Cerebrolysin® is composed of low-molecular-weight peptides and free amino

acids, which mimics the effects of naturally-occurring neurotrophic factors that
help improve and accelerate recovery of neurologic function. Cerebrolysin also
exerts pleitropic and multimodal effects and blocks the pathological cascade
of events involved in dementia, traumatic brain injury, and ischemic stroke at
various levels. Clinical trials involving more than 1,500 patients since 1994, has
shown favorable results on motor function, activities of daily living, cognitive
performance, and faster recovery with use of Cerebrolysin®. The Cerebrolysin in
Patients with Acute Ischemic Stroke in Asia (CASTA) trial has shown no overall
difference in outcomes between those who received Cerebrolysin and those in the
placebo group at 90 days. Outcome may have been affected by large number of

81
 mild strokes included in the trial. A favorable trend towards benefit was seen in the
more severely affected patients in post hoc analysis.

NeuroAidTM, a product that combines extracts of nine herbal and five animal
components in capsule form, has been shown to restore neurological and cellular
function in non-clinical models of ischemic stroke. A systematic review of earlier
clinical trials in non-acute stroke showed that NeuroAiDTM significantly enhances
recovery of functional outcome and neurological disability. The Chinese Medicine
NeuroAiDTM Efficacy on Stroke recovery (CHIMES) trial in acute stroke patients
showed a trend in favor of NeuroAiDTM, although this did not achieve statistical
significance. Post-hoc analysis revealed a significant reduction in risk of recurrent
fatal or non-fatal vascular event during three months of treatment.

Pre-planned subgroup analysis of Filipino patients included in the CHIMES

study showed a statistically significant effect of NeuroAiDTM on functional and
neurological outcomes. A prognosis-based responder analysis of the CHIMES data
revealed statistically significant treatment effect of NeuroAiDTM particularly among
patients with poorer prognosis for full functional recovery (modified Rankin Scale
[mRS] score of 0-1).
Table 3. Neuroprotective and Neurorestorative Drugs

DRUG TRIAL STUDY DESIGN RESULT

Cerebrolysin® CASTA: 1,070 patients with There was no significant
Cerebrolysin® acute ischemic stroke difference in functional outcome
in Patients with within 12 hours were between treatment groups at 90
Treatment

Acute Ischemic randomized to IV days.

Stroke in Asia Cerebrolysin® 30 ml
acute

daily or placebo for 10 Post hoc analysis shows

(Stroke 2012 days. favorable trend towards the
Mar;43(3):630-6) more severely affected patients
(NIHSS > 12).
Citicoline ICTUS: 2,298 patients with Global recovery at 90 days was
International moderate to severe similar to both groups (OR=1.03).
Citicoline Trial in acute ischemic stroke
Acute Stroke within 24 hours Citicoline appears more
were randomized to beneficial in patients aged > 70
(Lancet 2012 Jul citicoline 1000 mg years (p=0.001), patients with
28;380(9839):349- every 12 hours or moderate strokes NIHSS < 14
57) placebo for 6 weeks. (p=0.021), and in patients not
treated with rt-PA (p=0.041).

NeuroAiDTM CHIMES: Chinese 1,100 patients with There was no difference in

Medicine acute ischemic stroke primary efficacy outcome of
NeuroAiDTM of intermediate ordinal analysis in mRS scores
Efficacy in Stroke severity within at 90 days (OR=1.09, 95% CI,
Recovery 72 hours were 0.86-1.32). Trend of benefit
randomized to was observed for subgroup of
(Stroke 2013 NeuroAiD 4 caps TID
TM
patients receiving the drug after
Aug;44(8):2093- or placebo for 90 days. 48 hours.
100)
NeuroAiDTM treatment was
associated with significant
reduction in the risk of recurrent
vascular events.

“The use of drugs with neurorestorative and neuroprotective properties in acute stroke
remains as a matter of preference of the attending physician.”

82
 Bibliography

1. Alvarez-Sabín J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular
cognitive impairment. Cerebrovasc Dis. 2013;35(2):146-54.
2. Bellolio MF, Gilmore RM, Ganti L. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst
Rev. 2014 Jan 23;1:CD005346.
3. Capes S, Hunt D, Malmberg K. et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic
patients: A Systematic Overview. Stroke. 2001;32: 2426 – 2432.
4. Chankrachang S, Navarro JC, De Silva DA, et al. Towanabut S, Chua CL, Lee CF, Bousser MG, Chen C; CHIMES
Study Investigators. Prognostic Factors for Functional Outcome and Treatment Effect in the CHIMES Study.
Presented during the 23rd European Stroke Congress (ESC), Nice, France, 6-9 May 2014.
5. Chen CLH, Young SHY, Gan HH, et al. CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES): A
double-blind, placebo-controlled, randomized study. Stroke. 2013;44:2093-2100.
6. Chen CLH, Venketasubramanian N, Lee CF, et al.; CHIMES Study Investigators. Effects of MLC601 on early vascular
events in patients after stroke – The CHIMES Study. Stroke. 2013;44:3580-3583.
7. Clark WM, Warachi SJ, Pettigrew LC, et al.; for the Citicoline Stroke Study Group. A randomized dose response trial
of citicoline in acute ischemic stroke patients. Neurology. 1997;29:671-678.
8. Davalos A, Castillo J, Alvarez-Sabin J, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling
analysis of clinical trials. Stroke. 2002;33:2850-2857.
9. Davalos A, Sabín, J, Castillo J, et al. Citicoline in the treatment of acute ischemic stroke: an international randomized
multicenter placebo controlled study (ICTUS). Lancet. 2012 Jul 28;380(9839):349-57
10. Hajat C, Hajat S, Sharma P. Effects of postroke pyrexia on stroke outcome: a meta-analysis of studies in patients.
Stroke. 2000; 31(2):410– 414.
11. Heiss WD, Brainin M, Bornstein N, et al.; for the CASTA Investigators. Cerebrolysis in patients with acute ischemic
stroke in Asia: results of a double blind placebo controlled randomized trial. Stroke. 2012;43:630-636.
12. Heurteaux C, Gandin C, Borsotto M, et al. Neuroprotective and neuroproliferative activities of NeuroAid (MLC601,
MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010;58:987–1001.

Treatment
13. Hong Z, Bornstein N, Brainin M, Heiss WD. A double blind placebo controlled randomized trial to evaluate the

acute
safety and efficacy of Cerebrolysin in patients with acute ischemic stroke (CASTA). Int J Stroke. 2009; 4: 406 – 412.
14. Hurtado O, Cardenas A, Pradillo JM, et al. A chronic treatment with CDP choline improves functional recovery and
increases neuronal plasticity after experimental stroke. Neurobiol Dis. 2007; 26: 105 – 111.
15. Kreisel S, Alonso, A, Szabo K, et al. Sugar and nice-aggressive hyperglycemic control in ischemic stroke and what
can we learn from non-neurological intensive glucose control trials in the critically ill. Cerebrovasc Dis. 2010; 29:
518 – 522
16. Lizasoain I, Cardenas A, Hurtado O, et al. Targets of cytoprotection in acute ischemic stroke: present and future.
Cerebrovasc Dis. 2006: 21 (suppl 2)1–8.
17. Lyden P, Wahlgren N. Mechanism of action of neuroprotectants in stroke. J Stroke Cerebrovasc Dis. 2000; 9(6):9-14.
18. Moha Ou Maati H, Borsotto M, Chatelain F, et al. Activation of ATP-sensitive potassium channels as an element
of the neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen glucose deprivation.
Neuropharmacology. 2012;63:692–700.
19. Navarro JC, Gan HH, Lao AY, et al.; CHIMES Study Investigators. Baseline Characteristics and Treatment Responses
of Patients included from the Philippines in the CHIMES Study. Int J Stroke (published online 7 Jul 2014).
20. Quinn TJ, Lees KR. Hyperglycemia in acute stroke – to treat or not to treat. Cerebrovasc Dis. 2009; 27 suppl 1: 148
– 155.
21. Quintard H, Borsotto M, Veyssiere J, et al. MLC901, a traditional Chinese medicine protects the brain against global
ischemia. Neuropharmacology. 2011;61:622–631.
22. Sabin J, Roman G. The role of Citicoline in neuroprotection and neurorepair in stroke. Brain Sci. 2013, 3, 1395-1414
23. Secades J, Lorenzo J. Citicoline: Pharmacological and clinical review 2006 update: Methods Find Exp Clin
Pharmacol. 2006: 26 (suppl B): 1 – 56.
24. Siddiqui FJ, Venketasubramanian N, Chan ES, Chen C. Efficacy and safety of MLC601 (NeuroAiD®), a traditional
Chinese medicine, in poststroke recovery: a systematic review. Cerebrovasc Dis. 2013;35 (Suppl 1):8–17.
25. Venketasubramanian N, Chen CL, Gan RN, et al.; on behalf of the CHIMES Investigators, A double- blind, placebo-
controlled, randomized, multicenter study to investigate CHInese Medicine Neuroaid Efficacy on Stroke recovery
(CHIMES Study). Int J Stroke. 2009; 4:54-60.

83
 C. Anticoagulation In Acute Cardioembolic Stroke
a. Sources of Cardioembolic Stroke

Low or Uncertain Risk High Risk

Mitral valve prolapse AF (valvular or non-valvular)
Mitral annular calcification Rheumatic mitral stenosis
Patent foramen ovale (PFO) Prosthetic heart valves
Atrial septal aneurysm Recent myocardial infarction (MI)
Calcific aortic stenosis LV/LA thrombus
Mitral valve strands Atrial myxoma
Infective Endocarditis
Dilated cardiomyopathy
Marantic endocarditis

b. Features Suggestive of Cardioembolic Stroke

• Sudden onset of maximal deficit (<5 minutes)
• Decreased level of consciousness
• Rapid regression of initially massive symptoms (”spectacular shrinking deficit”)
• Wernicke’s aphasia or global aphasia without hemiparesis
• Visual field abnormalities
• Onset of symptoms after a Valsalva-provoking activity (e.g., coughing, bending)
• Infratentorial ischemic stroke (cerebellar, PCA, and multi-level infarcts, top-of-the basilar
syndrome)
• Hemorrhagic transformation and early recanalization of occluded intracranial vessel
• Neuroimaging finding of acute infarcts involving multiple vascular territories in the brain
(predominantly carotid and MCA territories), or multiple levels of the posterior circulation
Treatment
acute

c. Indications and Contraindications for Anticoagulation in Patients

with Cardioembolic Stroke

Probably indicated Contraindicated

Intracardiac thrombus
Mechanical prosthetic valve
Recent MI
Congestive heart failure (CHF)
Bridging measure for long-term
coagulation
Bleeding diathesis
Non-petechial intracranial hemorrhage
Recent major surgery or trauma
Infective endocarditis

d. When considering anticoagulation in acute cardioembolic stroke within 14 days,

the benefits of reducing early stroke recurrence should be weighed against the risk
of hemorrhagic transformation. The latter is higher in patients with large infarction,
severe strokes or neurological deficits, and uncontrolled hypertension.

e. How to Anticoagulate

1. Requirements for intravenous anticoagulation of patients with cardiogenic source

of embolism:
a. Heparin sodium in D5W
b. Infusion pump, if available
c. Activated partial thromboplastin time (aPTT) or clotting time

2. Procedure:
a. Start intravenous infusion at 600 - 800 units heparin per hour, ideally via
infusion pump. IV heparin bolus is not recommended.
b. Perform aPTT as often as necessary, every 4-6 hours after dose adjustments,
to keep aPTT levels at 1.5-2.5 times the control. The risk of major hemorrhage,
84
 including intracranial bleed, progressively increases as aPTT exceeds 80 seconds.
c. Infusion may be discontinued once oral anticoagulation with warfarin has
reached therapeutic levels or once antiplatelet medication is initiated for
secondary prevention.

To date, there has been no trial which directly compared the efficacy of UFH vs LMWH
in patients with acute cardioembolic stroke. However, LMWH has the advantage of
easier administration and does not require aPTT monitoring.

Bibliography

1. Adams H. Emergent use of anticoagulation for treatment of patients with ischemic stroke. Stroke.
2002;33:856-861.
2. Hart R, Palacio S, Pearce L. Atrial fibrillation, stroke and acute antithrombotic therapy. Stroke. 2002;33:2722-
2727.
3. Guedes L, Ferro J. A systematic review of immediate anticoagulation for ischemic stroke of presumed
cardioembolic mechanism. Stroke. 2008;39: e81-82.
4. Guyatt G, Akl E, Crowther M, et al. Antithrombotic therapy and prevention of thrombosis, 9th ed. American
College of Chest Physicians Evidence-based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):7S-47S
5. Jauch, E, Saver, J, Adams H, et al. Guidelines for the early management of patients with ischemic stroke:
guideline for healthcare professionals from the American Heart Association/American Stroke Association.
Stroke. 2013;44:870-947.
6. Marsh E, Llinas R, Hillis A. Hemorrhagic transformation in patients with acute ischemic stroke and an
indication for anticoagulation. Eur J Neuro. 2013;20(6): 962-967.

Treatment
7. Moonis, M, Fisher M. Considering the role of heparin and low-molecular weight heparin in acute ischemic

acute
stroke. Stroke. 2002;33:1927-1933.
8. Paciaroni M, Agnelli G, Micheli S. et al. Efficacy and safety of anticoagulant treatment in acute cardioembolic
stroke: A meta-analysis of randomized controlled trials. Stroke. 2007;38: 423–430.

85
 D. ADMINISTRATION OF rt-PA IN ACUTE ISCHEMIC STROKE
1. Eligibility for IV thrombolysis with rt-PA
• Age 18 years or older
• Clinical diagnosis of ischemic stroke which causes a measurable neurologic deficit.
• Time of symptom onset is well-established to be less than 180 minutes before the
initiation of treatment.

2. Patient Selection

A. Contraindications and Warnings

• Evidence of intracranial hemorrhage on pretreatment CT or MRI
• Evidence of multi-lobar infarction (>1/3 cerebral hemisphere) on neuroimaging
• Only minor or rapidly improving stroke symptoms
• Clinical presentation suggestive of subarachnoid hemorrhage (SAH), even with
normal CT
• Significant head trauma or prior stroke within 3 months
• History of previous intracranial hemorrhage (ICH)
• Known arteriovenous malformation or aneurysm
• Arterial puncture at a non-compressible site within 7 days
• Recent intracranial or spinal surgery
• Active internal bleeding
• Known bleeding diathesis, including but not limited to:
- Platelet count < 100,000/mm3
- Patient has received heparin within 48 hours and has an elevated aPTT
(greater than upper limit of normal for laboratory)
- Current or recent use of oral anticoagulants (e.g., warfarin sodium) with an
Treatment

elevated prothrombin time >15 seconds or INR >1.7

acute

• The use of rt-PA in patients receiving NOACs (e.g., direct thrombin inhibitors,
direct factor X inhibitors) maybe harmful and is not recommended unless PT-INR,
aPTT, and platelet counts are normal, or if the patient has not received any dose
of these agents >2 days (if with normal renal function)
• Abnormal blood glucose (i.e. <50 mg/dL or >400 mg/dL)
• On repeated measurements, the systolic blood pressure (SBP) is greater than
185 mm Hg or diastolic blood pressure (DBP) is greater than 110 mm Hg at the
time of initiation of therapy, and the patient requires aggressive treatment for
reducing blood pressures to within these limits.

B. Relative contraindications
Under certain circumstances, patients may receive thrombolytic therapy despite the
presence of 1 or more relative contraindication. Consider risk-benefit of IV rt-PA
treatment carefully if any of the following is present:
• Patient has had major surgery or serious trauma (excluding head trauma) within
previous 14 days
• History of gastrointestinal or urinary tract hemorrhage within previous 21 days
• Only minor or rapidly improving stroke symptoms (clearing spontaneously)
• Myocardial infarction within the past 3 months
• Patient was observed to have seizures at the time of onset of stroke symptoms
with post-ictal neurologic impairment
• Pregnancy

3. Intravenous Administration of rt-PA

• 0.9 mg/kg (maximum of 90 mg) infused over 60 minutes, with 10% of the total
dose administered as an initial intravenous bolus over 1 minute.
• The use of low-dose 0.6 mg/kg IV rt-PA is an option because of reduced cost,
however a recent review article involving small case series of Asian patients
showed a trend towards less favorable clinical outcome compared with the
standard dose.
86
 • Whether low-dose rt-PA is truly as efficacious or even safer will be addressed
in the ongoing Enhanced Control of Hypertension and Thrombolysis in Stroke
Disease (ENCHANTED) trial (ClinicalTrials.gov identifier NCT01422616).

4. Sequence of events
• Draw blood for tests while preparing for neuroimaging.
• Monitor blood pressure every 15 minutes and manage accordingly (see
Pretreatment BP).
• Perform neurologic examination.
• Perform neuroimaging using non-contrast CT or MRI scan. Search for any
evidence of hemorrhage.
• If the patient has severe head or neck pain, or is somnolent or stuporous,
confirm/rule out subarachnoid hemorrhage.
• If there is a significant abnormal lucency on imaging suggestive of infarction,
reconsider the patient’s history, since the stroke may have occurred earlier.
• Review required test results – hematocrit, platelet count, blood glucose, PT or
aPTT (in patients with recent use of oral anticoagulants or heparin).
• Review patient selection criteria.
• Infuse intravenous rt-PA: 0.9 mg/kg (initially 10% of total dose as bolus over 1
minute).
• Do not use cardiac dose.
• Do not exceed the 90 mg maximum dose.
• Monitor the patient closely and carefully, especially the BP and neurologic
status. Manage BP accordingly.
• No adjunctive treatment (e.g., heparin, warfarin, aspirin) should be given
during the first 24 hours after symptom onset and 24 hours post-rt-PA

Treatment
treatment. If heparin or other anticoagulant is indicated after 24 hours,
consider performing a follow-up non-contrast CT scan or MRI at 24 hours

acute
after IV rt-PA prior to initiating antiplatelet or anticoagulant agents to rule
out any intracranial hemorrhage.
• Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-
arterial pressure catheters if the patient can be safely managed without
them.

5. Blood Pressure control during thrombolytic therapy

Pretreatment BP should be < 185/110 mm Hg. Above this level, patient may be
treated with nitroglycerin paste and/or:
 Labetalol 10-20 mg IV over 1-2 minutes, may repeat one time; or
 Nicardipine 5 mg/hour, titrate up by 2.5 mg/hour every 5-15 minutes
(maximum: 15 mg/hour)

Once the desired BP is achieved, adjust to maintain proper BP limits. If after these
measures the BP does not decrease and maintain < 185/110 mm Hg, the patient
should not be treated with rt-PA.

During and After rt-PA treatment:

• BP monitoring should be as follows: every 15 minutes for 2 hours from the start
of rt-PA infusion, then every 30 minutes for 6 hours, and then hourly thereafter
for 16 hours. During antihypertensive therapy, monitor BP every 15 minutes.
Watch out for hypotension.
• If systolic BP >230 mm Hg and/or diastolic BP is 121-140 mm Hg, give labetalol
20 mg IV over 1 to 2 minutes. The dose may be repeated and/or doubled every
10 minutes, up to 15 mg. Alternatively, an IV infusion of labetalol 2 to 8 mg/
min may be initiated after the first bolus of labetalol, or a nicardipine infusion
at 5 mg/hour titrated up by 2.5 mg/hour every 5 to 15 minutes interval until the
desired BP is achieved. For persistently elevated BP, IV sodium nitroprusside may
be used.
87
 • If systolic BP is 180 to 230 mm Hg and/or diastolic BP is 105 to 120 mm Hg on
two readings (taken 5 to 10 minutes apart), give labetalol 10 mg IV over 1 to 2
minutes. The dose may be repeated and/or doubled every 10 to 20 minutes, up
to 15 mg. Alternatively, following the first bolus of labetalol, an IV infusion of
labetalol 2 to 8 mg/min may be initiated and continued until the desired BP is
reached.
• If upon the clinical judgment of the treating physician, an intracranial
hemorrhage is suspected, the administration of rt-PA should be discontinued
and an emergency CT scan or other diagnostic neuroimaging sensitive to the
presence of intracranial hemorrhage should be obtained.

6. Management of ICH following thrombolytic therapy

In the event that a hemorrhage is suspected (e.g., acute neurological deterioration,
new headache, acute hypertension, nausea, vomiting) during rt-PA therapy, do the
following:
• Discontinue rt-PA infusion (unless other causes of neurological deterioration are
apparent).
• Perform immediate CT scan or other diagnostic imaging sensitive to presence of
hemorrhage.
• Draw blood for STAT prothrombin time, aPTT, platelet count, fibrinogen, blood
type and cross-matching.
• Prepare for administration of 6 to 8 units of cryoprecipitate containing factor
VIII.
• Prepare for administration of 6 to 8 units of platelets.

If intracranial hemorrhage is present:

Treatment

• Obtain fibrinogen results.

• Consider administering cryoprecipitate or platelets if indicated.
acute

• Consider referring to a hematologist and/or neurosurgeon.

• Consider decision regarding further medical and/or surgical therapy.
• Consider second CT to assess progression of ICH.
• Emergent neurosurgical consultation is highly recommended.

7. Expansion of IV rt-PA treatment time window up to 4.5 hours

The eligibility for thrombolysis follows the same criteria as treatment within the
first 3 hours, with the following additional relative exclusion criteria:
• Patients older than 80 years old.
• Patients on oral anticoagulants, regardless of the INR.
• Patients with NIHSS score > 25.
• Patients with history of both ischemic stroke and diabetes.

The search for a thrombolytic agent which can be used beyond the 3 hours
of acute ischemic stroke is being investigated in the ongoing Desmoteplase
To Treat Acute Stroke (DIAS-3) study to which the Philippines is participatory.
This double-blind RCT will determine whether desmoteplase is safe and
effective in the treatment of patients with acute ischemic stroke when
given within 3-9 hours from the onset of stroke symptoms. Patients should
have an NIHSS score of 4-24 and a documented vessel occlusion or high-
grade stenosis on MRI or CTA in proximal cerebral arteries. This trial has
completed its target enrollment of 480 patients in December 2013, with
the last few randomized patients still undergoing follow-up evaluation.

88
Table 4. Randomized Controlled Trials (RCT) of Intravenous rt-PA in Acute Ischemic Stroke
TRIAL
NINDS t-PA trial: National
Institute of Neurological
Disorders and Stroke t-PA
trial
(N Eng J Med 1995; 3
33:1581 - 1587)
ECASS: European
Australasian Cooperative
Acute Stroke Study
(JAMA 1995; 274: 1017 -
1025)
ECASS II: Second European
Australasian Cooperative
Acute Stroke Study
(Lancet 1998; 352: 1245-1251)
ATLANTIS A: Alteplase
Thrombolysis for Acute
Non-interventional
Therapy in Ischemic
Stroke
(Stroke 2000; 31:811 – 816)
ATLANTIS B: Alteplase
Thrombolysis for Acute
Non-interventional
Therapy in Ischemic
Stroke
(JAMA 1999; 282:2019 –
2026)
J-ACT: Japanese Alteplase
Clinical Trial
(Stroke 2006;37:1810-1815)
ECASS III: European
Australasian Cooperative
Acute Stroke Study
(N Eng J Med 2008; 359:
1317–1329)
DESIGN
291 patients with acute
ischemic stroke < 3 hours
were randomized to IV
t-PA (0.9 mg/kg) or placebo
and assessed for 4-point
improvement in NIHSS or
resolution of neurological
deficit within 24 hours; 333
patients received IV t-PA
within 3 hours of symptom
onset and were assessed
for functional and clinical
outcome at 3 months.
620 patients with acute
ischemic stroke < 6 hours
were randomized to t-PA 1.1
mg/kg or placebo.
800 patients with acute
ischemic stroke < 6 hours
were randomized to rt-PA 0.9
mg/kg or placebo.
142 patients with acute
ischemic stroke < 6 hours
were randomized to rt-PA 0.9
mg/kg or placebo.
613 patients with acute
ischemic stroke within 3–5
hours were randomized to
t-PA or placebo.
103 patients within 3 hours of
ischemic stroke were given
0.6 mg/kg IV rt-PA as single
arm, open-label study.
821 patients with acute
ischemic stroke within 3 to
4.5 hours were randomized to
rt-PA 0.9 mg/kg or placebo.
RESULT
No difference in neurologic
improvement at 24 hours, but
patients given IV t-PA were 30%
more likely than controls to
have minimal or no disability
at 3 months, despite more
symptomatic ICH (6.4% vs 0.6%).
Overall, there was no difference
in mortality at 3 months.
No difference in disability using
Intention-to-treat analysis.
However, there were 109 major
protocol violations. Post hoc
analysis excluding these patients
indicated better recovery for t-PA
group at 90 days.
No significant difference was
seen in the rate of favorable
outcome at 3 months between rt-
PA- and placebo- treated group.
Treatment
acute
No significant difference was
seen on any of the planned
efficacy endpoints at 30 and 90
days between groups. The
risk of symptomatic ICH was
increased with rt-PA treatment
particularly in patients treated
between 5 to 6 hours.
No significant difference in
functional recovery at 90
days between groups. Risk of
symptomatic intracerebral
hemorrhage was increased in
t-PA.
36.9% achieved an mRS of 0-1
at 3 months; symptomatic ICH
occurred in 5.8%.
Data is comparable with
published data using IV rt-PA.
Significantly more patients in rt-
PA-treated group had favorable
outcome at 3 months (52.4% vs
45.2 %, p = 0.04). The incidence
of intracranial hemorrhage was
higher with rt-PA, but mortality
did not significantly differ
between the 2 groups.
(continued on next page)
89
 Table 4 (continued)

TRIAL DESIGN RESULT

IST III: Third International
Stroke Trial
(Lancet 2012 Jun
23;379(9834):2352-63)
3,035 patients with acute
ischemic stroke within 6
hours were randomized to rt-
PA 0.9mg/kg or placebo.
Open label study; no upper
limit for age and broader BP
eligibility.
The proportion of patients alive
& independent at 6 months
(OHS 0-2) was 37% in the rt-PA
group versus 35% in the placebo
group (OR=1.13, 95% CI 0•95—1•35,
p=0•181). Ordinal analysis showed
significant shift in Oxford
Handicap Score (OHS).

More deaths occurred during the

first 7 days in the rt-PA group
(11% vs 7%, OR=1.60, 95% CI,
1•22—2•08, p=0•001). At 6 months,
27% of patients have died in both
groups.

Bibliography

1. Del Zoppo G, Saver J, Juach E, Adams H Jr; American Heart Association Stroke Council. Expansion of
the Time Window for Treatment of Acute Ischemic Stroke with Tissue Plasminogen Activator, a science
advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40:2945–2948.
2. Jauch E, Saver J, Adams H, et al. Guidelines for the early management of patients with ischemic stroke:
guideline for healthcare professionals from the American Heart Association/American Stroke Association.
Treatment

Stroke. 2013;44:870-947.
3. Ramaiah S, Yan B. Low-Dose Tissue Plasminogen Activator and Standard-Dose Tissue Plasminogen
acute

Activator in Acute Ischemic Stroke in Asian Populations: A Review. Cerebrovasc Dis. 2013;36:161–166.

E. BLOOD PRESSURE MANAGEMENT IN ACUTE STROKE

A. BP Management in Acute Ischemic Stroke

(1) Definition/Formulae:

Mean Arterial Pressure (MAP) = 2 (Diastolic BP) + Systolic BP

3
Cerebral Perfusion Pressure (CPP) = MAP – ICP
Normal values: ICP: 5-10 mm Hg; CPP: 70-100 mm Hg

(2) Check if patient has any condition that may increase BP (e.g., pain, stress,
bladder distention, constipation) and address accordingly.

(3) Allow for “permissive hypertension” during the first week to ensure
adequate CPP, but ascertain cardiac and renal protection. Treat if SBP >220
mm Hg or DBP >120 mm Hg, or MAP>130

• Defer emergency BP therapy if MAP is within 110-130, or SBP = 185-220

mm Hg or DBP = 105-120 mm Hg, unless the patient is a candidate for
thrombolytic therapy, and/or in the presence of acute MI, CHF, aortic
dissection, acute pulmonary edema, acute renal failure, and hypertensive
encephalopathy.

90
 Rationale for Permissive Hypertension:

• In acute ischemic stroke, autoregulation is paralyzed in the affected

tissues with cerebral blood flow (CBF) passively following MAP. Rapid BP
lowering can lead to a further decrease in perfusion at the penumbra.
• Hypertension is typically present in acute stroke, with spontaneous
decline in the first 5-7 days with attainment of neurological stability. SBP
dropped by ≈28% during the first day whether or not medications were
given.
• Increased ICP during the acute phase of large infarcts reduces the net CPP
• There is lack of convincing evidence of benefit of treating arterial
hypertension. Several reports documented neurological deterioration
and poor outcome from rapid and steep BP reductions.
• SBP and DBP drops of >20 mm Hg were associated with early neurological
worsening, high rates of poor outcome or death, and larger volumes of
infarctions.
• There was no indication that BP-lowering treatment with an angiotensin
receptor blocker is beneficial in patients with acute stroke and raised BP.
If anything, the evidence suggested a harmful effect.
• The latest Efficacy of Nitric Oxide in Stroke (ENOS) trial, presented during
the 2014 European Stroke Congress, showed no benefit in functional
outcome in continuing prestroke BP-lowering therapy during the acute
phase of stroke. Much of the harm in continuing BP medication was
attributed to pneumonia among patients with dysphagia.

Treatment
acute
(4) The use of intravenous nicardipine is reasonable. It is readily available,
easy to administer and titrate, has short duration of action, and does not
significantly affect intracranial pressure. Other locally available intravenous
antihypertensives for acute stroke are listed in Table 5.

(5) Treat patients who are potential candidates for rt-PA therapy who have
persistent elevations in SBP >185 mmHg or DBP >110 mmHg with small doses
of IV antihypertensive agents. Maintain BP just below these limits.

(6) Arterial Hypotension in Acute Ischemic Stroke:

• Although rare in acute ischemic stroke, a baseline SBP <100 mm Hg, or DBP
<70 mm Hg is associated with higher rates of neurological worsening, poor
neurological outcomes, or death.
• The cause of arterial hypotension in acute stroke should be determined and
addressed: e.g., aortic dissection, volume depletion, blood loss, and decreased
cardiac output secondary to MI or cardiac arrhythmias.
• Correct hypovolemia with plain NSS, and treat arrhythmias to optimize cardiac
output
• Available vasopressors agents include dopamine, dobutamine, and
phenylephrine.

91
 acute
92 Treatment

Table 5. Intravenous Antihypertensive Agents for Control of BP in Acute Stroke

Onset
Duration Availability/
Drug Dose of Stability Adverse reaction Mechanism of Action
of action Dilution
action
Nicardipine 1-15 mg/hour 5-10 1-4 hours (10 mg/10 ml 1-4 hours Tachycardia, Inhibits calcium ion from
minutes amp); 10 mg in 90 headache, entering slow channel,
ml NSS/D5W flushing, dizziness, producing coronary,
somnolence, nausea vascular, smooth muscle
relaxation & vasodilatation
Hydralazine IV push 10-20 mg/dose 10-20 3-8 hours 25 mg/mL amp; 25 4 days Tachycardia, flushing, Direct vasodilatation of
q4-6 hours as needed, minutes mg/tab headache, vomiting, arterioles & decreased
may increase to 40 mg/ increased angina systemic resistance
dose

Labetalol 5 mg IV push over 2 2-5 2-4 hours 5 mg/ml in 40 ml 72 hours Orthostatic Alpha- & beta- blocker. Beta-
minutes, repeat with minutes vial; 250 mg in hypotension, adrenergic blocking activity
incremenal dose of 250 mL NSS/D5W drowsiness, dizziness, is 7x > than alpha-adrenergic
10, 20, 40, 80 mg until light-headedness, blockers.
desired BP is achieved or dyspnea, wheezing,
a total dose of 300 mg and bronchospasm Produces dose-dependent 
has been administered in BP without significant 
in HR or cardiac output

Esmolol 0.25-0.5 mg/kg IV push 2-10 10-30 100 mg/10 mL vial; 48 hours Hypotension, Short-acting beta-adrenergic
1-2 mins. followed by minutes minutes 2,500 mg in 250 bradycardia, AV blocking agent. At low
infusion of 0.05 mg/ mL D5W/NSS block, agitation, doses, it has little effect on
kg/min confusion, wheezing / beta 2 receptors of bronchial
broncho-constriction, & vascular smooth muscle
If there is no response, phlebitis
repeat 0.5 mg/kg bolus
dose &  infusion to 0.10
mg/kg/min maximum
infusion rate = 0.30 mg/
kg/min
 B. BP Management in Acute Hypertensive Intracerebral Hemorrhage
• BP is often markedly elevated in acute ICH, with elevations greater than that
seen in ischemic stroke.
• Mechanism:
o Stress activation of neuroendocrine system (sympathetic NS, renin-
angiotensin axis, glucocorticoid system) partly in response to increased ICP.
• The absence of ischemic penumbra allows for more aggressive BP management
• Hypertension could theoretically contribute to hydrostatic expansion of the
hematoma, perihematoma edema, and rebleeding.
• Hypotension may result in cerebral hypoperfusion especially in the setting of
increased ICP.

Clinical Evidence
• Phase II clinical trials on BP lowering (INTERACT and ATACH) have shown that
intensive BP lowering to SBP ≈ 140 mm Hg in acute ICH is feasible and probably
safe.
o Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage
Trial (INTERACT): trend to less hematoma volume growth in 24 hours
with intensive BP lowering to goal of SBP 140 mm Hg (versus 180 mm Hg);
with no excess in neurologic deterioration

o Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH)

trial: early, rapid BP lowering in ICH (with IV Nicardipine) is clinically
feasible and probably safe.

Treatment
Table 6. Phase III Clinical Trials on BP lowering in Acute ICH

TRIAL
INTERACT II: Intensive
Blood Pressure Reduction
in Acute Cerebral
Hemorrhage Trial–2
(N Eng J of Med 2013; 368:
2355-2365)
ATACH II:
Antihypertensive
Treatment on Acute
Cerebral Hemorrhage–2
(Neurocritical Care 2011; 15
(3): 559 – 576)
DESIGN
2,388 patients with spontaneous
ICH within 6 hours and SBP >
150 – 220 mm Hg randomized
to receive intensive treatment
to lower SBP to < 140 mm Hg vs.
guideline based to SBP < 180 mm
Hg using drugs of physician’s
choice for 1 week.
1,280 patients with acute ICH
randomized to receive intensive
treatment to lower SBP to < 140
mm Hg versus guideline-based
management to SBP < 180 mm Hg
within 24 hours of randomization
using IV Nicardipine.
acute
RESULT
There was no difference in the
rate of primary outcome of
death and disability between
2 treatment groups at 90 days.
Pre-specified ordinal analysis
showed significantly lower
mRS scores with intensive
treatment (OR for greater
disability=0.87, 95% CI, 0.77 –
1.00, p= 0.04).
ongoing
(Clinicaltrials.gov
identifier NCT01176565)

o Unlike SAH, isolated ICH does not have the same propensity to cause
cerebral vasospasm, thus BP lowering can be somewhat more aggressive.

(continued on next page)

93
 BP Management in Acute Hypertensive ICH (continued)
Recommendations:
• Treat if SBP > 180 mm Hg.
• Acute lowering of SBP to ≈ 140 mm Hg within 7 days is safe and improves
outcome in patients with small-moderate size ICH not requiring surgical
intervention (Class I, level B).
• If ICP monitor is available, keep CPP >70 mm Hg.

(See Chapter 6 for further details on Hypertensive ICH)

C. BP management in Acute Subarachnoid Hemorrhage

• Treat hypertension with modest reductions in BP to minimize vasospasm and

delayed cerebral ischemia (see Chapter 6 for further details on SAH).
• Preoperatively, for unsecured aneurysms, the use of IV Nicardipine to a target
SBP <150 mm Hg is reasonable.

Bibliography

1. Anderson, C, Huang, Y, Wang J. et al. for the INTERACT Investigators. Intensive blood pressure reduction
in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008; 7:391–99.
2. Castillo J, Leira R, Garcia MM, et al. Blood pressure decrease during the acute phase of ischemic stroke is
associated with brain injury and poor stroke outcome. Stroke. 2004; 35:520 –526.
Treatment

3. Connolly E Jr, Rabinstein A, Carhuapoma J, et al. Guidelines for the Management of Aneurysmal
Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/
acute

American Stroke Association. Stroke. 2012; 43:1711-1737.

4. Hubert GJ, Müller-Barna P, Haberl RL. Unsolved Issues in the Management of High Blood Pressure in Acute
Ischemic Stroke. Int J Hypertens. 2013;2013:349782.
5. Jauch E, Saver J, Adams H, et al. Guidelines for the early management of patients with ischemic stroke :
guideline for healthcare professionals from the American Heart Association/American Stroke Association.
Stroke. 2013;44:870-947.
6. Morgenstern L, Hemphill JC III, Anderson C, et al. Guidelines for the Management of Spontaneous ICH: A
Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association.
Stroke. 2010 Sep;41(9):2108-29.
7. Oliveira-Filho J, Silva SC, Trabuco CC, et al. Detrimental effect of blood pressure reduction in the first 24
hours of acute stroke onset. Neurology. 2003;61:1047–1051.
8. Patarroyo, S and Anderson C. Blood pressure lowering in acute phase of stroke: latest evidence and clinical
evidence. Ther Adv Chronic Dis. 2012; 3(4): 163–171.
9. Qureshi AI, Tariq N, Divani AA, et al.; ATACH Investigators. Antihypertensive treatment of acute cerebral
hemorrhage. Crit Care Med. 2010 Feb;38(2):637-48.
10. Sandset EC, Bath PM, Boysen G, et al. The angiotensin-receptor blocker candesartan for treatment of acute
stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011 Feb 26;377(9767):741-
50.

94
VII. MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE (ICP)
A. Signs and Symptoms of Increased ICP
1. Deteriorating level of sensorium
2. Cushing’s triad: hypertension, bradycardia, irregular respiration
3. Anisocoria

B. Management Options for Increased ICP

General:
1. Control agitation and pain with short-acting medications, such as NSAIDs
and opioids (Table 7).
2. Treat fever aggressively. Avoid hyperthermia.
3. Control seizures if present. May treat with phenytoin at a loading dose of
18-20 mg/kg slow IV, then maintained at 3-5 mg/kg; or Levetiracetam 500
mg IV q12. Status epilepticus should be treated accordingly.
4. Strict blood glucose control between 140-180 mg/dL.
5. Maintain normal fluid and electrolyte balance.
a. Avoid excessive free water or any hypotonic fluids such as D5W.
Potential sources of free water including hypotonic tube feedings,
medications mixed in D5W, and nasogastric tube flushes with water,
should be minimized.
b. Maintain normal volume status (i.e. 3.0-3.5 liters per day in a 60 kg
patient).
c. Encourage hyperosmolar state with hypertonic saline and/or induce
free water clearance with mannitol or diuretics.

Treatment
6. Use stool softeners to prevent straining.

acute
Specific:
1. Elevate the head at 30 to 45 degrees to assist venous drainage.
2. Do CSF drainage in the setting of hydrocephalus.
3. Administer osmotic therapy:
• Give Mannitol 20% IV infusion. Typical doses range from 0.5-1.5 g/kg
every 3-6 hours. Doses up to 1.5 g/kg are appropriate when treating a
deteriorating patient because of mass effect.
• Hypertonic saline is an option. It has the advantage of maintaining an
effective serum gradient or rise in osmolality for sustained periods with
lower incidence of intracranial hypertension.
• Always maintain serum osmolality at 300-320 mosmol/kg.
[Formula for Serum Osmolality = 2 (Na) + glucose/18 + BUN/2.8]
4. Hyperventilate only in impending herniation by adjusting tidal volume
to achieve target pCO2 levels of 30–35 mm Hg. Hyperventilation is
recommended only for a short term as its effect on CBF and ICP is short
lived ( 6 hours). Prophylactic hyperventilation without regard to patient’s
ICP level and clinical state should not be done.
5. Carefully intubate patients with respiratory failure (defined as SaO2 of less
than 90% by pulse oximetry and PaO2 <60mmHg, and/or PaCO2 > 55 mm
Hg by arterial blood gas [ABG] analysis).
6. Consider surgical evacuation or decompressive hemicraniectomy if
indicated.
7. ICP catheter insertion is useful for the diagnosis, monitoring and
therapeutic lowering of increased ICP. It is recommended in patients with
GCS ≤ 8, those with significant IVH, and hydrocephalus. CPP should be
maintained at 60-70 mm Hg.

95
 acute
96 Treatment

Table 7. Locally Available Sedatives and Narcotics

Drug Usual Dose Onset of Duration of Comments Availability/Dilution

Action Effect
Midazolam 0.025-0.035 mg/kg 1-5 min 2 hours Unpredictable sedation 15mg/3 mL amp
5 mg/5 mL amp
50 mg in 100 mL NSS/D5W
Diazepam 0.1-0.2 mg/kg Immediate 20-30 minutes Sedation can be reversed with 10 mg/2 mL amp; 50 mg in
flumazenil (0.2-1 mg at 0.2 mg/min 250 mL NSS/D5W
at 20 min intervals, max dose of 3
mg in 1 hr)
Propofol 5-50 μg/kg/min <40 sec 10-15 minutes Expensive (10 mg/mL) 100 mL vial
(premixed)
Ketorolac 50-100 mg IV 1 hour 6-8 hours NSAID 30 mg/mL amp

Tramadol 50-100 mg IV 1 hour 9 hours Centrally acting synthetic analgesic 50 mg/2mL amp; 100 mg/2mL
compound not chemically related to amp
opiates but thought to bind to opioid
receptors and inhibit reuptake of NE
and serotonin
Fentanyl 50-100 μg/hour 1-2 min >60 minutes Can be easily reversed with naloxone 100 μg/2mL; 2500 μg in 250 mL
(0.4-2 mg IVP; repeat at 2-3 min NSS/D5W
intervals, max dose 10,g) *110x more
potent than morphine

Morphine 2-5 mg/hour 5 min >60 minutes Opioid 10 mg/mL gr 1/6;

16 mg/mL gr 1/4

Dexmedetomidine 1 μg/kg/hour LD for 10 minutes 30-60 sec 3-5 minutes 200 μg/2mL vial
(Precedex®) then maintenance dosing at 0.4
μg/kg/hour (dose range: 0.2-0.7
μg/hour)
VIII. HEMICRANIECTOMY FOR MALIGNANT MIDDLE CEREBRAL ARTERY
(MCA) INFARCTION
Ten to fifteen percent of supratentorial infarcts will involve the entire MCA.1 Cerebral
ischemic infarcts are associated with cytotoxic, interstitial, and vasogenic brain edema
of varying extents. Depending on the severity and extent of edema formation, as well
as the patient’s compensatory mechanisms, ischemic brain edema in large MCA infarcts
may lead to transtentorial or transforaminal herniation, usually within 2-5 days from
ictus.2-3 Herniation accounts for 78% of deaths during the first week.4 This subgroup of
catastrophic infarcts was first labeled as malignant MCA infarcts by Hacke et al. in 1996.3

The prognosis of patients with malignant edema formation after MCA infarct is poor
despite maximum conservative treatment, and in randomized or larger prospective
observational studies, mortality averages 50–80%.5-10

Figure 1: Natural Course of Malignant MCA Infarction

Treatment
acute
Because of the limitations of current medical therapies in preventing brain herniation
and improving patient outcome, varying surgical decompression techniques have
been proposed and used to achieve the following objectives: decrease mass effect or
intracranial pressure from malignant brain edema, prevent brain herniation, reduce or
avert secondary injury to the brain, and reduce or avert further conversion of areas of
ischemic penumbra to infarct. This would ultimately translate to reduction in overall
mortality rates and improvement in long-term functional outcomes.

Criteria for Patient Selection

1. Patients who present clinically with a severe hemispheric stroke syndrome:
hemiplegia, forced eye deviation and head deviation to the side of the infarct,
aphasia, contralateral neglect, and progressive decline in the level of consciousness
usually within the first 48 hours.
2. Imaging findings showing an infarct volume involving >50% MCA territory.
3. Age: 60 years and below. Mortality rate was 20.8% and 51.3% in patients aged <
60 years and >60 years respectively. Poor outcome was seen in 33.1% of patients
< 60 years vs. 81.8% in patients >60 years.11 However, some authors suggested
that other factors might be more important than age, which include functional
and cognitive status at admission, social situation, extent of family support, and
psychosocial and financial burden of care.
4. Dominance of hemisphere involved: Though some have expressed concern that
doing decompressive hemicraniectomy for malignant MCA infarcts involving the
dominant hemisphere will lead to a worse functional outcome, this has not been
seen in several studies, due to recovery of varying extents of communication skills
or to the equally negative impact of hemiplegia.12
5. Exclusions: terminal illness, significant co-morbid conditions like significant cardiac
disease and bleeding disorders.
97
 6. The Massachusetts General Hospital (MGH) has proposed the STATE Criteria (Table
8) to determine eligibility for hemicraniectomy and a treatment algorithm (see
Clinical Pathway) on this criteria.

Table 8. State Criteria for Immediate Neurosurgical Consultation for Hemicraniectomy for
Malignant MCA Infarction13
Factor Criteria
NIHSS item 1a >1 or GCS < 8, and NIHSS >15 (non-dominant) or >20
Score*,**
(dominant)

Time <48 hours since last seen without neurological deficits

Age <60 years

Infarct lesion volume >150 cm3 (use ABC/2 formula for estimating
Territory
lesion volume), or >50% MCA territory infarction
Life expectancy ‘reasonable’ in the opinion of the Neurology
Attending or Neuro-ICU Fellow. In addition, the health care proxy
Expectations or family members understand that while the procedure is proven
to reduce disability and mortality, the patient may still survive with
severe disability.
If all the above “STATE” criteria are met, proceed to hemicraniectomy urgently (to OR within
4-6 hours).
*for intubated/sedated patients, monitoring of the level of alertness can be challenging and the
clinical judgment of the Neurology Attending is important in determining whether a patient
meets this criterion.
Treatment

**for patients who meet all STATE criteria except the level of drowsiness, patients should be
triaged to the Neuro ICU for close neuromonitoring.
acute

Indications for EMERGENT HEMICRANIECTOMY: STATE criteria met above, AND:

Early Signs of Herniation Asymmetry in pupil size
Midline Shift >10mm at septum pellucidum, or >5mm at pineal gland

Pre-surgical and surgical management13

1. If hemicraniectomy is offered, withhold anticoagulation and antiplatelets until
deemed safe post-procedure with input from neurosurgery.
2. For adequate external decompression, the size of the bone flap removed should
ideally be 12 cm (anterior-posterior) by 9 cm (superior-inferior), combined with
duraplasty.
3. Temporal lobectomy may be considered during the procedure, at the
neurosurgeon’s discretion. If performed, tissue should be submitted for
neuropathological examination.
4. The bone flap should be placed in a subcutaneous abdominal pouch or stored in
the bone bank.

Post-surgical management13
1. Admit the patient to an intensive care unit, preferably the Neuro ICU. The
Neurocritical Care attending will be the attending of record.
2. Once appropriate, a protective helmet should be worn until the bone flap is
replaced.
3. The bone flap should be replaced as soon as the patient can tolerate the surgery,
preferably within 12 weeks, unless the patient develops intercurrent infections or
other complications requiring delay.
98
Adjunctive therapy13
Although not proven efficacious, medical strategies may reduce the risk of developing
fulminant brain edema. These strategies should be used in all patients with large MCA
stroke and as an adjunct to hemicraniectomy (if the patient is deemed eligible). They
should not be used to defer or delay hemicraniectomy if STATE criteria are met.

A. General management: patients with raised intracranial pressure require special

attention to pain relief, avoidance of noxious stimuli, proper head positioning,
adequate oxygenation, maintenance of normothermia, and prevention of DVT.
Avoid oral or gastric feedings if the patient is likely to go to surgery imminently.
B. Hyperventilation: a temporary measure to reduce ICP if signs of brain herniation
develop. This should be avoided unless other measures have been exhausted and
there is a plan to proceed immediately to surgery.
C. Osmotic therapy
D. Invasive ICP monitoring (subarachnoid screw or bolt) is not required to determine
suitability for decompressive surgery. An external ventricular drain should be
considered if neuroimaging shows evidence of acute hydrocephalus. It may
be useful to monitor the ICP post-operatively if there is a concern that the
decompression was insufficient.

Key Points in the Surgical Management of Malignant MCA Infarction

1. Anticoagulation and antiplatelet therapy should be withheld until deemed safe
post-procedure.
2. Optimal medical therapy including osmotic therapy should be instituted while

Treatment
preparing the patient for hemicraniectomy and then postoperatively as indicated.

acute
3. Timing of surgery: Better outcomes have been shown if surgery is performed
early, within 24-48 hours from ictus14,17 and before the clinical signs of herniation
(e.g., pupillary dilatation, and posturing).15 Surgical procedure consists of
decompressive hemicraniectomy with duraplasty. Removal of bone flap decreases
ICP by 15% while opening the dura reduces ICP by 70%.16,17 Dimensions of the
bone flap removed should be generous, by which some institutions recommend
a size of 12 cm by 9 cm. Removal of a bone flap with a diameter of <10 cm has
been associated with increased incidence of shearing injury due to herniating
brain abutting against the edge of the craniectomy defect.17
4. Strokectomy (removal of infarcted tissue) should not be routinely done because
it is usually difficult to delineate between an infarcted versus ischemic tissue, and
outcomes have not been shown to be significantly better.
5. The removed bone flap may be stored in a subcutaneous abdominal pocket or at
a bone bank (if such is available).
6. Bone flap is replaced as soon as functional recovery has stabilized and the patient
has no systemic contraindications.

Outcomes:
Results of different studies have shown that decompressive hemicraniectomy with
duraplasty has improved survival rates to 67%-84% versus 20%-30% for patients
managed conservatively. Although the significant reduction in mortality from
surgery is irrefutable, its impact on functional outcome is still the subject of some
debate. Different prospective studies and RCTs have shown that decompressive
hemicraniectomy has increased the number of survivors with moderate or moderately
severe disability. Whether or not this translates to a poorer quality of life is relative,
because such an outcome is acceptable if patients and/or families value prolongation
of life more than the risk of almost certain death with medical management alone.18
99
 More recent trials have shown that decompressive surgery can improve long-term
functional outcome, number needed to treat (NNT) of 2 to achieve a mRS score of
≤4, and NNT of 4 to achieve an mRS score of ≤3 at one year. The decision as to
whether decompressive surgery be offered to a patient presenting with malignant
MCA infarction must be individualized.13

Table 9. Benefit of Hemicraniectomy

Time
Primary
Study # Inclusion to
Year Outcome Mortality (%) Good Outcome
Name Pts Criteria Tx
Measure
(hrs)

Surg Med Surg Med

DESTINY 2007 32 Age:18-60 36 Death at 17.6 53 47 27

30 days,
mRS <4 at
6 mos.
DECIMAL 2007 38 NIHSS: 24 mRS <4 at 25 77.8 50 22.2
>18-20 6 mos.
HAMLET 2009 64 Age: 18-55 96 mRS <4 at 22 59 25 25
12 mos.
HeADD NA 26 Age: 18-60 96 Death,
FIRST19 functional
outcome,
quality
Treatment

of life, pt. Results pending

perceptions,
acute

acute
health care
use at 21,
90, 100
days
HeMMI20 2012 29 Acute 72 Good n=5 n=6 n=3 n=4
unilateral status: mRS (38.5%)+ (54.5%)* (23.1%)* (36.4%)*
MCA 0-3; Death
ischemia
DESTINY II 2011 112 Age: 18-65; 48 Primary mRS 5-6 mRS 5-6 mRS 0-4 mRS 0-4
GCS: 10-14 Outcome: Tx Control Tx Control
(right) or mRS at 6 59.2% 84.1% 40.8% 15.9%
5-9 (left); mos.
(mRS 0-4 vs.
mRS 5-6)
Zhao et al. 2012 47 CT: 48 mRS at 6
ischemia mos Mortality (%) mRS>4 (%)
>50% Secondary
MCA Outcome:
mRS at 6 mos. 6 mos. 6 mos. 6 mos.
1 year; 12.5 60.91 33.3 82.6
mortality
at 6 and 12 12 mos. 12 mos. 12 mos. 12 mos.
mos. 16.7 69.6 25 87

For every 10 hemicraniectomies performed for MCA infarction, 5 patients will escape
death; at one year, 1 of these patients will have mild disability, 1 will have moderate
disability, and 3 will have severe disability.21 Among patients younger and older than 60
years old, decompressive surgery for malignant MCA infarction significantly increases
the probability of survival.
100
 CLINICAL PATHWAY FOR MALIGNANT MCA INFARCTS
(UPCM Department of Neurosciences Protocol for Malignant MCA Infarction)*

Patients with suspected large MCA infarct

• Age 18-65
• GCS 5-8 or NIHSS >15 (non-dominant) or NIHSS >20 (dominant)
• Pre-morbid MRS <3
• Hemiplegia, forced eye deviation, aphasia, contralateral neglect
• Consult within first 48 hours of symptom onset
• No comorbidities OR controlled comorbidities
• Family understands expectations and consents to surgical evaluation

Immediate
neurosurgical YES NO
Infarct volume 50% of MCA
referral for urgent Medical
territory on cranial CT 6 hours
decompressive management
from onset
hemicraniectomy
(OR in 4-6 hours)

Treatment
acute
Exclusion Criteria:
A. Pre-stroke MRS > 2
B. GCS 3 or 4
C. Contralateral ischemia or other brain lesion Clinical
that could affect outcome deteriorationa
D. Space-occupying hemorrhagic transformation
(> PH2b)
E. Life expectancy <3 years
F. Other serious illness that could affect
outcome YES
G. Known coagulopathy or systemic bleeding
disorder
H. Contraindication for anesthesia Repeat cranial CT scan
I. Pregnancy

a
Deterioration defined as decline in GCS score by 2 points
b
Dense hematoma >30% of the infarcted area with substantial space-occupying effect or any
hemorrhagic lesion outside the infarcted area

*Adapted from the STATE Criteria of the Massachusetts General Hospital Stroke Service

101
 References

1. Berrouschot J, Sterker M, Bettin S, et al. Mortality of space-occupying (malignant) middle cerebral artery
infarction under conservative intensive care. Intensive Care Med. 1998;24:620–623.
2. Ropper AH, Shafran B. Brain edema after stroke. Clinical syndrome and intracranial pressure. Arch Neurol.
1984;41:26–9.
3. Hacke W, Schwab S, Horn M, et al. “Malignant” middle cerebral artery infarction. Clinical course and
prognostic signs. Arch Neurol. 1996;53:309–15.
4. Heinsius T, Bogousslavsky J, Van Melle G. Large infarcts in the middle cerebral artery territory. Etiology and
outcome patterns. Neurology. 1998; 59:341–50.
5. Kasner SE, Demchuk AM, Berrouschot J, et al. Predictors of fatal brain edema in massive hemispheric
ischemic stroke. Stroke. 2001;32:2117–23.
6. Berrouschot J, Sterker M, Bettin S, et al. Mortality of space-occupying (malignant) middle cerebral artery
infarction under conservative intensive care. Intensive Care Med. 1998;24:620–3.
7. Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant middle cerebral artery
infarction: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007;6:215–22.
8. Vahedi K, Vicaut E, Mateo J, et al. Sequential-design, multicenter, randomized, controlled trial of early
decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke.
2007;38:2506–17.
9. Jüttler E, Schwab S, Schmiedek P, et al. Decompressive Surgery for the Treatment of Malignant Infarction of
the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007;38:2518–25.
10. Hofmeijer J, Kapelle LJ, Algra A, et al. Surgical decompression for space-occupying cerebral infarction (the
Hemicraniectomy After Middle Cerebral Artery infarction with Life- threatening Edema Trial (HAMLET)):
a multicentre, open, randomised trial. Lancet Neurol 2009;8:326–33.
11. Arac A, Blanchard V, Lee M, Steinberg GK. Assessment of outcome following decompressive craniectomy
for malignant middle cerebral artery infarction in patients older than 60 years of age. Neurosurg Focus. 2009
Jun;26(6):E3.
12. Lanzino, D, Lanzino G. Decompressive craniectomy for space-occupying supratentorial infarction:
Rationale, indications, and outcome. Neurosurg Focus. 2000;8: 1–7.
13. Marquevich V, Kimberly WT, Ogilvy CS, et al. Hemicraniectomy for Large MCA infarction.
Massachusetts General Hospital Stroke Service Website. http://www2.massgeneral.org/stopstroke/
protocolHemicraniectomyGuidelines.aspx. Updated January 13, 2011. Accessed April 15, 2014.
14. Schwab S, Steiner T, Aschoff A, et al. Early hemicraniectomy in patients with complete middle cerebral
artery infarction. Stroke. 1998;29: 1888–1893.
15. Schwab S, Hacke W. Surgical decompression of patients with large middle cerebral artery infarcts is effective.
Stroke. 2003:34:2304–2305.
16. Smith ER, Carter BS, Ogilvy CS. Proposed use of prophylactic decompressive craniectomy in poor-grade
aneurismal subarachnoid hemorrhage patients presenting with associated large sylvian hematomas.
Neurosurgery. 2002:51(1):117–124.
17. Tazbir J, Marthaler M, Moredich C, Keresztes P. Decompressive hemicraniectomy with duraplasty: a
treatment for large-volume ischemic stroke. J Neurosci Nurs. 2005 Aug;37(4):194-9.
18. Kelly AG, Holloway RG. Health state preferences and decision-making after malignant middle cerebral
artery infarctions. Neurology. 2010 Aug 24;75(8):682-7.
19. Frank JI, Schumm LP, Wroblewski K, et al.; HeADDFIRST Trialists. Hemicraniectomy and durotomy upon
deterioration from infarction-related swelling trial (HeADDFIRST). Stroke. 2014;45:781-787.
20. Chua A, Buckley BS, Lapitan MC, Jamora RD. Hemicraniectomy for Malignant Middke Cerebral Artery
Infarction (HeMMI): A randomized controlled clinical trial of decompressive surgery with standardized
medical care versus standardized medical care alone. Manuscript submitted for publication to Acta Medica
Philippina.
21. Mayer S. Hemicraniectomy: A Second chance in life for patients with space occupying MCA infarction.
Stroke. 2007; 38:2410-2412.

102
 CHAPTER IV
Guidelines for Antiplatelet Therapy in
Noncardioembolic Stroke or Transient
Ischemic Attack

Sixth
Edition
2014
 Guidelines for Antiplatelet Therapy in Noncardioembolic Stroke or
Transient Ischemic Attack

SSP 2014 Recommendations for Antiplatelet Therapy for

Noncardioembolic Ischemic Stroke or TIA

1. Patients with noncardioembolic ischemic stroke or TIA (atherosclerotic, lacunar, and

cryptogenic) and no contraindication should receive antiplatelet agents to reduce
the risk of recurrent stroke and other cardiovascular events.

2. Long term Aspirin (80–100 mg/day) monotherapy, or the combination of Aspirin 25

mg and extended-release (ER) Dipyridamole 200 mg twice daily (BID), Clopidogrel
75 mg once daily, Cilostazol 100 mg BID, or Triflusal 300 mg BID are all acceptable
options for initial therapy.

3. The selection of an antiplatelet agent should be individualized. Consider cost,

patient risk factor profiles, tolerance, and other clinical characteristics.

4. The combination of aspirin and clopidogrel might be considered for initiation

within 24 hours and continued within 90 days of a minor ischemic stroke or TIA.

5. The combination of aspirin and clopidogrel when continued for 2 to 3 years,

increases the risk of hemorrhage and is not recommended for routine long-term
secondary prevention after ischemic stroke or TIA.

6. For patients who have an ischemic stroke or TIA while taking aspirin, there is no
evidence that increasing the dose of aspirin provides additional benefit.
Antiplatelet

7. Although often considered for patients who have an ischemic stroke or TIA
Therapy

while already on aspirin, there is insufficient evidence to show that switching to

alternative antiplatelet agents or the use of antiplatelet combination reduces the
risk for subsequent events.

8. It is recommended that patients who develop recurrent stroke while on

antithrombotic therapy be re-evaluated for pathophysiology and risk factors.

Table 1. Major Trials Using Antiplatelets for Secondary Stroke Prevention

Drug Trial Design Results

Aspirin (ASA) ATC: Antiplatelet 65 trials involving 23% odds reduction in the
Trialists’ 60,196 patients composite outcome of MI,
Collaboration with symptomatic stroke, or vascular death.
atherosclerosis on ASA
(BMJ 2002; at 50–1500 mg/day. Highest relative risk reduction
324:71–86) was seen in the low- (75-150 mg)
and medium-dose (160–325 mg)
group

104
 Drug Trial Design Results
Ticlodipine CATS: Canadian 1,072 patients with recent Ticlopidine reduced the risk
American thromboembolic stroke of composite outcome of MI,
Ticlopidine Study were randomized to stroke, and vascular death by
Ticlopidine 250 mg BID or 30%.
(Lancet 1989; 1: placebo.
1215–1220)
TASS: Ticlopidine 3,069 patients with Ticlopidine reduced the risk of
Aspirin Stroke Study recent TIA or recent stroke or death at 3 years by 12%
cerebral infarction relative to ASA.
(N Eng J Med 1989; were randomized to
501-507) ticlopidine 250 mg BID Neutropenia was more common
or ASA 1300 mg/day. with Ticlopidine.
Clopidogrel CAPRIE: Clopidogrel 19,185 patients with At 1.6 years, clopidogrel reduced
versus ASA at Risk atherosclerotic disease the combined endpoint of
of Ischemic Events were randomized to ischemic stroke, MI, or vascular
clopidogrel 75 mg/day or death by 8.7% relative to ASA.
(Lancet 1996;348: ASA 325 mg/day
1329-1339) Benefit was greatest in patients
with PAD.
MATCH: 7,599 patients with No significant difference between
Management of prior stroke or TIA and groups in the combined endpoint
Atherothrom-bosis additional risk factors of ischemic stroke, MI, vascular
with Clopidogrel in were randomized to death, or re -hospitalization at 18
High Risk Patients clopidogrel 75 mg–ASA months (Clopidogrel plus ASA 15.7%
with TIA or Stroke 75 mg combination, vs Clopidogrel 16.7%, RRR=6.4%,
clopidogrel 75 mg p > 0.05).
(Lancet 2004; 364; monotherapy.
331–337) There was significant increase
in major bleeding with
combination treatment.
CHARISMA: 15,603 patients with Overall, clopidogrel plus ASA was
Clopidogrel for High either clinically evident not significantly more effective

Antiplatelet
Atherothrom-botic cardiovascular disease than ASA alone in reducing rate

Therapy
Risk and Ischemic (secondary prevention of MI, stroke or vascular death.
Stabilization, group) or with multiple
Management and risk factors (primary There was suggestion of benefit
Avoidance prevention group) of combination treatment among
were randomized to patients with symptomatic
(N Eng J Med 2006; clopidogrel 75 mg with atherosclerotic disease.
354:1-12) low-dose ASA (75–162
mg) or low-dose ASA There was significant increase
alone. in major bleeding with
combination treatment.

SPS 3: Secondary 3,020 patients with After a mean follow-up of 3.4

Prevention of recent symptomatic years, the rate of recurrent
Small Subcortical lacunar infarction stroke was not significantly
Strokes 3 within 180 days by MRI different between the 2 groups
were randomized to (clopidogrel + ASA 2.5%, versus
either clopidogrel 75 ASA 2.7% per year).
(N Eng J Med 2012; mg + ASA 325 mg or ASA
367: 817-825) 325 mg. The risk of major bleeding
and all-cause mortality was
significantly increased in the dual
antiplatelet therapy group.

105
 Drug Trial Design Results
Cilostazol CSPS: Cilostazol 1,095 patients with Active treatment with cilostazol
Stroke cerebral infarction in reduced the risk of recurrent
Prevention Study the past 6 months were ischemic stroke by 41.7%.
randomized to cilostazol
(J Stroke 100 mg BID or placebo.
Cerebrovasc Dis
2000;9:147–157)
TOSS 1: Trial of 135 patients with Progression of symptomatic
Cilostazol in recent ischemic stroke intracranial stenosis by MRA
Symptomatic within 2 weeks due to was significantly lower with
Intracranial symptomatic MCA or cilostazol and ASA compared
Arterial Stenosis Basilar artery stenosis with ASA alone.
by MRI/MRA were
(Stroke 2005; randomized to cilostazol
36:782–786) 100mg BID plus ASA 100
mg, or ASA 100 mg/day
for 6 months.
CSPS 2: Cilostazol 2,757 patients with The annual occurrence of stroke
Stroke Prevention cerebral infarction (infarction, ICH, and SAH) was
Study 2 within the previous 26 2.76 % in the cilostazol group vs
weeks were randomized 3.71% in the ASA group (HR=0.743,
(Lancet Neurology to cilostazol 100 mg BID p = 0.037), achieving the primary
2010; 9(10): 959-968) or ASA 81 mg a day for outcome of non-inferiority
1–5 years.
Hemorrhagic events occurred
less, but headache, tachycardia,
and diarrhea were more
frequent in the cilostazol-treated
group
TOSS 2: Trial 457 patients with acute There was no significant
of Cilostazol in ischemic stroke within difference in the rate of
Symptomatic 2 weeks secondary to progression of ICAS by MRA
Intracranial Stenosis stenosis of the MCA between 2 groups (cilostazol
Antiplatelet

or basilar artery were 9.3 % versus clopidogrel 15.5 %,

Therapy

(Stroke 2011;42: randomized to either p=0.09).

2883-2890) cilostazol 100 mg BID +
ASA 100 mg OD, versus Favorable changes in lipoprotein
clopidogrel 75 mg + profiles and a trend towards
ASA 100 mg OD for 6 less hemorrhagic complication
months. were observed in the cilostazol-
treated group.
Dipyridamole ESPS 1: European 2,500 patients with Active treatment with ASA and
Stroke Prevention strokes or TIAs were dipyridamole reduced the risk
Study 1 randomized to ASA 975 of stroke and death by 33%.
mg plus dipyridamole
(Lancet 1987; 2:325: 225 mg/day or placebo.
1261)
ESPS 2: European 6,602 patients with Stroke reduction compared to
Stroke Prevention recent TIA or stroke placebo were: ASA (18%), ER-DP
Study 1 were randomized to (16%), ASA plus dipyridamole
ASA 25 mg BID, extended (37.8%)
(J Neuro Sci 1996: release dipyridamole
143:1-13) (ER-DP) 200 mg BID, There was no increased
or both or placebo for risk of major bleeding with
2 years combination treatment
106
 Drug Trial Design Results
Dipyridamole ESPRIT: European/ 2,739 patients with Composite outcome of
Australasian Stroke recent TIA or minor stroke, MI, and death were
Prevention in stroke were randomized reduced by 20% with ASA plus
Reversible Ischemia to ASA 30–325 mg/day dipyridamole relative to aspirin
Trial plus dipyridamole 200 alone
mg BID or ASA 30 – 325
(Lancet 2006;367: mg/day alone There was no increased
1665–1673) risk of major bleeding with
combination treatment
Clopidogrel PROFESS: 20,332 patients with Similar rates of recurrent
versus ASA- Prevention Regimen recent stroke within ischemic stroke at median
Dipyridamole for Effectively the past 120 days were follow-up of 2.5 years between
(DP) Avoiding Second randomized to ASA groups (ASA-ER-DP 9% and
Strokes 25 mg plus extended- clopidogrel 8.8%)
release (ER)-DP 200 mg
(N Eng J Med 2008; BID or clopidogrel 75 There were more major
359: 1238 – 1251) mg/day hemorrhagic events with ASA-
DP 4.1% vs Clopidogrel 3.6%
Triflusal TACIP: Triflusal 2,113 patients with Similar efficacy between groups
Aspirin Cerebral recent TIA or ischemic in combined endpoint of stroke,
Infarction stroke within the MI and vascular death (ASA
Prevention past 6 months were 12.4% vs
randomized to triflusal Triflusal 13.1%)
(Stroke 2003; 34: 600 mg/day or ASA
840–848) 325 mg/day for median Triflusal was associated
follow-up of 30 months with significantly less risk of
hemorrhagic complications
(any minor and any cerebral or
major hemorrhages)
TAPIRSS: Triflusal 431 patients with recent No significant difference in the
versus Aspirin in TIA or combined endpoint of stroke,
the Prevention ischemic stroke within MI, vascular death, and major
of Infarction: A the past 6 months were bleeding between groups (ASA

Antiplatelet
Randomized Stroke randomized to triflusal 13.9% vs triflusal 12.7%)

Therapy
Study 600 mg/day or ASA
325 mg/day for median Triflusal was associated with
(Neurology 2004: 62: follow-up of 28 months significantly less overall risk of
1073 – 1080) hemorrhagic complications
Warfarin WARSS: Warfarin- L2,206 patients No difference between groups
versus ASA Aspirin Recurrent with a prior non- in recurrent ischemic stroke or
Stroke Study cardioembolic stroke death at 2 years (Warfarin 17.8%
were randomized to versus ASA 16%)
(N Eng J Med 2001: warfarin (INR 1.4–2.8) or
345:1444–1451) ASA 325 mg/day
WASID: Warfarin- Patients with stroke or No significant difference in
Aspirin in TIA caused by 50–99% 2-year ischemic stroke rates
Symptomatic stenosis of a major between groups (warfarin 17.2%
Intracranial Disease intracranial artery were vs ASA 19.7%)
randomized to dose
(N Eng J Med 2005; adjusted warfarin or
65: 859 - 864) ASA 1300 mg/day

107
 Comments:
• Although the optimal dose of aspirin is uncertain, there is no compelling evidence
that any specific dose is more effective than another. Gastrointestinal side effects
and bleeding are often dose-related and occur with higher doses (>325 mg/day).

• Data support the safety and efficacy of cilostazol for secondary stroke prevention
in Asian populations. There is paucity of data regarding the use of cilostazol for
secondary stroke prevention in non-Asian ethnic groups. The latest American
College of Chest Physicians (ACCP) 2012 guidelines included cilostazol in the list
of recommended antiplatelet agents.

• Triflusal is an antiplatelet agent that is structurally related to ASA. It has been

found to be as effective as aspirin in preventing vascular events after stroke with
lower rate of hemorrhagic complications in randomized studies conducted in
European and Latin American countries.

• The CHANCE (Clopidogrel in High-risk Patients with Acute Non-Disabling

Cerebrovascular Event) study conducted in China has demonstrated the benefit
of short-term dual antiplatelet therapy when given within 24 hours of minor
ischemic stroke and TIA. The safety and effectiveness of ASA and clopidogrel
combination initiated within 12 hours of ischemic stroke or TIA is being further
investigated in the ongoing RCT, Platelet Oriented Inhibition in TIA and Minor
Ischemic Stroke Trial (POINT) (ClinicalTrials.gov Identifier: NCT00991029) .
Nonvalvular
Fibrillation
Atrial

108
 CHAPTER V
Guidelines for Stroke Prevention in Nonvalvular
Atrial Fibrillation

I. Risk Stratification Tools

II. Risk Factor Modification

III. Recommendations for Nonvalvular Atrial Fibrillation

(NVAF) and Stroke

Iv. Practical Considerations in the Use of Anticoagulants

for Stroke Prevention in Atrial Fibrillation

Sixth
Edition
2014
 Guidelines For Stroke Prevention In Nonvalvular Atrial Fibrillation

Stroke is a serious and frequent but preventable complication of atrial fibrillation (AF),
the most common sustained cardiac arrhythmia in clinical practice. The rate of stroke
among adults with AF varies widely, ranging from 1% to 20% annually (mean, 4.5%)
depending on the individual’s comorbidities and history of prior cerebrovascular
events. AF is responsible for approximately 15% to 20% of stroke cases, which is
usually more severe or is associated with a higher mortality rate, greater disability,
and longer hospital stay relative to a non-AF stroke. AF increases the risk of stroke by
4 to 5 times, regardless of whether it is paroxysmal or sustained. The rate of stroke
recurrence is also higher among individuals with a prior stroke and AF.

Diagnosing AF before the first complications occur is a priority for stroke prevention.
Epidemiological studies reinforce the assumption that even short episodes of
‘silent’ AF convey an increased risk for stroke.1 In patients aged 65 years or older,
opportunistic screening by pulse palpation, followed by an ECG (particularly in those
with irregular pulses) is important to detect AF prior to the first stroke.

In 2003, the prevalence of AF among Filipinos aged 20 years and above is 0.2%2,
which is lower than the reported prevalence in the United States (1-2%).3 Globally,
the overall prevalence of NVAF is increasing because of ageing of populations as well
as the rising prevalence of chronic heart diseases and AF risk factors (e.g., diabetes
mellitus). There have been many studies on NVAF and Stroke Prevention in Atrial
Fibrillation (SPAF) because it is an important modifiable risk factor for stroke. Novel
oral anticoagulants (NOACs) have become available recently, which are at least
as effective as (or better than) the vitamin K antagonist (VKA) warfarin, with the
additional benefit of better safety profile and ease in prescribing.

This chapter is solely dedicated to nonvalvular atrial fibrillation (NVAF) and stroke.
For the discussion on valvular AF related to rheumatic heart disease (RHD) and
valvular heart disease (VHD), please refer to Chapter 2 (Guidelines for Primary and
Secondary Prevention of Stroke).

I. RISK STRATIFICATION TOOLS

For all patients with NVAF, the risk benefit of using antithrombotic medications
should be weighed against the major risk of bleeding, in particular, intracranial and
gastrointestinal bleeding. For warfarin, this involves balancing a bleeding risk of 1%
to 12% per year against the risk of ischemic events, whereas it is generally reserved
for individuals considered at high risk of thromboembolism.
Nonvalvular
Fibrillation
Atrial

Several stroke risk-stratification schemes have been developed. Whilst the CHADS2
(1 point each for Congestive Heart Failure, Hypertension, Age ≥75, and Diabetes;
2 points for Stroke/TIA) score is simple and popular, it does not include many
common stroke risk factors. Furthermore, CHADS2 was derived from the risk factors
identified in datasets of non-VKA-treated patients from the earlier trials on stroke
prevention. For more detailed and comprehensive stroke risk assessment in patients
with AF, particularly those with a CHADS2 score of 0-1, a risk factor–based approach
is recommended. The “major” and “clinically relevant non-major” stroke risk factors
(Table 1) are as follows:

110
 Table 1. Classification of Risk Factors for Stroke and Thromboembolism in NVAF

“Major” risk factors “Clinically relevant non-major” risk factors

• Previous stroke, TIA, or • Heart failure or moderate-to-severe LV dysfunction

systemic embolism (i.e. LVEF <40%)
• Hypertension
• Age > 75 years
• Diabetes Mellitus
• Female sex
• Age 65-74 years
• Vascular disease (prior myocardial infarction,
peripheral arterial disease, or aortic plaque)

The newer CHA2DS2-VASc system (Table 2) is more sensitive than CHADS2 and is the
current recommended tool for stroke risk stratification. Accumulated evidences show
that the CHA2DS2-VASc is better in identifying the ‘truly low-risk’ patients with AF. In
contrast to CHADS2, a score of 2 is now given if the patient is >75 years or has a history
of stroke, TIA, or thromboembolism (i.e. “major” risk factors). On the other hand, those
who are 65-74 years old, female, or have vascular disease, are each assigned with a score
of 1 in addition to other “clinically relevant non-major” risk factors.

Table 2. The CHA2DS2-VASc Scoring tool and Estimation of Annual Stroke Risk

% Annual
Risk Factors Score Total Score Stroke Risk

Congestive heart failure/LV

C dysfunction
1 0 0%

H Hypertension 1 1 1.3%
A2 Age ≥75 years 2 2 2.2%
D Diabetes mellitus 1 Add total score to 3 3.2%
estimate risk of stroke
S2 Stroke/TIA/TE 2 4 4.0%
Vascular disease (prior MI,
V PAD, aortic plaque) 1 5 6.7%

A Age 65–74 years 1 6 9.8%

Sc Sex category: Female 1 7 9.6%
8 6.7%
Maximum Score 9
9 15.2%

Although the risk for stroke is a continuum, a patient whose score is ≥2 is considered
high risk; score of 1 as moderate risk; and score of 0 as low risk. Current guidelines
recommend the use of oral anticoagulants for NVAF patients with CHA2DS2-VASc
Nonvalvular

score of ≥1 (except if the score of 1 is due to female gender alone), while those with a
Fibrillation

CHA2DS2-VASc score of 0 are rather preferred untreated.

Atrial

After estimating the risk of stroke, the risk of bleeding while on anticoagulant therapy
should also be estimated. It is therefore recommended to compute for the HAS-
BLED score (Table 3) for bleeding risk (Table 4), since the likelihood of a hemorrhagic
event becomes significant with higher scores. A HAS-BLED score of ≥3 is considered
high risk. Risk factor modification (e.g., decreasing systolic BP to <160 mm Hg and
reducing/avoiding concomitant use of drugs that can increase bleeding risk while on
anticoagulants) should be considered to lower the HAS-BLED score to <3.

111
 Table 3. The HAS-BLED Scoring System4
Risk Factors Details Score
H Hypertension SBP >160 mm Hg 1
Abnormal Chronic dialysis, renal transplant; Crea >200 mol/L, abnormal
renal and liver liver function = chronic hepatic disease (e.g., liver cirrhosis) or 1
A functions biochemical evidence of significant hepatic derangement (e.g., or
(1 point each) bilirubin > 2x upper limit of normal, in association with AST/ALT/ 2
ALP > 3x upper limit of normal)
S Stroke 1
B Bleeding Previous bleeding history and/or predisposition to bleeding 1
(e.g., bleeding diathesis, anemia)
Labile INRs Unstable/high INRs or poor time in therapeutic range (e.g., < 1
L 60%)
E Elderly (>65 years) 1
D Drugs or alcohol Concomitant use of drugs with oral anticoagulants such as 1
(1 point each) antiplatelet agents, nonsteroidal anti-inflammatory drugs, etc. or
Score alcohol if with alcohol abuse 2
Total Score (maximum of 9 points)

Table 4. Cumulative Risk for “Major Bleeding” using HAS-BLED score

HAS-BLED score Major Bleeds per 100 patient-years
0 1.13
1 1.02
2 1.88
3 3.74
4 8.70
5 12.50
“Major bleeding" is defined as any of
the following:
(1) intracranial bleeding;
(2) bleeding requiring hospitalization;
(3) hemoglobin decrease > 2 g/L;
(4) transfusion of >2 units of blood.

II. RISK FACTOR MODIFICATION

Antithrombotic agents (antiplatelets and anticoagulants) have been shown to prevent

strokes secondary to NVAF.

There are several randomized trials on SPAF using antiplatelets, either as monotherapy
or in combination with anticoagulants. However, different trials of the VKA warfarin
are not discussed in detail in this chapter. The bottom line messages from trials
and meta-analyses, from which the guidelines for SPAF (using VKA warfarin and
antiplatelets) were derived, are the following:
1. Aspirin can reduce the incidence of stroke by 24% when compared with placebo.
In contrast, warfarin can reduce stroke by 64%.
Nonvalvular

2. Warfarin when compared with aspirin reduces the incidence of stroke by 38%.
Fibrillation
Atrial

3. Adjusted-dose warfarin (INR 2-3) is better compared with low-intensity warfarin

plus aspirin.5
4. Dual antiplatelet therapy (Clopidogrel + Aspirin) is inferior to warfarin for SPAF.6
5. Among patients intolerant to warfarin, a dual antiplatelet therapy (DAPT) using
clopidogrel and aspirin is better than ASA alone7, but there was increased
bleeding risk with DAPT.
6. The combination of the antiplatelet Triflusal 600 mg and another VKA
(acenocoumarol), for patients with moderate risk of stroke, was shown to be
more effective than anticoagulation monotherapy and with a lower incidence of
hemorrhagic complication.8
112
 Recent analysis shows that the evidence for effective stroke prevention using
aspirin in AF is weak and with a potential for harm, as the risk of major bleeding or
intracranial hemorrhage (ICH) with aspirin is not significantly different with that of
oral anticoagulants (OACs) especially in the elderly. Given the availability of novel
oral anticoagulants (NOACs), the use of antiplatelet therapy (e.g., aspirin–clopidogrel
combination therapy, or-less effectively-aspirin monotherapy) for stroke prevention
in AF should be limited to few patients who refuse any form of OAC. Aspirin–
clopidogrel combination therapy has additional efficacy compared with aspirin
monotherapy, but with additional risk for major bleeding. Thus, aspirin monotherapy
when anticoagulation is indicated should be confined to those who refuse any OAC
and cannot tolerate aspirin–clopidogrel combination therapy due to, for example,
excessive bleeding risk. There is no evidence for the decrease in total or cardiovascular
mortality with aspirin (or antiplatelet drugs) in the AF population.

For warfarin to be superior to aspirin in stroke prevention in patients with NVAF, the
Time on Therapeutic Range (TTR) of the INR should be >60%. It is of note that only
about 50% of eligible patients actually take the drug, and often it is not prescribed by
doctors because of the fear of bleeding complications and the difficulty in titrating
and maintaining therapeutic INR range of 2-3. During the past 4 years, there were
several trials which tested the safety and efficacy of NOAC to warfarin. These NOACs,
which consist of a thrombin inhibitor (Dabigatran) and two factor Xa inhibitors
(Rivaroxaban and Apixaban), were compared to warfarin for primary and secondary
stroke prevention among patients with NVAF. The major characteristics of these
NOACs (and trials) are the following:

Table 5. Major Characteristics of Novel Oral Anticoagulants

Dabigatran Rivaroxaban Apixaban
Trade Name Pradaxa Xarelto Eliquis
Mechanism of action Direct thrombin Direct Xa inhibitor Direct Xa inhibitor
inhibitor
RE-LY-AF (2009); ROCKET-AF (2011); RCT, ARISTOTLE (2011); RCT,
Study design Randomized open double blind, double double blind, double
label dummy dummy
Number of patients;
follow-up period n=18,113; 24 mos. n=14,264 ; 40 mos. n=18,201; 40 mos.
(months)
CHADS2 (mean score) 2.2 3.5 2.1
Dose 110 mg or 150 mg BID 20 mg OD 5 mg BID
Dose in renal
impairment 110 mg BID; 2 hrs 15 mg OD 2.5 mg BID

Bioavailability / Tmax 6% >80%; 2-4 hrs 66%; 3 hrs

5-9 hours (young,
Nonvalvular
Fibrillation

Half-life 14-17 hours healthy) 8-15 hours

11-13 hours (elderly)
Atrial

Dosing Frequency BID OD BID

Renal Excretion 80% 33% 25%

A summary of comparison between NOACs and warfarin in SPAF is presented in Table

6. The major findings of trials include the following:

1. As compared with warfarin, dabigatran 150 mg BID was superior in risk reduction
for stroke and systemic embolism, with a similar risk for major bleeding but lesser
intracranial bleeding. The substudy showed that both ischemic and hemorrhagic
stroke events were lesser compared with warfarin.9
113
 2. As compared with warfarin, dabigatran 110 mg BID was not inferior in risk
reduction for stroke and systemic embolism, but with lesser major bleeding
including intracranial bleeding.9
3. As compared with warfarin, rivaroxaban 20 mg OD was not inferior in risk
reduction for stroke and systemic embolism, with similar major bleeding/life-
threatening bleeding but lesser intracranial bleeding. The substudy showed there
was similar ischemic stroke event but lesser hemorrhagic stroke.10
4. As compared with warfarin, apixaban 5 mg BID was superior in risk reduction
for stroke and systemic embolism, with lesser major bleeding, life-threatening
bleeding, and intracranial bleeding. The substudy showed that there was similar
ischemic stroke event but lesser hemorrhagic stroke events.11

Table 6. Effect of Novel Oral Anticoagulants (NOAC) relative to Warfarin

on Stroke Prevention in Atrial Fibrillation
Dabigatran Dabigatran Rivaroxaban Apixaban
Endpoints
150 mg BID 110 mg BID 20mg OD 5mg BID
Stroke and Systemic Embolism S NI NI S
Ischemic Stroke S NI NI NI
Hemorrhagic Stroke S S S S
All-Cause Mortality NI NI NI S
Vascular Mortality S NI NI No Data
Total Bleeding S S NI S
Major Bleeding NI S NI S
Life-threatening Bleed S S NI S
Intracranial Bleed S S S S
S = superior to warfarin; NI = Not inferior to warfarin

III. Recommendations for Nonvalvular Atrial Fibrillation (NVAF) and Stroke

The following recommendations for the use of antithrombotics (oral anticoagulants

and antiplatelets) for stroke prevention in patients with NVAF were based on the
recommendations of the American Heart Association (AHA), American Stroke
Association (ASA), European Society of Cardiology (ESC), and the European Heart
Rhythm Association (EHRA). The role of management related to cardioversion and
ablation in AF or those with AF and mechanical heart valves are not addressed in this
guideline.

A. SSP Recommendations for Screening Tools for Initiating Antithrombotic

Nonvalvular
Fibrillation

Treatment in Patients with NVAF

Atrial

1. The risk and benefits of giving oral anticoagulants among patients with NVAF
should be estimated before initiating treatment.
2. The CHA2DS2-VASc score is preferred over CHADS2 as a means of assessing risk in
nonvalvular AF, and also serves as a guide for initiating treatment.
3. Before starting anticoagulation, assessment of the bleeding risk using the HAS-
BLED scoring is recommended. A HAS-BLED score of >3 indicates “high risk”,
hence physicians should be cautious when using oral anticoagulants. If possible,
attempt to control the modifiable risk factors to bring down the score to <3 and
conduct regular review of the patient following the initiation of anticoagulation
therapy.
114
B. SSP Recommendations for Antithrombotic Treatment in Patients with NVAF
for the Prevention of Stroke
I. General Recommendations (see Table 1 for list of “major” and “clinically
relevant non-major” risk factors):
1. For patients with no risk factor (CHA2DS2-VASc=0), no antithrombotic therapy
is recommended.
2. For patients with one clinically relevant non-major risk factor (CHA2DS2-
VASc=1, by which the score of 1 is not due to female gender), oral
anticoagulant is recommended.
3. For patients with one major risk factor or ≥2 clinically relevant non-major risk
factors (CHA2DS2-VASc ≥2), oral anticoagulant is recommended.

II. Recommendations for Use of Specific Antithrombotic Agent

1. The selection of an antithrombotic agent should be individualized on
the basis of risk factors, cost, tolerability, patient preference, potential for
drug interactions, and other clinical characteristics, including time in INR
therapeutic range if the patient has been taking warfarin.
2. Oral anticoagulants, using adjusted-dose warfarin (target INR 2.5; range,
2.0–3.0) or one of the NOACs, either a direct thrombin inhibitor (dabigatran)
or an oral factor Xa inhibitor (rivaroxaban , apixaban) are recommended for
all patients with NVAF deemed to be at risk for stroke (CHA2DS2-VASc ≥1)
and who can receive it safely (Class I, level A).
3. For patients who are unable to take oral anticoagulants, aspirin monotherapy
is recommended (Class I, level A). The combination of clopidogrel and
aspirin carries a similar risk of bleeding with that of warfarin and therefore
is not recommended for patients with a hemorrhagic contraindication to
warfarin (Class III, level B).
4. For high-risk patients with AF (CHA2DS2-VASc ≥2) deemed unsuitable for
anticoagulation, dual- antiplatelet therapy with clopidogrel and aspirin
offers more protection against stroke than with aspirin alone, but with an
increased risk of major bleeding (Class IIb, level B).
5. Warfarin (Class I, level A), dabigatran (Class I, level B), apixaban (Class I, level
B), and rivaroxaban (Class IIa, level B) are all indicated for the prevention of
first and recurrent stroke among patients with NVAF.
6. When an OAC is recommended, one of the NOACs, either a direct thrombin
inhibitor (dabigatran) or an oral factor Xa inhibitor (rivaroxaban , apixaban),
should be considered rather than adjusted-dose VKA (INR 2-3) for most
patients with nonvalvular AF, based on their net clinical benefit (Class IIa,
Nonvalvular
Fibrillation

Level A).
Atrial

7. The safety and efficacy of combining dabigatran, rivaroxaban, or apixaban

with an antiplatelet agent have not been established (Class IIb, level C).
8. Baseline and subsequent regular assessment of renal function (creatinine
clearance, CrCl) is recommended following the initiation of any NOAC; this
should be done annually, although it should be done more frequently in
persons with moderate renal impairment (i.e. CrCl assessed 2–3 times per
year) (Class IIa, Level A).
9. NOACs (i.e. dabigatran, rivaroxaban, and apixaban) are not recommended in
patients with severe renal impairment (CrCl <30 mL/min) (Class III, Level A).

115
 IV. Practical Considerations on the Use of Anticoagulants for Stroke
Prevention in Atrial Fibrillation
In general, it is recommended for patients with NVAF who have stroke risk factor/s
(≥1) to receive effective stroke prevention therapy, which is essentially oral
anticoagulants with either well-controlled warfarin therapy (INR 2–3, with a high
percentage of TTR, i.e. at least 70% of the time) or one of the NOACs. Below are
some helpful tips when considering therapy with warfarin or any of the Food and
Drug Administration (FDA)-approved NOACs:

A. Warfarin
The ideal therapeutic range of warfarin is an INR of 2-3; the risk of bleeding is higher
with higher INR values, whereas the benefit of preventing stroke becomes poorer
below the INR of 2. The duration of warfarin treatment and time in optimal INR
therapeutic range (2.0–3.0) are predictors of favorable efficacy and safety. Achieving
and maintaining the INR of 2-3 are a challenge for many physicians, hence the
suggestions for warfarin monitoring and dosing (Table 7), and contraindications to
therapy (Tables 8) are as follows:

Table 7. Guidelines for Achieving Therapeutic Range of Warfarin

INR Value Action
<1.5 Increase weekly dose by 10-20%; Consider giving one extra dose
Retest INR in 4-8 days or per clinician’s discretion
1.5 to <2.0 Increase weekly dose by 5-10%
Retest INR in 7-14 days or per clinician’s discretion
2.0 to 3.0 No change
>3.0 to 3.5 Decrease weekly dose by 0-20%
Retest INR per clinician’s discretion
>3.5 to 4.0 Withhold 0-1 doses and/or decrease weekly dose by 0-20%
Retest INR per clinician’s discretion
>4.0 but <5.0 Withhold 1-2 doses and
Decrease weekly dose by 0-20% and
Retest INR in 3-7 days or per clinician’s discretion
5.0 to <9.0 Withhold 1-2 doses
without Retest INR in 1-2 days or per clinician’s discretion
significant Resume dosing once INR <3 .0, but weekly dose decreased by 5-20%
bleeding If the subject needs urgent surgery, then the subject should receive FFP
>9.0 without Withhold drug
significant Give Vitamin K (single 2.5-5mg oral dose)
bleeding Repeat INR test daily until INR <5.0
If INR remains too high, more Vitamin K doses can be considered
Nonvalvular

Resume dosing once INR <3 .0, but weekly dose decreased by 10-20%
Fibrillation

If the subject needs urgent surgery, then the subject should receive FFP
Atrial

Table 8. Contraindications to Warfarin Therapy12

Absolute contraindication
• known large esophageal varices
• significant thrombocytopenia
(platelet count less than 50 x
10^9/L)
• within 72 hours of major surgery
with risk of severe bleeding (defer
and reassess post-operatively)
116
Relative contraindication
• previous history of intracranial hemorrhage
(seek specialist opinion)
• recent major extra-cranial bleed within
the last six months where the cause has
not been identified or treated (defer the
decision for warfarin therapy)
Table 8. continued
Absolute contraindication
• previously documented
hypersensitivity
(e.g. priapism, ischemic necrosis)
• acute clinically significant bleed
(defer and reassess stroke versus
bleeding risk within three months)
• decompensated liver disease or
deranged baseline clotting screen
(initial INR > 1.5)
• pregnancy and within 48 hours
postpartum.
Relative contraindication
• peptic ulcer (PU) within last three months
(defer until PU treatment is completed;
ensure that preventative therapy is initiated
whilst on anticoagulant)
• recent history of recurrent falls in patient
at higher risk of bleeding (i.e. HAS-BLED
score >3)
• dementia or marked cognitive impairment
with poor compliance to medications and
lack of carer support
• chronic alcohol abuse
• untreated or poorly controlled hypertension,
consistently greater than 160/90 mm Hg.

B. Novel oral anticoagulants (NOACs): Direct Thrombin Inhibitor (Dabigatran)

and Factor Xa Inhibitors (Rivaroxaban and Apixaban).
The advantages of novel oral anticoagulants (NOACs) over VKAs for
thromboembolic prevention in patients with NVAF include the following:
a. predictable effect without need for monitoring
b. fewer food and drug interactions
c. more predictable half-life/elimination
d. improved efficacy/safety ratio
e. short onset and offset of action
f. significantly less intracranial bleeding

Listed below are some recommendations of the AHA regarding NOACs13:

I. Dabigatran
1. Dabigatran is a useful alternative to warfarin for the prevention of stroke
and systemic thromboembolism in patients with paroxysmal to permanent
AF and risk factors for stroke or systemic embolization, who do not have
a prosthetic heart valve or hemodynamically significant valve disease,
severe renal failure (CrCl <15 mL/min), or advanced liver disease (impaired
baseline clotting function) (Class I, level B).
2. Dabigatran 150 mg BID is an efficacious alternative to warfarin for the
prevention of first and recurrent stroke in patients with NVAF and at least
1 additional risk factor (CHADS2=1) who have CrCl >30 mL/min (Class I,
level B).
3. Because there are no data to support the use of dabigatran in patients with
more severe renal failure, dabigatran is not recommended in patients with
Nonvalvular
Fibrillation

a CrCl <15 ml/min (Class III, level C).

Atrial

II. Rivaroxaban
1. In patients with NVAF, who are at moderate or high risk of stroke (e.g.,
prior history of TIA, stroke, or systemic embolization or ≥2 additional risk
factors), rivaroxaban 20 mg/day is a reasonable alternative to warfarin
(Class IIa, level B).
2. In patients with renal impairment (CrCl of 15 to 50 mL/min) and NVAF, who
are at moderate or high risk of stroke (e.g., prior history of TIA, stroke, or
systemic embolization or ≥2 additional risk factors), rivaroxaban 15 mg
daily may be considered; however, its safety and efficacy have not been
established (Class IIb, level C).
117
 3. Rivaroxaban should not be used if the the CrCl is <15 mL/min (Class III, level C).

III. Apixaban
1. Apixaban 5 mg BID is an efficacious alternative to aspirin in patients with NVAF
deemed unsuitable for vKA therapy who have at least 1 additional risk factor and
no more than 1 of the following characteristics: age ≥80 years, weight ≤60 kg, or
serum creatinine ≥1.5 mg/dL (Class I, level B).
2. Apixaban 5 mg BID is a relatively safe and efficacious alternative to warfarin in
patients with NVAF deemed appropriate for vKA therapy who have at least 1
additional risk factor and no more than 1 of the following characteristics: age ≥80
years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL, (Class I, level B).
3. Although its safety and efficacy have not been established, apixaban 2.5 mg
twice daily may be considered as an alternative to warfarin in patients with
NVAF deemed appropriate for vitamin K antagonist therapy who have at least 1
additional risk factor and ≥2 of the following criteria: age ≥80 years, weight ≤60
kg, or serum creatinine ≥1.5 mg/dL (Class IIb, level C).
4. Apixaban should not be used if the CrCl is <25 mL/min (Class III, level C).

• Dabigatran cannot be crushed and has to be taken as a whole. Both rivaroxaban and
apixaban can be crushed for NGT use.

• There is no direct test for determining the serum levels of the NOACs, but prolongation
of aPTT for Dabigatran and PT for Rivaroxaban have been shown to closely correlate
with plasma concentration.

C. Practical Points on using NOACs in Different Scenarios

The SSP adopts and endorses the European Heart Rhythm Association’s (EHRA)
2013 Practical Guide on the Use of NOACs in Patients with NVAF [Eur Heart
J. 2013 Jul;34(27):2094-106]. Practical answers have been formulated for the
following concrete clinical scenarios14:

i. practical start-up and follow-up scheme for patients on NOACs

ii. how to measure the anticoagulant effect of NOACs
iii. drug–drug interactions and pharmacokinetics of NOACs
iv. switching between anticoagulant regimens
v. ensuring compliance with NOAC intake
vi. how to deal with dosing errors
vii.
patients with chronic kidney disease
viii.
what to do if there is a (suspected) overdose without bleeding, or if a
Nonvalvular
Fibrillation

clotting test indicates a risk of bleeding?

Atrial

ix. management of bleeding complications

x. patients undergoing a planned surgical intervention or ablation
xi. patients undergoing an urgent surgical intervention
xii.
patients with AF and coronary artery disease
xiii.
cardioversion in a NOAC-treated patient
xiv.
patients presenting with acute stroke while on NOACs
xv.
NOACs vs. VKAs in AF patients with a malignancy.

118
D. Guide for patients presenting with acute stroke while on NOACs
The decision regarding continuation of NOACs after ischemic stroke recurrence
depends on the infarct size. Clinical study data regarding re-institution of
anticoagulation are missing. Some advocate as a rule of thumb the 1-3-6-12-
day rule:
1. Re-institution of anticoagulation in patients with a transient ischemic attack
(TIA) is recommended after one (1) day. Bridging with LMWH is not required
(Class III, level C).
2. Re-institution of anticoagulation in patients with small, non-disabling infarct
is recommended after three (3) days.
3. Re-institution of anticoagulation in patients with a moderate stroke
is recommended after six (6) days. In the presence of hemorrhage,
anticoagulation should not be given.
4. Re-institution of anticoagulation in patients with large infarcts involving large
parts of the arterial territory should be delayed given the risk of hemorrhagic
transformation. Treatment should not be before two (2) or even three (3)
weeks.
5. If stroke occurred despite adequate anticoagulation and patient compliance,
alternative causes for ischemic stroke should be investigated (Class I Level C).

E. Switching from one antithrombotic agent to another

Situation requiring Shifting Action on when and how to substitute
From VKA to NOAC INR <2.0: immediate
INR 2.0–2.5: immediate or next day
INR >2.5: use INR and VKA t 1/2 to estimate time to INR <2.5

From parenteral anticoagulant Start once UFH is discontinued (t 1/2=2h)

(e.g., unfractioned heparin
[UFH], low-molecular-weight
heparin [LMWH]) to NOAC
From NOAC to VKA
From NOAC to NOAC
From Aspirin or Clopidogrel
to NOAC
(may be longer in patients with renal impairment).
Start when next dose would have been given.
Administer concomitantly until INR is in appropriate range.
Measure INR just before next intake of NOAC.
Re-test 24h after last dose of NOAC.
Monitor INR in first month until stable values (2.0–3.0) are
achieved.
Initiate when next dose is due except where higher plasma
concentrations are expected (e.g., renal impairment).
Switch immediately, unless combination therapy needed.
Nonvalvular

F. What to do if with bleeding while on NOACs:

Fibrillation

1. The absence of available antidote for NOACs is a major concern and the
Atrial

manufacturers are currently working for their antidote.

2. Because of the short half-life of the NOACs, time is the best measure. In
case of bleeding: stop, interrupt or delay the next dose of the drug. Inquire
about the time of last intake, concomitant treatment with antiplatelets or
p-glycoprotein, and check on renal function.

3. Dabigatran was reported to have increased plasma concentration while

on the following medications: amiodarone, dronedarone, antifungals (e.g.,
azoles), quinidine, verapamil, and atorvastatin.
119
 4. Rivaroxaban was reported to have increased plasma concentration while on the
following medications: antifungals (e.g., azoles), clarithromycin, erythromycin,
cyclosporine, HIV-protease inhibitors, quinidine, and amiodarone.

5. Measure for non-life threatening bleeds while on NOACs: maintain diuresis, do

local hemostatic measures, fluid replacements, give packed RBCs if necessary
or platelet concentrates in case of thrombocytopenia, fresh frozen plasma as
expanders (although there is no proof that it can reverse the process), and trial
with tranexamic acid as adjuvant.

Management of bleeding complications while on NOACs

I. NON-LIFE-THREATENING BLEEDING
Direct Thrombin Inhibitor (Dabigatran) Factor Xa Inhibitor (Rivaroxaban, Apixaban)
• Inquire about last intake + dosing regimen • Inquire about last intake + dosing regimen
• Estimate normalization of hemostasis • Normalization of hemostasis: ±24h
Normal renal function: 24h • Local hemostatic measures
CrCl 50-80 ml/min: 24-36h • Fluid replacement (colloids if needed)
CrCl 30-50 ml/min: 36-48h
CrCl <30 ml/min: 48h
• Maintain diuresis
• Local hemostatic measures
• Fluid replacement (colloids if needed)
• RBC substitution if necessary • RBC substitution if necessary
• Platelet substitution (in case of thrombo- • Platelet substitution (in case of thrombo-
cytopenia 60 x 10^9/L or thrombopathy) cytopenia 60 x 10^9/L or thrombopathy)
• Fresh frozen plasma as plasma expander • Fresh frozen plasma as plasma expander
(not as reversal agent) (not as reversal agent)
• Tranexamic acid can be considered as • Tranexamic acid can be considered as
adjuvants adjuvants
• Desmopressin can be considered in special • Desmopressin can be considered in special
cases (coagulopathy or thrombopathy) cases (coagulopathy or thrombopathy)
• Consider dialysis (primary evidence:
~ 65% after 4h)
=
• Charcoal hemoperfusion is not recommended
(no data)
II. LIFE-THREATENING BLEEDING
Direct Thrombin Inhibitor (Dabigatran) Factor Xa Inhibitor (Rivaroxaban, Apixaban)
• All of the above • All of the above
• Prothrombin complex concentrate (PCC) 25 • Prothrombin complex concentrate 25 U/
Nonvalvular
Fibrillation

U/g (may be repeated once or twice but no kg (may be repeated once or twice but no
Atrial

clinical evidence) clinical evidence)

• Activated PCC 50IE/kg; max 200 IE/day:
no strong data about additional benefit
over PCC; can be considered before PCC (if
available)
• Activated (recombinant) factor VII (rFVIIa;
90mg/kg); no data about additional benefit +
expensive (only animal evidence)
• Activated PCC 50IE/kg; max 200 IE/day: no
strong data about additional benefit over PCC;
can be considered before PCC (if available)
• rFVIIa; 90mg/kg; no data about additional
benefit + expensive (only animal evidence)

120
 G. Unresolved issues related to NOAC
It is important to acknowledge several unresolved issues related to the clinical
use of dabigatran, rivaroxaban, and apixaban. There are no published data which
directly compared dabigatran, rivaroxaban, and apixaban to one another, but
only comparisons of each to warfarin. The duration of follow-up in the clinical
trials was limited. Moreover, because of the short half-life of these drugs,
noncompliant patients or those who miss medication doses might be at risk
for thromboembolism. Treatment decisions should account for the differences
in medication costs, which could also affect patient compliance. It is not
known whether patients receiving these agents, who are otherwise eligible for
thrombolysis, can be treated safely with a thrombolytic agent (i.e. intravenous
recombinant tissue-type plasminogen activator [rt-PA]) for an acute ischemic
stroke. There are currently no antidotes that immediately reverse the effects of
dabigatran, apixaban, or rivaroxaban in cases of hemorrhage.

References

1. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management
of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation.
Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012
Nov;33(21):2719-47.
2. Dans AL, Morales D, Abola T, et al. for NNHes 2003 Group. Atherosclerosis – related diseases and risk
factors. National Nutrition and Health Survey (NNHeS). Phil J Int Med. 2005 May- June, 43;103-115.
3. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications
for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation
(ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5.
4. Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding
risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/ Liver
Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly)
score. J Am Coll Cardiol. 2011;57:173–180.
5. Stroke Prevention In Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose
warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III
(SPAF III) randomised clinical trial. Lancet. 1996 Sep 7;348(9028):633-8.
6. Connolly SJ, Pogue J, Eikelboom J, et al. ACTIVE W Investigators. Benefit of oral anticoagulant over
antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control
achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118:2029–
2037.
7. Connolly SJ, Pogue J, Hart RG, et al; ACTIVE Investigators. Effect of clopidogrel added to aspirin in patients
Nonvalvular

with atrial fibrillation. N Engl J Med. 2009;360:2066– 2078.

Fibrillation
Atrial

8. Pérez-Gómez F, Alegría E, Berjón J, et al. NASPEAF Investigators. Comparative effects of antiplatelet,

anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation. A
randomized multicenter study. J Am Coll Cardiol. 2004;44:1557-66.
9. Connolly SJ, Ezekowitz MD, Yusuf S, et al. RE-LY Steering Committee and Investigators. Dabigatran versus
warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–1151.
10. Patel MR, Mahaffey KW, Garg J et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in
nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–891.

121
 11. Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban
versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365:981–992.
12. Queensland Health Services Support Agency. Guidelines for Warfarin Management in the Community,
version 1.0. 2012. http://www.health.qld.gov.au/qhcss/mapsu/documents/warfarin-guidelines.pdf Accessed
February 19, 2014.
13. Furie KL, Goldstein LB, Albers GW, et al. Oral Antithrombotic Agents for the Prevention of Stroke in
Nonvalvular Atrial Fibrillation: A Science Advisory for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke. 2012;43:3442-3453
14. Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral anticoagulants
in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2013 Jul;34(27):2094-106.

122
CHAPTER VI
Guidelines for the Management of
Hemorrhagic Stroke

I. Hypertensive Intracerebral Hemorrhage

II. Aneurysmal Subarachnoid Hemorrhage

III. Cerebral Arteriovenous Malformation

Sixth
Edition
2014
 Guidelines for the Management of Hemorrhagic Stroke

INTRACRANIAL HEMORRHAGE
Intracranial hemorrhage results from rupture of a vessel anywhere within the
cranial cavity. It can be classified according to: 1) location (i.e. extradural, subdural,
subarachnoid, intracerebral, intraventricular); 2) nature of the ruptured vessel/s (i.e.
arterial, capillary, venous); and 3) causes (i.e. primary or secondary). Bleeding into
the subdural and epidural spaces is principally the result of trauma by rupture of
veins traversing the subdural space and by laceration of middle meningeal vessels
respectively. Subarachnoid hemorrhage (SAH) can be caused by trauma or rupture of
intracranial aneurysms or arteriovenous malformations (AVMs). On the other hand,
intraparenchymal and intraventricular hemorrhages (IVH) are most often related to
hypertension. The scope of this chapter, however, is limited to non-traumatic causes of
intracranial hemorrhage, namely: spontaneous (hypertensive) intracerebral hemorrhage
(ICH), aneurysmal SAH, and vascular malformations of the brain (particularly AVMs).

Intracerebral Hemorrhage (ICH)

The overall incidence of ICH is 24.6 per 100,000 person-years (PY) (95% confidence
interval [CI], 19.7-30.7), with incidence ratios ranging from 0.10 to 9.6 in persons aged
<45 years and >85 years, respectively.1 The incidence is higher among Asians at 51.8
(38.8-69.3) per 100,000 PY, which is almost twice as that of other ethnicities. ICH is
seen more frequently among men, however this difference is not significantly lower in
women.

ICH was traditionally classified according to its primary or secondary causes. The more
recent SMASH-U classification was proposed to further categorize ICH according to
its underlying diseases/causes: Structural lesions (e.g., cavernomas, AVMs), Medication
(e.g., anticoagulant-induced), Amyloid angiopathy, Systemic diseases (e.g., liver cirrhosis,
thrombocytopenia, various rare conditions), Hypertension, and Undetermined causes.
An algorithm for this classification scheme is presented in Figure 1.

Epidemiological studies suggest that ICH is more likely to be a result of a complex

interplay of several risk factors, most commonly hypertension (more than half of primary
ICH events) and cerebral amyloid angiopathy (CAA).3 Hypertensive intraparenchymal
hemorrhages (also known as hypertensive hemorrhage or hypertensive ICH) usually
result from spontaneous rupture of small penetrating branches of the arteries in the
circle of Willis. This event may possibly be secondary to weakened arteriolar walls and
formation of microaneurysms (Charcot-Bouchard aneurysm). One meta-analysis of risk
factors for ICH revealed that hypertensive individuals have almost 3.5-fold greater risk
compared with normotensive individuals.4 CAA, on the other hand, has been implicated
as an important cause of ICH among elderly non-hypertensive patients. These patients
usually have recurrent lobar hemorrhages, which is possibly due to amyloid-mediated
damage of vessels, subsequent aneurysm formation, and fibrinoid necrosis.

Other secondary causes of ICH include vascular malformations (e.g., AVMs, aneurysms,
cavernous angiomas), tumors, coagulopathy (i.e. hereditary or acquired, including
anticoagulation therapy), trauma, Moyamoya disease, tumors, and illicit drug abuse.
These conditions should be considered especially in younger nonhypertensive
Hemorrhagic

individuals or in patients whose hemorrhage occur in other (uncommon) areas of the

brain. Among patients with blood dyscrasias (e.g., acute leukemia, aplastic anemia,
Stroke

polycythemia vera, thrombocytopenic purpura, scurvy), the hemorrhages may be

multiple and of varied sizes.

124
 History, imaging, or pathology of: traumatic ICH, subdural/
epidural hemorrhage, or bleeding from co-localized tumor?
Non-stroke YES NO
Imaging or pathology of primary SAH or ischemic stroke with
hemorrhagic transformation (including post-rt-PA therapy)?
Stroke, Yes NO
Non-ICH
Imaging or pathology-confirmed structural vascular
malformation at the ICH site?
Structural Yes
Lesion NO
Systemic or other determined cause for ICHa, excluding
anticoagulation, hypertension or amyloid angiopathy?
Systemic/ Yes NO
Other Disease
Lobar, cortical, or cortico-subcortical hemorrhage and age ≥ 55?
Medication- Yes NO
induced
Warfarin with INR ≥2.0, NOACs within 3 days, full-dose heparin or
thrombolysis for a condition other than stroke (e.g., systemic)?
Amyloid Yes
Angiopathy NO
Deep or infratentorial hemorrhage with pre-ICH hypertensionb?

Hypertension Yes NO

Undetermined

Figure 1. Classification Scheme for SMASH-U ICH Etiology2

modified from Meretoja et al. SMASH-U: a proposal for etiologic classification of intracerebral
hemorrhage. Stroke. 2012 Oct;43(10):2592-7
a
Liver cirrhosis is implicated in known liver disease combined with spontaneously elevated INR or
liver enzymes (>3x upper limit of reference range), and thrombocytopenia (platelet count <50 E9/L).
b
Hypertension is defined as: a) most recent pre-ICH BP ≥160/100 mm Hg, either on or off
antihypertensive therapy or; when pre-ICH BP was not known, either b) mention of a pre-ICH
hypertension by the patient, relative, or medical records together with a left ventricular (LV)
hypertrophy as a biomarker of hypertension, or c) any pre-ICH use of antihypertensive medication.

The most common sites of hemorrhage include the basal ganglia (40%-50%),
particularly the putamen and the adjacent internal capsule; thalamus (10%-15%);
cerebellar hemispheres (5%-10%); pons (5%-12%); and lobar areas (20%-50%) (e.g.,
central white matter of the temporal, parietal, or frontal lobes). Putaminal hemorrhages
usually originate from the ascending lenticulostriate branches of the MCA, while
thalamic bleeds arise from the ascending thalamogeniculate branches of the PCA. Other
commonly identified sources include the paramedian branches of the basilar artery
for pontine hemorrhage, and penetrating branches of the PICA, AICA, and SCA for
cerebellar hemorrhage. An inferior cerebellar hemorrhage is a neurologic emergency
and needs to be diagnosed promptly, as early surgical evacuation of hemorrhages >3
cm in diameter may prevent tonsillar herniation and apnea. Bleeding into one lobe
of the cerebral hemisphere or cerebellum usually remains confined within the brain
parenchyma, whereas extension into the intraventricular space has greater likelihood
of a fatal outcome.

Clinical Manifestation
The clinical picture depends on the location and size of the hematoma. Usual signs
and symptoms include headache, vomiting, SBP >220 mm Hg, impaired consciousness,
and evolution of focal motor or sensory signs over a period of minutes to hours.5 Most
hypertensive intraparenchymal hemorrhages develop over 30 to 90 minutes, whereas
Hemorrhagic

anticoagulant-induced ICH may evolve for as long as 24 to 48 hours. Neurologic

Stroke

deterioration is also common within the first few hours after ICH onset; more than
20% of patients will experience a decrease in the GCS score of ≥2 points between
the pre-hospital phase and upon initial evaluation at the emergency department.6 In

125
 moderate to large hematomas, consciousness is sometimes impaired initially, and this
often becomes prominent within the first 24 to 48 hours. The risk of early neurologic
deterioration and the high rate of poor long-term outcomes therefore underscores
the need for aggressive early management.5 To aid in the risk stratification and
prognostication of patients, it is reasonable to use a validated grading scale for ICH
(Table 1) as presented below:
Table 1. Determining the ICH score and 30-day mortality risk associated with total ICH score7
ICH Total ICH 30-day
Component score points score mortality
Glasgow Coma Scale (GCS) No
3-4 2 0
mortality
5-12 1
13-15 0 1 13%
ICH volume
>30 1
<30 0 2 26%
Intraventricular
Add total score to
hemorrhage (IVH) 3 72%
Yes estimate mortality
1
No 0 risk
Infratentorial origin of ICH 4 97%
Yes 1
No 0 5 100%

Age (years) 100%

> 80 1 6*
0 (estimate)
< 80
Total score (0-6)
Note: GCS score indicates score on initial presentation (or after resuscitation); ICH volume is the volume
on initial CT calculated using the ABC/2 (Kothari) method; IVH is the presence of any IVH on initial CT.
*although a score of 6 is possible using this scale, no patient has been observed to present with this
combination of findings; this ICH score is highly considered to be fatal.

Alternatively, the FUNC scorea is another validated assessment tool that predicts,
at hospital admission, which patient with primary ICH is likely to attain functional
independence at 90 days following ICH.8
As discussed in the previous chapters, the SSP advocates the use of classification
schemes according to the severity of neurologic deficits at the onset (i.e. mild, moderate,
and severe stroke) to determine appropriate diagnostics and management in the acute
care setting (see Chapter 3). Rapid neuroimaging (CT scan or MRI) is recommended to
distinguish between ischemic and hemorrhagic stroke. While hematoma often enlarges
within 24-48 hours, major issues in treatment should be considered. These include:
• Enlargement of the hematoma within 24 to 48 hours.
• Prevention of hemorrhagic expansion by early correction of coagulation and
platelet abnormalities.
• Early control of elevated BP.
• Control of intracranial hypertension with maximum medical and/or surgical
intervention.
• Definitive diagnosis of the cause of the hemorrhage and its appropriate
treatment.
The succeeding sections present the approach and specific treatment/s of the
Hemorrhagic

following conditions: a) hypertensive ICH; b) aneurysmal SAH; and c) cerebral AVM. The
management of ICH secondary to thrombolytic therapy is discussed under the section
Stroke

on rt-PA treatment (Chapter 3).

FUNC score is available at http://www2.massgeneral.org/stopstroke/funcCalculator.aspx
a

126
I. Hypertensive Intracerebral Hemorrhage (HICH)

Early Specific Treatment of HICH

A. Medical Management
a. Treat if SBP > 180 mm Hg. Recent studies have shown that acute lowering of SBP
to ≈140 mm Hg is probably safe (Class IIa, level B), but its clinical efficacy remains
to be determined.
b. Manage increased intracranial pressure (ICP) accordingly (see Chapter 3). If an ICP
monitor is available, keep the cerebral perfusion pressure (CPP) >70 mm Hg.
c. Provide an appropriate treatment for a bleeding abnormality:
i. Administer factor replacement (factor VII) or platelet concentrates in patients
with severe coagulation factor deficiency or severe thrombocytopenia (Class
I, level C). Transfusion for platelet dysfunction in patients with normal platelet
counts is still unclear and investigational (Class IIb, level B).
ii. For ICH patients whose international normalized ratio (INR) is elevated due to
oral anticoagulants, warfarin should be withheld. Give intravenous vitamin K
and correct INR with fresh frozen plasma (FFP) (Class I, level C). Prothrombin
complex concentrates (PCCs) may be a reasonable alternative to FFP (Class IIa,
level B).
iii. For patients taking novel oral anticoagulants (NOACs) for stroke prevention,
strategies to reverse the INR in ICH may be used because NOACs have no
true antidote. Oral activated charcoal for drug absorption and reduction
of bioavailability may also be considered. Other strategies for INR reversal
include FFP, PCC, or recombinant factor VIIa (rFVIIa). The latter is not routinely
recommended as sole agent for reversing the effects of NOACs in ICH (Class
III, level C) and in those with increased thromboembolic risk (Class III, level
A). Hemodialysis for dabigatran maybe considered especially if with impaired
creatinine clearance.9
iv. It is reasonable to give a dose of vitamin K since PT/INR results may not be
immediately available. The blood bank has to be alerted so that blood type can
be determined in case an FFP is required.10,11
d. Give anticonvulsants for clinical seizures and proven subclinical or electrographic
seizures (Class I, level A). EEG monitoring should be considered in ICH patients
with depressed mental status that is out of proportion to the degree of brain injury
(Class IIa, level B). The use of AEDs as prophylaxis is not recommended (Class III,
level B).
e. Prevent and treat respiratory complications. Endotracheal intubation & assisted
ventilation is performed in coma patients or those with respiratory failure (defined
as SaO2 <90% by pulse oximetry and PaO2 <8 kPa [60mmHg], and/or PaCO2 >7 kPa
[55mmHg] by arterial blood gas analysis).
f. Prevent and treat infection/s.
g. Maintain adequate nutrition and proper fluid and electrolyte balance. Institute
bedsore precautions.
h. Manage fever aggressively to normal levels with antipyretics and other therapeutic
cooling devices such as cooling blankets.
i. Monitor blood glucose levels and maintain within the normal range.
j. Where possible, rehabilitate patients early once stable (Class IIa, level B).
k. Institute prophylaxis for deep-vein thrombosis and pulmonary embolism using
Hemorrhagic

intermittent pneumatic compression devices in addition to anti-embolic stockings

(Class I, level B).
Stroke

127
 l. After cessation of bleeding is documented by repeat imaging, low-dose subcutaneous
LMWH or UFH may be considered for prevention of venous thromboembolism (VT)
in immobile patients after 1-4 days from onset of ICH (Class IIb, level B). Patients
who develop an acute proximal VT, particularly those with clinical or subclinical
pulmonary emboli, should be considered for acute placement of a vena cava filter
(Class IIB, level C).
m. In cases of intraventricular hemorrhage (IVH), thrombolysis with rt-PA should not
be routinely used because of the uncertainty in its safety and efficacy
(Class IIb, level B).

B. Surgical Treatment
In principle, the benefits of surgical evaluation of ICH include reduction of risk and
extent of mechanical compression of the brain. As surgical approach would present
a higher risk of bleeding (in addition to the general surgical risks), the decision
and indications for surgical or non-surgical intervention (Table 2) in ICH remains
controversial. Nonetheless, management decision would depend on consideration
of many factors, including the hematoma size, extent, and location, as well as the
patient’s clinical status.

Table 2. Recommendations for Selecting Patients for Surgical/Non-surgical Management in ICH

Candidates for immediate surgery Non-surgical Candidates
• Patients with cerebellar hemorrhage >3 cm who • Patients with small hemorrhages (<10
are neurologically deteriorating or have brainstem cc) or minimal neurological deficits
compression and hydrocephalus from ventricular • Patients with GCS <5 except those
obstruction who have cerebellar hemorrhage and
• Patients with bleed associated with a structural lesion brainstem compression
such as an aneurysm, AV malformation or cavernous • Patients with pontine or midbrain
angioma if there is a chance for good outcome and the hemorrhage
vascular lesion is surgically accessible
• Clinically deteriorating patients especially young with
moderate or large lobar hemorrhage
• Ventricular drainage for patients with intraventricular
hemorrhage with moderate to severe hydrocephalus

All other patients who may benefit from surgery:

• Patients with basal ganglia or thalamic hemorrhage
• Patients with GCS 5 and above
• Patients with supratentorial hematoma with volume >30 cc

II. Aneurysmal Subarachnoid Hemorrhage (aSAH)

A. Clinical Diagnosis
About 80 percent of patients with aSAH present with sudden, severe headache usually
described as “the worst headache of my life”, hence a high level of suspicion should exist in
patients complaining of acute severe headache.12 This may or may not be associated with
nausea/vomiting, stiff neck, brief loss of consciousness, photophobia, and focal neurologic
deficits. In up to 20% of patients, seizures may occur after aSAH, most frequently during the
first 24 hours; this is more common among patients with associated ICH, hypertension, and
MCA and anterior communicating (AComm) aneurysms.13,14

Physical and neurological examination may reveal retinal or subhyaloid hemorrhages,

papilledema, signs of meningeal irritation, altered or diminished level of consciousness,
and localizing neurologic signs. The latter includes CN III palsy (suggesting posterior
Hemorrhagic

communicating aneurysm), CN VI palsy (increased ICP or posterior fossa aneurysm), bilateral

lower extremity weakness or abulia (AComm aneurysm), and combination of hemiparesis
Stroke

and aphasia or visuospatial neglect (MCA aneurysm).15 Because aSAH is associated with high
risk of rebleeding and poor outcomes, an urgent evaluation (and treatment) of suspected
aSAH is recommended.12
128
B. Neurodiagnostic Examinations (Figure 2)
1. A non-contrast cranial CT (NCCT) scan (also known as non-enhanced CT scan)
should be performed and interpreted immediately. A hyperdense lesion in the
basal cisterns is usually diagnostic, although a parenchymal clot in the temporal or
basal frontal region or an IVH are also suggestive of an aneurysmal rupture. The
sensitivity of CT scan in detecting SAH (Table 3) depends on the timing of imaging
in relation to ictus from hemorrhage.

Table 3. Sensitivity of CT scan in detecting SAH based on the time of imaging from SAH onset16

Duration of SAH CT scan sensitivity

12 hours 98-100 %
24 hours 93 %
6 days 57-85 %

2. The use of MRI for diagnosing aSAH may be reasonable if the CT result is negative.
However, a negative MRI result does not obviate the need for a cerebrospinal fluid
(CSF) analysis.
3. Lumbar puncture with CSF analysis, in the absence of focal neurological signs, is
strongly recommended if the cranial CT result is negative or is unavailable.
a. Important considerations in the examination of CSF:
• timing of LP in relation to SAH
• RBC and WBC
• presence of xanthochromia
b. Multiple specimens (at least 3 tubes) should be collected to rule out traumatic
tap. The opening pressures should be measured.
4. Cerebral angiography is the gold standard in determining the cause of SAH. Early
catheter angiography should be performed in good- and poor-grade cases of
SAH. If the initial angiogram is negative, a repeat cerebral angiogram should be
performed after 7-14 days.
5. Good quality CT angiography (CTA) or magnetic resonance angiography (MRA) are
acceptable options to catheter angiography in the following situations:
 poor-grade patients
 when catheter angiography cannot be performed in a timely fashion
 as a follow-up diagnostic if the initial angiogram is negative

C. Grading of SAH
The initial clinical severity of aSAH should be determined immediately by the
use of simple validated scales (Tables 4 and 5) to aid in treatment decisions and
prognostication:
Table 4. Clinical Grading Scales for Subarachnoid Hemorrhage
Grade Hunt-Hess Classification WFNS scale
Asymptomatic or mild headache, slight nuchal rigidity,
I GCS score 15; no motor deficit
normal mental status
Moderate to severe headache, nuchal rigidity, no
II GCS score 13-14; no motor deficit
neurological deficit other than cranial nerve palsy
GCS score 13-14, with motor
III Drowsiness, confusion or mild focal signs
deficits
Stupor, moderate to severe hemiparesis, possibly early GCS score 7-12; with or without
IV
Hemorrhagic

decerebrate signs motor deficits

GCS score 3-6; with or without
Stroke

V Deep coma, decerebrate rigidity, moribund appearance

motor deficits
GCS: Glasgow Coma Scale (see Appendix B); WFNS: World Federation of Neurosurgical Societies

129
 Patient suspected to have SAH

(+) Evidence of SAH on

(-) Evidence of SAH on NCCT scan
non-contrast cranial CT (NCCT)

Cerebral angiography Lumbar puncture

(gold standard)
or CT/MR angiography for
select cases
(see section B-4)
Unequivocally Abnormal but Normal CSF
abnormala equivocalb analysis

Normal (+) Aneurysm

Cerebral angio or CTA/MRA

Repeat CTA/MRA
(+) Aneurysm Normal
in 7-14 days

Further imaging (including Prompt

brain stem, spinal cord); grading/ Observe
follow-up as necessary treatment

Figure 2. Diagnostic Algorithm for Subarachnoid Hemorrhage15

modified from Suarez J, Tarr R, Selman W. Aneurysmal Subarachnoid Hemorrhage. N Engl J Med. 2006;
354:387-396.
a
unequivocally abnormal CSF: xanthochromia, elevated RBC count unchanged from tubes 1 to 4
b
abnormal but equivocal CSF: elevated CSF without xanthochromia or analysis of only 1 tube

Table 5. Radiologic Grading Scale for Subarachnoid hemorrhage (Fisher Grading System)

Grade Description (Blood on CT)

1 No subarachnoid blood detected

2 Diffuse or vertical layers* <1 mm thick

3 Localized clot or vertical layer* >1 mm thick

4 Intracerebral or intraventricular clot with diffuse or no SAH+

* Vertical layer refers to blood in the subarachnoid spaces including inter-hemispheric

fissure, insular cistern, and ambient cisterns
+ reflux of blood into the ventricles frequently indicates obstruction of CSF circulation,
and is associated with high incidence of hydrocephalus

D. General Symptomatic Treatment

1. Absolute bed rest in a quiet, comfortable environment is recommended. Limit
Hemorrhagic

visitors until the aneurysm is secured.

2. Monitor neuro-vital signs closely, including cardiac and pulmonary status.
Stroke

3. Intubate poor-grade SAH patients carefully and safely. Use short-acting muscle
relaxant or anesthesia (if needed) to avoid further compromise of ICP.

130
 4. Start soft diet for alert patients or nasogastric tube (NGT) feedings for patients
with impaired consciousness, but maintain on NPO if there is a planned immediate
intervention.
5. Give analgesics for headache. Avoid aspirin and other NSAIDs.
6. Give gastrointestinal prophylaxis for stress gastritis. Use proton pump inhibitors
(PPI) or H2-blockers.
7. Give anti-emetics for nausea and vomiting.
8. Maintain normothermia. However, hypothermia maybe a reasonable procedure
during aneurysm surgery in selected cases. Aggressive control of fever by use of
antipyretics and/or cooling blankets is reasonable during the acute phase of aSAH.
9. Maintain normal blood glucose levels.
10. Give sedatives for restlessness or agitation.
11. Give stool softeners.
12. Start deep vein thrombosis (DVT) prophylaxis using pneumatic compression
device (if available) with or without thigh-high anti-embolic stockings. Withhold
subcutaneous low-molecular-weight heparin (LMWH) or unfractionated heparin
(UFH) until the aneurysm is secured.

E. Early Specific Treatment of SAH

1. Calcium Channel Blockers: Nimodipine 60 mg every 4 hours by mouth or via
NGT for 3 weeks is recommended (Class I, level A). It remains uncertain, however,
whether nimodipine acts through neuroprotection, reduction of vasospasm, or
both.
2. Anticonvulsants: Prophylactic anticonvulsants may be considered in the
immediate post-hemorrhagic period for poor-grade SAH especially with giant
aneurysm. Long-term anticonvulsants are generally not recommended, but it may
be considered in patients with higher seizure risk such as those with prior seizures,
parenchymal hematoma, infarct, or MCA aneurysms.
3. Manage increased ICP (see Chapter 3). Ensure proper patient positioning with 30o
to 35o head of bed position to facilitate adequate venous outflow.
4. BP management: although the optimal BP goal and the choice of antihypertensive
agent remains unsettled, the use of IV Nicardipine drip to a target SBP of < 150
mm Hg in the preoperative phase (unsecured aneurysms) is reasonable.
5. Maintain euvolemia and avoid using hypotonic fluids. Central venous pressure
(CVP) and pulmonary wedge pressure (PWP) monitoring maybe considered to
assess volume status of select patients.
6. Manage hyponatremia caused by syndrome of inappropriate antidiuretic hormone
(SIADH) or salt-wasting. The use of fludrocortisone or hypertonic saline are
reasonable.
7. Statins should not be given routinely during the acute stages of SAH as it was not
shown to have significant benefit in long- and short-term clinical outcomes.17
8. Anti-fibrinolytic agents are not recommended. Although it reduces the risk of re-
bleeding, they are associated with higher risk of cerebral ischemia.

F. Prevention and Management of Vasospasm

1. Maintain euvolemia and normal circulating blood volume to prevent delayed
cerebral ischemia (DCI) (Class I, level B).
2. Induce hypertension for patients with DCI, unless the baseline BP is elevated or the
cardiac status precludes it (Class I, level B).
3. The use of transcranial Doppler (TCD) study is reasonable for monitoring
development of arterial vasospasm (Class IIa, level B). Other newer modalities such
Hemorrhagic

as CT and MRI perfusion studies are useful to identify potential regions of brain
ischemia.
Stroke

4. Acute treatment with intravenous magnesium sulfate (MgSO4) is reasonable based

on preliminary studies to help reduce cerebral vasospasm.

131
 Prevention and Management of Vasospasm (continued)
5. Endovascular angioplasty (chemical +/-mechanical) is an effective way of managing
vasospasm. The intervention has to be performed early before the clinical signs of
irreversible infarction (e.g., hemiplegia) become evident.

G. Treatment of SAH
Obliteration of the aneurysm from the circulation as early as possible is the main goal
of SAH treatment. This can be achieved through surgical clipping or endovascular
coiling.

H. Timing of Surgery
1. Definitions: Early surgery is ideally performed within 72 hours from ictus.
Late surgery is when the surgery is performed beyond 3 days from
ictus.

2. Indications:
a. Early, immediate surgery is recommended for good- to moderate-grade (Hunt
and Hess or WFNS grades I-III) aSAH to minimize the risk of a devastating
rebleed.

b. For poor-grade aSAH (Hunt and Hess or WFNS Grades IV-V), early surgery is
recommended in the presence of:
 Hematoma
 Hydrocephalus

Surgery may be delayed in the presence of:

Ischemia
Severe angiographic vasospasm

c. Advanced age (i.e. elderly) is not a contraindication for early surgical management
in the absence of an organ failure.

I. Coiling
• Can be performed early in both good- and poor-grade patients
• Reduces the rate of rebleeding for poor grade patients who would otherwise be
treated conservatively
• Vasospasm is not a contraindication and can be dealt with endovascular coiling
• Can be performed under local anesthesia if needed

J. Place of Treatment
SAH patients should be admitted to Acute Stroke Unit or Intensive Care Unit
depending on the level of stroke severity (see Chapter 3). In the absence of an ASU/
ICU, patients may be placed in a quiet, regular room with very close monitoring.
Hemorrhagic
Stroke

132
III. Cerebral Arteriovenous Malformation
Cerebral arteriovenous malformations (AVMs) are congenital high-flow, high-pressure
vascular lesions that shunt arterial blood directly to the venous system via a nidus,
which lacks an intervening capillary bed. Although AVMs are relatively uncommon, they
are increasingly recognized lesions that cause serious neurological symptoms or even
death. AVMs belong to the four major types of vascular malformations of the brain as
described by McCormick18:
1. Arteriovenous malformations
2. Venous angioma
3. Cavernous malformation
4. Capillary telangiectasia

It should be noted that the above lesions are different from one another and thus
should not be subsumed to be all under “cerebral AVM”. Clinically, AVM is the most
aggressive of the four types, which carries a morbidity and mortality risk of 30%-50%
and 10% respectively for each bleed. The most common presentations include brain
hemorrhage (50%), seizures (25%)19, headache, and focal neurologic deficits. The latter
may be explained by the mass effect of an enlarged AVM or hypertension in the draining
veins. Occasionally, the deficit occurs due to the siphoning of blood flow away from
adjacent brain tissue (vascular steal phenomenon). The bleeding risk in patients with
unruptured AVM is 2%-4% per year, which is higher in the centrally-located AVMs and in
AVMs with greater volumes.20 The overall annual mortality rate from AVM hemorrhage is
1% for adults and 2% for children. The lifetime risk of ICH in a person with AVM can be
estimated by the following formula21:

ICH lifetime risk in a patient with AVM (%) = [105] – [patient’s age (in years)]

The enlargement of lesion and the risk of developing associated neurological symptoms
both increase with patient age. The prevalence of AVM is probably greater than the
usually quoted 0.14%, with a slight male preponderance. AVMs are most commonly
discovered in young adults aged 20 to 40 years (mean age, 33 years), but children are
more likely to present with hemorrhage than adults. Specific AVM risk factors/features
that increase the risk of hemorrhage include the following22:

Consistent risk factors: deep venous drainage, single draining vein, venous
stenosis, high MAP in the feeding artery
Inconsistent risk factors: intranidal aneurysms, deep location of AVM,
small nidus, venous stasis
Potential risk factors: systemic hypertension, increasing age, smoking,
pregnancy, vertebrobasilar supply, perforating supply

Although the scope of this section is limited to cerebral AVMs (thus excludes dural
and spinal AVMs, as well as angiographically occult AVMs), the other types of
intracranial vascular lesions (including AV fistulae [AVFs] and developmental venous
anomalies [DVA]) are mentioned, as these can present with similar manifestations and
neuroimaging features of the AVMs. These lesions must be distinguished from one
another because the natural course and treatment strategies differ. A summary of the
Hemorrhagic

major intracranial vascular malformations (and treatment options) is presented at the

end of this chapter (Table 9).
Stroke

133
 Diagnosis
Diagnosing cerebral AVMs is usually a challenge and requires high-resolution imaging
studies (i.e. CT and MRI scans), supplemented by a digital subtraction angiography (DSA).
AVMs would appear as irregular or globoid masses within the cerebral hemispheres or
the brain stem. To help clinicians differentiate AVMs from other vascular malformations,
a practical imaging-based approach is presented in Figure 3. Capillary telangiectasias
and DVAs are often incidental findings; these can be found in association with cavernous
malformations (CM) but are not generally considered targets for treatment.19

Cerebral catheter angiography (or DSA) remains as the gold standard for diagnosing
AVMs (and AVFs) (Table 6). It can describe the vascular morphology and hemodynamics
(e.g., feeding arteries, venous drainage patterns, presence of aneurysm) which are
essential for treatment planning.

Table 6. Comparison of vascular structures visualized during DSA23

DSA phase (seconds elapsed) Normal AVM AVF

Early arterial phase (1-2 sec) Main arteries Feeding arteries Feeding arteries

Late arterial phase (2-3 sec) Arterial branches Nidus Draining veins and
sinuses

Capillary phase (3-4 sec) Arterioles Draining veins

and sinuses

Early venous phase (5-6 sec) Venules and veins

Late venous phase (6-7 sec) Veins and sinuses

After radiologic identification of the vascular lesion and its anatomy, grading schemes
are used to guide in treatment planning for a specific AVM as well as predicting surgical
risks and outcomes. Until present, the most widely used grading scale is the Spetzler-
Martin (S-M) system, which classifies AVMs according to size, location, and venous
drainage (Table 7).

Table 7. Spetzler-Martin Scale for Grading AVMs25

Graded Feature Points Assigned * largest diameter of nidus on non-
magnified angiogram (is related to and
Nidus size* therefore implicitly includes other factors
relating to difficulty of AVM excision, e.g.,
Small (<3 cm) 1 number of feeding arteries, degree of
Medium (3-6 cm) 2 steal)

Large (>6 cm) 3 + eloquent sites include: sensorimotor,

Location language, and visual cortex; hypothalamus
and thalamus; internal capsule; brain
Non-eloquent site 0 stem; cerebellar peduncles; and deep
cerebellar nuclei.
Eloquent site+ 1
Venous drainage++ ++ “superficial” refers to all drainage
through the cortical venous system;
Superficial only 0 “deep” refers to all drainage through the
Hemorrhagic

deep veins (e.g., internal cerebral vein,

Deep 1 basal vein, or pre-central cerebellar vein)
Stroke

Total scores range from 0-5; high scores suggest high

risk of permanent neurologic deficit after surgery

134
 Suspected intracranial vascular malformation

(+) abnormal vessels in parenchyma (-) abnormal vessels in

parenchyma

Compact nidus Diffuse nidus Fine basal network

appearance?

Early draining Consider

Single Multiple veins? AVFs
(esp. CN I, VII)

Caput medusa
Yes No appearance?

Consider Consider Consider Differentiate Consider

Cerebral Consider proliferative- Consider between pial
AVM/ Pial CAMS type Brain Proliferative DVA Moyamoya
Angiopathy and dural disease
AVM AVMs AVFs

Figure 3. Proposed imaging-based diagnostic approach to suspected intracranial vascular

malformations24
modified from Geibprasert et al. Radiologic assessment of brain arteriovenous malformations: what
clinicians need to know. Radiographics. 2010 Mar;30(2):483-501
AVM: arteriovenous malformation; AVF: arteriovenous fistula; CAMS: cerebrofacial arteriovenous metameric
syndrome; CN: Cranial Nerve; DVA: developmental venous anomaly

The S-M grade corresponds to the total score summed from each category (e.g., S-M
grade I for a total score of 1). In general, lower-grade lesions have lower treatment-
associated morbidity than are higher-grade lesions. However, the S-M grading scale
does not include other characteristics associated with hemorrhagic risks such as
aneurysms, venous stasis, or venous aneurysm. Thus, comprehensive clinical and
radiologic evaluation are required for selecting the best management approach for
patients with AVM.

Furthermore, the S-M grade does not work well as a predictor of outcomes after
radiosurgery because it underrates the effect of the volume of the target. A modified
radiosurgery-based AVM score (Panel 1) is an example of a validated grading system
which predicts outcomes versus complications (Table 8) of AVMs after radiosurgery
(whether Gamma Knife or Linac-based).

Panel 1. Arteriovenous Malformation (AVM) Score for Radiosurgery26

AVM score = (0.1)(volume) + (0.02)(age) + (0.5)(location)

Parameter information:
Hemorrhagic

• volume: in mL/cc
• age: in years
Stroke

• location: frontal/temporal/parietal/occipital/intraventricular/corpus
callosum/cerebellar = 0; basal ganglia/thalamus/brainstem = 1

135
 Table 8. Correlation of AVM Scores with Radiosurgical Outcomes26

% chance of excellent % chance of decline in

AVM score
outcome modified Rankin Scale (mRS)

<1.00 89 (79-94) 0 (0-8)

1.01-1.50 70 (59-79) 13 (7-22)

1.51-2.00 64 (51-75) 20 (12-32)

>2.00 46 (33-60) 36 (24-50)

Management
The decision to treat (or not to treat) AVMs depends on the lifetime cumulative risk
of hemorrhage from rupture versus the risk/s of intervention for a particular patient.
Nonetheless, the aims of treatment are to reduce the risk of hemorrhage, alleviate
neurological symptoms, and preserve or maximize the patient’s functional status with
an acceptable treatment risk. Management decisions are also influenced by the local
experience and the expertise of the treating physician.

Over the past decade, there have been advancements in the treatment of intracranial
AVM. An imaging-confirmed lesion is usually suited for one or more of the following
treatment strategies: observation with conservative (medical) management,
microsurgical excision, stereotactic radiosurgery (SRS) (e.g., gamma knife surgery),
endovascular embolization, or a combination of modalities. The selection of treatment
modality or its combination depends on which has the greatest therapeutic effectiveness
and safety according to both patient characteristics and AVM architecture. For AVM
patients amenable to surgical management, microsurgical resection is the optimal
treatment option (as well as for cavernous malformation).19 The main goal is for a
complete nidal obliteration, as subtotal obliteration does not provide protection from
future hemorrhage. Endovascular embolization may serve as adjunct to microsurgery
(particularly in pre-surgical occlusion of deep arterial feeding vessels in large AVMs),
or before SRS for reducing the size of nidus.27 However, one meta-analysis noted that
embolization before SRS was associated with a higher hemorrhage rate and an increased
risk of complications.28 Radiosurgery was reported to have AVM obliteration rates of
60% to 90%, although this may be lower for AVMs with high flow on conventional
angiograms.29 Post-SRS complications include edema, blood-brain barrier (BBB)
breakdown, and necrosis.30 For further details on the management of AVMs, see Figure 4.

For cavernous malformations (CM), the treatment of choice is microsurgery. The surgical
risks for deep-seated lesions can be as high as 53% for new or worsening neurologic
deficits and 36% for permanent new deficits. The perioperative complication rate was
28%.31 Reports from centers performing gamma knife radiosurgeries indicate a hemor-
rhage reduction rate of 1% after a 2-year latency.32-35 For CMs situated in challenging or
difficult locations, radiosurgery may be a treatment option.
Hemorrhagic
Stroke

136
 Suspected intracranial vascular malformation

Symptomatic
Asymptomatic/
Incidental findings
A

Does the patient present with acute emergent symptoms?

No
Yes
Assess AVM characteristics and suitability
Resolve acute condition C
B (medical/surgical)
of treatment

No
Does the patient have poor clinical status?
S-M Grade S-M Grade S-M Grade
Yes I - II III IV - V

May or may not proceed with definitive

AVM treatment. Outcome may still
be poor despite definitive treatment. D III-A E III-B F
Discuss prognosis with relatives.

Offer neurosurgical AVM excision Microsurgery + SRS +/- Mainly

embolization embolization conservative
and/or
If no consent, offer SRS and/or palliative
endovascular treatment treatment

Figure 4. Approach to Cerebral AVM

COMMENTS

AA
Observation may be the most appropriate approach for asymptomatic or large
volume AVMs (average 4-5 cm), especially when the AVM has not bled. The
natural history of hemorrhagic risk without treatment is 1-4% with an annual
mortality rate of 1% from a bleeding AVM. In an observational study, there was
no significant difference in the 5-year seizure risk between conservative and invasive
treatment irrespective of whether the AVM had presented with hemorrhage or epileptic
seizures.36 However, the current recommended treatment, long-term risk, and outcomes
of hemorrhage remain controversial. Close monitoring is the most appropriate option
for patients with AVM but without a history of hemorrhage. The interim data of the
prematurely halted ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous
Malformations) study also show that medical management is superior to intervention
(invasive treatment) in patients with unruptured brain AVMs. However, this study is flawed
in that it grouped endovascular treatment, open neurosurgery and radiotherapy, and
combinations of such, under the intervention arm.37 There were no details about specific
embolic materials used, kind of surgery performed, or the technique for delivering
radiation. Moreover, the risks of each of these were clearly different. This study was
Hemorrhagic

discontinued by its Data and Safety Monitoring Board (DSMB) after 33 months, which was
too short for evaluation of long term outcomes of AVMs. Because of its early termination,
Stroke

the study population also fell short of its projected number of subjects (n=800).

137
 BB
Treatment of AVM especially by surgical means is generally an elective procedure
unless the patient presents with intracranial hematoma or life-threatening
hydrocephalus secondary to hematoma. In such emergency situation, excision
of AVM should only be indicated for superficial AVMs, otherwise hemorrhage or
hematoma-related complications should be resolved first, followed by a careful post-
operative angiogram and treatment plan. If the patient’s post-op condition remains poor,
then treatment options–whether conservative management or proceeding with the least
invasive treatment–should be discussed with the family.

BC
Accurate assessment of treatment plan especially of operative risks should be
discussed with the patient and/or family members. The Spetzler-Martin (S-M)
grading scale (Table 7) is still the most widely used tool for classifying AVMs,
predicting outcomes, and planning treatment.

BD
For S-M grades I and II lesions with a history of hemorrhage, microsurgery may
be the best option. Favorable outcomes has been observed in 92%-100% and
94%-95% of patients respectively, with possibility of immediate cure without a
latency period. Patients with significant co-morbidities or those who refuse to
have the surgery done may opt for alternative treatment options such as stereotactic
radiosurgery (SRS).

BE
S-M Grade III lesions represent a heterogenous group of AVMs with increased
technical difficulty and potential morbidity as compared to lower grade lesions.
These are generally managed with microsurgery or SRS often with adjunctive
endovascular therapy, with excellent or good outcomes in 68%-96% of cases.
SM grade III is further subdivided into two: grade III-A (size >6 cm) and grade III-B
(venous drainage and/or eloquence). For S-M grade III-A, microsurgery with adjunctive
endovascular therapy in the form of embolization is the preferred treatment. For S-M
grade III-B, radiosurgery with or without embolization can be done. SRS typically takes
up 2-3 years for complete nidal obliteration to manifest, with a success rate of 60-90%.38
The actual hemorrhage rate from a patent AVM (before complete obliteration during the
latency interval) is 4.8% annually during the first two years after SRS, and 5% per year
on the 3rd to 5th year post-SRS. The process is cumulative, with the earliest obliterations
noted within 2-3 months; 50% of the effect often seen within one year, 80% within two
years, and 90% within three years. If at the end of third year, a residual AVM is identified
by imaging, then repeat radiosurgery may be considered.

BF
For S-M Grades IV and V lesions, an individualized multi-modal approach is
recommended only if the intervention is deemed beneficial and safe. Excellent or
good outcomes can be seen in 71%-75% and 50%-70% of S-M Grade IV and S-M
Grade V respectively with competent vascular neurosurgeons. If patients will be
managed conservatively, angiography should be done every 5 years to monitor for the
development of feeding vessel aneurysm or outflow stenosis. Endovascular technique
(embolization) alone is very often inadequate to permanently obliterate AVMs. There
is no evidence that partial AVM embolization alters long-term hemorrhagic risk, and as
such, it is not recommended for AVMs. However it has 3 potential goals when used before
radiosurgical intervention for AVMs: (1) to decrease target size to <3 cm in diameter,
because smaller volumes have higher cure rates with less morbidity; (2) to eradicate
angiographic predictors of hemorrhage, such as intranidal aneurysms or venous
Hemorrhagic

aneurysms; and (3) in an attempt to reduce symptoms related to venous hypertension.

Re-canalization has been reported in 14%-16% of cases. Palliative embolization can be
Stroke

also applied for patients with large, inoperable AVMs who are suffering from progressive
neurologic deficits secondary to venous hypertension and/or arterial steal phenomenon.

138
 Table 9. Summary of Brain Vascular Malformations19

Vascular
Lesion Diagnosis Treatment Option(s)
Anatomy
a) Microsurgery
Primary pial artery supply b) SRS
Angio, CTA,
AVM collecting into a nidus and then c) Embolization
MRI
on to draining vein(s) d) Multimodality
e) Observation
a) Microsurgery
Dural
Meningeal artery supply draining Angio, CTA, b) SRS
arteriovenous
into a sinus or leptomeningeal MRI
fistula (AVF) c) Embolization
vein
d) Observation

Direct fistula between pial artery Angio, CTA, a) Microsurgery

Pial AVF
and leptomeningeal vein MRI b) Embolization

Cavernous Clustered dilated endothelial-

MRI a) Microsurgery
malformation lined cells
b) Embolization

Clustered dilated capillaries

Capillary
interspersed in parenchyma MRI Observation
Telangiectasia
without mass effect

Angio,
Developmental Thickened veins interspersed in
contrast CT/ Observation
Venous Anomaly parenchyma
MRI

References

1. Van Asch C, Luitse M, Rinkel G, et al. Incidence, case fatality, and functional outcome of intracerebral
haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis.
Lancet Neurol. 2010 Feb;9(2):167-76.
2. Meretoja A, Strbian D, Putaala J, et al. SMASH-U: a proposal for etiologic classification of intracerebral
hemorrhage. Stroke. 2012 Oct;43(10):2592-7.
3. Ikram M, Wieberdink R, Koudstaal P. International Epidemiology of Intracerebral Hemorrhage. Curr
Atheroscler Rep. Aug 2012;14(4):300–306.
4. Ariesen MJ, Claus SP, Rinkel GJ, et al. Risk factors for intracerebral hemorrhage in the general population: a
systematic review. Stroke. 2003;34(8):2060–5.
5. Morgenstern LB, Hemphill JC III, Anderson C, et al. Guidelines for the Management of Spontaneous
Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/
American Stroke Association. Stroke. 2010;41:2108-2129.
6. Moon J, Janjua N, Ahmed S, et al. Prehospital neurologic deterioration in patients with intracerebral
hemorrhage. Crit Care Med. 2008;36:172-175.
7. Hemphill JC III, Bonovich DC, Besmertis L, et al. The ICH score: a simple, reliable grading scale for
intracerebral hemorrhage. Stroke. 2001; Apr;32(4):891-7.
8. Rost N, Smith E, Chang Y, et al. Prediction of functional outcome in patients with primary intracerebral
hemorrhage: the FUNC score. Stroke. 2008 Aug;39(8):2304-9
9. James F, Palys V, Lomboy J, et al. The role of anticoagulants, antiplatelet agents and their reversal strategies in
Hemorrhagic

the management of intracerebral hemorrhage. Neurosurg Focus. 34 (5):E56, 2013, AANS 2013.
10. Yasaka M, Sakata T, Minematsu K, et al. Correction of INR by prothrombin complex concentrate and
Stroke

vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res. 2002; 108:25.
11. Fredriksson K, Norrving B, Stromblad LG. Emergency reversal of anticoagulation after intracerebral
hemorrhage. Stroke. 1992; 23:972.

139
 12. Conolly E Jr, Rabinstein A, Carhuapoma J, et al. Guidelines for the Management of Aneurysmal Subarachnoid
Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American
Stroke Association. Stroke. 2012;43:1711-1737.
13. Ohman J. Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and
surgery. Neurosurgery. 1990;27:578-581.
14. Sundaram M, Chow F. Seizures associated with spontaneous subarachnoid hemorrhage. Can J Neurol Sci.
1986 Aug;13(3):229-31.
15. Suarez J, Tarr R, Selman W. Aneurysmal Subarachnoid Hemorrhage. N Engl J Med. 2006; 354:387-396.
16. Bederson J, Conolly E Jr, Bajjer H, et al. Guidelines for the Management of Aneurysmal Subarachnoid
Hemorrhage: A statement for Healthcare Professionals from a Special Writing Group of the Stroke Council,
American Heart Association. Stroke. 2009 Mar;40(3):994-1025.
17. Kirkpatrick PJ, Turner CL, Smith C, et al. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH):
a multicentrerandomised phase 3 trial. Lancet Neurol. 2014 May 15.
18. McCormick WF. The pathology of vascular ("arteriovenous") malformations. J Neurosurg. Apr
1966;24(4):807-16.
19. Gross B, Du R. Diagnosis and treatment of vascular malformations of the brain. Curr Treat Options Neurol.
2014 Jan;16(1):279.
20. Soderman M, Andersson T, Karlsson B, et al. Management of patients with brain arteriovenous
malformations. Eur J Radiol. 2003 Jun;46(3):195-205.
21. Brown RD. Simple risk predictions for arteriovenous malformation hemorrhage. Neurosurgery.
2000;46:1024. Letter.
22. Stieg P, Batjer H, Samson D, eds. Intracranial Arteriovenous Malformations. New York: Informa Healthcare
USA, Inc.; 2007:137.
23. Malik G, Bhangoo S. Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous
Fistulas). In: Ellenbogen RG, Abdulrauf SU, Sekhar LN (eds). Principles of Neurological Surgery, 3rd ed,
Philadelphia: Elsevier, 2012.
24. Geibprasert S, Pongpech S, Jiarakongmun P, et al. Radiologic assessment of brain arteriovenous
malformations: what clinicians need to know. Radiographics. 2010 Mar;30(2):483-501.
25. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg
1986;65:476-83.
26. Wegner RE, Oysul K, Pollock BE, et al. A modified radiosurgery-based arteriovenous malformation
grading scale and its correlation with outcomes. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1147-50.
27. Miyamoto S, Takahashi J. Management of intracranial arteriovenous malformations. Brain Nerve. 2008
Oct;60(10):1103-13.
28. vanBeijnum J, van der Worp HB, Buis DR, et al. Treatment of brain arteriovenous malformations: a
systematic review and meta-analysis. JAMA. 2011 Nov 9;306(18):2011-9.
29. Taeshineetanakul P, Krings T, Geibprasert S, et al. Angioarchitecture determines obliteration rate after
radiosurgery in brain arteriovenous malformations. Neurosurgery. 2012 Dec;71(6):1071-9.
30. Parkhutik V, Lago A, Aparici F, et al. Late clinical and radiological complications of stereotactical
radiosurgery of arteriovenous malformations of the brain. Neuroradiology. 2013 Mar;55(4):405-12.
31. Abla AA, Lekovic GP, Turner JD, et al. Advances in the treatment and outcome of brainstem cavernous
malformation surgery: a single-center case series of 300 surgically treated patients. Neurosurgery. 2011
Feb;68(2):403-14.
32. Hasegawa T, McInerney J, Kondziolka D, et al. Long-term results after stereotactic radiosurgery for patients
with cavernous malformations. Neurosurgery. 2002 Jun;50(6):1190-7.
33. Lunsford LD, Khan AA, Niranjan A, et al. Stereotactic radiosurgery for symptomatic solitary cerebral
cavernous malformations considered high risk for resection. J Neurosurg. 2010 Jul;113(1):23-9.
34. Liscak R. Radiosurgery of brain cavernomas--long-term results. Prog Neurol Surg. 2013;27:147-56.
35. Monaco EA, Khan AA, Niranjan A, et al. Stereotactic radiosurgery for the treatment of symptomatic
brainstem cavernous malformations. Neurosurg Focus. 2010 Sep;29(3):E11.
36. Josephson C, Bhattacharya J, Counsell C, et al. Seizure risk with AVM treatment or conservative
management: prospective, population-based study. Neurology. 2012 Aug 7;79(6):500-7.
37. Mohr JP, Parides MK, Stapf C, et al.; international ARUBA investigators. Medical management with or
without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre,
non-blinded, randomised trial. Lancet. 2014 Feb 15;383(9917):614-21.
38. Sonier M, Gete E, Herbert C, et al. Intensity-modulated stereotactic radiosurgery for arteriovenous
Hemorrhagic

malformations: guidance for treatment planning. Radiat Oncol. 2014 Mar 10;9:73.
Stroke

140
 NEUROIMAGING
CHAPTER VII
Neuroimaging in Acute Stroke

COMPUTERIZED TOMOGRAPHY (CT) SCAN

PERFUSION CT IMAGING

CT ANGIOGRAPHY

MAGNETIC RESONANCE IMAGING (MRI)

IMAGING FOR HEMORRHAGIC STROKE

Sixth
Edition
2014
NEUROIMAGING
NEUROIMAGING IN ACUTE STROKE
Neuroimaging modalities are employed to aid in the detection or confirmation of the
presence of ischemia (Figure 1) or hemorrhage. These further help improve localization
of site/s of insult – e.g., intra-axial/parenchymal vs. extra-axial hemorrhage (Figure 2).
Important stroke mimics (e.g., tumors, subdural hematoma) may also be identified.
At present, the modalities commonly used in the Philippines are the Computerized
Tomography (CT) scan and Magnetic Resonance Imaging (MRI).

Figure 1. Subacute Left Middle Cerebral Artery (MCA) Infarct

A and B. Subacute left MCA infarct

seen as hypodense areas (white
arrows) in the fronto-parietal region,
insula, and part of the basal ganglia.

A B

Figure 2. Acute Subarachnoid Hemorrhage (SAH)

C and D. Acute SAH and Acute ICH

respectively. Blood in acute SAH
and ICH are hyperdense. These are
brought about by the increased
concentration of protein due to clot
retraction from globin particles.

C D

COMPUTERIZED TOMOGRAPHY (CT) SCAN

The most widely available brain imaging modality in the Philippines is the non-contrast
cranial CT (NCCT) scan. It has traditionally been utilized in rapid initial assessment of
brain status and provides straightforward detection of hemorrhages. However, it has a
low sensitivity for detection of ischemia in the first 24 hours post-ictus (particularly in
the first 3 to 4.5 hours, wherein thrombolytic treatment is best administered). Possible
NCCT scan findings in early ischemia are the following:

1. Hyperdense middle cerebral artery or “dot sign” (Figure 3)

2. Obscuration of the lentiform nucleus (Figure 4)
3. Loss of gray-white matter differentiation
4. Insular ribbon sign
5. Sulcal effacement

142
 NEUROIMAGING
Figure 3. Hyperdense Middle Cerebral Artery (MCA)

A. Hyperdense left MCA sign

(black arrow) seen at the time of
admission. B. Completed infarct
noted three days after admission
(white arrows).

A B
In the hyperdense MCA (Figure 3), a blood clot is formed within a major intracranial
arterial trunk lumen. Subsequent clot retraction leads to very high concentrations
of protein or globin components, which results in the said hyperdensity. Among the
above-enumerated CT findings, this is the least definite sign of hyperacute stroke and
must therefore be correlated clinically. Likewise, if the hyperdensity is noted bilaterally,
its value as an early radiologic sign of stroke is no longer as significant as when it is seen
only at one side.

Figure 4. Obscuration of the Lentiform Nucleus

A. The right lentiform nucleus

is obscured, a sign of hyperacute
infarct (double black arrows) with
normal left lentiform nucleus
(single black arrow). B. Completed
stroke 3 days after initial imaging
(white arrow).

A B

Obscuration of the lentiform nucleus (Figure 4) is characterized by the loss of density

of this structure against the normally more hypodense internal and external capsules.
This is due to the failure of the ion pumps to maintain cellular homeostasis leading to
unabated cellular influx of water, thus causing cytotoxic edema. This same mechanism
explains:

a) the hypodense appearance of the insular cortex (which is one of the most sensitive
parts of the brain to ischemia)

b) the loss of gray-white matter interface at the insular area (Figure 5) and other
ischemic parts of the cortex (Figure 6)

c) sulcal effacement (Figure 7) as a result of swelling of the cortical region

143
NEUROIMAGING
NEUROIMAGING

Figure 5. Cortical Ribbon Sign

A. Cortical ribbon sign seen as loss

of the normal dense appearance
of the insular cortex in hyperacute
infarct (black arrow) compared to
the normal cortical ribbon (white
arrow). B. The same patient exhibiting
a completed infarct after two days
(white arrowhead) at the right
insular cortical and subcortical region
involving the external capsule and
lateral aspect of the right lentiform
nucleus. A B

Figure 6. Loss of Gray-White Matter Interface at the Right Temporal Region

A. Loss of gray-white matter

interface at the right temporal region.
Cytotoxic edema in hyperacute infarct
swells the neurons rendering the
area to be hypodense and featureless
(double arrow) compared with the
normal left side (single arrow). B.
The infarct is completed after three
days. There is more pronounced
hypodensity due to vasogenic edema,
indicating acute phase of the infarct.
A B

Figure 7. Sulcal effacement

The cortical sulci are flattened at

the left frontoparietal region (white
arrows) as compared with the normal
sulci at the right side. There is also
loss of gray-white matter interface

PERFUSION CT IMAGING
Due to the low sensitivity of NCCT scan in estimating the volume of ischemic core
against the volume of the penumbra or tissue at risk during the hyperacute phase
of stroke, perfusion CT imaging (if available) is now being added to the acute stroke
imaging protocol. This modality allows determination of the penumbra and the size
of the infarct core, which may not be detected by conventional CT. If the size of the
144
 NEUROIMAGING
NEUROIMAGING
infarct core exceeds one-third of the volume of MCA distribution, thrombolytic therapy
may no longer be indicated; otherwise, the risk of complications such as hemorrhagic
conversion may increase. Perfusion CT imaging is performed by monitoring the first
pass of iodinated contrast agent through the cerebral circulation. As the contrast
agent passes through the brain tissue, there will be transient hyperattenuation directly
proportional to the amount of contrast material in the vessels and blood in that region.

Color-coded perfusion maps are created through the commercially available software,
showing the cerebral blood volume (CBV, the volume of blood flowing in a volume
of brain), mean transit time (MTT, the average time it takes blood to transit through a
volume of brain), and cerebral blood flow (CBF, the amount of blood passing through a
volume of brain in a specified amount of time). CBV and CBF maps depict the infarct core
similar to the area of restricted diffusion in diffusion-weighted MRI (DW-MRI), which was
thought to be the brain tissue that is no longer salvageable even with reperfusion. CBF
represents the altered area of the brain that is at risk of infarction, or the penumbra,
which may eventually become infarcted if the blood supply is not restored in time. It is
the most useful perfusion parameter in predicting viable penumbra and the penumbra
that would convert to infarction. MTT shows the most prominent regional abnormality
representing the ischemic penumbra, depicted as an area of increased (or lengthening
of the) MTT. Comparing the volume of the infarct core with the volume of the tissue at
risk is called the tissue mismatch.

The penumbra will typically show increased MTT with mildly decreased CBF and normal
or mildly increased CBV. On the other hand, the infarcted tissue will demonstrate
markedly decreased CBF and markedly decreased CVB with surrounding increased MTT.

CT ANGIOGRAPHY
CT angiography (CTA) is another important addition to neuroimaging because of the
enhanced detection of cerebrovascular diseases and also helps improve prognostication.
CTA can reveal the status of large cervical and intracranial arteries and locate vascular
occlusion site/s. It can also detect the presence of atherosclerotic disease, arterial
dissection, and determine degree of collateral blood flow. This information serves as a
guide for thrombolysis.

Intra-arterial thrombolysis has a higher recanalization rate for occlusions of the internal
carotid artery, MCA stem, and the basilar artery. CTA can visualize occlusions of the
vertebrobasilar system supplying the posterior circulation, which is often difficult to
detect with non-enhanced CT (NECT) scan examination.

The extent of arterial leptomeningeal collateral vessels beyond the occlusion site in
some patients with better pial collateral formation appears to correlate with a better
prognosis. These parameters are included in the multimodal CT scan examination,
which provides fast, accurate, and straightforward information. However, this requires
multi-detector CT scanners, which may not be available in smaller hospitals and medical
centers.

The use of CT angiography source images (CTA-SI), a post-contrast injection method,

can directly identify the core of infarcts seen as a hypodensity against the rest of the
brain parenchyma. CTA-SI was said to be synonymous with MR-diffusion weighted
imaging (DWI), although the latter is more sensitive in smaller infarcts and infarcts in
the brain stem and posterior fossa.

One difficulty encountered in selecting patients for thrombolysis is the objective

assessment of the infarct core volume, whether its size is still within one-third (1/3) the
volume of the MCA distribution. This process can be aided using the Alberta Stroke
Program Early CT Score (ASPECTS), a 10-point quantitative topographic CT-based
145
NEUROIMAGING
scoring system that determines infarct core volumes particularly in acute ischemic
strokes of the anterior circulation. In the ASPECTS, the following regions of the brain are
each assigned with corresponding points: subcortical structures are allotted 3 points (1
point each for the caudate nucleus [C], lentiform nucleus [L], and internal capsule
[IC]); while the MCA cortex is allotted 7 points (1 point each for the insular cortex [I],
and for each of the MCA territories [M1 through M6]). To compute for ASPECTS, one
(1) point is subtracted from a base score of 10 (which is the perfect score assigned to
normal brain) for any evidence of early ischemic change detected in each of the defined
regions. The normal CT scan therefore receives ASPECTS of 10 points. An ASPECTS score
<7 is equivalent to an infarct core volume of more than one-third the size of MCA
distribution and is therefore considered ineligible for thrombolysis.

MAGNETIC RESONANCE IMAGING (MRI)

The MRI is used to evaluate the signal characteristics of the cerebral parenchyma, brain
stem, cerebellum, and the surrounding structures. Its ability to detect cerebral ischemia
with high accuracy is enhanced by diffusion-weighted imaging (DWI), which is based on
the demonstration of restricted diffusion of water molecules as a result of movement of
extracellular water into the intracellular compartment (i.e. cytotoxic edema). In normal
tissues, on the other hand, there is random movement of water molecules according
to Brownian motion. The area of infarcted tissue will then be demonstrated as a bright
signal in DWI. DWI is more sensitive than non-contrast enhanced CT scan (NECT),
although it is highly dependent on the type of magnet available in the hospital.

MRI can also demonstrate the penumbra or tissue at risk through the use of perfusion
MRI (PWI, perfusion-weighted imaging). The volume of brain involvement in DWI
and PWI can be compared to determine the mismatch between the two parameters.
The penumbra or tissue at risk is determined as the volume of brain with diminished
perfusion beyond that of the infarct core, known as diffusion/perfusion mismatch.

The imaging protocols used for creating images of the human anatomy are called
pulse sequences, which show different levels of accuracy in imaging of ischemic and
hemorrhagic strokes. High field gradients typically found in magnets of at least 1.5
Tesla (T) to 3.0 T are needed to create accurate DW images, which can be aptly called
echo planar imaging (EPI). During the acute phase of stroke, the infarcted area on
DWI shows a hyperintense or bright MR signal (Figure 8), while the surrounding tissues
appear normal which is darker than the lesion. The apparent diffusion coefficient
(ADC) maps depict the area of restricted diffusion as low-intensity signal (reverse-in-
brightness). Correlating DWI findings with the ADC map greatly increases the specificity
of this method. Abnormal DWI signal in acute stroke with reduced ADC signal has been
observed in as early as 30 minutes after the onset of ischemia. The ADC map continues
to decrease in intensity and reaches its peak in 3 to 5 days and then slowly increases
again.

Figure 8. Isotropic Diffusion-Weighted Imaging

A. Bright signal indicative of

hyperacute infarct in the left
MCA distribution. B. Apparent
diffusion coefficient (ADC) map of
the same patient shows the area
of restricted diffusion as a dark
signal. This confirms the presence
of an infarct versus “shine-through
artifacts,” which appear bright on
both sequences but are not real
infarcts. A B
146
 NEUROIMAGING
Other pulse sequences may be able to detect stroke as bright signals, such as T2-
weighted fluid attenuated inversion recovery (T2 FLAIR) images or T2 weighted fast
spin echo or T2 spin echo images (T2TSE or T2 SE), although their findings can be seen
beyond the cut-off time for thrombolysis.

MRI can be used to examine the vasculature of the brain and the neck with magnetic
resonance angiography (MRA), which does not use intravenous contrast material.
Contrast-enhanced MRA can also be performed for more accurate depiction of vessel
anomalies (e.g., aneurysms). The advantage of a non-contrast study is that it can be
repeated several times as necessary to produce adequate images without the risks
associated with contrast material injection (i.e. gadolinium in both MRI and MRA).

Table 1. The MRI Guide to Dating Ischemic Stroke

Early Late Acute Subacute
IMAGING Chronic
hyperacute hyperacute (1 day - 1 (1-3 weeks)
SEQUENCE (>3 weeks)
(0-6 hours) (6-24 hours) week)

Hypointense
for 7-10 days;
Hypointense may pseudo-
ADC map Hypointense Hypointense Hyperintense
normalize at
10-15 days; then
hyperintense

Hyperintense
Variable in T2-
for 10-14 days;
shine through;
then iso/hypo;
DWI Hyperintense Hyperintense Hypointense hypointense in
hyperintensity if
cystic encephalo-
T2 shine-through
malacia
is seen

Low signal (in

Variable
Usu. High signal gliosis and cystic
FLAIR (usually high Hyperintense
hyperintense intensity encephalo-
after 6 hours)
malacia
Low signal;
Low signal; hyperintense Low signal;
Usu. hyperintense with cortical hyperintense
T1 Isointense hypointense with cortical necrosis most with cortical
after 16 hours necrosis at common after 2 necrosis
3-5 days weeks

Variable; usu.
Hyperintense;
Isointense high after 8
T2 Hyperintense fogging may be Hyperintense
hours
seen at 2-3 weeks

Hemorrhagic Microbleeding
SWI or trans. most Hemorrhagic and hemorrhagic
May see hemorrhagic
gradient- likely within trans. transformation
transformation within 0-12
echo 48h; risk uncommon after (new incidence
hours (unlikely)
remains for 1 week unlikely)
up to 5 days
modified from Allen LM, et al. Radiographics. 2012;32 (5): 1285-97.
ADC: apparent diffusion coefficient; FLAIR: fluid attenuated inversion recovery images; SWI:
susceptibility-weighted imaging

147
NEUROIMAGING
Another advantage of the MRI is its potential in determining the approximate age of
ischemia, which is especially useful in cases where the stroke onset is upon the awakening
of the patient. The DWI, ADC map, and T2 FLAIR sequences are most important in
dating infarcts, whereas T2- and T1-weighted studies also help in establishing the age
of infarct. Based on MR findings, the age of infarct can be classified as: early hyperacute
(0-6 hours old), late hyperacute (6-24 hours old), acute (1-7 days old), subacute (1-3
weeks old), and chronic (>3 weeks old) (Table 1). Susceptibility weighted imaging
(SWI) is another imaging sequence that is especially useful in evaluating intracranial
hemorrhage.

Imaging for Hemorrhagic Stroke

Intracerebral hemorrhage (ICH) is very well detected by CT scan, even in the hyperacute
phase. CT scan is the imaging method of choice should the clinical history point to a
possible hemorrhage as the cause of stroke. Hematomas are radiographically visualized
as area/s of hyperdensity during the hyperacute phase to acute phase (reflecting clot
formation, retraction, lysis and hyperconcentration of globin particles from extravasated
blood), which then becomes isointense with the cortex towards the subacute phase.

An important parameter used in determining prognosis in ICH is the hematoma volume,

where the most accurate method of measurement is the pixel method. In this method,
the outline of the hematoma is marked and then the volume is determined by the
number of pixels (or small squares) comprising the hematoma area using a computer
system attached to the CT scan. The pixel size is fixed and represents volume elements
or voxels (area of pixel including the slice thickness of CT scan picture).

A more practical way of estimating volume in ICH is by measuring hematoma in the CT

scan film using a formula devised by Kothari et al., as:

MODIFIED KOTHARI METHOD

Hematoma volume (in cc) = A x B x C

2
where:
A= Largest diameter of hematoma (in cm)
B= Diameter perpendicular to A (in cm)
C= Number of slices on CT scan with hemorrhage x slice thickness (in cm)

The steps in measuring hematoma volume using the modified Kothari method are
described in Figures 9A-F. In determining the number of hemorrhage slices for the value
[C]:
- If the hemorrhage area for a particular CT slice is about the same size or >75% of
the area seen on the slice where hemorrhage is largest, the slice is considered 1
hemorrhage slice.
- If the hemorrhage area is approximately 25% to 75% of the largest hematoma
volume, the slice is considered half (1/2) hemorrhage slice.
- If the slice hematoma volume is less than 25% of the largest hematoma volume,
the slice is negated and no value is assigned to that CT slice.

The accumulated values for each of the measurements are added together that will
represent [C] or the height of the hematoma. The Kothari method is fairly accurate when
compared to the hematoma volume measured using a formula for a sphere, which is not
the usual shape of hematomas.

148
 NEUROIMAGING
Figure 9.A.

Select CT scan images

of a patient who suffers
from acute intracerebral
hemorrhage at the right
basal ganglia whose
hematoma volume is to
be determined. 10mm CT
slices were obtained.

Figure 9.B

First CT slice [1] with hematoma

volume 25-75% of largest
volume. Following the Kothari
formula, the equivalent
thickness of this slice will be
one-half of its original thickness
(0.5 cm).

Figure 9.C.

The second slice [2] shows the

largest hematoma size in the
series. Lines A and B represent
largest hematoma diameters.
Slice thickness is equivalent
to one whole slice thickness
(1.0 cm).

149
NEUROIMAGING

Figure 9.D.

The last slice [4] in the series shows

intracerebral hematoma whose size
is no longer significant, its height is
considered non-contributory and is
therefore not assigned any value.

Figure 9.E.

The third slice [3] shows

hematoma volume to be almost
as large as slice (2) and is also
assigned the full thickness (1.0
cm).

Figure 9.F.

Actual computation of hematoma size

using the ABC/2 (Kothari) method.

While the demonstration of hematomas by CT scan is straightforward and has a short

learning curve, in MRI it is more complicated, because the appearance of hematomas in
T1- and T2-weighted images will depend on the age of blood product (i.e. degradation
of hemoglobin) within the lesion. Computing for hematoma volume using MRI is also
complicated because the margin of the hematoma may not be exact or may extend
beyond the physical margin of the actual lesion. Typically, the positive blooming
changes (representing microhemorrhages) are not easily demonstrated in T1- and
T2-weighted imaging, whereas Gradient Recall Echo (GRE) imaging is more sensitive,
particularly in detecting microhematomas in chronic hypertensive patients who are not
compliant with medications. The SWI can also detect microhemorrhages reportedly
150
 NEUROIMAGING
six times more than GRE can. The SWI can provide additional information when used
with DWI, such as: detecting hemorrhage/s within a region of infarction, demonstrating
area/s of hypoperfusion and ascertaining the necessity of perfusion MRI, detecting
acute thromboemboli occluding the arteries (up to the insular branches), and detecting
microbleeds which can help predict probability of hemorrhagic transformation in patients
who are considered for thrombolysis. The MRI provides an excellent presentation of the
evolution (stages) of blood products, particularly when it is intracerebral (Table 2), and is
much more accurate than CT scan when establishing the age of hematoma.

Table 2. Temporal Evolution of Intracerebral Hemorrhage

Clinical Approximate time of Intensity on Intensity on

Biochemical form
Stage appearance T1 TSE T2 TSE
Immediately to first several
Hyperacute Oxy-Hb in RBCs
hours
≈ 
Acute Deoxy-Hb in RBCs Hours to days ≈, 
Early
subacute
Met-Hb in RBCs First several days  
Subacute to
chronic
Extracellular Met-Hb Days to months  
Ferritin and
Remote Days to indefinitely ≈, 
Hemosiderin

The oxyhemoglobin seen in the hyperacute phase of hematoma is typically isointense

to slightly hypointense in T1 TSE, while in T2 TSE it appears as slightly hyperintense (Fig.
10). During the acute phase, the blood products will degrade into deoxyhemoglobin,
which appears as isointense to slightly hypointese in T1 TSE, or markedly hypointense
in T2 TSE (Fig. 11). A few days after (early subacute phase), the blood products will
degrade further to methemoglobin (confined intracellularly), seen as hyperintense in
T1 TSE or markedly hypointense in T2 TSE (Fig. 12). In the late subacute phase, the
methemoglobin becomes extracellular because of the lysis of RBC, which will show
hyperintensity on both T1 and in T2 TSE (Fig. 13). The blood products will finally become
hemosiderin and ferritin during the chronic phase, described as hypointense in both T1
and in T2 TSE (Fig. 14).

T1 TSE T2 TSE GRE

Figure 10. Hyperacute left lentiform nucleus hemorrhage, appearing as slightly
hypointense in T1 TSE (single arrow), hyperintense in T2 TSE (arrow head) and
bright with blooming dark signal in GRE (double arrows).
151
NEUROIMAGING

Figure 11.

T1 TSE T2 TSE GRE

Acute intracerebral hematoma with intraventricular extension, appearing as slightly
hypointense to isointense in T1 TSE (single arrow), dark in T2 TSE (arrow head), dark
blooming signal in GRE (double arrows).

Figure 12.

T1 TSE T2 TSE GRE

Early Subacute, Acute and Old Hematoma. The right frontal subcortical hyperintense
signal (single black arrow) in T1 TSE appears as a low signal lesion with surrounding
hyperintense vasogenic edema in T2 TSE. The same lesion is noted as blooming dark
signal in GRE. This represents subacute hematoma. The left sub-insular isointense lesion
(double black arrow) in T1 TSE, seen as a dark signal in T2 TSE or blooming dark signal in
GRE, represents acute phase of hematoma. The left thalamic hypointense to hyperintense
signal area in T1 TSE (single white arrow), which appear dark in T2 TSE or as blooming
dark signal in GRE, i indicative of an acute to early subacute hematoma. The small dark
signal lesion in the right thalamus (white arrow head) with surrounding hemosiderin
ring in T1 TSE appears bright in T2 TSE with surrounding dark signal hemosiderin. This is
also noted as blooming dark signal in GRE.

152
 NEUROIMAGING
Figure 13.

T1 TSE T2 TSE GRE

Late subacute hematoma at the left posterior parietal region exhibiting hyperintense
signal lesion in T1 TSE (black arrow), hyperintense signal lesion with dark signal
hemosiderin rim in T2 TSE (white arrowhead), hyperintense signal with a dark
signal rim in GRE (double arrow).

Figure 14.

T1 TSE T2 TSE GRE

Old or chronic hemorrhage in the right lentiform nucleus, seen as elongated hypointense
lesion in T1 TSE (single black arrow), markedly hypointense area with a central faint
bright signal (representing encephalomacia) in T2 TSE (white arrow head), and elongated
blooming dark signal area in GRE (double arrow).

In cases of subarachnoid hemorrhage (SAH), the most sensitive pulse sequence is T2

FLAIR. In this pulse sequence, SAH appears as a hyperintense area in the subarachnoid
space, in contrast to the normal hypointense appearance of the CSF. While the GRE pulse
sequence can show early hemorrhages, this may not always hold true in SAH. In T2 FLAIR
however, there is possibility of acquiring artifactual bright signals from fluid motion and
pulsation, which can mimic blood products, thus this will have to be correlated with
other pulse sequence such as GRE.

153
NEUROIMAGING
The SSP Neuroimaging Guidelines for Stroke
A. Hyperacute or Acute Ischemic Stroke
1. Non-contrast CT (NCCT) scan of the head is the initial neuroimaging study
of choice in acute stroke because of its cost, speed and availability. The main
objective of immediate imaging is to exclude hemorrhagic stroke. A non-
contrast study obviates the need to wait for a serum creatinine result.
2. Cranial MRI – DWI surpasses NCCT scan in detecting early ischemic changes
and excluding some stroke mimics. The MRI can be the initial imaging of choice
in patients who are candidates for rtPA therapy, if this imaging is available in
the health facility, and if this does not result in undue delay in administering
thrombolytic agent.
3. A vascular study (CTA or MRA) to detect stenosis or occlusion is useful to further
the diagnosis of stroke, improve triaging of patients to get the best treatment
available, and determine prognosis. It is probably indicated in specialized centers
together with the initial imaging evaluation, if vascular imaging is available and
if it does not unduly delay thrombolytic treatment.
4. Cerebral infarcts are often not documented by CT scan within 3 hours of the
stroke onset. However “early” infarct signs maybe seen in 60% of cases.
5. In cases of early neurologic deterioration secondary to large infarcts, edema
or suspected hemorrhagic conversion, a follow-up NCCT scan of the head is
recommended.
6. The MRI has the following technical advantages over the NCCT scan:
a. DWI for documenting early ischemia/infarction.
b. GRE for detecting microbleeds, hemorrhagic transformation, and chronic
hemorrhages.
c. T2-weighted imaging for small infarcts, lacunes, or infarcts located in the
brainstem or posterior fossa.
d. Despite of its superior yield, the MRI is more expensive, time- consuming,
and less readily available.

B. Intracerebral Hemorrhage (ICH)

1. CT scan and MRI-T2 appear to have equal efficacy documenting acute ICH.
2. CT can accurately document the location of the hemorrhage and the presence
of mass effect, ventricular extension and hydrocephalus.
3. In hypertensive ICH, a repeat NCCT scan after 24 hours of ictus is recommended
especially in cases showing clinical deterioration to document hematoma
enlargement and/or development of hydrocephalus.
4. Hematoma volume can be estimated by CT using planimetric method or at the
bedside using the Modified Kothari method
5. Computation of hematoma volume (Modified Kothari method) is fairly
demonstrable.
6. In suspected cases of AV malformation, aneurysm, or tumor bleed, a contrast CT
and/or CTA or MRI/MRA of the head may be warranted.

C. Subarachnoid hemorrhage (SAH)

1. NCCT scan of the head is strongly recommended as the initial procedure for
diagnosis.
2. The diagnostic yield of CT goes down from 92% within the first 24 hours to 50%
within 7 days of onset.

Bibliography
1. Camargo ECS, Furie KL, Singhal AB, et al. Acute brain infarct: detection and delineation with CT
angiographic source images versus nonenhanced CT scans. Radiology. 2010; 244:541–548.
2. de Lucas EM, Sanchez E, Gutierrez A, et al. CT Protocol for Acute Stroke: Tips and Tricks for General
Radiologists. Radiology. 2008; 28:1673-1687.
3. Latchaw RE, Alberts MJ, Lev MH, et al. Recommendations for Imaging of Acute Ischemic Stroke: A
Scientific Statement from the American Heart Association. Stroke. 2009; 40, 3646- 3678.
154
 NEUROIMAGING
Falx cerebri
Frontal lobe
Frontal horn of Sulci
lateral ventricle Lateral ventricle
Pariental lobe
Septum pellucidum

Pineal gland Occipital lobe

Occipital
horn of
lateral ventricle

3rd ventrical

Midbrain

Quadrigeminal cistern

Frontal lobe Frontal sinus

Temporal lobe Orbital roof
Orbital
Sylvian fissure cavity
Pons

Chiasmatic
cistern
Cerebellum Mastoid
air cells Temporal lobe
4th ventricle
Cerebellum

Figure 15. Normal CT scan

Adapted from: Lindsay K, Bone I. Neurology and Neurosurgery Illustrated, 4th Edition. New York: Churchill
Livingstone, 2004. p.36; with permission.

Interpretation of Cranial CT findings:

1. Hypodense (dark/black on CT)

a. Normal- CSF, fat, air in sinuses/mastoids
b. Abnormal - infarction (arterial/venous), necrosis, encephalitis, resolving
hematoma, abscess, air after surgery

2. Hyperdense (white on CT)

a. Normal - bone, physiologic calcification of the pineal gland, choroid plexus,
basal ganglia and falx cerebri
b. Abnormal: blood, calcifications (e.g., from tumor, granuloma, AVM/aneurysm,
hamartoma)

3. Mixed density (white and dark)

Abnormal - hemorrhagic infarcts, tumors, abscess, AVM, contusion
155
CHAPTER VIII
Complications of Stroke
I. Post-Stroke Pain

II. Post-Stroke Seizures

III. Post-Stroke Depression

IV. Post-Stroke Dementia

Sixth
Edition
2014
 Complications of Stroke

I. POST-STROKE PAIN
A. Overview
i. Patients with stroke may suffer from a range of pain syndromes which include
COMPLICATIONS

central post-stroke pain (CPSP), hemiplegic shoulder pain (HSP), complex regional
POST-STROKE

pain syndromes (CRPS), spasticity, musculoskeletal pain, tension-type headache,

and other novel pain subtypes. The term "post-stroke pain" (PSP), although
often perceived as synonymous to central neuropathic pain (which includes pain
secondary to spinal cord injury or multiple sclerosis), pertains to all pain types
that follow a cerebrovascular insult. The diagnosis of PSP requires exclusion of
all causes of pain unrelated to stroke as there is no standard diagnostic criteria at
present.
ii. Central post-stroke pain (CPSP) is a specific neuropathy that was classically
attributed to a thalamic stroke (known as Dejerine-Roussy syndrome [DRS]).1
However, in contrast to DRS, the stroke lesion in CPSP can be extra-thalamic or
at any levels of the central somatosensory pathway. The pain in CPSP can be
spontaneous or evoked; it is variously described as “burning”, “aching”, “lacerating”,
“pricking”, combined, or even out of proportion to the nociceptive stimulus.
iii. Various mechanisms have been implicated in the pathogenesis of Post-stroke
Complex Regional Pain Syndrome (CRPS); these include pro-inflammatory
processes, biomechanical factors, and microtrauma to the hemiplegic shoulder.2
CRPS is characterized by the following: allodynia (i.e. pain evoked by a stimulus
which is not normally painful); hyperalgesia (i.e. increased response to a normally
painful stimulus); abnormal vasomotor activity in the region of pain; and
autonomic signs and symptoms.3 In general, there are two subtypes of CRPS: type
I (formerly known as reflex sympathetic dystrophy), which occurs after an illness
or injury without an overt nerve damage; and type II (previously called causalgia),
which follows a distinct nerve lesion.4 Nonetheless, the distinction virtually has
no consequence for the general approach to management. Based on these
definitions, post-stroke CRPS would fall under type I; however, microtrauma to the
nerves cannot be unequivocally excluded.
iv. Hemiplegic Shoulder Pain (HSP) is a peripheral nociceptive pain which can be
secondary to adhesive capsulitis (50%), shoulder subluxation (44%), rotator cuff
tear (22%), and shoulder-hand syndrome (16%).5 Clinical features include reduced
pinch grip, decreased shoulder shrug strength, abnormal muscle tone, and sensory
impairment.6 Shoulder-hand syndrome (SHS) refers to CRPS specifically seen in
hemiplegia.2

B. Epidemiology
i. There is limited data on the incidence of post-stroke pain in the Philippines. To
date, the largest study which determined the prevalence of chronic pain after
ischemic stroke is the Prevention Regimen for Effectively Avoiding Second Strokes
(PRoFESS) trial, where over 15,000 stroke survivors were followed-up (mean, 2.5
years) for pain syndromes commencing after stroke. Results show that about 10.6%
of patients developed new chronic pain, by which the majority had unclassified
pain syndromes, followed by central type of pain, peripheral neuropathic pain,
pain from spasticity and shoulder subluxation, and the combination of subtypes.
The risk factors for PSP included increased stroke severity, female gender, alcohol
intake, recent depression, diabetes mellitus, use of statin or antithrombotics, and
peripheral vascular disease.7 Individuals who have experienced non-central causes
of pain were more likely to develop cognitive decline.7
ii. The incidence of CPSP is approximately 8% of the general population.8 In most
cases (about 63%), the onset of symptoms present within the first month of stroke9,
although it can manifest at any time within the first 12 months.
158 iii. Post-stroke shoulder pain develops in approximately one-third10 to as high as
 54%11 of stroke survivors during their recovery. The presence of HSP within the first
12 weeks after stroke is strongly associated with prolonged hospital stay and poor
recovery of arm function.12
iv. The reported frequencies of post-stroke CRPS are highly variable; incidence may
range from 2% during acute rehabilitation up to about 50% at 28 weeks after the
stroke event.2

COMPLICATIONS
C. Risk Modification

POST-STROKE
i. Currently, no intervention has been proven to alter the development of central post-
stroke pain. Primary and secondary prevention of stroke risk factors, with emphasis
on the above risk factors for CPSP, may help lessen the incidence and/or risk for
developing CPSP.
ii. HSP and CRPS may be prevented through proper and early rehabilitation including
joint positioning and proper range of motion (ROM) activities.

D. Diagnosis
i. All patients with stroke need to be asked for any experience of pain. In the history,
focus on the pain character, quality, location, temporal profile, modifying factors,
and concomitant symptom/s (if any). Clinicians may follow an algorithm (Figure 1)
to help guide in the diagnostic assessment.

Was the pain present before Yes

stroke? Consider pre-existing causes Treat with oral
of pain and treat accordingly analgesics
No
No

Is the pain located to the head Yes Consider post-stroke

and cervical region? headache Is the patient taking
No dipyridamole or other
drugs causing headache?

Is the pain located to the

shoulder on the affected side?
AND is the shoulder subluxated
or does mobilization of the
shoulder cause or worsen
pain?
No
Is the pain located on the
ipsilateral side of the stroke
lesion and is associated with
sensory signs?
No
Yes Yes
Consider hemiplegic
shoulder pain and treat
accordingly
Discontinue drug;
for dipyridamole,
switch to aspirin and/
or clopidogrel (unless
No Consider other causes of pain contraindicated)
and treat accordingly
Yes

Yes Consider muscular pain Is the pain responsive

Is the pain associated with to spasticity treatment?
severe spasticity? (secondary to spasticity)
and treat accordingly
Yes No

Consider Central Post-Stroke

Pain and treat accordingly

Figure 1. Algorithm for the assessment of Post-stroke Pain13

modified from: Magrinelli et al. Neuropathic pain: diagnosis and treatment. Prac Neurol 2013
Oct;13(5):292-307
159
 ii. Central Post-Stroke Pain (CPSP)
CPSP has no pathognomonic features, hence all other causes of obvious
nociceptive, peripheral neuropathic, or psychogenic origin of pain must be
excluded.1 A miscellany of screening tools for general neuropathic pain may be
used, however its specific diagnostic value for CPSP is unknown. In cases where
CPSP is the primary consideration, patients may be evaluated according to a
proposed grading system (Panel 1) as follows:
COMPLICATIONS
POST-STROKE

Panel 1. Proposed Diagnostic Criteria* for CPSP1

1. Exclusion of other likely causes of pain
2. Pain with a distinct neuroanatomically plausible distribution
3. A history suggestive of stroke
4. Indication of the distinct neuroanatomically plausible distribution by
clinical neurological examination
5. Indication of the relevant vascular lesion by imaging (either CT or MRI)
*Based on grading system for neuropathic pain by Treede and co-workers
Note: CPSP is defined as “possible” if criteria 1, 2, and 3 are fulfilled, “probable” if criteria
1, 2, and 3 plus either criteria 4 or 5 are fulfilled, and “definite” if criteria 1–5 are fulfilled.

iii. Post-stroke Hemiplegic Shoulder Pain (HSP)

The clinical features and diagnostic assessment for the common etiologies of
HSP are the following:

Table 1. Post-Stroke Hemiplegic Shoulder Pain14

Disorder Clinical Examination Muscle tone Diagnostic Procedure/s
Inferior Standing scapular plane
Acromiohumeral separation Flaccid
Subluxation x-ray
Positive abduction test result; Flaccid or Arthrography
Rotator Cuff Tear positive drop arm test spastic Subacromial injection of
result Magnetic resonance imaging

Shoulder-hand
Metacarpophalangeal (MCP) Flaccid or
syndrome (CRPS Triple-phase bone scan
joint compression test; skin spastic
type I) Stellate ganglion block
color changes

Adhesive External rotation <15 degrees; Spastic Arthrography

capsulitis early scapular motion

Impingement Pain with abduction of 70-90

Spastic Subacromial injection of
syndrome degrees; end range pain with
lidocaine
forward flexion

Biceps tendinitis Positive Yergason test result Flaccid or Tendon sheath injection of
spastic lidocaine

iv. Post-stroke Complex Regional Pain Syndrome (CRPS)

CRPS is diagnosed based on clinical and research criteria (Panel 2). Stroke-specific
signs and symptoms of CRPS include: pain and limited ROM of the shoulder,
wrist, and hand (with sparing of the elbow); edema, warmth, and erythema of
the wrist and hand; and tenderness of the MCP joint.2 Additional tests such
as MRI, triple-phase bone scans, and nerve conduction studies (NCS) may be
considered if deemed appropriate to exclude other differential diagnoses.

160
 Panel 2. Diagnostic Criteria for Complex Regional Pain Syndrome15
(2004 Budapest CLINICAL Diagnostic Criteria)
1. Continuing pain, which is disproportionate to any inciting event
2. Must report at least one SYMPTOM in three of the four (3/4) following categories:
Sensory reports of hyperesthesia and/or allodynia

COMPLICATIONS
reports of temperature asymmetry and/or skin color changes and/or skin
Vasomotor

POST-STROKE
color asymmetry
Sudomotor/
reports of edema and/or sweating changes and/or sweating asymmetry
edema
reports of decreased range of motion and/or motor dysfunction (weakness,
Motor/trophic
tremor, dystonia) and/or trophic changes (hair, nail, skin)

3. Must display at least one SIGN* at time of evaluation in two or more (2/4 or more) of the
following categories:
evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/
Sensory
or deep somatic pressure and/or joint movement)
evidence of temperature asymmetry and/or skin color changes and/or
Vasomotor
asymmetry
Sudomotor/
evidence of edema and/or sweating changes and/or sweating
edema
evidence of decreased range of motion and/or motor dysfunction
Motor/trophic
(weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

4. There is no other diagnosis that better explains the signs and symptoms. asymmetry

For RESEARCH purposes, diagnostic decision rule should be at least one symptom in all four
symptom categories and at least one sign (observed at evaluation) in two or more sign categories.
*A sign is counted only if observed at the time of diagnosis

E. Recommendations
All post-stroke patients with pain, after a careful clinical examination, should be treated
and monitored regularly thereafter. An effort to differentiate between nociceptive
pain (i.e. pain secondary to musculoskeletal injury) and neuropathic pain (i.e. pain
secondary to dysfunction/injury to the somatosensory system) is the initial step in
management. Nociceptive pain is generally managed with oral analgesics (e.g., WHO
analgesic ladder) similar to the management of pain associated with other medical
cases. However, there are certain pain medications that are contraindicated (e.g.,
COX-2 inhibitor) in patients with a history of stroke or cardiovascular events. Likewise,
NSAIDs should be avoided in patients with impaired renal function. Physicians should
always verify drug information when prescribing medications for pain in terms of
special precautions, anticipated side effects, and drug interactions. For the specific
subtypes of post-stroke pain, the treatment strategies/recommendations are as
follows:

i. Central Post-stroke Pain

1. Treatment protocols for CPSP usually require multi-modal approaches and
combination of various pharmacologic agents (Table 2), with due attention to
drug interactions, side effects, and precautions. It should be noted that CPSP is
usually resistant to treatment; however, the main goal of management is pain
reduction to aid in the rehabilitation and other non-pharmacologic approaches.
The recommendations of the American Heart Association/American Stroke
Association (AHA/ASA) for CPSP are as follows16:
a. Amitriptyline or lamotrigine are first-line pharmacologic treatment for CPSP
(Class IIa, level B).
b. For the elderly, nortriptyline may be a reasonable substitute for amitriptyline
161
 because of the latter’s associated side effects (Class IIa, level B).
c. Treatment with gabapentin and venlafaxine may be considered on the basis of
their efficacy in other neuropathic pain syndromes (Class IIb, level C).
d. Pregabalin, carbamazepine, levetiracetam, or opioids were not found to be
effective (Class III, level B).

Table 2. Pharmacologic Treatment Options for Central Neuropathic Pain17

COMPLICATIONS
POST-STROKE

Drug Starting dose Maximum dose Comment

especially useful in constant burning pain;
Amitryptiline 10-25 mg/day 75 mg/day
only 2nd line in depression
used as alternative first-line treatment to
Lamotrigine 25 mg/day 200-400 mg/day
TCAs

Gabapentin 300 mg/day 3600 mg/day slow elevation diminishes side-effects

Venlafaxine 37.5-75mg/day 225 mg/day (XR) off-label treatment for neuropathic pain

Pregabalin 75-150 mg/day 600 mg/day slow elevation diminishes side-effects

2. Non-pharmacologic measures:
a. Although there are evidences on the safety and efficacy of repetitive transcranial
magnetic stimulation (rTMS) and vestibular caloric stimulation (VCS)18, the SSP
makes no recommendation regarding the use of these interventions.
b. In the absence of randomized controlled trials, invasive motor cortex stimulation
(MCS) and deep brain stimulation (DBS) may be considered only in treatment-
resistant, well-selected CPSP patients.18
c. Psychological interventions may be used as part of a multidisciplinary approach
to pain management.

3. For cases of severe and persistent pain refractory to initial management, or that
which causes distress or limitation to daily functions or activities, referral to a pain
specialist is recommended.

ii. Hemiplegic Shoulder Pain

Several non-pharmacologic measures have been proposed in the management of
HSP. All patients with a suspected or confirmed HSP should be referred to a physiatrist
for further management. The following recommendations were adopted from foreign
guideline documents16,19,20 for post-stroke HSP:
1. Gentle stretching and mobilization techniques focusing on external rotation and
abduction is preferred for pain reduction and improving range of motion (Class
I, level B). Avoid using overhead pulleys (Class III, level A). The shoulder should
not be passively moved beyond 90 degrees of flexion and abduction unless there
is upward rotation of the scapula and lateral (external) rotation of the humerus.
2. It is uncertain whether joint position strategies (i.e. positioning or strapping of
hemiplegic shoulder) help prevent or reduce HSP (Class IIb, level C).
3. Functional electrical stimulation (FES) of the hemiplegic shoulder may help reduce
or prevent shoulder subluxation, but it does not appear to reduce or prevent pain.
Intramuscular electrical stimulation may be reasonable for persistent HSP (Class
IIb, level B).
4. Intramuscular botulinum toxin A injection may be used in the case of local
spasticity, however it is uncertain whether it reduces HSP or improve passive ROM
(Class IIb, level A).
5. The use of ice, heat, soft tissue massage, and oral NSAIDs before or after exercise
are reasonable for temporizing pain relief (Class IIa, level C).
6. Other interventions may be reasonable to perform in patients with persistent HSP,
162
 including intra-articular steroid injection (Class IIb, level C), aromatherapy (Class
IIb, level B), and slow-stroke back massage (Class IIb, level B).
7. Oral corticosteroids appear to improve shoulder-hand syndrome for at least the
first 4 weeks (Class IIb, level B).
8. Mirror therapy can reduce pain associated with shoulder-hand syndrome (Class
I, level A).

COMPLICATIONS
The readers may refer to the full version of the Philippine Academy of Rehabilitation

POST-STROKE
Medicine (PARM) clinical practice guidelines for stroke rehabilitation.a

iii. Post-stroke CRPS pain

At present, there is no single definitive intervention for post-stroke CRPS due to
lack of evidences. However, there is a consensus that the approach should be
interdisciplinary (e.g., co-management with rehabilitation medicine, rheumatology),
with the objectives of reducing the edema and pain, preservation of musculoskeletal
integrity, and functional restoration.2 The following recommendations are limited to
the relief of pain in adult CRPS (thus excluding other specialty-specific interventions):
1. Pharmacologic treatment for pain:
a. Bisphosphonates are efficacious in relieving CRPS-related pain.21,22 The target
doses in randomized controlled trials are as follows:

Table 3. Pharmacologic Treatment for CRPS-related Pain21

Drug Dose Comment
Suitable for patients with CRPS <6 months
Pamidronate 60 mg IV as single dose
duration as one-off treatment
7.5 mg IV OD x 3 days (or 40
Alendronate For early phases of CRPS
mg PO OD x 8 weeks)

Clodronate 300 mg IV OD x 10 days For early phases of CRPS

b. A short course of oral corticosteroids (e.g., prednisolone 30 mg/day for up to 12
weeks) may be given in the acute stage of the CRPS.22 Topical dimethylsulphoxide
(DMSO) 50% cream may be given to reduce pain in CRPS.22,4
c. Other drugs with established efficacy for neuropathic pain (e.g., tricyclic
antidepressants, selective serotonin-norepinephrine reuptake inhibitors) may be
considered, however there is limited specific evidence of their benefit in CRPS.4

2. Physiotherapy and/or occupational therapy should be instituted as early as

possible. Graded motor imagery and mirror therapy have been shown to have
evidence of efficacy in CRPS.22
3. Intravenous (IV) regional sympathetic blockade should not be used routinely, as
several RCTs have shown evidence of its non-efficacy in CRPS.21,22
4. Patient education and psychological interventions (i.e. cognitive behavioral
therapy) are integral to the management of CRPS.21

The discussion on other treatment options for CRPS (e.g. invasive therapies/
procedures) is beyond the scope of this section because there are mixed results/
conflicting evidences with regard to efficacy of its use. Nevertheless, when pain
symptoms are persistent or if the above treatment options are unsuccessful,
patients should be referred to a pain specialist even if other management (e.g.,
physiotherapy) is ongoing.21

a
Available at http://www.eparm.org

163
 References
1. Klit H, Finnerup N, Jensen TS. Central Post-Stroke Pain: clinical characteristics, pathophysiology, and
management. Lancet Neurol. 2009; 8:857-68.
2. Chae J. Poststroke complex regional pain syndrome. Top Stroke Rehabil. 2010 May-Jun;17(3):151-62.
3. Parkitny L, McAuley JH, Di Pietro F, et al. Inflammation in complex regional pain syndrome: a systematic
review and meta-analysis. Neurology. 2013 Jan 1;80(1):106-117.
4. Perez RS, Zollinger PE, Dijkstra PU, et al. Evidence based guidelines for complex regional pain syndrome.
BMC Neurol. 2010; 10: 1471-1485.
COMPLICATIONS

5. Lo SF, Chen SY, Lin HC, et al. Arthrographic and clinical findings in patients with hemiplegic shoulder pain.
POST-STROKE

Arch Phys Med Rehabil. 2003 Dec;84(12):1786-91.

6. Ward AB. Hemiplegic Shoulder Pain. J Neurol Neurosurg Psychiatry. 2007 August; 78(8): 789.
7. O'Donnell MJ, Diener HC, Sacco RL, et al.; PRoFESS Investigators. Chronic pain syndromes after ischemic
stroke: PRoFESS trial. Stroke. 2013 May;44(5):1238-43.
8. Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain. Pain.
1995;61(2):187–193.
9. Harvey R. Central Post-Stroke Pain Syndrome. In: Benzon H, Rathmell JP, Wu Cl, et al. (eds.) Practical
Management of Pain, 5th ed. Philadelphia, PA: Mosby; 2014:374-380.
10. Coskun Benlidayi I, Basaran S. Hemiplegic shoulder pain: a common clinical consequence of stroke. Pract
Neurol. 2014 Apr;14(2):88-91.
11. Lindgren I, Jönsson AC, Norrving B, Lindgren A. Shoulder pain after stroke: a prospective population-
based study. Stroke. 2007;38:343–348.
12. Roy CW, Sands MR, Hill LD. Shoulder pain in acutely admitted hemiplegics. Clin Rehabil. 1994;8:334–340.
13. Magrinelli F, Zanette G, Tamburin S. Neuropathic pain: diagnosis and treatment. Prac Neurol. 2013
Oct;13(5):292-307.
14. Black-Schaffer RM. Stroke in Young Adults. In: Frontera W, Silver J, Rizzo T. (eds.) Essentials of Physical
Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation. 2nd ed. Philadelphia:
Saunders; 2008:894.
15. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional
pain syndrome. Pain Med. 2007 May-Jun;8(4):326-31.
16. Holloway RG, Arnold RM, Creutzfeldt CJ, et al. Palliative and End-of-life Care in Stroke: A Statement
for Healthcare professionals from the American Heart Association/American Stroke Association. Stroke.
2014;45:000-000.
17. Albet SJ, Kesselring J. Neurorehabilitation. In: Brainin M, Heiss W-D. (eds.) Textbook of Stroke Medicine.
Cambridge, UK: Cambridge University Press; 2009:287.
18. Kumar B, Kalita J, Kumar G, Misra UK. Central poststoke pain: a review of pathophysiology and treatment.
Anesth Analg. 2009;108(5):1645-1657.
19. Mehta S, Teasell R, Foley N. Painful Hemiplegic Shoulder. Evidence-Based Review of Stroke Rehabilitation.
16th ed. 2013. EBRSR Web site. Available at: http://www.ebrsr.com/sites/default/files/Chapter11_
HemiplegicShoulder_FINAL__16ed.pdf. Accessed June 20, 2014.
20. Miller EL, Murray L, Richards L, et al. Comprehensive overview of nursing and interdisciplinary
rehabilitation care of the stroke patient: a scientific statement from the American Heart Association. Stroke.
2010 Oct;41(10):2402-48.
21. Goebel A, Barker CH, Turner-Stokes, et al. Complex regional pain syndrome in adults: UK guidelines for
diagnosis, referral and management in primary and secondary care. London: Royal College of Physicians,
2012.
22. Salibi A, Searle AE, Lindau TR. Complex Regional Pain Syndrome: A Systemic Review of the Literature, the
Past, Present and Future Management. J Pain Relief. 2014;3:128.

II. POST-STROKE SEIZURES

A. Epidemiology
1. Prevalence and Incidence of Post-Stroke Seizures
i. Post-stroke seizure is classified as early-onset if it occurs within seven (7) days
after ictus, and late-onset if it occurs beyond 7 days. Early post-stroke seizures
are postulated to be secondary to a cellular biochemical dysfunction1, while
late-onset seizures are considered as a true post-stroke epilepsy secondary to
gliosis and development of meningocerebral cicatrix.2
ii. Stroke patients, particularly those with hemorrhagic stroke, have a significantly
higher risk of developing epilepsy. Epilepsy often develops within the first three
(3) years after a hemorrhagic stroke. The incidence appears to accumulate with
time after the stroke event.3

2. Epidemiology of Post-Stroke Seizures Based on Stroke Subtype

164
 i. The rate of post-stroke epilepsy is highest among patients with multiple stroke
subtypes (7.7%), followed by intracerebral hemorrhage (4.3%), subarachnoid
hemorrhage (4.2%), other/unspecified intracranial hemorrhage (2.5%), and
ischemic stroke (1.6%).3
ii. The estimated rates of early post-ischemic stroke seizures and late onset seizures
range from 2% to 33% and 3% to 67% respectively.4
iii. The subtype of ischemic stroke (i.e. cardioembolic stroke), stroke location (i.e.

COMPLICATIONS
cortical), and possibly stroke severity, are considered as possible predictors of

POST-STROKE
post-stroke seizures.4
3. Outcome of Patients with Post-Stroke Seizures
i. The general outcome of patients with early-onset seizures is poor with a high
incidence of status epilepticus and in-hospital mortality rate. Patients with late-
onset seizures have a 50% recurrence rate within a 5-year period. The disability in
stroke patients, including progressive vascular decline, is increased with recurrent
seizures and status epilepticus.5

B. Risk Modification
1. Primary Prevention
i. Risk Factors Associated with Post-Stroke Seizures
(a) Patients with severe stroke at onset, hemorrhagic stroke, or stroke involving the
cerebral cortex may be at increased risk of developing post-stroke seizures.
However, the risk factors are still under debate.4
(b) Identified risk factors for the development of early seizures in patients with
aneurysmal subarachnoid hemorrhage include aneurysm in the middle cerebral
artery (MCA), thickness of clot, associated intracerebral hematoma, re-bleeding,
infarction, poor neurological grade, and history of hypertension.6
ii. Effects of Prophylaxis or Early Treatment on Late Post-Stroke Seizures
(a) There is limited data on the efficacy of anticonvulsants in the management of
post-ischemic stroke seizures. The recommendation is based on the current
management guidelines for seizures complicating any neurological illness.
To date, there is no proven advantage of prophylactic use of anticonvulsants
after ischemic stroke.7 As per recommendations of most recent guidelines,
prophylactic anticonvulsants should not be given in patients with spontaneous
intracerebral hemorrhage (Class III, Level B).
(b) Short-term prophylactic anticonvulsant therapy is commonly used in patients
with aneurysmal subarachnoid hemorrhage, although the evidence supporting
its use remains lacking.6

C. Recommendation
i. The general principles of seizure management using anticonvulsant medications in
patients with early- or late-onset seizures may be applied, although there is still no
consensus as to the preferred medication/s, dosage/s, and duration of treatment
(Class IIa, level B).
ii. The choice of anticonvulsants should be guided by the individual characteristics
of patients, including concurrent medications and other comorbidities (Class IIa,
level B).
iii. The use of prophylactic anticonvulsant medications may be considered in the
immediate post-hemorrhagic period in aneurysmal subarachnoid hemorrhage
(Class IIb, level B), although routine and long-term use of anticonvulsants is not
recommended (Class III, level B). The use of anticonvulsants may be considered for
patients with identified risk factors for developing late-onset seizures such as prior
seizures, intracerebral hematoma, intractable hypertension, and MCA infarction or
aneurysm (Class IIb, level B).

165
 III. POST-STROKE DEPRESSION
A. Epidemiology
1. Post-stroke depression is regarded as the most common and important
neuropsychiatric complication affecting about one-third of post-stroke patients.
It leads to significant negative effects in terms of motor and cognitive recovery,
functional return to previous activities, and over-all survival. It peaks at about three
(3) to six (6) months after stroke, whereas the prevalence declines to about 50% of its
COMPLICATIONS

initial rate thereafter.8

POST-STROKE

2. Depression appears to have a cumulative incidence of up to 52% within five (5) years
of stroke, with a pooled prevalence of about 29% that remains stable in the first 10
years after stroke as seen in the different trials.9
B. Risk Modification
1. Depressed mood, reduced appetite, and crying are the symptoms considered to be
more sensitive in the diagnosis of post-stroke depression. Apathy, feelings of guilt,
and lack of insight are considered as less reliable indicators.10
2. Beck Depression Inventory, Hamilton Depression Rating Scale, and Clinical Global
Impression may be used for evaluating depression in stroke patients.11
3. Predictors of depression after stroke include disability after stroke, history of
depression prior to stroke, cognitive impairment, stroke severity, lack of family or
social support, and anxiety. The location of stroke lesion is not considered as a
predictor of post-stroke depression.9
4. The use of antidepressants after stroke is effective in reducing the symptoms of
depression.12 Prophylaxis using antidepressants is associated with a significant
reduction in the incidence of post-stroke depression.13 Selective Serotonin Reuptake
Inhibitors (SSRIs) are the recommended pharmacologic therapy for patients with
post-stroke depression because of their favorable tolerability profiles.14
5. SSRIs appear to improve dependence, disability, neurological impairment, and
depression after stroke.15 Giving fluoxetine to non-depressed stroke patients during
the first three (3) months enhanced maximum motor recovery. The benefits of SSRIs
were still evident at one (1) year even after the discontinuation of treatment.16
6. SSRI use among patients with ischemic stroke was associated with a lower risk of
new-onset ischemic events. However, it was associated with an increased overall
bleeding risk, and a non-significantly increased risk of intracranial bleeding.17
7. At present, there is no scientific evidence prescribing an optimal length of duration
of treatment. However, a duration of 4 to 6 months followed by gradual tapering is
suggested.14
C. Recommendation
i. The use of Beck Depression Inventory, Hamilton Depression Rating Scale, or
Clinical Global Impression as rating scales to evaluate post-stroke depression is
reasonable (Class IIa, level C).
ii. The use of antidepressants for the treatment of post-stroke depression is
recommended (Class I, level A).
iii. The use of antidepressants for the prevention of post-stroke depression may be
reasonable (Class IIb, level B).

IV. POST-STROKE DEMENTIA

A. Epidemiology
1. Prevalence and Incidence of Post-Stroke Dementia
i. Post-stroke dementia refers to a dementia whose onset is after the diagnosis of
symptomatic stroke. It is estimated to increase at an average of 3% per year.18
ii. The prevalence of post-stroke dementia varies in relation to the time interval post-
stroke, definition of dementia, location and size of the infarct, and other criteria
used. In a population-based study by Kokmen et al., the prevalence of dementia
was 30% within one year post-stroke, with the incidence increasing from 7% after
166
 1 year to as high as 48% after 25 years.19
iii. The most common disease contributing to the development of cognitive
impairment is cerebral infarction; other factors such as small-vessel disease and
white matter ischemic changes contribute to its development in older people up
to about >75%.20
iv. Neuroimaging findings of silent cerebral infarcts, white matter changes, and global
and medial temporal lobe atrophy are associated with increased risk of post-

COMPLICATIONS
stroke dementia.21 Strategic locations include left angular gyrus, inferomesial

POST-STROKE
temporal region, mesial frontal region, anterior and dorsomedial thalamus, left
capsular genu, and caudate nuclei.
v. Patients with vascular dementia usually present with cognitive impairment related
to compromised executive functioning involving goal-directed behavior, initiation
of sequences, and problem-solving activities; these are assessed with the use of
trail making test or clock drawing test.22

B. Risk Modification
1. In general, the risk of developing dementia is increased with ageing, fewer years
of education, history of diabetes mellitus, atrial fibrillation, and recurrent stroke.23
Post-stroke dementia may be more frequent among patients aged 80 years and
above.24
2. Due to the strong relationship between vascular risk factors and the development
of stroke, control of high blood pressure (BP), blood cholesterol levels, thrombosis,
and blood viscosity can also reduce post-stroke dementia.25
3. BP lowering was associated with decreased cognitive decline as manifested by a
reduction in the Mini-Mental Status Examination (MMSE) of 3 to 4 or more points,
with an odds ratio (OR) of 0.92. The noted reduction in dementia however, was not
significant (OR=0.93).25 The PROGRESS trial indirectly compared the effect of BP
lowering by comparing post-stroke patients randomized to combination therapy
with perindopril and indapamide or monotherapy with perindopril. There were
larger reductions in BP, stroke recurrence, and “all dementia” among those who
have received combination therapy as compared with the control group.26
4. Currently there are no randomized trials that established the use of statins for the
prevention and treatment of post-stroke dementia.
5. Also, there are no randomized trials that established the use of cholinesterase
inhibitors for the prevention of post-stroke dementia. However, the use of
donepezil for treatment of established mild to moderate vascular cognitive
impairment showed an improvement in the cognitive function as measured by
MMSE and ADAS-Cog.27
6. Cerebral amyloid angiopathy (CAA) is a relatively common and important factor
leading to age-related small-vessel disease and vascular cognitive impairment.
Comorbid vascular risk factors such as hypertension, diabetes mellitus, and
smoking may worsen the effect of CAA and are potential targets for treatment.20

C. Recommendation
1. The use of neuroimaging with CT or MRI is recommended in supporting the
diagnosis of vascular cognitive impairment (Class IIb, level B).
2. It is reasonable to use Magnetic Resonance Imaging with Gradient Recall Echo
sequences in patients who present with cognitive impairment to detect the presence
of multiple lobar hemorrhagic lesions characteristic of a probable CAA (Class IIa,
level B).
3. In patients with a suspected CAA, treatment of cardiovascular risk factors is
reasonable (Class IIa, level C).
4. Control of vascular risk factors, which leads to a decreased risk of developing stroke,
is reasonable (Class IIa, level C).
5. The use of cholinesterase inhibitors for the prevention of post-stroke dementia is
not recommended (Class III, level B).
6. The use of cholinesterase inhibitors, specifically donepezil, for the treatment of post-
stroke dementia is recommended (Class I, level B).
167
 References
1. Luhmann HJ. Ischemia and lesion induced imbalances in cortical function. Prog Neurobiol. 1996;48:131-
166.
2. Lesser RP, Luders H, Dinner DS, Morris HH. Epileptic seizures due to thrombotic and embolic
cerebrovascular disease in older patients. Epilepsia. 1985;26:622-630.
3. Chen TC, Chen YY, Cheng PY, et al. The incidence rate of post-stroke epilepsy: A 5-year follow-up study in
COMPLICATIONS

Taiwan. Epilepsy Research. 2012;102:188-194.

POST-STROKE

4. Camilo O, Goldstein L. Seizures and epilepsy after ischemic stroke. Stroke. 2004;35:1769-1775.
5. De Reuck J. Management of stroke related seizures. Acta Neurologica Belgium. 2009;109:271-276.
6. Connoly ES, Rabinstein A, Carhuapoma R, et al. Guidelines for the Management of Aneurysmal
Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/
American Stroke Association. Stroke. 2012;43:00-00.
7. Jauch E, Saver J, Adams H, et al. Guidelines for the early management of patients with acute ischemic
stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke
Association. Stroke. 2013;44:870-947.
8. Ebrahim S, Barer D, Nouri F. Affective illness after stroke. Br J Psychiatry. 1987;151:52-56.
9. Ayerbe L, Ayis S, Wolfe C, Rudd A. Natural history, predictors, and outcomes of depression after stroke:
systematic review and meta-analysis. Br J Psychiatry. 2013;202:14-21.
10. Raskind M. Diagnosis and treatment of depression comorbid with neurologic disorders. Am J Med.
2008:121;S28-37.
11. Berg A, Psych L, Lonnqvist J, et al. Assessment of depression after stroke: a comparison of the different
screening instruments. Stroke. 2009;40:523-529.
12. Chen Y, Guo JJ. 2006. Meta-analysis of antidepressant treatment for patients with poststroke depression.
Stroke. 2006:37:1365–1366.
13. Chen Y, Patel NC, Guo JJ, et al. 2007. Antidepressant prophylaxis for poststroke depression: a meta-analysis.
Int Clin Psychopharmacol. 2007;22:159–66.
14. Turner-Stokes L, Hassan N. Depression after stroke: a review of the evidence base to inform the development
of an integrated care pathway. Part 2: Treatment alternatives. Clin Rehabil. 2002;16:248–60.
15. Mead G, Hsieh C, Lee R, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane
Database Syst Rev. 2012;14;11:CD009286.
16. Chollet F, Tardy J, Albucher JF, et al. Fluoxetine in motor recovery after acute ischaemic stroke (FLAME): a
randomised placebo-controlled trial. Lancet Neurol. 2011;10:123-130.
17. Mortensen JK, Larrson H, Johnsen SP, Andersen G. Poststroke use of selective serotonin reuptake inhibitors
and clinical outcome among patients with ischemic stroke: a nationwide propensity score – matched follow-
up study. Stroke. 2013;44:420-426.
18. Pendlebury S, Rothwell P. Prevalence, incidence, and factors associated with pre-stroke and post-stroke
dementia: a systematic review and meta-analysis. Lancet Neurol. 2009.
19. Kokmen E, Whisnant JP, O’Fallon WM, et al. Dementia after ischemic stroke: a population-based study in
Rochester, Minnesota (1960-1984). Neurology. 1996;46:154 –159.
20. Gorelick P, Scuteri A, Black S, et al. Vascular contributions to cognitive impairment and dementia: a
statement for healthcare professionals from the American Heart Association/American Stroke Association.
Stroke. 2011;42:2672-2713.
21. Leys D, He´non H, Mackowiak-Cordoliani MA, Pasquier F. Post-stroke dementia. Lancet Neurol.
2005;4:752–759.
22. Roman G. Vascular dementia: distinguishing characteristics, treatment and prevention. J Am Geriatr Soc.
2003.51;S296-304.
23. Srikanth VK, Quinn SJ, Donnan GA, et al. Long-term cognitive transitions, rates of cognitive change, and
predictors of incident dementia in a population-based first-ever stroke cohort. Stroke. 2006;37:2479 –2483.
24. Ivan C, Seshadri S, Beiser A, et al. Dementia after stroke: the Framingham Study. Stroke. 2004;35: 1264–
1268.
25. Anokolekar S, Geegenage C, Anderton P, et al. Clinical trials for preventing post stroke cognitive
impairment. J Neurol Sci. 2010;209:168-174.
26. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and
indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch
Intern Med. 2003;163(9):1069–75.
27. Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev.
2004;1:CD004395.

168
 CHAPTER IX
Special Topics In Stroke Management

I. Stroke in Infants and Children

II. Stroke in the Young
III. Stroke in Pregnancy and the Puerperium
IV. Movement Disorders in Stroke
V. Small Vessel Diseases: Lacunar Stroke and Microbleeds

Sixth
Edition
2014
 Special Topics In Stroke Management
I. STROKE IN INFANTS AND CHILDREN
A. Epidemiology
Pediatric stroke occurs with an annual incidence of 2-8 per 100,000 individuals.1 In
the Philippines, 730 cases were documented from 2004 to 2009 in three (3) existing
child neurology training institutionsa, with hemorrhagic stroke as the most common
type (61%), followed by arterial ischemic stroke (AIS) (37%) and cerebral venous
sinus (sinovenous) thrombosis (CSVT or CVT) (2%). These findings are in contrast to
observations in foreign literature that ischemic stroke is either more common or just
as common as hemorrhagic stroke.2

According to the International Pediatric Stroke Society (IPSS), the frequency of AIS
is highest during the neonatal period.3 In the Philippines, the highest frequency
of pediatric AIS was noted in the first to fifth year. Neonatal ischemic stroke is
underdiagnosed locally because of the paucity of focal findings in this age group,
hence the low index of suspicion and underutilization of appropriate neuroimaging
special
topics

studies. Furthermore, cranial sonography has a low sensitivity (30.6%) for detecting
AIS in term neonates.4 Based on local data, hemorrhagic stroke is most frequent in
children aged 29 days to <1 year old. This high frequency is possibly correlated with
the occurrence of acquired prothrombin complex deficiency (APCD).

B. Etiology/Risk Factors
I. Ischemic Stroke
Stroke usually results from an interplay of multiple risk factors. However, as much as
30% of children with stroke do not have an identifiable risk factor despite extensive
investigations.2 The four main risk factors for childhood AIS are the following:
1. Congenital and acquired cardiac conditions (most common in foreign literature)
2. Cerebral arteriopathies (e.g., arterial dissection, Moyamoya disease, transient
cerebral arteriopathy, CNS vasculitis)
3. Hypercoagulable states (e.g., Protein C deficiency, systemic lupus
erythematosus, post-chemotherapy)
4. CNS infection (leading risk factor in the Philippines)b

Post-varicella angiopathy is also considered as a cause of stroke if the patient has

history of varicella infection within 12 months of stroke onset.5 Within 0-6 months
post-varicella infection, there is also a 4-fold increased risk of stroke.6 Recent trauma
and acute infection are also common independent risk factors for childhood AIS.7
Maternal factors such as hypertension, smoking during pregnancy8, and intrapartal
fever9 are also associated with perinatal stroke.

Recurrence is usually within 6 months from the initial stroke, and is associated with
the presence and severity of vasculopathy and prothrombotic risk factors. The risk
of recurrence is 10%-25% among infants and children and <5% in neonates. The
presence of multiple risk factors is associated with 48% recurrence, versus 8% among
those with single or no risk factors identified.10

II. Hemorrhagic Stroke

The causes of hemorrhagic stroke in the pediatric group include cerebrovascular
malformations (e.g., arteriovenous and cavernous malformations, aneurysms,
developmental venous anomaly, capillary telangiectasia), hematologic and
coagulation disorders (e.g., APCD), and tumor bleed. APCD is prevalent among
breastfed infants; it occurs because of the deficiency of vitamin K-dependent clotting
factors.
a
Child neurology training institutions: Philippine Children’s Medical Center, Philippine General Hospital,
University of Santo Tomas Hospital
b
Mycobacterium tuberculosis is the most common etiologic agent identified in CNS infections
170
C. Clinical Presentation
Older children may present with sudden onset of focal neurological deficits similar
to adults, although this is not common among neonates, whose strokes are heralded
by seizures or decreased sensorium. Predictors of neonatal stroke (versus hypoxic
ischemic encephalopathy) include focal motor seizure with onset beyond the 12 hours
of life.11 Thus, a high index of suspicion is required in neonates, and that stroke should
be a differential diagnosis especially among those with inherent risk factors. Perinatal
ischemic stroke is diagnosed in infants (beyond age 28 days) presenting with early
hand preference or asymmetry of grasp at about 4 to 8 months, and in whom it is
presumed that an ischemic event occurred perinatally.12

Stroke Mimics
Some conditions that mimic stroke in children are different from adults. These
include hemiplegic migraine, mitochondrial encephalopathy, lactic acidosis and
stroke (MELAS) syndrome, post-ictal (Todd’s) paralysis, and demyelinating diseases
(e.g., multiple sclerosis).13

D. Diagnostic Work-up
Cranial MRI with diffusion-weighted imaging (DWI) and magnetic resonance

Special
Topics
angiography (MRA) of the head +/- neck (as needed especially if an arterial dissection
is considered) are the diagnostic imaging studies of choice for AIS in children. MRA
of the head +/- neck or CT angiography (CTA) is used to look for arteriopathies as a
cause of stroke. However, if the MRA or CTA findings are equivocal and that a higher
resolution is needed, catheter angiography remains as the gold standard especially
in cases of hemorrhagic stroke. In cases of CSVT, cranial CT or MR venogram (MRV)
should be requested.

Cranial ultrasound can be helpful in neonates and young infants with open anterior
fontanels. It can be done at bedside and does not require sedation. It is a good
neuroimaging tool in the detection of germinal matrix-intraventricular hemorrhage
(IVH) among neonates. However, cranial ultrasonography has low sensitivity (30.6%)
for detecting arterial ischemic stroke in term neonates.4

Work-up in children also includes thrombophilia screening such as anti-thrombin

III, protein C, protein S, activated protein C resistance, lipoprotein (a), homocysteine,
anti-cardiolipin antibodies, lupus anticoagulant, factor VIII, factor IX, factor XI,
plasminogen, and fibrinogen. These laboratory tests are locally available in specialized
centers. Testing for genetic mutations such as prothrombin gene 20210 A, methylene
tetrahydrofolate reductase (MTHFR), and Factor V Leiden are not locally available on
commercial scale. Echocardiography with bubble study is done to look for cardiac risk
factors. If suspected, work-up for vasculitis (e.g., ANA, ANCA) and CNS infection should
be performed.

E. Management
The SSP adopts the guidelines of the American Heart Association/American Stroke
Association (AHA/ASA) for the management of stroke in infants and children. A
multimodal approach to stroke management is recommended to improve patient
outcomes.2
I. Arterial Ischemic Stroke
1. Medical Management
i. Treat the underlying risk factor/s (Class I, level C).
ii. Recommendation for Antithrombotic agents:
A. Acute Stroke
1. Tissue plasminogen activator (t-PA) has been used for acute stroke in selected centers
abroad.14,15 It is not recommended for children with AIS outside of a clinical trial (Class
III, level C). There no consensus yet regarding its use in older adolescents meeting the
adult t-PA eligibility criteria.
171
 2. Heparin (i.e. unfractioned [UFH], low-molecular-weight [LMWH]) may be given up to 1
week after an ischemic stroke pending further evaluation to determine the cause of
the stroke (Class IIb, level C).
B. Secondary Stroke Prophylaxis
1. LMWH for cardioembolic strokes (Class I, level C), extracranial arterial dissection (Class
IIa, level C), selected prothrombotic states (Class I, level C), and recurrent strokes or
TIA while on therapeutic aspirin.
2. Warfarin for cardioembolic strokes (Class IIa, level C), extracranial arterial dissection
(Class IIa, level C), and selected prothrombotic states (Class IIa, level C).
3. Antiplatelets: Aspirin (Class IIa, level C) with a dose of 3-5 mg/kg/day, or reduced to 1-3
mg/kg/day if with dose-related side effects; or Clopidogrel if unable to take aspirin
or aspirin failure.

2. Surgical management
i. Revascularization surgery for Moyamoya syndrome (Class I, level B) with
progressive ischemic symptoms or evidence of inadequate blood flow or
cerebral perfusion reserve in individuals without contraindication to surgery.
ii. Decompressive hemicraniectomy as needed.
special
topics

3. Supportive management
i. Control of fever and hypertension, maintenance of normal oxygenation, and
normalization of serum glucose levels are recommended (Class I, level C).
ii. Treatment of dehydration and anemia is reasonable (Class IIa, level C).
iii. Supplemental oxygen in the absence of hypoxemia, seizure prophylaxis, and
hypothermia are not recommended (Class III, level C).

4. Rehabilitation
i. Age-appropriate rehabilitation therapy is recommended (Class I, level C).
ii. Psychological assessment is recommended to document cognitive and
language deficits for planning therapy and educational programs (Class I, level
C).

II. Cerebral Sinovenous Thrombosis (CSVT)16

Class I Recommendation
1. Supportive measures include appropriate hydration, control of epileptic
seizures, and treatment of elevated intracranial pressure (ICP) (Class I, level C).
2. Children with CSVT should have a complete blood count (Class I, level C).
Anemia and infection are risk factors in the development of CSVT.
3. Children with suspected bacterial infection should receive appropriate
antibiotics (Class I, level C).
4. Periodic assessments of the visual fields and visual acuity should be done, and
appropriate measures to control elevated ICP and its complications should be
instituted (Class I, level C).
5. If anticoagulation is initially withheld, repeat neuroimaging (including venous
imaging) is recommended in the first week after diagnosis to monitor for
propagation of the initial thrombus, new infarcts, or hemorrhage (Class I, level
C).

Class II Recommendation
1. Children with CSVT may benefit from a thorough thrombophilia screen to
identify underlying coagulation defects, some of which could affect the risk
of subsequent re-thromboses and influence therapeutic decisions (Class IIb,
level B).
2. Children with CSVT may benefit from investigation for underlying infections
with blood cultures and sinus radiographs (Class IIb, level B).
3. ICP monitoring may be considered during the acute phase of CSVT (Class IIb,
level C).
172
 4. It is reasonable to repeat neuroimaging studies in children with CSVT to
confirm vessel recanalization or recurrence of thrombus (Class IIa, level C).
5. Given the frequency of epileptic seizures in children with acute CSVT,
continuous electroencephalography monitoring may be considered for
individuals who are unconscious and/or mechanically ventilated (Class IIb,
level C).
6. In children with acute CSVT diagnosed beyond the first 28 days of life, it
is reasonable to institute either intravenous UFH or subcutaneous LMWH,
whether or not there is secondary hemorrhage, and continue LMWH or
warfarin therapy for 3-6 months (Class IIa, level C).
7. In neonates with acute CSVT, treatment with LMWH or UFH may be considered
(Class IIb, level B) and continued for 6 weeks to 3 months (Class IIb, level C).
8. If initial anticoagulation is started, it is reasonable to perform a head CT or
MRI in the first week after treatment to monitor for additional hemorrhage
(Class IIa, level C).
9. In selected children with CSVT, administration of a thrombolytic agent may be
considered (Class IIb, level C).
10. The usefulness and safety of endovascular intervention is uncertain in
pediatric patients, and its use may only be considered in carefully selected

Special
Topics
patients with progressive neurological deterioration despite intensive and
therapeutic levels of anticoagulant (Class IIb, level C).

III. Hemorrhagic Stroke2

Class I Recommendation
1. Children with non-traumatic brain hemorrhage should undergo a thorough
evaluation including standard cerebral angiography when non-invasive tests
have failed to establish an origin, in an effort to identify treatable risk factors
before another hemorrhage occurs (Class I, level C).
2. Children with severe coagulation factor deficiency should receive appropriate
factor replacement therapy, and children with less severe factor deficiency
should receive factor replacement after trauma (Class I, level A).
3. Given the risk of repeat hemorrhage from congenital vascular anomalies, these
lesions should be identified and corrected whenever it is clinically feasible.
Similarly, other treatable hemorrhagic risk factors should be corrected (Class
I, level C).
4. Stabilizing measures in patients with brain hemorrhage should include
optimizing respiratory effort, controlling systemic hypertension, controlling
epileptic seizures, and managing increased ICP (Class I, level C).

Class II Recommendation
1. It is reasonable to follow-up asymptomatic individuals who have a condition
that predisposes them to intracranial aneurysms with a cranial MRA every 1
to 5 years, depending on the perceived level of risk posed by an underlying
condition (Class IIa, level C). Should the individual develop symptoms that
could be explained by an aneurysm, CTA or catheter angiography (CA) may
be considered even if the patient’s MRA fails to show evidence of aneurysm
(Class IIb, level C). Given the possible need for repeated studies over a period
of years, CTA may be preferable to CA for screening individuals at risk for
aneurysm (Class IIb, level C).
2. Children with SAH may benefit from measures to control cerebral vasospasm
(Class IIb, level C).

Class III Recommendation

1. Surgical evacuation of a supratentorial intracerebral hematoma is not
recommended for most patients (Class III, level C). However, information from
a small number of patients suggest that surgery may help selected individuals
with developing brain herniation or extremely elevated ICP.
173
 References

1. Kirton A, Hill M, deVeber G. Arterial ischemic stroke in neonates and children: Review & Current issues.
Curr Pediatr Rev. 2006;2:1-14.
2. Roach S, Golomb M, Adams R, et al. Management of Stroke in Infants and Children: A Scientific Statement
from a Special writing group of the American Heart Association Stroke Council and the Council on
Cardiovascular Disease in the Young. Stroke. 2008;39:2644-2691.
3. Golomb MR, Fullerton HJ, Nowak-Gottl U, et al.; International Pediatric Stroke Study. Male predominance
in childhood ischemic stroke findings from the International Pediatric Stroke Study. Stroke 2009;40:52–7.
4. Golomb MR, Dick P, MacGregor D, et al. Cranial sonography has a low sensitivity for detecting arterial
ischemic stroke in term neonates. J Child Neurol. 2003;18:98-103.
5. Askalan R, Laughlin S, Mayank S, et al. Chickenpox and stroke in childhood: a study of frequency and
causation. Stroke. 2001;32:1257-62.
6. Thomas SL, Minassian C. Ganesan V, et al. Chickenpox and Risk of Stroke: A self-controlled case series
analysis. Clin Infect Dis. 2014 Jan;58(1):61-8.
7. Hills NK, Johnston SC, Sidney S, et al. Recent trauma and acute infection as risk factors for childhood
arterial ischemic stroke. Ann Neurol. 2012;72:850-8.
8. Darmency-Stamboul V, Chantegret C, Ferdynus C, et al. Antenatal factors associated with perinatal
arterial ischemic stroke. Stroke. 2012; 43:2307-12.
special
topics

9. Mann JR, McDermott S, Pan C, Hardin JW. Maternal hypertension and intrapartum fever are associated
with increased risk of ischemic stroke during infancy. Dev Med Child Neurol. 2013; 55:58-64.
10. Lanthier S, Carmant L, David M, et al. Stroke in children: the coexistence of multiple risk factors predicts
poor outcome. Neurology 2000; 54:371-378.
11. Rafay MF, Cortez MA, de Veber GA, et al. Predictive value of clinical and EEG features in the diagnosis of
stroke and hypoxic ischemic encephalopathy in neonates with seizures. Stroke. 2009;40:2402-7.
12. Kirton A, de Veber GA. Cerebral palsy secondary to perinatal ischemic stroke. Clin Perinatol. 2006
Jun;33(2):367-86.
13. Shellhaas RA, Smith SE, O’Tool E, et al. Mimics of childhood stroke: characteristics of a prospective
cohort. Pediatrics. 2006;118:704-9.
14. Janmaat M, Gravendeel JP, Uyttenboogaart M et, al. Local intra-arterial thrombolysis in a 4-year old male
with vertebrobasilar artery thrombosis. Dev Med Child Neurol. 2009 Feb;51(2):155-8.
15. Amlie-Lefond C, deVeber G, Chan AK, et al. Use of alteplase in childhood arterial ischemic stroke: a
multicentre, observational, cohort study. Lancet Neurol. 2009;8:530-6.
16. Saposnik G, Barinagarrementeria F, Brown R, et al. Diagnosis and management of cerebral venous
thrombosis. Stroke. 2011. 42:1158-92.

174
II. STROKE IN THE YOUNG
The term “Stroke in the Young” (SIY) is defined as stroke occurring in individuals
whose age is 45 years or less. Other studies, however, set the age of 50 as the upper
limit of SIY because of the similitude of stroke mechanisms observed in younger
patients and those between 45-49 years of age.

A. Epidemiology
SIY accounts for about 10% to 14% of stroke cases.1 In this age group, the annual
incidence of ischemic stroke is 10-23 cases per 100,000 individuals, and 3-9 cases
per 100,000 for hemorrhagic stroke. The Northern Manhattan stroke study noted
the following percent distributions of SIY subtypes: 50% for ischemic strokes, 30%
for subarachnoid hemorrhage (SAH), and 20% for intracerebral hemorrhage (ICH).2

The incidence of SIY may be higher in developing countries because of the high
incidence of cerebrovascular diseases from undiagnosed or uncontrolled vascular
risk factors, as well as uncommon causes such as infections and rheumatic heart
disease. This observation was consistent in a number of Asian SIY studies.3-5 However,

Special
little is known about SIY in the Philippines due to few published studies.

Topics
B. Recognition Of Stroke And Differential Diagnosis
In most cases, the signs and symptoms of SIY are similar to that of older patients.
Young patients with stroke, however, may initially present with various uncommon
signs and symptoms, which can be more difficult to recognize. The misdiagnosis
of stroke in young patients occur because of overdiagnosis (i.e. attributing a non-
stroke condition to stroke) or underdiagnosis (i.e. attributing an actual stroke to
a nonstroke condition).6 The suspicion for stroke is usually low in young adults
because traditional vascular risk factors are less frequent, absent, or atypical to
some patients.

The most frequent mimics or causes of overdiagnosis include acute confusional

state or delirium, syncope, seizures, acute vestibular syndrome, migraine, infections,
brain tumors, encephalopathy, toxins, gastroenteritis, and conversion disorder.
Other less frequent causes include cardiac events, viral encephalitis (i.e. herpes
simplex virus [HSV]), demyelinating diseases, and neuromuscular disorders (e.g.,
myasthenia gravis). Predictors of underdiagnosis of SIY in the emergency setting
include young age of onset and the occurrence of posterior fossa infarcts.7 In a
prospective study which assessed the impact of emergency room (ER) neurologists
on patient management and outcome, dizziness is the most common symptom
associated with missed diagnosis of stroke.8

Adolescents and children may present with seizures or headache at the onset of
stroke. The prevalence of seizures during acute stroke is more common in younger
individuals and in those with hemorrhagic strokes or cortical infarcts.9 Although
the most frequent diagnosis for motor weakness following a seizure event is a
postictal (Todd’s) paralysis, stroke should not be immediately excluded until proven
otherwise.

Another common cause of misdiagnosis in young stroke patients is the attribution

of headache (isolated or with associated non-specific symptoms) to migraine. In
such cases, the abruptness of onset favors the diagnosis of stroke than complicated
migraines. Likewise, the sensory deficit is usually abrupt in stroke as compared to
the “migrating” quality in migraine (about 20-30 minutes) (See Appendix C for IHS
Diagnostic Criteria). Isolated headaches can also occur with arterial dissections,
cerebral venous thrombosis (CVT), and SAH.9

175
 C. Etiology

C.1. Ischemic Stroke

Similar to the elderly, the causes of ischemic stroke in young patients are
heterogenous but relatively uncommon. They vary with age, ethnicity, and
geographic area. Although young adults infrequently develop stroke from
atherosclerosis, traditional vascular risk factors (e.g., elevated cholesterol, presence
of CHD, hypertension, smoking, illicit drug use) are present in many cases as in
older individuals. Under age 55, diabetes mellitus10 and obesity are considered
powerful risk factors. The aggregate frequencies of ischemic SIY etiology across
different population groups are shown in Table 1.

Table 1. Frequency of Ischemic Stroke Etiology in Young Adults

Classificationa Frequencyb
Large-vessel atherosclerosis 4% - 19%
Cardiac embolism 8% - 31%
special
topics

Small artery occlusion 12% - 21%

Other determined etiology 13% - 26%
Undetermined 24% - 40%
a
Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) schema
b
Data combined from the following published studies on SIY using TOAST criteria: Lee et al.4,
Mazziotti and Reisin11, Rolfs et al.12, Yesilot Barlas et al.13, and Kittner et al.14

Arteriopathies are the most common cause of ischemic stroke in young patients.
Under this category, cervical arterial dissection is most common, accounting for
about 15% of ischemic strokes.15 This should be considered in cases of sudden neck
movements or chiropractic manipulation or vigorous exercise.7 A stroke following
prolonged immobilization or during Valsalva’s maneuver should raise suspicion of
a paradoxical embolism through a patent foramen ovale (PFO), which is the most
frequently reported cause of cardioembolic stroke in young adults.16 For young
stroke patients with history of multiple miscarriages or deep venous thrombosis,
a hypercoagulable state must be considered.7 The most common acquired
thrombophilia associated with SIY is the antiphospholipid antibody syndrome (APS).
All other causes of ischemic SIY are shown in Table 2.

C.2. Hemorrhagic Stroke

Young patients with nontraumatic ICH represent a heterogenous group. In a
retrospective study of ICH patients aged 15-40 years, the most frequent risk
factors were tobacco use (20%), hypocholesterolemia (35%), hypertension,
(13%), and alcohol use (10%).17 ICH has been related also to the use of drugs
with amphetamine-like properties, including phenylpropanolamine (most
common), ephedrine, pseudoephedrine, and phencyclidine.

The most common cause of ICH in young adults is ruptured vascular

malformations (i.e. arteriovenous malformation [33%] and cavernous angioma
[16%]).17 However, the most common cause of hematomas located in the brain
stem is a cavernous angioma. Other causes of ICH in young adults include
hypertension (11%), cerebral venous thrombosis (5%), and sympathomimetic
drug use (4%). Cryptogenic ICH was considered in 15% of cases.17

176
 Table 2. Causes and Risk Factors for Ischemic Stroke in Adolescents and Young Adults7

Source Disease
Arterial • Cerebral artery dissection
causes • Reversible cerebral vasoconstriction syndrome/postpartum cerebral
angiopathy/Call-Fleming syndrome
• Moyamoya disease
• Sickle cell disease
• Transient cerebral arteriopathy of childhood
• Premature atherosclerosis, lipohyalinosis
• Radiation-induced arteriopathy
• Migraine-induced stroke
• Illicit drug abuse (e.g. cocaine, amphetamines, ecstasy)
• Infectious arteriopathies: Post-varicella; tuberculous, fungal, or bacterial
meningitis; syphilis, HIV
• Inflammatory arteriopathies: Takayasu arteritis, giant cell arteritis, primary
angiitis of the CNS, polyarteritis nodosa, Behçet disease, Churg-Strauss
syndrome, Kohlmeier-Degos disease
• Genetic or inherited arteriopathies: Fabry disease, fibromuscular dysplasia,
dolichoectasia, Susac’s syndrome, cerebral autosomal dominant arteriopathy

Special
with subcortical infarcts and leukoencephalopathy, TREX1 mutation disorders,

Topics
mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
(MELAS), hyperhomocysteinemia, neurofibromatosis type 1
Cardiac • Patent foramen ovale (PFO)
causes • Congenital heart diseases
• Infectious and non-bacterial thrombotic endocarditis
• Rheumatic valvular heart disease
• Post-cardiac surgery or catheter intervention
• Arrhythmias (e.g. atrial fibrillation, sick sinus syndrome)
• Cardiac tumors (e.g. atrial myxoma, papillary fibroelastoma)
• Recent myocardial infarction
• Dilated cardiomyopathy
Hematologic • Heparin-induced thrombocytopenia
causes • Hypercoagulable state due to deficiencies of Proteins C, S, or Antithrombin;
factor V leiden mutation, prothrombin factor II (G20210A) mutation
• Acquired hypercoagulable states: Cancer, pregnancy, hormonal contraceptive
use, use of anabolic steroids, erythropoietin, nephrotic syndrome,
antiphospholipid antibody syndrome
• Primary hematologic disorders: Polycythemia vera, essential
thrombocythemia, paroxysmal nocturnal hemoglobinuria, thrombotic
thrombocytopenic purpura, leukemia, lymphoma, multiple myeloma

D. Diagnostic Procedures
Due to the broad spectrum of etiologies, the diagnostic procedures are invariably
numerous. However, the clinical cues, family history, and stroke characteristics may
help tailor the diagnostic work-up for a thorough evaluation. In a retrospective
study of young adults with stroke, there was a low yield for Holter monitoring
(1%), toxicology screening (5%), and vasculitis panel (<5%), but relatively high for
cardiac ultrasound (51%) and cerebral angiography (64%).1 The common diagnostic
(and ancillary) tests for SIY are presented in Table 3. In cases where the etiology is
elusive, the diagnostic evaluation may be expanded in order to identify the specific
or rare causes of stroke. A local descriptive study of 25 SIY cases noted that only
few physicians conduct further ancillary tests because of the diversity of etiologies
for ischemic stroke in younger patients.18 In such case, it is the role of the physician
to exercise judicious and appropriate use of additional diagnostic tests in view of
establishing the final diagnosis.

177
 Table 3. Laboratory Evaluation for SIY7

Common Tests Tests for specific stroke etiologies

Complete blood count with differential counts
Erythrocyte sedimentation rate
Urinalysis
Prothrombin time (with INR), activated partial
thromboplastin time
Serum electrolytes, liver and renal function
tests
Blood glucose, glycosylated hemoglobin level
Lipid panel, lipoprotein (a) level, C-reactive
protein level
Pregnancy test
Head CT, brain MRI
Cerebral arterial imaging: CT, MR, or digital
subtraction angiograph of the head and neck,
carotid artery Duplex Ultrasound, transcranial
Doppler ultrasound
special
topics
Serum and urine toxicology screens
Lower extremity ultrasound, pelvic CT or MR
venography (in patients with PFO)
Advanced brain imaging
CSF examination
Rheumatologic panel blood tests
Infectious disease panel tests
Hypercoagulable panel tests; protein C, protein
S, and antithrombin levels, prothrombin gene
mutation, factor V Leiden mutation, etc.
Hematologic panel tests
Ophthalmologic evaluation
Biopsy
Genetic tests for conditions such as
CADASIL, Retinal vasculopathy with
cerebral leukodystrophy (RVCL), methylene

Brain perfusion imaging e.g., CT-perfusion or tetrahydrofolate reductase (MTHFR) c.677C>T

MR-perfusion (optional) pleomorphism, etc.
Transthoracic and/or transesophageal
echocardiography
Holter monitoring

E. Management

E.1. Early Specific Treatment

Acute treatment of young adults with stroke is similar to that of older patients
(see Chapter 3). The management of blood pressure, glucose levels, oxygenation,
fluid and electrolyte balance, and temperature, as well as thrombolysis do not vary
significantly. However, thrombolysis is approved only for patients whose age is 18
years old and above. Likewise, admission to a stroke unit is highly recommended.

E.2. Delayed Management and Secondary Prevention

The SSP adopts the recommendations of the American Heart Association/American
Stroke Association (AHA/ASA) for the management of select risk factors for stroke
in young adults. These recommendations also apply to elderly stroke patients. The
recommendations for primary and secondary prevention of the more common stroke
risk factors (e.g., hypertension, diabetes, dyslipidemia) are presented in Chapter 2.

E.2.1. Arterial dissection19

1. For patients with ischemic stroke or TIA and extracranial carotid/vertebral artery
dissection, antithrombotic treatment with either antiplatelet or anticoagulant
therapy for at least 3 to 6 months is reasonable (Class IIa, level B). However,
the relative efficacy of antiplatelet therapy compared with anticoagulation is
unknown in these set of patients (Class IIb, level B).
2. For patients with stroke or TIA and extracranial carotid/vertebral artery
dissection with recurrent cerebral ischemic events despite medical therapy,
endovascular therapy (stenting) may be considered (Class IIb, level C).
3. For patients with stroke or TIA and extracranial carotid/vertebral artery
dissection with recurrent cerebral ischemic events refractory to medical therapy,
or who are not candidates for endovascular therapy, surgical treatment may be
considered (Class IIb, level C).

E.2.2. Patent Foramen Ovale19

1. There are insufficient data to conclude whether anticoagulation is equivalent
or superior to aspirin for secondary stroke prevention in patients with PFO
178 (Class IIb, level B).
 2. For patients with ischemic stroke or TIA and a PFO who are not undergoing
anticoagulation therapy, antiplatelet therapy is recommended (Class I, level B).
3. For patients with ischemic stroke or TIA and both PFO and venous source of
embolism, anticoagulation is indicated, depending on the stroke characteristics
(Class I, level A). When anticoagulation is contraindicated, an inferior vena cava
filter is reasonable (Class IIa, level C).
4. For patients with cryptogenic ischemic stroke or TIA and PFO without evidence
for deep venous thrombosis (DVT), available data do not support a benefit for
PFO closure (Class III, level A).
5. In the setting of PFO and DVT, PFO closure by a transcatheter device may be
considered depending on the risk of recurrent DVT (Class IIb, level C).

E.2.3. Migraine with Aura20

1. Treatments to reduce the frequency of migraine is reasonable, although it is
uncertain whether prophylactic migraine treatment reduces the risk of first
or recurrent stroke (Class IIb, level C). Therapy with triptans and ergots is
contraindicated.7
2. In patients with migraine who are currently smoking, it is reasonable to strongly
recommend smoking cessation, especially among women with migraine with

Special
Topics
aura (Class IIa, level B).

E.2.4. Oral Contraceptives (OCs)20

1. In women with additional stroke risk factors (e.g., cigarette smoking, prior
thromboembolic events), it is reasonable to advise against the use of OCs
(Class III, level B).
2. In women who chose to use OCs despite the increased risk associated with
its use, aggressive therapy of stroke risk factors may be reasonable (Class IIb,
level C). Progestin-only contraceptives may be an option but it should be
discontinued if the woman was taking it when stroke occurred.7
3. Routine screening for prothrombotic mutations before initiation of hormonal
contraception is not recommended (Class III, level A).
4. Measurement of BP before initiation of hormonal contraception is
recommended (Class I, level B).

E.2.5. Hypercoagulable states19

1. Depending on the abnormality and clinical circumstances, anticoagulation
may be considered in patients who are found to have abnormal findings on
coagulation test after an initial ischemic stroke or TIA (Class IIb, level C).
2. Antiplatelet therapy is recommended for patients who are found to have
abnormal findings on coagulation tests after an initial ischemic stroke or TIA if
anticoagulation therapy is not administered (Class I, level A).

E.2.6. Antiphospholipid Antibodies19

1. Routine testing for antiphospholipid antibodies is not recommended for
patients with ischemic stroke or TIA without other manifestations of the
antiphospholipid antibody syndrome (APS), and who have an alternative
explanation for their ischemic event (Class III, level C).
2. For patients with ischemic stroke or TIA who have an antiphospholipid antibody
but do not fulfill the criteria for APS, antiplatelet therapy is recommended
(Class I, level B).
3. For patients with ischemic stroke or TIA who meet the criteria for APS,
anticoagulant therapy might be considered depending on the perception of
risk for recurrent thrombotic events and bleeding (Class IIb, level C).
4. For patients with ischemic stroke or TIA who meet the criteria for APS but in
whom anticoagulation is not begun, antiplatelet therapy is indicated (Class I,
level A).

179
 E.2.7. Sickle Cell Disease19
1. For patients with sickle cell disease (SCD) and prior ischemic stroke or
TIA, chronic blood transfusions to reduce hemoglobin S to <30% of total
hemoglobin are recommended (Class I, level B).
2. For patients with SCD and prior ischemic stroke or TIA for whom transfusion
therapy is not available or practical, treatment with hydroxyurea may be
considered (Class IIb, level B).

E.2.8. Hyperhomocysteinemia19
1. Routine screening for hyperhomocysteinemia among patients with a recent
ischemic stroke or TIA is not indicated (Class III, level C).
2. In adults with a recent ischemic stroke or TIA who are known to have mild
to moderate hyperhomocysteinemia, supplementation with folate, vitamin B6,
and vitamin B12 safely reduces levels of homocysteine, although it has not
been shown to prevent stroke (Class III, level B).

E.2.9. Others
1. Annual influenza vaccination can be useful for patients at risk for stroke (Class
special

IIa, level B).

topics

2. Screening for cardiac conditions in the absence of neurologic conditions or a

specific cause is not recommended (Class III, level A).
3. Referral for genetic counseling may be considered for patients with rare
genetic causes of stroke (Class IIb, level C).
4. Although antibiotic prophylaxis is not the standard of care in acute stroke,
current guidelines support prompt treatment of stroke-related infections.
5. In patients who are users of illicit drugs, in addition to primary treatment
for drug abuse, it may be reasonable to advise further neuropsychological
screening tests.

E.3. Rehabilitation
The SSP adopts the guidelines of the Philippine Academy of Rehabilitation
Medicine (PARM) for stroke rehabilitation (see Chapter 11). An empirical study
on coping with stroke at young age suggest three important considerations for
post-stroke rehabilitation services: workplace reintegration, mental imagery, and
psychosocial support for the person with stroke and their family.21

F. Prognosis
In the Helsinki Young Stroke registry, the cumulative mortality risks of SIY (at 95%
CI) were 2.7% (1.5-3.9%) at 1 month, 4.7% (3.1-6.3%) at 1 year, and 10.7% (9.9-
11.5%) at 5 years.22 For individuals aged ≥45 years, the 5-year mortality rate was
higher (14.7%) than for individuals aged <45 years (7%). The mortality is also higher
for large-artery atherosclerosis (~30%) and cardioembolic (~20%) subtypes as
compared with that of small vessel diseases (5% to 7%). The five-year recurrence
rate for stroke and vascular events is 11.5% (95% CI). Predictors for the higher
rates of recurrence include type 1 diabetes mellitus, heart failure, large-artery
atherosclerosis, increasing age, and prior TIA.23 The 5-year rate for post-stroke
epilepsy in young patients with first ischemic stroke is 10.5%, although the rate is
higher among patients with severe neurologic deficits (34%).24 For those with mRS
score ≤2, the functional independence ranges from 78%-94%. In a prospective
cohort study of young stroke survivors, epilepsy was identified as an independent
predictor of poor long-term functional outcome (mRS score >2) after ischemic
stroke (OR=3.38; 95% CI, 1.33-8.60), but not to TIA and ICH.25 Post stroke depression,
on the other hand, may range from 28%-46%.7

The rising incidence of SIY reflects the need for increasing the awareness of young
adults and adolescents about stroke, its risk factors, and the signs and symptoms.
Stroke awareness campaigns may be initiated in schools, at workplaces or physicians'
180
 offices, or through the traditional media and the newer 'social media’. Furthermore,
there is a need for improved documentation of SIY cases as well as further research
to better understand the etiologies and mechanisms of stroke unique to this age
group.

References

1. Ji R, Schwamm LH, Pervez MA, Singhal AB. Ischemic stroke and transient ischemic attack in young
adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol. 2013 Jan;70(1):51-7.
2. Jacobs BS, Boden-Albala B, Lin IF, Sacco RL. Stroke in the young in the northern Manhattan stroke study.
Stroke. 2002;33:2789–2793.
3. Mehndiratta MM, Agarwal P, Sen K, Sharma B. Stroke in young adults: a study from a university hospital
in North India. Med Sci Monit. 2004;10(9):535-41.
4. Lee TH, Hsu WC, Chen CJ, et al. Etiologic study of young ischemic stroke in Taiwan. Stroke. 2002;
33:1950-5.
5. Sher K, Shah S, Kumar S. Etiologic patterns of ischaemic stroke in young adults. J Coll Physicians Surg
Pak. 2013 Jul;23(7):472-5.
6. Kuruvilla A, Bhattacharya P, Rajamani K, Chaturvedi S. Factors Associated with Misdiagnosis of Acute
Stroke in Young Adults. J Stroke Cerebrovasc Dis. Nov;20(6):523-7.

Special
Topics
7. Singhal AB, Biller J, Elkind MS, et al. Recognition and management of stroke in young adults and
adolescents. Neurology. 2013 Sep 17;81(12):1089-97.
8. Moulin T, Sablot D, Vidry E, et al. Impact of emergency room neurologists on patient management and
outcome. Eur Neurol. 2003;50:207-214.
9. Edlow JA, Selim MH. Atypical Presentations of Acute Cerebrovacular Syndromes. Lancet Neurol. 2011
Jun;10(6):550-60.
10. Kissela BM, Khoury J, Kleindorfer D, et al. Epidemiology of ischemic stroke in patients with diabetes: the
Greater Cincinnati/Northern Kentucky Stroke Study. Diabetes Care. 2005;28:355–359.
11. Mazziotti J and Reisin R. Cardiovascular Risk Factors in Young Adults with Stroke from the AISYF
Study (P2.110). American Academy of Neurology Web site, 29 Apr. 2014. http://www.neurology.org/
content/82/10_Supplement/P2.110 Accessed June 24, 2014.
12. Rolfs A, Fazekas F, Grittner U, et al. Acute cerebrovascular disease in the young: the Stroke in Young Fabry
Patients study. Stroke. 2013 Feb;44(2):340-9.
13. Yesilot Barlas N, Putaala J, Waje-Andreassen U, et al. Etiology of first-ever ischaemic stroke in European
young adults: the 15 cities young stroke study. Eur J Neurol. 2013 Nov;20(11):1431-9.
14. Kittner SJ, Stern BJ. Wozniak M, et al . Cerebral infarction in young adults: The Baltimore-Washington
Cooperative Young Stroke Study. Neurology. 1998;50:890-4.
15. Putaala J, Metso AJ, Metso TM, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever
ischemic stroke: the Helsinki young stroke registry. Stroke. 2009; 40:1195.
16. Larrue V, Berhoune N, Massabuau P, et al. Etiologic investigation of ischemic stroke in young adults.
Neurology. 2011;76:1983-1988.
17. Ruíz-Sandoval JL, Cantú C, Barinagarrementeria F. Intracerebral hemorrhage in young people: analysis of
risk factors, location, causes, and prognosis. Stroke. 1999 Mar;30(3):537-41.
18. Espeleta GP, Pinzon PM, Baliguas B, et al. Adherence to the Clinical Practice Guidelines of the Stroke
Society of the Philippines in the Management of Ischemic Stroke in Young Adults. Phil J Int Med. Oct-Dec
2011;49(4):191-198.
19. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45:000-000.
20. Bushnell C, McCullough LD, Awad IA, et al. Guideline for the Prevention of Stroke in Women: A Statement
for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke.
2014;45;000-000.
21. Kuluski K, Dow C, Locock L, et al. Life interrupted and life regained? Coping with Stroke at a Young Age.
Int J Qualitative Stud Health Well-being. 2014, 9: 22252.
22. Putaala J, Curtze S, Hiltunen S, et al. Causes of Death and Predictors of 5-Year Mortality in Young Adults
After First-Ever Ischemic Stroke: the Helsinki Young Stroke Registry. Stroke. 2009 Aug;40(8):2698-703.
23. Putaala J, Haapaniemi E, Metso AJ, et al. Recurrent ischemic events in young adults after first-ever
ischemic stroke. Ann Neurol. 2010;68:661–671.
24. Naess H, Nyland HI, Thomassen L, et al. Long-term outcome of cerebral infarction in young adults. Acta
Neurol Scand. 2004;110:107–112.
25. Arntz R, Maaijwee N, Rutten-Jacobs L, et al. Epilepsy after TIA or stroke in young patients impairs long-
term functional outcome: The FUTURE Study. Neurology. 2013;81:22:1907-1913.
181
 III. STROKE IN PREGNANCY AND THE PUERPERIUM
Stroke is an uncommon occurrence during pregnancy and the puerperium. However,
the risk of stroke in pregnant women is more than double that of the non-pregnant
women of same age and race.1 Although the precise pathophysiology of pregnancy-
related stroke remains unclear, it has been hypothesized to be associated with the
physiologic changes of pregnancy–including hypercoagulability states, venous
stasis, and vascular damage (i.e. Virchow’s triad)–which predispose women to higher
risk of thromboembolic diseases.

A. Epidemiology
The incidence of pregnancy-related stroke ranges from 11 to 34 per 100,000
deliveries.2 During pregnancy, the relative risk (RR) for ischemic stroke (IS) and
intracerebral hemorrhage (ICH) is 0.7 (95% confidence interval [CI];0.3-1.6) and 2.5
(95% CI, 1.0-6.4) respectively.3 The risk of stroke rises in the third trimester and is
highest during parturition and up to 6 weeks post-partum, with adjusted RRs of 8.7
(95% CI, 4.6-16.7) for IS and 28.3 (95% CI, 13.0-61.4) for ICH.3 In a recent retrospective
study, the incidence of acute cerebrovascular diseases following hospitalization for
special

labor and delivery was 14.8 per 100,000 (95% CI, 13.2-16.5).4 The rates of maternal
topics

mortality vary by stroke subtype: 0%-26% for ischemic stroke, 20.3% for ICH, 27%-40%
for subarachnoid hemorrhage (SAH), 28% for cerebral arteriovenous malformation
(AVM), and 9% for cerebral venous thrombosis (CVT).5-8

In the Philippines, there is very limited data on the prevalence of pregnancy-related

stroke. In the Philippine General Hospital (PGH), for example, two to three pregnant
patients with stroke were admitted annually from 2004 to 2007, while two cases of
intracranial bleed secondary to ruptured AVM during pregnancy were documented
from 2006 to 2008.9

B. Risk Factors
The hypertensive disorders of pregnancy (e.g., pre-eclampsia [PE], eclampsia)
are the leading causes of ischemic and hemorrhagic strokes in this population,
accounting for 25%-50% of cases.10 Prepregnancy hypertension is also associated
with increased risk of antenatal stroke.2 Interestingly, PE shares common risk factors
and pathophysiology with stroke, including endothelial dysfunction, hypertension,
dyslipidemia, hypercoagulability, and abnormal cerebral vasomotor reactivity.11
Women with a history of PE are at risk of developing stroke for at least one year
post-partum, which signifies influence of hormonal factors on long-term risk.12 In
addition, post-partum PE predisposes women to higher risk of stroke, and may be
the underlying cause of post-partum headaches.2 Similarly, children born of pre-
eclamptic mothers are also at risk of developing stroke as adults.13

Migraine headaches, on the other hand, have been associated with a 17-fold increased
risk of stroke in pregnancy especially of the ischemic subtype (OR 30.7, 95% CI, 17.4-
34.1).14 Other medical and pregnancy-specific conditions associated with stroke
include gestational diabetes (GDM), thrombophilia, systemic lupus erythematosus
(SLE), infection, choriocarcinoma, and amniotic fluid embolism.3,15 Nonetheless, the
presence of traditional vascular risk factors (e.g., DM, cigarette smoking) increases
their stroke risk.

The risk of future stroke is also increased in postmenopausal women who have had
pregnancy complications (as mentioned), however the basis of this association is not
entirely known.2

For pregnancy-related ICH, the risk is higher particularly in the setting of PE/eclampsia
(odds ratio [OR] 10.39, 95% CI, 8.32-12.98), preexisting hypertension (OR 2.61, 95%
CI, 1.34-5.07), coagulopathy (OR 20.66, 95% CI, 13.67-31.23), tobacco use (OR 1.95,
182
 95% CI, 1.11-3.42), and advanced maternal age (OR 2.11, 95% CI, 1.69-2.64).6 It was
believed that the risk of rupture of pre-existing intracranial aneurysm or AVMs is
highest during the antepartum or postpartum period, although recent studies show
that aneurysmal or AVM rupture is not significantly increased during pregnancy and
the puerperium.16,17

Cerebral venous thrombosis (CVT), although rare, is an important cause of stroke

in pregnancy and the puerperium especially among Asian women.18 Risk factors for
CVT include cesarean section (CS) delivery, dehydration, and infection. The most
frequent symptom is headache, while less frequent symptoms include epileptic
seizures, hemiparalysis, and aphasia.19 Reversible cerebral vasoconstriction syndrome
(RCVS) (also known as Call-Fleming syndrome or postpartum cerebral angiopathy) is
another important cause of pregnancy-related stroke especially in the postpartum
period. It typically presents as acute severe recurrent headaches with angiographic
evidence of segmental narrowing or beading of intracranial arteries.10 Another direct
consequence of PE/eclampsia and RCVS is the Posterior Reversible Encephalopathy
Syndrome (PRES), characterized by early prominent seizures, generally dull headaches,
hypertensive encephalopathy, and visual disturbances in the setting of reversible
vasogenic edema on neuroimaging.10

Special
Topics
Whereas PE/eclampsia is specific to pregnancy, PRES, RCVS, and CVT also occur in
non-pregnant individuals.10

C. Etiology
The causes of ischemic and hemorrhagic stroke in pregnancy are as follows:

Table 1. Etiology of Pregnancy-related Stroke20

Ischemic causes
Occlusive Arterial Disease Arterial Hypotension
Peripartum cardiomyopathy Border zone infarction
Atrial fibrillation Sheehan syndrome
Prosthetic heart valves
Infective and non-bacterial thrombotic endocarditis Other
Rheumatic Heart Disease Amniotic fluid embolism
Paradoxical embolism Hematologic disorders: Sickle cell disease,
Patent foramen ovale DIC, ITP, TTP
Hemorrhagic causes
Intracerebral hemorrhage Subarachnoid hemorrhage
Pre-eclampsia/Eclampsia Ruptured aneurysm
Arterial hypertension Ruptured AVM
Choriocarcinoma DIC
Ruptured vascular malformation
Cerebral dural venous sinus thrombosis
DIC: disseminated intravascular coagulation; ITP: idiopathic thrombocytopenic purpura;
TTP: thromobotic thrombocytopenic purpura

D. Diagnosis And Evaluation

1. All pregnant or puerperal women presenting with persistent acute neurological
deficit (with or without headache) need urgent and thorough evaluation. If a
pregnant woman presents with transient neurological symptoms (with or without
headache), migraine with aura10 and eclampsia must be carefully ruled out.
2. It is very important to establish the diagnosis of stroke (and type) as early as
possible. For pregnant patients, the preferred imaging modality is Magnetic
Resonance Imaging (MRI). Although there are no documented adverse fetal effects
reported from MRI exposure at 1.5 Tesla [T], the use of MRI should be warranted by
the risk–benefit ratio. If an MRI is not available for urgent evaluation, a noncontrast
183
 cranial CT (NCCT) scan with abdominal/pelvic shielding may be performed, only
if the benefit outweighs the risk. The procedure (including the risks) should be
discussed with the patient and family.
3. Standard laboratory tests (see Chapter 3) are performed according to the severity
of stroke. If the clinical findings point to an arteriopathy, cardiac, or hematologic
pathology, additional diagnostic evaluations (e.g., hypercoagulable panels,
echocardiography) may be requested (see section on Stroke in the Young).

E. Recommendations
The SSP adopts the recommendations of the American Heart Association/American
Stroke Association (AHA/ASA) for the management of risk factors and treatment of
stroke during pregnancy and the puerperium.

i. Prevention of Pre-eclampsia2
1. Women with chronic primary or secondary hypertension or previous pregnancy-
related hypertension should take low-dose aspirin from the 12th week age of
gestation (AOG) until delivery (Class I, level A).
special
topics

2. Calcium supplementation (>1g/day, orally) should be considered for women

with low dietary intake of calcium (<600mg/day) to prevent pre-eclampsia
(Class I, level A).

ii. Treatment of Hypertension during Pregnancy and Puerperium2

1. Severe hypertension (defined as systolic BP >160mm Hg, or diastolic BP
>110mm Hg) should be treated with safe and effective antihypertensive
medications (Class I, level A). The common oral antihypertensive agents used in
pregnancy are as follows:
Table 2 Examples of Common Oral Antihypertensive Agents used during Pregnancy 2,21
Pregnancy Drug
Drug Dosage Comments
Categorya
Nifedipine 30-120 mg/day PO of slow- Category C Do not use the sublingual
(Class I, level A) release (SR) preparation (SL) form
Labetalol 200-2400mg/day PO in 2-3 Category C Avoid in patients with
(Class IIa, level B) divided doses asthma and congestive
heart failure
Methyldopa 0.5-3 g/day PO in 2-3 Category C May not be as effective
(Class IIa, level C) divided doses for severe hypertension
a
Implemented by the U.S. Food and Drug Administration (FDA); Category C indicates that risks
have been identified in animal studies and/or that no well-controlled studies in humans have
been published; therefore drug should be given only if the potential benefits outweigh potential
risks to the fetus.

2. Moderate hypertension may be treated accordingly, given the evidence for

possible increased stroke risk at the currently defined systolic and diastolic BP
cutoffs, as well as evidence for decreased risk for the development of severe
hypertension with treatment (Class IIa, level B).
3. Atenolol, ACE inhibitors, and ARBs are contraindicated in pregnancy because of
the associated fetal abnormalities (Class III, level C). Diuretics are considered as
second-line drugs, and adjusted doses may be especially useful in women with
known salt-sensitive hypertension, particularly in the setting of reduced renal
function.21
4. Women with chronic hypertension during the post-partum period should be
maintained on their antihypertensive regimen, with dosage adjustments to reflect
the decrease in intravascular volume and renal function occurring after delivery.
They should be monitored for the development of post-partum pre-eclampsia
(Class IIa, level C).
184
 5. In addition to pharmacological control of BP, the use of magnesium sulfate (MgSO4)
is well-established for seizure prophylaxis and has also been demonstrated to
decrease the risk of stroke in women with severe hypertension in pregnancy and
eclampsia.
6. It is reasonable to evaluate all parous women, as early as 6 months post-partum
and beyond the childbearing age, for history of pre-eclampsia/eclampsia, which
will be documented as a stroke risk factor; likewise they will be evaluated (and
treated) for presence of cardiovascular risk factors (Class IIa, level C).

iii. Acute Stroke Treatment

(See also: Chapter 3)
1. Pregnancy is a relative contraindication for treatment with tissue plasminogen
activator (t-PA). In the lack of RCTs on thrombolytic therapy during pregnancy, the
decision to treat pregnant women with t-PA is controversial. The risks and benefits
must be carefully assessed on a case-by-case basis and should be discussed with
the obstetrician, the patient, and the family.22
2. There are no clear guidelines for medical treatment of ICH or SAH in pregnancy.23
Drugs like mannitol (Category C) for increased intracranial pressure or nimodipine
(Category C) for vasospasm must be used with caution. The use of antiepileptic

Special
Topics
drugs (AEDs) for proven seizures should be used with caution, as AEDs have
varying degrees of teratogenicity. The decision to operate after intracranial
hemorrhage during pregnancy depends on neurosurgical indications, whereas
the method of delivery should be based on obstetric considerations.
3. Although some evidence suggests an increased tendency of rupture of cerebral
aneurysms or AVMs during pregnancy, treatment of "unruptured" aneuryms
or AVMs is not routinely recommended (Class IIa, level B). It should be noted
that the presence of unruptured cerebral aneurysm or AVM does not pose a
contraindication for pregnancy, and should not influence the decision for method
of delivery.20

iv. Secondary Prevention of Stroke

There is limited data with regard to the safety and efficacy of antithrombotic therapy
for stroke (e.g., antiplatelets, anticoagulants) during pregnancy. Thus, physicians
should always balance the benefit of treatment with the competing risks to the mother
and fetus. Low-molecular-weight heparin (LMWHs) (Category B) and unfractionated
heparin (UFH) (Category C) are quite safe for the fetus when properly selected, dosed,
and monitored24, however these drugs may have adverse effects such as bleeding
at the uteroplacental junction25, maternal osteoporosis, and thrombocytopenia. The
following recommendations for antithrombotic therapy are based on the guidelines
of the AHA/ASA2,26 and the American College of Physicians (ACCP)27:
1. For pregnant women with prior ischemic stroke or TIA, and with presence of high-
risk thromboembolic conditions (e.g., mechanical heart valves, coagulopathy)
that require anticoagulation outside of pregnancy, the following options are
reasonable (Class IIa, level C):
a. adjusted-dose low-molecular-weight heparin (LMWH) twice daily (BID)
throughout pregnancy, with Factor Xa monitoring (achieve the recommended
peak anti-Xa activity 4 hours post-injection)
b. adjusted-dose unfractionated heparin (UFH) administered subcutaneously
every 12 hours throughout pregnancy, with aPTT monitoring (should keep the
midinterval aPTT at least twice the control, or maintain anti-Xa heparin level of
0.35-0.70 U/mL)
c. UFH or LMWH (as above) until week 13, followed by substitution of warfarin
until close to delivery, when LMWH or UFH is resumed.
2. For pregnant women receiving adjusted-dose LMWH therapy for a high-risk
condition which requires anticoagulation outside of pregnancy, and when
delivery is planned, it is reasonable to discontinue LMWH >24 hours before the
induction of labor or cesarean section (Class IIa, level C).
185
 3. For pregnant women with prior ischemic stroke or TIA, and with presence of a low-
risk situation in which antiplatelet therapy is the recommended treatment outside
of pregnancy, the use of UFH or LMWH, or no treatment, may be considered
during the first trimester of pregnancy depending on the clinical situation (Class
IIb, level C). Beyond the first trimester period, the use of low-dose aspirin (50-150
mg/day) (Category D) is reasonable (Class IIa, level B).

Table 3. Summary of Antithrombotic Therapy for TIA and Stroke during Pregnancy
Age of Gestation (AOG) Patients with low-risk conditions Patients with high-risk conditions
Weeks 1-12 UFH or LMWH or no treatment UFH or LMWH
Weeks 13-26 Aspirin UFH or LMWH or warfarin
Weeks 27-40 Aspirin UFH or LMWH
LMWH: low-molecular-weight heparin; UFH: unfractionated heparin

4. For pregnant women with acute cerebral venous thrombosis (CVT), anticoagulation
with full-dose LMWH rather than UFH is reasonable (Class IIa, level C) and should
special

be continued throughout pregnancy. LMWH or vitamin K antagonist (with target

topics

INR of 2.0-3.0) should be continued for >6 weeks post-partum (for a total
minimum duration of therapy of 6 months) (Class I, level C).
5. For breastfeeding women who have had ischemic stroke or TIA, and with a high-
risk condition that would require anticoagulation outside of pregnancy, it is
reasonable to use warfarin, UFH, or LMWH (Class IIa, level C). In the presence of
low-risk condition in which antiplatelet therapy is the treatment recommendation
outside of pregnancy, low-dose aspirin may be considered (Class IIb, level C).

References

1. Go AS, Mozaffarian D, Roger VL, et al.; American Heart Association Statistics Committee and Stroke
Statistics Subcommittee. Heart disease and stroke statistics--2014 update: a report from the American
Heart Association. Circulation. 2014 Jan 21;129(3):e28-e292.
2. Bushnell C, McCullough LD, Awad IA, et al. Guideline for the Prevention of Stroke in Women: A Statement
for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke.
2014;45;000-000.
3. Kittner SJ, Stern BJ, Feeser BR, et al. Pregnancy and the risk of stroke. N Engl J Med. 1996 Sep 12;
335(11):768-74.
4. Hovsepian DA, Sriram N, Kamel H, et al. Acute Cerebrovascular Disease Occurring After Hospital
Discharge for Labor and Delivery. Stroke. 2014 Jul;45(7):1947-50.
5. Jaigobin C, Silver FL. Stroke and pregnancy. Stroke. 2000 Dec;31(12):2948-51.
6. Bateman BT, Schumacher HC, Bushnell CD, et al. Intracerebral hemorrhage in pregnancy: frequency, risk
factors, and outcome. Neurology. 2006 Aug 8;67(3):424-9.
7. Dias M, Sekhar L. Intracranial hemorrhage from aneurysms and arteriovenous malformations during
pregnancy and the puerperium. Neurosurgery 1990;27(6):855-66.
8. Cantú C, Barinagarrementeria F. Cerebral venous thrombosis associated with pregnancy and puerperium.
Review of 67 cases. Stroke. 1993 Dec; 24(12):1880-4.
9. Capistrano JL, Ang-Munoz C. A Case Report on Stroke Rehabilitation during Pregnancy. Acta Medica
Philippina. 2010;44(2):52-56.
10. Edlow JA, Caplan LR, O'Brien K, Tibbles CD. Diagnosis of acute neurological emergencies in pregnant
and post-partum women. Lancet Neurol. 2013 Feb;12(2):175-85.
11. Bushnell C, Chireau M. Preeclampsia and Stroke: Risks during and after Pregnancy. Stroke Res Treat.
2011; 2011: 858134.
12. Tang CH, Wu CS, Lee TH, et al. Preeclampsia-eclampsia and the risk of stroke among peripartum in
Taiwan. Stroke. 2009 Apr; 40(4):1162-8.
13. Kajantie E, Eriksson JG, Osmond C, et al. Pre-eclampsia is associated with increased risk of stroke in the
adult offspring: the Helsinki birth cohort study. Stroke. 2009 Apr; 40(4):1176-80.
14. Bushnell C, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US
population based case-control study. BMJ. 2009 Mar 10;338:b664.
15. James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and
the puerperium. Obstet Gynecol. 2005 Sep;106(3):509-16.
186
16. Kim YW, Neal D, Hoh BL. Cerebral aneurysms in pregnancy and delivery: pregnancy and delivery do not
increase the risk of aneurysm rupture. Neurosurgery. 2013 Feb;72(2):143-9; discussion 150.
17. Liu XJ, Wang S, Zhao YL, et al. Risk of cerebral arteriovenous malformation rupture during pregnancy and
puerperium. Neurology. 2014 May 20;82(20):1798-803.
18. Khan M, Wasay M, Menon B, et al. Pregnancy and puerperium-related strokes in Asian women. J Stroke
Cerebrovasc Dis. 2013 Nov;22(8):1393-8.
19. Gao H, Yang BJ, Jin LP, Jia XF. Predisposing factors, diagnosis, treatment and prognosis of cerebral
venous thrombosis during pregnancy and postpartum: a case-control study. Chin Med J (Engl). 2011
Dec;124(24):4198-204.
20. Dafer RM. Stroke in Pregnancy and Puerperium. In: Biller J. Evidence-based Management of Stroke.
Harley Nr Shrewsbury, UK: TFM Publishing, Ltd; 2013:239-249.
21. American College of Obstetricians and Gynecologists' (ACOG) Task Force on Hypertension in Pregnancy.
Hypertension in pregnancy. Obstet Gynecol. 2013; 122:1122.
22. Selim MH, Molina CA. The use of tissue plasminogen-activator in pregnancy: a taboo treatment or a time
to think out of the box. Stroke. 2013 Mar;44(3):868-9.
23. Tate J, Bushnell C. Pregnancy and stroke risk in women. Womens Health (Lond Engl). 2011 May;7(3):363-
74.
24. Gibson PS, Powrie R. Anticoagulants and pregnancy: when are they safe? Cleve Clin J Med. 2009
Feb;76(2):113-27.
25. Del Zotto E, Giossi A, Volonghi I, et al. Ischemic Stroke during Pregnancy and Puerperium. Stroke Res
Treat. 2011; 2011: 606780.

Special
Topics
26. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45;000-000.
27. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy:
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl):e691S–736S.

IV. MOVEMENT DISORDERS IN STROKE

A. Overview
Movement disorders are a special group of neurologic diseases that present with
abnormality of movement without paralysis. They present in various forms but in
general are a spectrum of movement abnormalities ranging from hypokinesia (i.e.
decrease or poverty in movement) to hyperkinesia (i.e. increase or florid movements).
They are manifestations of an impaired function of the basal ganglia and its
connections. Deficits in basal ganglia function maybe due to a wide array of causes.
Primary abnormalities include genetic, neurodegenerative, and heredodegenerative
diseases. Secondary causes include those seen in infections and its sequelae, trauma,
autoimmune disorders, exposure to environmental toxins and medications (that
impair basal ganglia function), as well as structural defects from mass lesions and
stroke.

B. Movement Disorders In Stroke

Movement disorders as a manifestation or sequela of stroke, although rare, have been
well-documented and extensively reported. The Lausanne Stroke Registry reported an
incidence of 0.08% and prevalence of 1% in 2,500 patients who developed secondary
movement disorders from stroke, while another study which involved 1,500 patients
showed a frequency of 3.9%.1,2 It may occur in any stroke type but it is more likely
to develop in hemorrhagic than ischemic strokes.3 In ischemic events, movement
disorders are seen in vascular insults involving the MCA and PCA, which supply the
basal ganglia.4 It may be the presenting symptom of an acute event or as a delayed
complication from the cerebrovascular insult. The temporal clinical manifestations
(Table 1) are quite varied.

187
 TABLE 1. Secondary Movement Disorders in Stroke4

Movement Disorder Onset Localization

Parkinsonism Delayed Subcortical
Ballism/Chorea Acute Subthalamic nuclei, caudate, putamen, thalamus
Chorea Acute Subthalamic nuclei, putamen, caudate, cortex
Dystonia Delayed Putamen, caudate, pallidum, thalamus, midbrain
Myoclonus Acute Cortex, basal ganglia, midbrain, pons, spinal cord, post
anoxia
Holme’s tremor Acute Brainstem, cerebellum, thalamus
Tics Acute Basal ganglia, frontal lobe

Movement disorders as an acute manifestation of stroke follow the general principles

in stroke presentation. They are abrupt in onset, mostly presenting unilaterally, and
have vascular lesions contralateral to the clinical symptoms. Hyperkinetic movement
disorders appear much earlier as a sequela of stroke, appearing within the first month
special

after a vascular insult, while Parkinsonism is commonly seen as a late complication

topics

of stroke.2 Majority of these abnormal movements will resolve in 6 months.1 Transient

manifestations of dyskinesias may represent as a form of transient ischemic attack.5

Movement disorders of an acute onset are not always vascular in origin. These may be
seen in tardive dyskinesias in patients on antipsychotic medications or those taking
levodopa/carbidopa preparations. Abrupt withdrawal of these medications, on the
other hand, may present with sudden generalized rigidity with associated fever and
dysautonomia, features of neuroleptic malignant syndrome (NMS). Hyperglycemic
hemichorea can also mimic stroke with an acute onset of chorea. Blood sugar levels
at the time of consult can be proven useful in these situations.

In vascular Parkinsonism, the predominant features are symmetrical rigidity and

bradykinesia, with lower extremities more affected than the upper extremities, and
associated with gait apraxia. The symptoms may be static or progressive, which
are poorly responsive to dopamine replacement. This is in contrast to idiopathic
Parkinson’s disease where the rigidity and bradykinesia are asymmetric with
associated shuffling and freezing of gait. The symptoms are progressive but with
good response to levodopa. In corticobasoganglionic disease (CBGD), on top of
features of Parkinsonism, patients manifest initially with unilateral ideomotor or
ideational apraxia. This will progress bilaterally, though asymmetric, with associated
gait apraxia. Also, this is poorly responsive to levodopa.

Movement disorders-whether primary or secondary-are diagnosed clinically,

although neuroimaging is warranted in cases where there is uncertainty in the
diagnosis. It is important to look for any hemispheric asymmetry, mass lesions, as
well as the integrity of the basal ganglia structures and the ventricular system.

C. Treatment
Treatment strategies for stroke-related movement disorders are dependent in
the type of movement disorder. Generally, hyperkinetic movement disorders are
managed with dopamine blockade utilizing antipsychotics, anticholinergics, and
benzodiazepines. Chemodenervation using botulinum toxin A maybe an option if
there is absence or inadequate response to medications. Medications for essential
tremors may be tried among patients with Holmes’ tremors.

A trial with dopamine replacement using levodopa/carbidopa preparations maybe

considered in vascular forms of parkinsonism, although the response is generally
poor. Physiotherapy may be a good practice option for these patients.
188
 References

1. Ghika-Schmid F, Ghka J, Regli F, J Bogousslavksy. Hyperkinetic movement disorders during and after
acute stroke: The Lausanne Stroke Registry. J Neurol Sci. 1997 Mar 10;146(2):109-16.
2. Alarcon F, Zijlmans JCM, Duenas G, Cevallos N. Post-stroke movement disorders: report of 56 patients. J
Neurol Neurosurg Psychiatry. 2004 Nov;75(11):1568-74.
3. Kim JS. Delayed onset mixed involuntary movements after thalamic stroke. Brain. 2001;124:299-309.
4. Bansil S, Prakash N, Kaye J, et.al. Movement Disorders after Stroke in Adults: A review. Tremor Other
Hyperkinet Mov (N Y). 2012;2. pii: tre-02-42-195-1.
5. Siniscalchi A, Gallelli L, Labate A, et.al. Post-stroke Movement Disorders: Clinical Manifestations and
Pharmacologic Management. Curr Neuropharmacol. 2012 Sep;10(3):254-62.

V. SMALL VESSEL DISEASES: LACUNAR STROKE AND MICROBLEEDS

I. Epidemiology
A. Definition and Prevalence of Small Vessel Disease
1. Cerebral small vessel disease (SVD) refers to a spectrum of clinical, cognitive,

Special
Topics
and behavioral abnormalities attributed to pathology involving the small
penetrating arteries and arterioles in the brain.1 It accounts for about 20% to
25% of all ischemic strokes with an annual incidence of 15 per 100,000 people.2
2. Lacunar infarct is defined radiologically as an ischemic lesion of vascular origin
measuring 5 mm to 15 mm in its greatest diameter, presumed to be secondary
to occlusion of single, small, perforating arteries supplying the deep subcortical
areas of the brain.
3. Cerebral microbleeds (CMB) are demonstrated in 18% of individuals aged 60 to
69 years, and in about 38% of individuals above 80 years with the use of MRI
Gradient Recall Echo (MRI-GRE) sequences.3 The spectrum of classical lesions
seen on MRI includes leukoaraiosis, lacunes, and cerebral microbleeds.4

B. Pathologic Features of Small Vessel Disease

1. In ischemic lesions due to SVD, the lumen occlusion is believed to be due to a
chronic state of hypoperfusion of the white matter leading to degeneration of
myelinated fibers. This is thought to be an incomplete infarction or selective
necrosis in the neurons. Acute obstruction of a small vessel leads to focal and
acute ischemia and complete tissue necrosis. This hypothesis, however, remains
unproven.5
2. CMBs appear to be common in the ageing brain; it can occur at the capillary
level particularly involving the putamen. Microbleeds were seen in pathologic
studies of aging brain in the presence or absence of hypertension. Deposition
of amyloid was also not appreciated at the site of microbleeds. These two
observations suggest that the presence of hypertension and/or amyloid
deposition may not be required for CMBs to occur.6

C. Cognitive Impairment/Vascular Dementia

1. Cognitive impairment and vascular dementia appears to be common after
lacunar infarction. The prevalence of dementia after a lacunar infarct is about
20%, while the incidence of mild cognitive impairment (MCI) or dementia
is about 37%. This suggests that an associated SVD increases the risk for
developing cognitive impairment.7
2. CMBs occur in about 85% of patients with subcortical vascular dementia, and is
considered as one of the most important factors causing cognitive impairment.
The number of CMB appears to be a predictive factor of impairment in multiple
cognitive domains.8

189
 II. Risk Modifications
A. Primary Prevention
1. Genetic/Familial Risk Factors
i. Systolic blood pressure, pulse pressure, hypertension, and smoking are all
related to the presence of deep or infratentorial microbleeds. Diastolic blood
pressure, on the other hand, has been associated with lobar microbleeds. No
association has been found yet between serum cholesterol level and lobar
microbleeds.9
ii. Hypertension and diabetes mellitus (DM) appears to be more commonly
seen in patients with lacunar infarction relative to those having nonlacunar
infarction. Analysis confined to studies using risk factor-free ischemic subtype
definitions reveal only a very minimal excess of hypertension with lacunar
versus nonlacunar infarction, while there was no difference for diabetes.10
iii. There is no clear evidence suggesting any association between smoking,
previous TIA, excess alcohol consumption, and elevated cholesterol level and
lacunar versus nonlacunar stroke subtypes.
iv. Higher levels of plasma total homocysteine appear to have associations with
special

the severity of atherosclerotic plaques and prevalence of lacunar infarction.11

topics

v. There is a strong independent association between CMB and antiplatelet-

related intracerebral hemorrhage (ICH). Patients with a large number of CMBs,
particularly in a lobar distribution, are at higher risk of developing ICH, which
then outweighs the use of antiplatelet therapy in this population.12
vi. Higher levels of high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6),
and interleukin-18 (IL-18) are all associated with CMB suggesting the influence
of an inflammatory process in this phenomenon.13

B. Secondary Prevention
1. Use of Antiplatelet Therapy
i. The use of aspirin shows a beneficial effect in the secondary prevention of
atherothrombotic cerebral infarction.14
ii. Cilostazol was found to reduce the risk of secondary stroke by about 47%
compared with placebo, with the greatest reduction seen in patients with
lacunar infarction (43.4% in cilostazol versus placebo).15 A follow-up study
showed noninferiority of cilostazol to aspirin, however it was not specific to
SVD but rather for general stroke prevention.16
iii. A review article on antiplatelet trials in the Asian population supports the
superiority of cilostazol to aspirin in the secondary prevention of vascular
events (including stroke, myocardial infarction, and vascular death), all strokes,
and hemorrhagic stroke after a stroke of arterial origin. Cilostazol is likewise
associated with few major bleeding incidence compared with aspirin.17

2. Use of Combination Antiplatelet Therapy

i. In patients with recent lacunar infarction, combination antiplatelet therapy
using clopidogrel and aspirin did not significantly decrease the risk of recurrent
stroke, but it did significantly increase the bleeding risk and death.18
ii. In the Prevention Regimen For Effectively avoiding Secondary Strokes
(PRoFESS) study where more than 50% of subjects had small vessel infarcts
(SVI) as an index event, there was no difference between clopidogrel and
aspirin/extended-release dipyridamole in the prevention of recurrent strokes.19

3. Use of High-Dose Statins and Outcomes

i. The use of statins for secondary prevention of SVI was not addressed in the
AHA/ASA guidelines, although it recommends “intensive lipid-lowering” to
decrease the risk of stroke and other cardiovascular events among patients
with ischemic stroke or TIA presumed to be of atherosclerotic origin and a
low-density lipoprotein cholesterol (LDL-C) level of ≥100 mg/dl with or
190
 without objective evidence for other atherosclerotic cardiovascular diseases.20
ii. There are existing bodies of evidence that patients with SVD may develop
chronic silent CMBs that could potentially lead to larger hemorrhagic foci or
eventually to a frank ICH.21
iii. In the SPARCL trial, subjects with SVD treated with high-dose statins had a
benefit in the combined risk of any fatal or nonfatal stroke that is almost
equal to the benefit in the overall study population, with no difference in
terms of treatment-related fatal ICH.22

III. Recommendations
A. Neuroimaging
The use of cranial MRI to document the presence of small vessel disease, white
matter lesions, and cerebral microbleeds is recommended (Class I, level A).

B. Modification of Risk Factors

Recommendations for the management of treatable vascular risk factors
(hypertension, diabetes, and lipids) as well as modifiable behavioral risk factors
(cigarette smoking, alcohol consumption, physical activity, metabolic syndrome)
in patients with SVD follow that of the recommendations for prevention of stroke

Special
Topics
recurrence in general (Class IIa, level A).

C. Specific Medical Management

1. Use of Single Antiplatelet Therapy
i. The oral administration of aspirin (initial dose of 325 mg) within 24 to 48 hours
after stroke onset is recommended for most ischemic stroke patients (Class
I, level A).
ii. The oral administration of clopidogrel for the treatment of acute ischemic
stroke is not well established (Class IIb, level C).
iii. The use of cilostazol (100 mg twice daily) for the secondary prevention of
recurrent strokes in patients with SVD is recommended (Class I, level A).

2. Use of Combination Antiplatelet Therapy

The use of dual antiplatelet therapy (aspirin plus clopidogrel) does not
significantly decreases the risk of recurrent lacunar infarction (Class IIa, level B)
but significantly increases the risk for bleeding (Class III, level A).

3. Use of Statins and other Interventions

i. Giving high-dose statins in patients with SVD and SVI remains controversial.
It is yet to be determined if the benefits of giving high-dose statins outweigh
the risks (Class IIb, level B).
ii. There is still paucity of available data regarding the optimal blood pressure,
serum glucose, and medications for secondary prevention of SVI (Class IIb,
level B).
iii. Reduction of the plasma total homocysteine levels through folate
supplementation may be considered for patients with ischemic stroke and
hyperhomocysteneimia (Class IIb, level B), however, there is still no evidence
suggesting that homocysteine level reduction prevents stroke recurrence.

References

1. Lammie G. Pathology of small vessel stroke. Br Med Bull. 2000;56:296–306.

2. Fisher CM. Lacunar infarcts: a review. Cerebrovasc Dis. 1991;1:311-320.
3. Vernooij M, van der Lugt A, Ikram M, et al. Prevalence and risk factors of cerebral microbleeds: the
Rotterdam Scan Study. Neurology. 2008;70:1208–1214.
4. Viswanathan A, Chabriat H. Cerebral microhemorrhage. Stroke. 2006;37:550-555.
5. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic
challenges. Lancet Neurol. 2010;9:689-701.
6. Fisher M, French S, Ji P, et al. Cerebral microbleeds in the elderly a pathological analysis. Stroke.
191
 2010;41:2782-2785.
7. Makin S, Turpin S, Dennis M, et al. Cognitive impairment after lacunar stroke: systematic review and
meta-analysis of incidence, prevalence, and comparison with other subtypes. J Neurol Neurosurg
Psychiatry. 2013;84:893–900.
8. Seo SW, Lee BH, Kim EJ, et al. Clinical significance of microbleeds in subcortical vascular dementia.
Stroke. 2007;38:1949-1951.
9. Poels M, Vernooij M, Ikram M, et al. Prevalence and risk factors of cerebral microbleeds: an update of the
Rotterdam Scan Study. Stroke. 2010;41:S3-S106.
10. Jackson C, Sudlow C. Are lacunar strokes really different? a systematic review of differences in risk factor
profiles between lacunar and nonlacunar infarcts. Stroke. 2005;36;891-901.
11. Sasaki T, Watanabe M, Nagai Y, et al. Association of plasma homocysteine concentration with
atherosclerotic carotid plaques and lacunar infarction. Stroke. 2002;33:1493-1496.
12. Gregoire S, Jager H, Yousry T, et al. Brain microbleeds as potential risk factor for antiplatelt-related
intracerebral haemorrhage: hospital-based, case-control study. J Neurol Neurosurg Psychiatry.
2010;81:679-684.
13. Miwa K, Tanaka M, Okazaki S, et al. Relations of blood inflammatory marker levels with cerebral
microbleeds. Stroke. 2011;42:3202-3206.
14. Bousser M, Eschwege E. Haguenau M, et al. “AICLA” controlled trial of aspirin and dipyridamole in the
secondary prevention of atherothrombotic cerebral ischemia. Stroke. 1983;14:5-14.
15. Gotoh F, Tohgi H, Hirai S, et al. Cilostazol stroke prevention study: a placebo-controlled double-blind trial
for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis. 2000;9(4):147-157.
special
topics

16. Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention of secondary stroke (CSPS 2): an
aspirin controlled, double-blind, randomised non-inferiority trial. Lancet Neurol. 2010;9:959–968.
17. Kamal A, Naqvi I, Husain M, et al. Cilostazol versus aspirin for secondary prevention of vascular events
after stroke of arterial origin. Stroke. 2011;42:e382-e384.
18. Benavente O, Hart R, McClure L, et al. Effects of clopidogrel added to aspirin in patients with lacunar
stroke. N Engl J Med. 2012;367:817-25.
19. Sacco R, Diener H, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for
recurrent stroke. N Engl J Med. 2008;359:1238-1251.
20. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with
stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2014;45:000-000.
21. Fan Y, Mok V, Lam W, et al. Cerebral microbleeds and white matter changes in patients hospitalized with
lacunar infarcts. J Neurology. 2004;251:537-541.
22. Goldstein L, Amarenco P, Szarek M, et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive
Reduction in Cholesterol Levels study. Neurology. 2008;70:2364-2370.

192
 CHAPTER X
Guidelines for Nursing Care of the Stroke
Patient

I. Competency Statements of the Stroke Nurse in

Various Phases and Roles in Stroke Care

II. Stroke Nurse Certification Program

Sixth
Edition
2014
 Guidelines for Nursing Care of the Stroke Patient
The Critical Care Nurses Association of the Philippines, Inc. (CCNAPI) and representatives
from different tertiary care hospitals formulated the Competency Statements of Stroke
Nurse in Various Phases and Roles in Stroke Care in accompaniment with the SSP guidelines
for stroke prevention, treatment, and rehabilitation. The recommendations were adopted
from the Guidelines for Nursing Care of the American Heart Association/American Stroke
Association (AHA/ASA). The standards of professional nursing practice, as stipulated in
the 2012 National Nursing Core Competency Standards (NNCCS) by the Professional
Regulatory Commission (PRC)–Board of Nursing (BON), are likewise promoted.

I. Competency Statements of the Stroke Nurse in Various Phases

and Roles in Stroke Care1,2

Phase 1: Emergency/Hyperacute Phase

A. From the Field to the Emergency Department (ED):
Stroke Patient Triage and Care
1. EDs should establish standard operating procedures (SOPs) and protocols to
triage stroke patients expeditiously (Class I, level B).
2. Standard procedures and protocols should be established for benchmarking time
to evaluate and treat eligible stroke patients with rt-PA expeditiously (Class I,
level B).
3. Target treatment with rt-PA should be within 1 hour of the patient’s arrival in the
ED (Class I, level A).
Nursing
care

4. Eligible patients can be treated between the 3-hour to 4.5-hour window when
evaluated carefully for exclusions to treatment (Class I, level B).

B. Emergency Nursing Interventions in the Emergency/

Hyperacute Phase of Stroke
1. Emergency personnel should be highly trained in stroke care (Class I, level B).
2. Frequent neurological/stroke assessments should be done (Class I, level C). These
should be done more frequently in patients receiving rt-PA treatment.
3. It is reasonable to give supplemental oxygen to patients with an oxygen saturation
(SaO2) of <94% and decreased level of consciousness (Class I, level C). There is
little evidence for “routine” supplementation with oxygen.
4. The patient’s head should be positioned in neutral alignment with the body, and
the head of the bed should be elevated by 25 to 30 degrees to help the patient
handle oral secretions, especially if dysphagia is present (Class I, level C). In cases
of increased intracranial pressure (ICP), the recommended elevation is 30 to 45
degrees.
5. Patients in the ED should be maintained on NPO until the ability to swallow is
assessed (Class I, level B). The use of a bedside swallowing screen for dysphagia
(see Appendix D) in acute stroke patients is recommended.
6. Intravenous (IV) access should be obtained in at least 2 sites, with 1 site for the
administration of rt-PA (if the patient is a candidate for thrombolysis) and 1 site
for delivery of IV fluids or other medications (Class I, level C).

2012 National Nursing Core Competency Standards

Available at http://www.strokesocietyphil.org
194
Phase 2: Acute Phase
A. Nursing Care on Continued Stabilization of the Stroke Patient
1. Stroke neurological assessments should be performed every 4 hours after the
hyperacute phase of stroke; the frequency should be based on the patient’s
stability and other comorbid conditions (Class I, level B).
2. Temperatures ≥99.6°F (≥37.6 °C) should be managed aggressively (Class I, level
C).
3. Continuous cardiac monitoring of the stroke patient should be provided for at
least 24 hours to 48 hours after stroke to detect potential cardiac problems (Class
I, level B).

4. Careful, frequent monitoring and assessment for worsening of neurological

deficits or bleeding should be performed for up to 24 hours after thrombolytic
therapy (Class I, level B).
5. Oxygenation should be evaluated with an oxygen saturation monitor (e.g., pulse
oximeter) (Class I, level C).
6. Monitor for aspiration pneumonia by routine chest auscultation and evaluation
for signs of respiratory compromise and dysphagia (Class I, level C).
7. Document and immediately report all seizure activity (Class I, level B).
Anticonvulsant treatment, as directed by the physician, should be given promptly.
Prophylactic treatment of seizures is not recommended.

Nursing
B. Diagnostic Testing

care
1. All nurses should be familiar with the basic neuroimaging tests for stroke patients
so that they can educate and prepare patients and families (Class I, level C).

C. General Supportive Care

1. Infections, such as pneumonia and urinary tract infection (UTI), should be

identified and be treated empirically (Class I, level B).
2. Early bowel and bladder care should be instituted to prevent complications such
as constipation and urinary retention or infection (Class I, level A).
3. If possible, the use of indwelling catheters should be avoided to prevent the risk
of UTI (Class I, level A). If an indwelling catheter is required, excellent perineal
care and prevention of infection modalities should be instituted to prevent
complications (Class IIa, level C).
4.Early implementation of anticoagulant therapy or physical compression modalities
should be considered for all stroke patients who cannot ambulate at 2 days and
who are at risk for deep vein thrombosis (DVT) or pulmonary embolus (Class I,
level A). Early mobility should always be attempted if safe for the patient (Class
I, level B).
5. Fall precautions should be initiated. The patient should be advised to refrain from
ambulating if without a watcher or assistance (Class I, level B).
6. Frequent turning should be instituted in bedridden patients to prevent skin
breakdown (Class I, level A).
7. The use of Braden Scale (Appendix E) can assist in the prediction of stroke patients
at high risk of developing pressure ulcers (Class I, level A).
8. Range of motion exercise should start in the early phase of acute stroke care once
risk has been assessed (Class I, level C) (see Chapter 11).

195
 9. A swallow screen should be performed in the first 24 hours after stroke, preferably
by a speech pathologist (Class I, level B).
10. Nurses should be familiar with bedside swallow assessment (see Appendix D)
if a formal evaluation cannot be done within the specified period. Stroke patients
should be kept NPO until the screen has been performed (Class I, level B).
11. Patients who cannot swallow should have a nasogastric tube (NGT) placed, or
if severity warrants, a percutaneous endoscopic gastrostomy (PEG) tube should
be placed (Class I, level B). Assessment of proper hydration is included in this
recommendation.
12. The stroke patient can be fed either by IV infusion or through NGT or PEG tubes
(Class IIa, level B).
13. Nurses may provide passive range-of-motion (ROM) exercises between physical
therapy visits to help patients maintain joint mobility and prevent complications of
immobility (Class IIb, level C).

References

1. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the Early Management of Patients with Acute Ischemic
Stroke: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke
Association. Stroke. 2013;44:870–947.
2. Miller EL, Murray L, Richards L, et al. Comprehensive Overview of Nursing and Interdisciplinary
Rehabilitation Care of the Stroke Patient: A Scientific Statement from the American Heart Association.
Stroke. 2010;41:2402–2448.
Nursing
care

II. STROKE NURSING CERTIFICATION PROGRAM

The Critical Care Nurses Association of the Philippines, Inc. (CCNAPI) collaborated with
the Stroke Society of the Philippines (SSP) to develop a Stroke Nursing Certification Pro-
gram (SNCP) to provide recognition of the nurse clinicians’ attainment of knowledge,
skills, and attitudes to promote excellence in care and safety of stroke patients. The first
SNCP was held in 2014 and utilized the following materials/guidelines in its curricu-
lum: Association of Neurovascular Clinicians (ANVC) Core Curriculum for Neurovascular
Nursing, National Health Service (NHS) London Stroke Nurse Competency Guidelines,
and the NHS Education for Scotland (NES). The concepts have been modified to align
with the local context and meet the Philippine nursing scope of practice.

This SNCP offers qualified nursing and advanced practice clinicians with the opportu-
nity to showcase their expertise primarily in acute neurovascular practice. The SNCP is
a Continuing Professional Development applied for credit units under the Professional
Regulation Commission – Board of Nursing.

Qualification Requirements

All nurses attending the SNCP must be currently employed in intensive care units and
have performed at least a total of 1000 clinical care hours (6 months) in the immediate
12 months preceding their application to the program. Clinical care hours may include
provision of any of the following:
• Direct clinical / patient care
• Participation in research or quality improvement projects, Administration,
• Stroke center coordination, or
• Provision of nursing staff or patient education

196
Program Objective
This program aims to validate the participant’s mastery of skills, knowledge and abili-
ties through an educational program and certification process, at the same time meet
ongoing learning and practice requirements towards credentialing in the specialty of
critical care nursing.

Program Methodology:
This 2-month program is a blended program composed of 56 hours face-to-face
classroom methods combined with computer-mediated activities for case analysis
and a total of 280 clinical hours as practicum. The student is provided with the ANVC
Core Curriculum Reference book at the beginning of the program. The structured class
is supported with the self-paced learning activity through the “Moodle”, which is the
platform to augment the face-to-face courses.

Program Content
I. Didactic Phase
II. Clinical Practicum

a. 240 Hours (6 weeks) Home Hospital Practicum: During the entire duration of
the program, the participants will report to the ASU Chair (or SSP-designated
physician) of their respective hospitals for the mentored clinical activity.
Likewise, other educational activity will be established in a Moodle Program
which will be participated by the nurses during this period.

Nursing
b. 40 Hours (5 days) Observational Exposure in selected hospitals

care
III. Moodle
(Computer-mediated Activity): Case discussion and educational activities will be
facilitated off-site through the virtual learning environment utilizing Moodle as the
platform (Open Source Course Management System [CMS]).

Evaluation: Requirements and Examinations

a. Attendance and Participation (Didactic, Moodle and Practicum)
b. Moodle Activity Compliance: Case Reports and Discussions
c. Nursing Care Plan Formulation
(Innovative Nursing Practice / Best Practice)
d. Comprehensive / Certification Examinations and Quizzes

Stroke Nursing Certification Program List of Topics (Didactic Phase)

Available at http://www.strokesocietyphil.org
197
 CHAPTER XI

Guidelines for Stroke

Rehabilitation

A. General Rehabilitation Principles

B. Lower Extremity Rehabilitation
C. Upper Extremity Rehabilitation
D. Communication
E. Dysphagia and Swallowing
F. Post-Stroke Spasticity

Sixth
Edition
2014
 Guidelines for Stroke Rehabilitation
The SSP adopts the Guidelines for Stroke Rehabilitation by the Philippine Academy of
Rehabilitation Medicine (PARM). The readers may refer to the full version of the PARM
guidelinesa for comprehensive understanding of the recommendations presented in
this chapter. A PARM writing guide (Table 1) was created to standardize differently-
worded recommendations and differently-reported strengths of body of evidence for
recommendations extracted from several published guidelines.

Table 1. PARM Guide for Writing Recommendations and Summarizing the Underpinning
Strength of the Body of Evidence of included Recommendations.

Strength of the body of evidence PARM Statement

Strong evidence: Consistent grades of high quality evidence with “Strongly endorses”
uniform thought1, and at least a moderate volume of references to
support the recommendation(s)
With evidence: A mix of moderate and high quality evidence with “Endorses”
uniform thought and at least a low volume of references; or a mix of
high and low quality evidence with uniform thought, and high volume
of references; or high level evidence coupled with GPPs, and at least
moderate volume of references; or one Level I paper with at least
moderate volume references
Some evidence: Single level II (A) paper; or inconsistent grades of “Recommends”
high and low evidence with uniform thought and moderate volume
references; or consistent grades of low level evidence with uniform
thought and at least a moderate volume of references
Conflicting evidence: A mix of levels of evidence with non-uniform “Suggests”
thought, irrespective of the volume of references with or without
GPPs
Insufficient evidence: Low or inconsistent levels of evidence with low
volume references with or without GPPs
No evidence: Absence of evidence for any aspect of the patient journey “Does not endorse”
1
‘Uniform thought’ was the term coined by the PARM group to identify when differently worded
STROKE
REHAB

recommendations from different guidelines had the same intent. This assisted PARM to resolve the issue of
different wording of recommendations, despite using the same underpinning references.

MANAGEMENT AND PREVENTION STRATEGIES

A. General Rehabilitation Principles

A summary of recommendations for inpatient and outpatient rehabilitation of stroke is
presented below:
Table 2. PARM Recommendations for Inpatient Rehabilitation after Stroke

Recommendation Body of Evidence

i. Patients should be mobilized as early and as frequently as possible Strong evidence
once medically stable, preferably within 24 hours of stroke onset
unless contraindicated (see Table 3). Increasing the intensity
of rehabilitation has beneficial effects on functional outcomes,
including gait.

a
Available at http://www.eparm.org/
200
 ii. Patients should receive as much therapy as “needed” and tolerated, With Evidence
to adapt, recover and/or re-establish their pre-morbid or optimal
level of functional independence.
iii. Patients undergoing active rehabilitation should be provided with a Insufficient evidence
minimum of 1 hour active practice per day, at least five days a week
for both physical and occupation therapy

Table 3. PARM Criteria for “medically stable patient” and Contraindications to Acute Stroke
Rehabilitation
Criteria for “medically stable patient” Contraindications to acute stroke
rehabilitation
1. Any age diagnosed to have first or recurrent stroke 1. Deterioration within the first hour of
admitted within 24 hours admission to the stroke unit or direct
2. Systolic BP between 120-220 mm Hg admission to intensive care
3. Oxygen saturation of 92% (with or without 2. Concurrent progressive neurologic
supplementation) disorder
4. Heart rate between 40-100 beats per minute 3. Acute coronary syndrome
5. Temperature < 38.5 degrees Celsius 4. Severe heart failure

Table 4. PARM Recommendations for Outpatient Rehabilitation after Stroke

Recommendation Body of Evidence

i. Stroke patients with moderate or severe symptoms should be Strong evidence
referred to a rehabilitation facility or to a specialist with some
experience in stroke aids
ii. Rehabilitation delivered in the home setting should be offered to
all stroke survivors as needed. If home rehabilitation is unavailable,
patients requiring rehabilitation should receive center-based care.
iii. Patients should receive as much therapy if tolerated in order to With evidence
adapt, recover and/or re-establish their premorbid or optimal level
of functional independence.
iv. Rehabilitation should be structured to provide with as much practice Some evidence

STROKE
as possible within the first six months after stroke.

REHAB
v. The medical team, including the patient and family, must analyze Insufficient evidence
the patient’s medical/functional status and prognosis in order to
establish the most appropriate setting. The severity of patient’s
impairment, rehabilitation needs, availability of family/social support
and community resources, goals and preferences, will determine the
optimal environment of care.

B. Lower Extremity Rehabilitation

1. Assessment
PARM recommends the use of standardized, valid, and reliable tools in documenting the
level of assistance needed for mobility and self-care for both inpatient and outpatient
settings. These include manual muscle testing, range of motion (ROM) assessment,
and Modified Ashworth Scale. At a minimum, Functional Independence Measure (FIM)
mobility items, Berg Balance Score, and 10-meter walk should be used to assess gait
velocity, Functional Ambulation Classification, and assistance needed during daily
activities.

201
 2. Treatment modalities for Gait, Mobility, and Balance

Table 5. PARM Recommendations for Lower Extremity Rehabilitation after Stroke

Recommendation Body of Evidence
i. Repetitive practice of walking will improve gait speed, functional Strong evidence
ambulation and walking distance.
ii. Muscle strength training improves strength; there is evidence that
it also improves functional ambulation
iii. Regular aerobic exercise improves cardiorespiratory fitness, gait
speed and functional outcome. Considerations in incorporating a
cardiorespiratory program include the patient’s co-morbidities and
functional limitations, stroke risk factor profile, mood, and possibly
cognitive abilities.
iv. Neurodevelopmental techniques (NDT) for motor learning is equal
to other treatment approaches.
v. Task-specific training can improve transfer skills, mobility, and gait, With evidence
but there is insufficient evidence that improves balance
vi. Gait-oriented physical fitness training in medically stable patients
can improve gait speed and endurance. There is some evidence that
it may reduce the degree of dependence on other people during
walking
vii. The use of ankle foot orthosis improves walking speed, efficiency
and gait pattern or weight bearing during stance.
viii.The use of treadmill training can be used in conjunction with
gait training, but it is no more effective than ground training in
improving functional gait.
ix. Visual feedback during balance platform training does not have an
effect on balance, gait or mobility outcomes after stroke
x. Patients should be prescribed with modified activities to allow age-
appropriate target heart rates to be achieved for 20 to 30 minutes
three times per week
xi. Cueing for cadence and virtual reality training could be used in Some evidence
conjunction with gait training.
xii. Patients should be screened for risks of falls, which includes
identification of medical, functional, cognitive and environmental
STROKE

factors associated with potential falls and fall injuries. A program

REHAB

for fall prevention should be comprehensive and individualized.

xiii. Aquatic therapy improves functional balance
xiv. Functional electrical stimulation (FES) and Electromyographic Conflicting Evidence
(EMG) biofeedback may be used as adjunct in gait training.
xv. Joint position biofeedback may be used as additional modality in Insufficient Evidence
conjunction with gait training.
xvi. Force platform biofeedback training, tai chi, and cycling may
improve balance

C. Upper Extremity Rehabilitation

1. Assessment and Intensity of Training
PARM recommends assessment of independent activities of daily living (IADLs), leisure,
and participation using tools such as the Frenchay Activities Index and Canadian
Occupational Performance Measure (COPM) for maintained functional independence
and optimal participation. PARM strongly endorses increasing the intensity of
rehabilitation to upper limb function of post-stroke patients. Rehabilitation should be
structured within the first six months of stroke.
202
2. Therapeutic Approaches
Table 6. PARM Recommendations for Upper Extremity Rehabilitation after Stroke

Recommendation Body of Evidence

i. Constraint-induced movement therapy (CIMT) should be used in Strong evidence
individuals with at least 10 degrees of finger extension, limited
balance problems, and intact cognition. It confers modest
improvement in upper limb function. However there is conflicting
evidence whether it has long term benefits.
ii. Electromechanical/robotic devices/robot-assisted therapy/
mechanical assisted training is effective in improving upper limb
function.
iii. Electrostimulation and/or FES of the shoulder girdle can reduce
shoulder subluxation and pain.
iv. Progressive upper extremity strengthening exercises is effective in
improving upper limb function. Also there is evidence that strength
training does not increase spasticity, hence should not be avoided
in those with spasticity.
v. Splinting the wrist in either in neutral or extended wrist position
does not reduce wrist contracture after stroke; however there is
conflicting evidence whether it has significant effects on upper
limb function, spasticity, or activity limitations.
vi. Repetitive task training is effective in improving upper limb With evidence
function. There is some evidence that varied repetitive task practice
(e.g., CIMT, robot-assisted therapy) will improve upper extremity
motor coordination in individuals with some voluntary finger
extension.
vii. FES should be used on the wrist and forearm to reduce motor
impairment and improve functional motor recovery of patients
with stroke. It can be administered within two months of stroke
onset, to induce contraction of the supraspinatus and/or posterior
deltoid muscles.
viii.EMG biofeedback systems is no better than conventional therapy
in improving upper limb outcomes and should not be used on a
routine basis.

STROKE
ix. Bilateral training helps improve upper extremity function, but may

REHAB
not be better than unilateral practice.
x. Imagery / mental practice / mental imagery may be used as Conflicting evidence
adjunct to normal practice in improving upper limb function after
stroke.
xi. Virtual reality and mirror therapy may be used as adjunctive Insufficient evidence
strategy for upper limb treatment.
xii. Neurodevelopmental technique (NDT) may be used for motor
retraining following stroke.

D. Communication
1. Aphasia
a. Screening
i. PARM recommends that all patients should be screened for communication
deficits using valid and reliable screening tools; motor speech evaluations
include acoustic, auditory-perceptual, and physiological measures to assess
respiration, phonation, resonance, articulation, prosody, and intelligibility.
Aphasia evaluations should assess all communication modalities, including
listening, speaking, reading, writing, and, in severe cases, alternate modes such
as gesturing and drawing.
203
 ii. It is recommended that aphasia in stroke patients should be referred for
speech and language therapy.
iii. PARM suggests that for patients with right-hemisphere cognitive
communicative disorders be assessed for higher-level language and
pragmatic abilities in a variety of communication modalities. Communication,
cognitive function, and the capacity for decision making should be routinely
assessed in patients with aphasia.

b. Management
Table 7. PARM Recommendations for Management for Aphasia for Stroke patients

Recommendation Body of Evidence

i. Treatment of communication and/or cognitive disorders facilitate Strong evidence
restoration of impaired abilities. Compensatory strategies with
procedures selected on a case-by-case basis should be taught to
address the patient’s specific deficits and needs.
ii. Constraint-induced language therapy for management of aphasia. Some evidence
iii. Speech therapy for a minimum of two hours per week.
iv. Piracetam is not beneficial for aphasia.
v. Alternative means of communication such as gesture, drawing, Insufficient Evidence
writing, augmentive and alternative communication devices.
vi. Other interventions for aphasia: treatment of aspects of
language (including phonological and semantic deficits, sentence
level processing, reading and writing) derived from cognitive
neuropsychology models, use of gestures, supported conversation
techniques, and delivery of therapy programs via computer.
vii. Group therapy and conversation groups.
viii.All written information on health, aphasia, social and community
supports should be available in an aphasia-friendly format.

2. Dyspraxia
i. PARM suggests that patients with suspected dyspraxia of speech should receive
a comprehensive assessment.
ii. Treatment includes integral stimulation approach with modelling, visual cueing,
STROKE
REHAB

and articulatory placement cueing, and principles of motor learning to structure

practice sessions and delivery of feedback on performance and accuracy; there
is insufficient evidence on the use of PROMPT therapy and augmentative and
alternative communication modalities (e.g. gesture, speech-generating devices).

3. Dysarthria
i. PARM suggests that patients with unclear or unintelligible speech should be
assessed to determine the nature and cause of speech impairment.
ii. There is insufficient evidence regarding following interventions: biofeedback or
voice amplifier, intensive therapy aiming to increase loudness, and strategies
such as decreased rate, over-articulation or gesture and oral musculature
exercises.
iii. There is insufficient evidence regarding daily use of augmentative and alternative
communication devices for patients with severe dysarthria.

204
E. Dysphagia and Swallowing
1. Screening
Table 8. PARM Recommendations for Screening of Patients with Dysphagia

Recommendation Body of Evidence

i. All patients with a swallowing problem should be assessed by a Strong evidence
speech pathologist or an individual trained in the field.
ii. Water swallow test should be used as part of the screening for
aspiration risk in stroke patients.
iii. All stroke patients should be screened for dysphagia before being With evidence
given food or drink.
iv. Instrumental testing for swallowing evaluation should not be
used in acute stroke patients. However if bedside screening fails,
PARM recommends the use of videofluoroscopic modified barium
swallow study or flexible endoscopic examination of swallowing.
v. Gag reflex should not be used as a screening tool for dysphagia.

2. Bedside and Instrumental Assessment of Dysphagia

Table 9. PARM Recommendations for Bedside and Instrumental Assessment of patients with
Dysphagia

Recommendation Body of Evidence

i. PARM endorses the use of a standardized clinical bedside assessment Strong evidence
(CBA) by a professional skilled in the evaluation of dysphagia.
ii. The Modified barium swallow test and fibre optic endoscopic
evaluation of swallow are both valid methods for assessing
dysphagia.
iii. Use of pulse oximetry in determining oxygen saturation in Some evidence
swallowing among stroke patients.
iv. Standard criteria should be established for the interpretation of the
results of radiological and fibre optic assessments.
v. Cervical auscultation should be used in the assessment of dysphagia. Insufficient Evidence

STROKE
REHAB
vi. Patients who fail the swallowing screening should be referred to
a speech pathologist for a comprehensive assessment. This may
include instrumental examination (i.e. VMBS and/or FEES).

3. Management of Dysphagia
Table 10. PARM Recommendations for Management of patients with Dysphagia

Recommendation Body of Evidence

i. Use of suprahyoid muscle-strengthening exercises. With evidence
ii. Early feeding (i.e. within 24 hours) to reduce fatality among stroke Some evidence
patients
iii. Electrical stimulation in the treatment of dysphagia.
iv. Diet modification, compensatory techniques (postures and Conflicting evidence
maneuvers), use of restorative strategies (e.g., shaker head lifting
exercises), and thermotactile stimulation
v. Multipronged dysphagia interventions, lingual exercises muscle Insufficient evidence
strengthening, and use of low risk feeding strategies.

205
 4. Percutaneous Endoscopic Gastrostomy (PEG)/Nasogastric Tube (NGT) insertion

Table 11. PARM Recommendations for PEG/NGT insertion for stroke patients

Recommendation Body of Evidence

i. NGT feeding is the preferred method during the first month post- Some evidence
stroke for individuals who do not recover functional swallow.
ii. Use of PEG insertion over open gastrostomy is recommended due
to its lower mortality and morbidity profile.
iii. PEG feeding is the recommended feeding route for long term (> 4 Insufficient evidence
weeks) enteral feeding. Patients requiring long term tube feeding
should be reviewed regularly.
iv. Patient’s and carer’s perceptions and expectations of PEG feeding
should be considered, and the benefits, risks, and burden of care be
fully explained before the initiation of feeding.
v. Assessment of nutritional risk should be carried out within the first
48 hours with regular re-assessment thereafter during the patient’s
recovery and be recorded prior to discharge.
vi. On-going monitoring of nutritional status post-stroke should
include the following parameters: biochemical measures (e.g., low
pre-albumin, impaired glucose metabolism), swallowing status,
unintentional weight loss, eating assessment and dependence, and
nutritional intake.

F. Post-Stroke Spasticity
Table 12. PARM Recommendations for management of post-stroke spasticity

Recommendation Body of Evidence

i. Oral antispasticity medications (e.g., tizanidine, dantrolene, Strong Evidence
baclofen, diazepam, gabapentin) are effective in decreasing lower
extremity spasticity
ii. Botulinum toxin injection, either in conjunction with rehabilitation With Evidence
STROKE
REHAB

therapy or oral medication, can be used in patients with moderate

to severe spasticity.
iii. Anti-spasticity positioning, range of motion exercise, stretching and Some evidence
splinting can decrease or prevent contracture.
iv. FES and/or EMG biofeedback can be used in the management of spasticity.
v. Benzodiazepines should be avoided for the treatment of spasticity
because of its side effects.
vi. Intrathecal baclofen can be used when other treatment options fail. Conflicting evidence
vii. Injection of 50% ethyl alcohol into tibial nerve motor branches Insufficient evidence
and neurosurgical procedures (e.g., tibial nerve neurotomy, dorsal
rhizotomy, dorsal root entry zone lesion) as treatment in reducing
spasticity.

206
I. Acute Post-Stroke Rehabilitation

Patient with stroke during acute phase

Obtain medical history and physical examination.

Initial assessment of complications, impairment and rehabilitation
needs including NIHHS, GCS, MRS, FIMS/Barthel Index.

Initiate secondary prevention and prevention of complications.

Acute post-stroke patient assessed for rehabilitation

Determine nature and extent of rehabilitation needs and services

based on stroke severity, functional status and social support.

Mild Stroke Moderate Stroke Severe Stroke

Go to II, III, or IV Go to II Go to II

A. Initial brief assessment

1. Risk factors for recurrent stroke and coronary heart disease
2. Medical comorbidities (DM, hypertension, increase ICP, re-bleed, re-stroke)
3. Consciousness and cognitive status
4. Brief swallowing assessment

STROKE
REHAB
5. Skin assessment and pressure ulcers
6. Mobility and need for assistance of movement
7. Deep-vein thrombosis (DVT) risk assessment

B. Assessment of rehabilitation needs

1. Prevention of complications: swallowing problems, skin breakdown, DVT,
bowel and bladder dysfunction, malnutrition, pain, contractures, SHS/CRP,
pulmonary
2. Assessment of impairments: communication impairments, motor impairment,
cognitive deficits, visual and spatial deficiency, psychological or emotional
deficits, sensory deficits
3. Psychosocial assessment and family or caregivers support
4. Assessment of function (e.g., functional independence measure or FIM)
5. Financial support

207
 II. Inpatient Rehabilitation

Post-Stroke Patient in inpatient rehabilitation

Determine level of care based on medical status, cognitive and motor

function, social support, and access to medical care and services

Discuss rehabilitation program with patient and family.

Determine and document treatment plan.

Initiate rehabilitation programs and interventions

Reassess progress, future needs and risks with team. Is patient progress toward treatment goals?

No Yes

Address treatment adherence and barriers to Is patient ready for community living?
improvement. If medically unstable, refer to
acute services. If with other health factors, refer
to other health services
No Yes

Severe stroke and/or maximum

Go to III
dependence, or poor prognosis for
functional recovery?
STROKE
REHAB

Yes No Is patient ready for community living?

Educate patient, family, and caregiver about

future plans and home therapy. Discharge
patient to home or community.

Reassessment of Rehabilitation Progress

1. General (medical status)
2. Functional status (FIM, etc.): mobility, activities of daily living (ADL) and
instrumental ADLs, communication, nutrition, cognition, mood/affect/
motivation, sexual function
3. Family support: Resources, caretaker transportation
4. Patient and family adjustment
5. Reassessment of goals
6. Risk for recurrent cerebrovascular events
208
III. Outpatient Rehabilitation

Post-stroke patient ready for home

Does patient need outpatient

Reassess periodically No Go to IV
rehabilitation services?

Go to IV

Reassess progress, rehabilitation interventions

and optimal environment for outpatient
rehabilitation

Discuss shared decisions regarding rehabilitation

program and treatment plan with patient and family.
Continue secondary prevention.

Continue rehabilitation intervention at nearby

center or hospital, or use rehabilitation services

No Did patient plateau or achieve optimal function? Go to IV

Assessment of Discharge Environment

STROKE
REHAB
1. Functional needs
2. Motivation and preferences
3. Intensity of tolerable treatment: equipment, duration
4. Availability and eligibility
5. Transportation
6. Home assessment for safety

209
 IV. Community-Based Rehabilitation

Post-stroke patient ready for community living

Does patient need community-

No
based rehabilitation services?

Arrange primary-care
Yes
follow-up. Provide
home rehabilitation
program.
Determine optimal environment for community-
based rehabilitation

Discuss shared decision regarding rehabilitation

program and treatment plan with patient and family

Continue rehabilitation intervention with patient

and family/caregiver education

Did patient plateau or achieve optimal function?

Discharge to the home

or community setting.
Reassess periodically No Yes
Arrange primary care
follow-up. Provide
home rehabilitation.
STROKE
REHAB

210
 CHAPTER XII
Post-Stroke Evaluation for Resuming Activities
and Preoperative Assessment

I. Return to Work
II. Fitness to Drive
III. Fitness for Sex
IV. Fitness for Air Travel
V. Guidelines on the Discontinuation and Reinstitution
Of Anticoagulants and Antithrombotics in Stroke
Patients Undergoing a Surgical Procedure
VI. Preoperative Stroke Risk Assessment for Post-Stroke
Patients In Whom Carotid Endarterectomy has been
advised
VII. Preoperative Stroke Risk Assessment For Post-Stroke
Patients In Whom Other Surgical Procedures has
been advised
VIII. Preoperative Stroke Risk Assessment For Post-Stroke
Patients in Whom Coronary Artery Bypass Graft
Surgery has been advised
Sixth
Edition
2014
 Post-Stroke Evaluation for Resuming Activities and
Preoperative Assessment

Patients with prior stroke, especially those with residual neurological deficits, are
frequently asked to see a neurologist or an internist for medical clearance before he/she
can return to work or resume specific activities such as driving and air travel. Similarly,
post-stroke patients who will undergo certain surgical procedures need to be assessed
for the risk of recurrence.

The SSP adopts the recommendations set forth by the Stroke Council of the Philippine
Neurological Association (PNA) for post-stroke evaluation. It should be noted that these
recommendations only serve as a guide for physicians, as decision-making should be
based on clinical judgment with full consideration of individual factors. For details on
the topics, the readers may refer to the PNA-Stroke Council’s Post-Stroke Evaluation
Project (2010).

I. Return to work
Stroke survivors are usually left with some degree of impairment for a relative period
of time or even permanently, which potentially lessens the likelihood of securing an
employment. Only after careful evaluation of the patient–particularly on the severity
of stroke, functionality, ability for self-care, and absence of complications/co-morbid
conditions–can then he/she be considered to resume work, if there is an intent to do so.
Physicians are usually asked to evaluate the extent of disability or impairment incurred
by the patient as related to stroke, as well as determine restriction/s. These may also
serve as basis for medical claims in insurance companies (government and private) and
employers. For example, the Social Security System (SSS) uses a criterion referred to
as Whole-Person Impairment Estimate (WPIE) to determine the amount of disability
benefit provided to the pensioner. A sample of the disability scores using the WPIE is
shown in Table 1.

Table 1. Sample of Whole-Person Impairment Estimates (WPIE), SSS, Philippines

Aphasia % impairment of the
body (OB)
a. Slight (can understand and produce language symbols) 15% OB
b. Moderate (cannot understand but could attempt to produce 50% OB
language symbols)
c. Severe (inability to understand or produce language symbols) 100% OB
POST-STROKE
EVALUATION

Paralysis
a. Paresis of one extremity 25% OB
b. Paresis of two or more extremities 50% OB
c. Paralysis of one extremity 50% OB
d. Paralysis of two or more extremities 100% OB
e. Paralysis of more than two extremities 100% OB
Cerebrovascular Accident (6 to 12 months after stroke)
a. with persistent hemiplegia 100% OB
b. with persistent hemiparesis 50% OB
A disability score of 75% or higher is considered permanent disability, while a score of 74% and below is considered
partial disability.
212
Because little has been studied worldwide regarding resumption of work after a stroke,
the following recommendations were substantially based on the consensus of local
stroke experts regarding work-related absences for each scenario in the context of
Philippine healthcare and labor system:

1. For patients with single TIA, return to work after 5 days following discharge from
the hospital may be considered provided the cause of the TIA is identified and
treated.
2. For patients with recurrent TIAs, return to work after at least 30 days from the
last episode may be considered provided that the cause of TIA is identified and
addressed.
3. For patients hospitalized for TIA who underwent carotid endarterectomy (CEA),
return to clerical work may be considered after 14 days following discharge
from the hospital, while return to manual work may be considered after 28 days
following discharge from the hospital.
4. For patients with acute ischemic or hemorrhagic stroke, the possibility of returning
to work is dependent on the functional motor assessment, visual fields, digital
dexterity as well as the cognitive and behavioral assessment of an individual after a
stroke.
5. If there is uncertainty regarding cognitive consequences of stroke, it is advised that
the patient be referred to a neuropsychologist for psychometric evaluation.
6. If there is uncertainty regarding finger dexterity to perform specific motor skill, it is
advised that the patient be referred to an occupational therapist for task evaluation
under the supervision of a physiatrist.
7. It is important to consider the nature and responsibilities of the job and the
willingness of the employer to relocate the patient to an area that would best fit
his/her current physical condition.
8. For patients with acute ischemic or primary intracerebral hemorrhagic (PICH) stroke
with a Modified Rankin Scale (mRS) (See Appendix B) score of 0 to 1 on the first
follow-up consult, return to clerical or manual work may be considered after 30
days of physical and/or occupational therapy. If there is improvement in the score,
then return to work is recommended.
9. For patients with acute ischemic or PICH stroke with an mRS of 2 on the first
follow-up consult, a 3-month period of physical and/or occupational therapy is
recommended. If an improvement is seen in all clinical assessments described in
item 4 after the designated return visit, returning to clerical or manual work may
be considered. If the mRS remains at 2, further reassessment after 3 months is
recommended. If there is no improvement at the end of total 6-month recovery
period, it is reasonable for the physician to recommend a permanent disability
POST-STROKE
EVALUATION

status for manual work. Clerical or managerial work however, may be considered at
this time.
10. For patient with acute ischemic or PICH stroke with an mRS of 3 on the first follow-
up consult.
11. For patients with ICH who has undergone craniotomy or craniectomy, the possibility
of returning to work may be considered using the same recommendations described
in items 8-10.

II. Fitness to Drive

The Philippine Land Transportation Office (LTO) currently has no guidelines for evaluating
fitness to drive after a stroke or TIA. The following recommendations for driving were
213
 developed by the Stroke Council based on several foreign guideline recommendations.

1. All stroke patients should be advised about fitness to drive before discharge from
the hospital (Class I, level C). The physician should inquire into the type of license
held.
2. Patients with a single TIA may resume driving after at least 4 weeks post-recovery
for non-professional licensees, or 6 weeks for professional licensees, provided that
the cause of TIA was identified and treated (Class IIb, level C).
3. Patients with recurrent TIAs may resume driving after at least 3 months from the
last episode for both professional and non-professional licensees, provided that the
cause of TIA was investigated and addressed (Class IIb, level C). Individuals should
undergo a regular medical assessment.
4. Post-stroke patients should be advised against driving for a period of at least 4
weeks after the acute stroke (Class I, level C).
5. Return to driving may be considered in such time as full clinical recovery is noted,
without a significant residual disability that may compromise safety while driving
(Class IIa, level C).
6. Upon reassessment after a full clinical recovery and at least one month following a
stroke, the mRS score can be used as a basis for recommendations for driving (Class
IIb, level C):

Table 2. Recommendations for Driving based on modified Rankin Scale (mRS) scores

mRS score Recommendation

0-1 Consider resumption of driving
2 Further reassessment after 3 months
3 Refrain from driving
4-5 No driving

7. Cognitive and behavioral assessment must be emphasized in addition to

functional assessment in post-stroke patients. If there is any doubt regarding
cognitive consequences of stroke, it is advised that the patient be referred to a
neuropsychologist for psychometric evaluation (Class IIa, level B).
8. Patients with stroke-related seizures may be allowed to resume driving after at least
3 months of seizure-free interval (Class I, level B).
9. The presence of homonymous hemianopia or quadrantanopsia is considered unsafe
for driving (Class IIa, level B). If indicated, visual field assessment is recommended
to determine fitness to drive.
POST-STROKE
EVALUATION

10. In the presence of diplopia, it is reasonable to advise a patient to refrain from

driving (Class IIb, level C). Driving may be resumed upon confirmation that diplopia
is controlled by corrective glasses or patch which the patient wears while driving.

III. Fitness for Sex

The question of safety to engage in sex after stroke is an important matter to some
patients. If applicable, this should be discussed with the patient during discharge
planning or follow-up visits. The following are general recommendations on the issues
related to sex after stroke:

1. Sexual activity may be resumed after a stroke event once they are physically and
214
 emotionally ready (Class IIa, level C).
2. Post-stroke patients may use phosphodiesterase type 5 (PDE5) inhibitors such as
sildenafil, tadalafil, or vardenafil upon physician’s recommendation (Class IIa, level
A).
3. The use of oral contraceptive pills (OCPs) should be discouraged among female
post-stroke patients, especially those with concomitant hypertension, diabetes,
cigarette smoking or history of thromboembolic events (Class III, level C).

IV. Fitness for Air Travel

Traveling at high altitudes has known effects in the normal human physiology because
of the low barometric pressures and environmental stresses. All individuals with pre-
existing medical conditions are required to undergo clinical evaluation and secure
a medical clearance prior to air travel. Physicians assessing fitness of air passengers
must consider all possible conditions or complications that may potentially develop or
aggravate during flight, to prevent any hazard or annoyance to other passengers as well
as interruption in flight operation. The following are general recommendations for air
travel for post-stroke/TIA patients, however these do not reflect recommendations for
other medical conditions. It is strongly advised to check with the guidelines or policies
of the respective airline company for passengers with other medical conditions.

1. After a transient ischemic attack, a passenger may be allowed for air travel after
two weeks.
2. After a stroke, a passenger may be allowed for air travel after two months.
3. Following a neurosurgical intervention, avoid air travel within seven days.
4. Special devices like oxygen, wheelchairs, etc., should be requested two weeks
prior to intended travel.
5. Travel insurance should be comprehensive and should include provisions for
repatriation.

V. Guidelines on Discontinuation and Reinstitution of Anticoagulants and

Antithrombotics in Stroke Patients undergoing a Surgical Procedure

The following recommendations are based on several foreign-derived bodies of evidence

regarding discontinuation and reinstitution of anticoagulants and antithrombotics in
stroke patients undergoing a surgical procedure:

1. Warfarin should be stopped for 5 days prior to an elective surgical procedure if

the INR is being maintained at 2-3. If the INR is greater than or equal to 3 or if the
patient is elderly, warfarin should be stopped 6 days prior to the procedure (Class
POST-STROKE
EVALUATION

II, level A).

2. The prothrombin time should be repeated immediately prior to surgery and the
INR must be at least 1.5 or below before proceeding with surgery, or 1.2 or below
for a neurosurgical procedure.
3. Antiplatelets such as Aspirin and Clopidogrel should be stopped 7 to 10 days
prior to surgical procedure (Class I, level A).
4. If a patient on warfarin requires urgent surgery, a fresh frozen plasma can be
given if emergent. If the surgery can be done within the next 24 to 48 hours,
vitamin K 1 mg IV is recommended (Class II, level A).
5. The thrombosis risk while off warfarin should be assessed as to whether it is high,
intermediate, or low risk and bridging therapy should be given when applicable.
215
 6. There are certain ophthalmic, endoscopic, dermatologic, and dental procedures
which do not require interruption of warfarin therapy because of low risk of
bleeding (Class II, level A).
7. Patients undergoing surgery with an acute coronary syndrome should continue
aspirin up to the day of surgery as the benefits may outweigh these risks (Class II,
level A).
8. The role of ASA in stroke prevention is stronger in the peri-operative period in the
setting of CEA. Aspirin therefore should not be stopped in patients undergoing
CEA (Class I, level A).
9. The time for resumption of warfarin after surgery depends on the surgical
procedure that was performed. The following are the suggested post-operative
anticoagulant management for each bleeding risk category:

Table 3. Suggestion for Post-operative Anticoagulation according to Bleeding Risk

Bleeding Risk Examples of procedure Suggested anticoagulant

High Neurosurgical procedures,
prostatectomy, heart valve
replacement, CABG, renal biopsy, major
cancer surgery
Moderate Intra-abominal, intra-thoracic, or
orthopedic surgery; pacemaker
insertion
management
Start on the evening of the day
after surgery (Day 1 post-op)
Start on the evening of the day of
surgery (Day 0 post-op)

10. Aspirin or Clopidogrel can be safely restarted 6 hours after surgery. For patients
undergoing Coronary Artery Bypass Grafting (CABG), aspirin should be restarted 6
hours after the procedure (Class I, level A).

VI. Pre-operative Stroke Risk Assessment for Post-stroke patients in whom

Carotid Endarterectomy (CEA) has been advised
1. Factors associated with increased stroke risk with CEA including medical,
neurologic, and angiographic risks and surgical skill should be considered in pre-
operative assessment.
2. When CEA is indicated for patients with TIA or minor stroke, with minimal
evidence of infarction on imaging or mass effect, a stable deficit and normal
level of consciousness, surgery within 2 weeks is suggested rather than delaying
surgery (Class IIa, level B).
3. For patients with completed moderate stroke or those with unstable or progressive
POST-STROKE
EVALUATION

deficits, delay surgery for 4-6 weeks, or reschedule operation when neurological
recovery has stabilized or reached a plateau.
4. For patients with acute stroke and depressed level of consciousness, or those with
evolving symptoms, urgent angiography and surgery are not indicated because
of higher associated morbidity and mortality rates.
5. In patients with symptomatic active lesion in both carotid and coronary circulation,
data is currently insufficient to declare superiority of timing of CEA either before
or simultaneous with CABG.
6. Endarterectomy in asymptomatic patients should be done by experienced
surgeons with documented low peri-operative stroke and death rates.

216
VII. Pre-operative stroke risk assessment for post-stroke patients in whom
other surgical procedures has been advised
1. Elective general surgery should be deferred and all patients should undergo
complete neurovascular evaluation, prior to contemplated surgery.
2. Elective general surgery should be performed at least 4 weeks after a moderately
sized cerebral infarct (greater than 1/3 of MCA distribution).
3. Symptomatic carotid stenosis should be repaired before non-emergent general
surgical procedure.
4. Bridging therapy with low molecular weight heparin or intravenous heparin
should be considered for high risk patients when anticoagulation or antiplatelet
agent is discontinued for surgery.

VIII. Pre-operative stroke risk assessment for patients in whom Coronary

Artery Bypass Graft (CABG) surgery has been advised
1. Physicians must inquire specifically about history of TIA or stroke within the
past 6 months and fully investigate and treat the underlying etiology, especially
if evaluation was not done or was incomplete or if neurologic conditions has
worsened.
2. A recent preoperative stroke represents a situation in which delaying surgery may
reduce the peri-operative neurological risk. If coronary anatomy and symptoms
permit, a delay of 4 weeks or more after stroke risk is prudent, before proceeding
with CABG.
3. A risk point assessment system (Table 4) may be used to predict the risk of stroke
and mortality in patients undergoing isolated CABG surgery.

Table 4. Pre-operative calculation of Risk of Stroke in CABG patients

Variable Weighted Total Probability

score Score for stroke
for stroke (%)
60-69 3.5 0 0.3
Age
70-79 5 1 0.4
>80 6 2 0.7
Female gender Add total 3 0.9
weighted scores
Ejection fraction <40 1.5 to predict risk of 4 1.1
Diabetes 1.5 stroke 5 1.5
POST-STROKE
EVALUATION

Prior CABG 1.5 6 1.9

Vascular disease (including 2 7 2.8
stroke/TIA)
Renal failure or creatinine 2 8 3.5
>2mg/dL
Urgent surgery 1.5 9 4.5
Emergent surgery 2.5 10 >5
adapted from Charlesworth et al. Ann Thorac Surg 2003;76:436–443.

217
 4. Screening for carotid stenosis among patients undergoing CABG surgery is
strongly recommended among patients who are 65 years or older and have other
significant risk factors such as diabetes, peripheral vascular disease, history of
smoking, or carotid bruit on examination and history of cerebrovascular disease
(Class IIa, level C).
5. Non-invasive Doppler ultrasound (e.g., Carotid Duplex) is the most appropriate
screening method for carotid stenosis. CT- and MR- angiography are alternative
non-invasive techniques.
6. Management and decision-making in patients with carotid stenosis before
cardiac surgery should be individualized. Each patient should be assessed
according to the severity of the disease both clinically and anatomically in each
system.

CABG in the setting of symptomatic severe carotid disease

1. For patients with symptomatic severe carotid stenosis, consider: 1) combined
carotid revascularization and CABG surgery, or 2) staged procedure (e.g., CABG
after carotid revascularization). Neither strategy has been established as being
superior. The safety of CEA compared to stenting should be considered for the
extracranial stenosis.
2. When the risk of complications and death from cardiac causes exceed that of
stroke (urgent coronary surgery), carotid revascularization after CABG (reversed
stage) or a combined approach may be undertaken. Preliminary evidence
suggests carotid stenting may be more suitable than CEA. Stroke risk is increased
if reversed stage procedure is used in which CABG precedes CEA.

CABG in the setting of Asymptomatic Severe Carotid Disease

1. At a minimum, the evaluation of patients for CABG with asymptomatic carotid
stenosis should include a detailed neurological exam, history taking designed to
elicit unreported symptoms of TIA and brain imaging to rule out silent ipsilateral
infarcts.
2. Patients with asymptomatic high grade carotid stenosis may derive benefit
with additional evaluation such as Transcranial Doppler, MR Angiography, CT
Angiography, and Perfusion imaging to assess status of cerebral hemodynamics,
collateral circulation, and vascular reserve capacity.
3. It is not clearly established which is the best approach for patients with
asymptomatic severe carotid disease. Data at best is conflicting regarding
potential benefit of CEA for asymptomatic disease prior or concomitant CABG.
4. CEA before CABG (staged) or concomitant to CABG is “acceptable but not
proven” in patients with asymptomatic unilateral high grade stenosis or bilateral
POST-STROKE
EVALUATION

internal carotid stenosis of 80% or more (Class IIa, level C).

CABG in the setting of Intracranial stenosis

There is insufficient data to recommend prophylactic endovascular procedures for
patients with symptomatic intracranial disease undergoing vascular procedures.

218
CHAPTER XIII
Guidelines on the Establishment and
Operation of Stroke Units

I. The Stroke Center

II. Stroke Unit Organization
III. Stroke Unit Certification
IV. Workshop for the Establishment of Stroke Unit
V. Stroke Center Levels
VI. Directory of Stroke Units

Sixth
Edition
2014
 Guidelines on the Establishment and Operation of Stroke Units

I. THE STROKE CENTER

A. Major Aspects of Acute Stroke Care in Stroke Center
1. Acute Stroke Teams: Hospital-based stroke teams should be available round-
the-clock, seven days a week in order to evaluate within 15 minutes any
patient who may have suffered a stroke.
2. Written Care Protocols: The availability of written protocols is the key in
reducing time to treatment and treatment complications.
3. Emergency Medical Services (EMS), which are vital in the rapid transport and
survival of stroke patients.
4. Emergency Department (ED): The ED staff should be trained in diagnosing and
treating stroke and must have good lines of communication with both EMS
and the acute stroke team.
5. Stroke Unit (SU): Where patients can receive specialized monitoring and care.
6. Neurosurgical Services: These should be provided to stroke patients within
two hours of admission when the services are deemed necessary.
7. Support of the Medical Organization: The facility and its staff, including the
administration, should be committed to the SU.
8. Neuroimaging: capability to perform an imaging study within 25 minutes
of the physician’s order. The physician should evaluate the image within 20
minutes of completion.
9. Laboratory Services: should be available round-the-clock, seven days a week.
10. Outcomes/Quality Improvement: Primary Stroke Centers should have a
database or registry for tracking the type and number of stroke patients seen,
their treatments, timelines for treatments, and some measurements of patient
outcome.
11. Educational Programs: The professional staff should receive at least eight
hours per year of continuing medical education (CME) credits. In addition
to professional education, the Stroke Center should plan and implement at
least two annual programs to educate the public about stroke prevention,
diagnosis, and availability of emergency treatment.

B. Definition of a Stroke Unit

A Stroke Unit (SU) is a hospital unit that cares for stroke patients exclusively
or almost exclusively, with a specially-trained staff and a multidisciplinary
approach to treatment and care.1

C. Characteristics of a Stroke Unit

Organization Specialization Education

• Coordinated
multidisciplinary team care
• Nursing integration with
multi-disciplinary care
STROKE UNITS
• Medical and nursing interest • Education and
• Expertise in stroke and training program for
rehabilitation staff, patients and
caregivers

• Involvement of caregivers
in rehabilitation process

220
 D. Goals of a Stroke Unit
1. Improve chances of survival 3. Shorten length of hospital stay
2. Reduce disability 4. Shorten length of rehabilitation

E. Types of Stroke Units
E.1. Acute Admission Units:
1. Intensive Care Units (ICU) – dedicated SUs with facilities such as ventilators
and intensive invasive and non-invasive monitoring equipment. The units
focus on the very acute care of a selected group of acute stroke patients, but
have little or no focus on rehabilitation.
2. Acute Stroke Units (ASU) – dedicated SUs that accept patients acutely but
discharge them early (within 7 days); they have modest focus (at best) or none
on rehabilitation. The units usually do not have intensive care facilities, but
usually have facilities for non-invasive monitoring of vital signs.
3. Combined Acute/Rehabilitation SU – dedicated SUs which accept stroke
patients acutely for acute treatment, combined with early mobilization and
rehabilitation for an average period of at least one to two weeks.
4. Mixed Acute Units – units that treat stroke patients and patients with other
diagnoses. These units accept patients acutely. Some units have a program of
care similar to that of ASUs or combined SU.

E.2. Delayed Admission Units:

1. Rehabilitation Stroke Units – dedicated units that accept patients after
a minimum delay of seven days after stroke onset. These units focus on
rehabilitation.

2. Mixed Assessment/Rehabilitation Units – wards or units which have an interest

and expertise in the assessment and rehabilitation of disabling illness, but do
not exclusively manage stroke patients.

F. Effects of Stroke Unit Care on Recovery

Analysis of Cochrane Database involving 23 trials showed a significant
reduction of death (odds ratio [OR]=0.88), death or dependency (OR=0.75),
and death or institutionalization (OR=0.77) among patients treated in an SU
compared to those treated in the general wards.2

Two trials evaluated the long-term effects of stroke unit care. On the 5-year
follow-up, admission in combined acute/rehabilitation SUs reduced death
(OR=0.59; Number Needed to Treat [NNT]=9), death or dependency (OR=0.36;
NNT=6), and death or institutionalization (OR=0.48; NNT=9). Ten-year follow-
up of patients admitted in combined acute/rehabilitation SUs similarly showed
a reduction in death (OR=0.45), death or dependency (OR=0.45), and death or
institutionalization (OR=0.42).3-5 Patients admitted in a rehabilitation SU even
after a minimum delay of seven days post-stroke resulted in reduced death
(OR=0.66; NNT=10) and death or dependency (OR=0.83; NNT=90).6

The stroke unit therefore benefits stroke patients of both sexes, all ages, and
STROKE UNITS

those with mild, moderate or severe strokes.2,7 Comparing the different SU

models, the unit with the strongest evidence of benefit is the combined acute/
rehabilitation SU model, and to some extent the dedicated rehabilitation SU.2

221
 II. STROKE UNIT ORGANIZATION
A. Basic Equipment
1. At least 2 dedicated beds for stroke patients
2. Cranial computerized tomography scan (available 24 hours)
3. Emergency laboratory facility
4. Monitoring equipment (e.g. respiration, Holter, pulse oximetry)
5. Ultrasound (continuous wave, transcranial duplex, transthoracic or
transesophageal echocardiogram)
6. Angiography (CTA, MRA, or conventional)
(items 1-4 are necessary)

Monitoring:
1. Basic – Holter, blood pressure, O2 saturation, respiration, temperature
2. Special – transcranial Doppler, embolus detection, electroencephalography,
central breathing patterns (sleep apnea)

B. Tasks
1. Admission within the unstable phase (in general, <24 hours)
2. Monitoring of vital and neurological parameters
3. Immediate diagnosis (etiology, pathogenesis)
4. Immediate treatment and secondary prevention
5. In general, length of stay not longer than seven days

C. Patient Selection
1. Indications for Admission to the Stroke Unit:
a. Acute stroke (0-72 hours)
b. Awake, somnolent patient
c. Symptoms fluctuating or progressive
d. TIAs with high stroke risk (non-valvular AF, stenosis)
e. Vital parameters unstable
f. Thrombolysis; anticoagulation
g. New investigational treatment or procedure

2. Admission to Acute Stroke Unit Not Indicated:

a. Patients with severe impairment of consciousness (should be admitted to
an ICU instead)
b. Severely disabled patients by previous strokes
c. Very old patients or those with multiple comorbidities

3. Patients with the following should be admitted to an ICU instead of ASU:

a. Stupor and coma
b. Central respiratory disorders requiring artificial ventilation
c. Space-occupying cerebral infarctions with risk of herniation
d. Severe cardiopulmonary insufficiency
e. Hypertensive-hypervolemic treatment

D. The Stroke Team

STROKE UNIT

1. Personnel
a. Physicians
b. Nurses

222
 c. Physiatrists
d. Occupational therapists
e. Speech pathologists
f. Nutritionists
g. Social workers

2. Personnel with special interest in stroke are medical doctors or paramedical

staff who:
a. Have undergone continuing education on stroke and other related
activities or subspecialties on stroke
b. Have been attending at least one national or international meeting or
conference on stroke in a year
c. Have undergone stroke fellowship or preceptorship training in stroke
d. Is a member or officer of a national or international organization devoted
to stroke.

III. STROKE UNIT CERTIFICATION

A. Steps in Applying for Stroke Unit Certification
1. Hospitals applying for SU certification should write a letter of intent to the
president of the Stroke Society of the Philippines.
2. A letter of endorsement from the Hospital Administration should accompany this
letter of application stating that full support will be given in the establishment of
the SU.

B. Minimum Requirements for Hospitals requesting for Stroke Unit Certification

1. The floor plan of the existing or proposed SU and number of beds
2. Availability of 24-hour cranial CT scan or MRI
3. Availability of 24-hour laboratory facilities
4. Availability of medical personnel who will head the SU (in the following order):
1) Neurologist
2) Other specialist preferably neurosurgeon, cardiologist, internist, or
physiatrist with special interest in stroke
3) Other physicians
5. Availability of nursing staff dedicated to stroke care

IV. WORKSHOP FOR THE ESTABLISHMENT OF STROKE UNIT

A. Topics/Activities for Stroke Unit Workshop
1. Organization of Stroke Services
2. Pre-hospital management (if EMS are available)
3. Emergency Room management
4. Stroke Unit
5. Group Activity
i. Participants will be divided into 2-3 groups.
ii. Each subgroup will do SWOT analysis of:
STROKE UNIT

a) Pre-hospital Management (if existing)

b) Emergency Room Management
c) Stroke Unit

223
 B. Participants in the Stroke Unit Workshop
1. Physicians composed of neurologists, neurosurgeons, and emergency physicians;
ED and SU nurses, administrator/s.
2. SSP should identify members willing to carry out workshop in SU establishment.

V. RECOMMENDATIONS
1. Stroke patients should be treated in stroke units (Class I, level A). Admission to
stroke unit decreases death, dependency, and institutionalization.
2. Stroke units should provide coordinated multidisciplinary care provided by
medical, nursing, and healthcare staff who specialize in stroke care (Class I).

Bibliography

1. Aboderin I, Venables G. Stroke Management in Europe: Pan European Consensus meeting on stroke
management. J Intern Med. 1996;240:173–180.
2. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane
Database Syst Rev. 2002;(1):CD000197.
3. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment: long term effects. Stroke.
1997;28:1861-1866.
4. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment improves long term quality of life: a
randomized controlled trial. Stroke. 1998;29:895-899.
5. Indredavik B, Slordahl SA, Bakke F, et al. Stroke unit treatment: 10 year follow-up. Stroke.
1999;30:1524-1527.
6. Lincoln NB, Husbands S, Trescoli C, et al. Five year follow-up of a randomized controlled trial of a
stroke rehabilitation unit. BMJ. 2000:320; 549.
7. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after
stroke. Stroke Unit Trialists’ Collaboration. BMJ. 1997;314(7088):1151-1159.
STROKE UNIT

224
 Strategy for Implementation of Guidelines
To effectively implement the guidelines set forth in the previous sections, it is
recommended that Stroke Centers (Table 1) be established in every region. Stroke
Centers shall be designated according to levels as follows:

Table 1. Stroke Center Levels

Stroke Center Level I II III

Basic Requirements
Personnel MD Neurologist Neurologist
Neurosurgeon Neurosurgeon
Optional: Stroke Nurse Stroke Nurse
RN, Midwife, BHW Radiologist Neuroradiologist,
Physiatrist Neurosonologist
Physiatrist
Vascular surgeon
Facilities Clinic CT scan CT scan
ECG Cardiac Diagnostic
Laboratory services: ECG,
Stroke Unit Doppler
Operating Room Laboratory
Stroke Unit
Operating Room
Angiography
Rehab Unit
Activities
Stroke Prevention and ü ü ü
Public Education
Recognition of Stroke ü ü ü
Acute Treatment
TIA or mild stroke ü ü ü
Moderate and severe strokes refer to Level II or III) ü ü
Complicated strokes (refer to Level III) (refer to level III) ü
Diagnostic tests (refer to Level II or III) ü ü
Rehabilitation ü ü ü
Secondary prevention of ü ü ü
stroke and follow-up visits
Research ü
Training of Stroke ü
Personnel
STROKE UNIT

225
 Table 2. Directory of Stroke Units in the Philippines

Type of No.
Contact
Hospital Stroke of Director
Number
Unit (SU) Beds
METRO MANILA
Capitol Medical Center Acute SU 4 Dr. Abdias Aquino 372-3825
Quezon Avenue, Quezon City (ASU) local 4614
Chinese General Hospital and Acute SU 4 Dr. Johnny Lokin 711-4141
Medical Center (ASU) local 608
Blumentritt Street, Sta. Cruz, Manila
East Avenue Medical Center Mixed 5 Dr. Ceferino Rivera 928-0611
East Avenue, Diliman, Quezon City acute unit local 503
Jose Reyes Memorial Medical Center Mixed 10 Dr. Romulo Esagunde 711-9491
Rizal Avenue, Sta. Cruz, Manila acute unit local 262
Makati Medical Center ASU 2 Dr. Raquel Alvarez 888-8999
Amorsolo Street, Legaspi Village, local 2452
Makati City
Manila Central University Mixed 6 Dr. Rolando Perez 367-2031
Epifanio delos Santos Avenue, acute unit local 2013
Caloocan City
Manila Doctors Hospital Mixed 10 Dr. Carlos Chua 524-3011
United Nations Avenue, Ermita, Manila acute unit local 8118
Metropolitan Medical Center Mixed 7 Dr. Herminigildo Gan 254-1111
G. Masangkay Street, Sta. Cruz, Manila acute unit local 4145
Philippine General Hospital Mixed 6 Dr. Carlos Chua 554-8400
Taft Avenue, Manila acute unit local 2420
Philippine Heart Center ASU 8 Dr. Maria Lina 925-2401
East Avenue, Diliman, Quezon City Renales local 2483
San Juan De Dios Educational Mixed 2 Dr. Raquel Alvarez 831-9731
Foundation, Inc. Hospital acute unit local 1226
Roxas Boulevard, Pasay City
St. Luke’s Medical Center, Global City ASU 4 Dr. Vincent De 789-7700
Rizal Drive cor. 32nd Street, Taguig City Guzman local 4104

St. Luke’s Medical Center, Quezon City ASU 3 Dr. Maria Cristina 723-0101
E. Rodriguez Sr. Avenue, Quezon City Macrohon-Valdez local 7399
The Medical City Mixed 8 Dr. Artemio Roxas, Jr. 635-6789
Ortigas Avenue, Pasig City acute unit local 6281
University of the East Ramon ASU 2 Dr. Erman Fandialan 715-0861
Magsaysay Memorial Medical Center local 368
Aurora Boulevard, Quezon City
University of Santo Tomas Hospital ASU 5 Dr. Jose Navarro 731-3001
Espana Boulevard, Sampaloc, Manila local 2368
STROKE UNIT

226
 Type of No.
Contact
Hospital Stroke of Director
Number
Unit (SU) Beds
LUZON
Baguio General Hospital and Mixed 7 Dr. Socorro Sarfati (074)
Medical Center acute unit 442-4216
BGHMC Driveway, Baguio City
Baguio Medical Center ASU 2 Dr. Dionisio Claridad/ (074)
Military Cut-off Road, Baguio City Dr. Socorro Sarfati 442-3338
Bicol Medical Center ASU 4 Dr. Rhoderick (054)
Concepcion Pequena, Naga City Cevallos 811-7800
Daniel Mercado Medical Center ASU 3 Dr. Edna Cuasay (043)
Tanauan City, Batangas 778-1810
local 327
Lorma Medical Center ASU 3 Dr. Raymond (072)
San Fernando City, La Union Espinosa 700-0000
local 144
Lucena United Doctors Hospital ASU 4 Dr. Gerald Salazar (042)
Maharlika Highway, Lucena City, 373-6161
Quezon Province local 210
Mt. Carmel Diocesan General Hospital ASU 4 Dr. Glicerio Alincastre (042)
Allarey Extension, Lucena City, Quezon 710-2576
Province
Naga Imaging Cooperative Center ASU 4 Dr. Fe Delos Reyes (054)
Doctor’s Hospital 475-0000
Diversion Road, Naga City
Urdaneta Sacred Heart Hospitals Mixed 3 Dr. Emerson (075)
McArthur Hi-way, Urdaneta City, acute unit Patawaran 568-7747
Pangasinan
VISAYAS
Cebu Doctors Hospital Mixed 8 Dr. Emirito Calderon (032)
Osmeña Boulevard, Cebu City acute unit 253-2972
Chong Hua Hospital ASU 2 Dr. Rogelio Chua (032)
Don Mariano Cui Street, Fuente 255-8000
Osmeña, Cebu City local 7201
The Medical City-Iloilo ASU 3 Dr. Joel Advincula (033)
Tabucan, Mandurriao, Iloilo City 335-5505
STROKE UNIT

227
 Type of No.
Contact
Hospital Stroke of Director
Number
Unit (SU) Beds
MINDANAO
Butuan Doctor’s Hospital ASU 2 Dr. Marie Antoinette (085)
J.C. Aquino Avenue, Butuan City Dellosa 342-7000
Davao Doctors Hospital Mixed 12 Dr. Dorotheo (082)
E. Quirino Avenue, Davao City acute unit Floresca, Jr. 221-2102
local 664
Polymedic Medical Plaza ASU 2 Dr. Arturo Surdilla (088)
National Highway‚ Kauswagan, 858-5241
Cagayan De Oro City
Western Mindanao Medical Center ASU 4 Dr. Lucilla Barrera (062)
Veterans Avenue Extension, Soriano 991-2506
Zamboanga City local 207
Northern Mindanao Medical Center Mixed 7 Dr. Arturo Surdilla (088)
Corrales Avenue, Cagayan De Oro City acute unit 8564147
local 303
TOTAL OF 33 STROKE UNITS

Appendix A. International Classification of Diseases, 10th Revision, Clinical

Modification (ICD-10-CM), Codes for Cerebrovascular Diseases*

I60 Nontraumatic subarachnoid hemorrhage

I61 Intracerebral hemorrhage
I62 Other nontraumatic intracranial hemorrhage
I63 Cerebral infarction
I64 Stroke, not specified as hemorrhage or infarction
I65 Occlusion and stenosis of precerebral arteries, not resulting in cerebral infarction
I66 Occlusion and stenosis of cerebral arteries, not resulting in cerebral infarction
I67 Other cerebrovascular diseases
I67.0 Dissection of cerebral arteries, nonruptured
I67.1 Cerebral aneurysm, nonruptured
I67.2 Cerebral atherosclerosis
I67.3 Progressive vascular leukoencephalopathy
I67.4 Hypertensive encephalopathy
I67.5 Moyamoya disease
I67.6 Nonpyogenic thrombosis of intracranial venous system
I67.7 Cerebral arteritis, not elsewhere classified
I67.8 Other specified cerebrovascular disease
I67.9 Cerebrovascular unspecified
I68 Cerebrovascular disorders in disease classified elsewhere
I69 Sequelae of cerebrovascular disease
 APPENDIX
G45 Transient cerebral ischemic attacks and related syndromes
G46 Vascular syndromes of brain in cerebrovascular diseases
(code first underlying cerebrovascular disease [I60-I69])
G46.0 Middle cerebral artery syndrome
G46.1 Anterior cerebral artery syndrome
G46.2 Posterior cerebral artery syndrome
G46.3 Brain stem stroke syndrome
G46.4 Cerebellar stroke syndrome
G46.5 Pure motor lacunar syndrome
G46.6 Pure sensory lacunar syndrome
G46.7 Other lacunar syndromes
G46.8 Other vascular syndromes of brain in cerebrovascular diseases

*Note: the list is not exhaustive

International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM).
Hyattsville, MD: National Center for Health Statistics; [Accessed July 17, 2014].
Available at: http://www.cdc.gov/nchs/icd/icd10cm.htm.

Appendix B. Stroke Scales

B.1 Glasgow Coma Scale

Category Score
Eye Opening
• Spontaneous 4
• To speech 3
• To pain 2
• None 1
Best Motor Response
• Obeys 6
• Localizes 5
• Withdraws 4
• Abnormal flexion (decorticate) 3
• Abnormal extension (decerebrate) 2
• None 1
Best Verbal response
• Oriented 5
• Confused 4
• Inappropriate words 3
• Incomprehensible sounds 2
• None 1

229

230
B2. National Institutes of Health Stroke Scale (NIHSS)
Ia. Level of
Consciousness (LOC)
0 = Alert, keenly responsive
1 = Not alert, but arousable by
minor stimulation to obey, 2 = Answers neither question
answer or respond
2 = Not alert, requires repeated
stimulation to attend, or is
obtunded and requires strong
or painful stimulation to make
movements (not stereotyped)
3 = Responds only with reflex
motor or autonomic effects or
totally unresponsive, or totally
unresponsive, flaccid, areflexic
3. Visual
0 = No visual loss
1 = Partial hemi anopia
2 = Complete hemianopia
3 = Bilateral hemianopia (blind,
including cortical blindness)
Ib. LOC Questions
0 = Answers both questions correctly 0 = Performs both tasks correctly
1 = Answers one question correctly
correctly
4. Facial palsy
0 = Normal symmetrical movement
1 = Minor paralysis (flattened
nasolabial fold, asymmetry on
smiling)
Ic. LOC Commands
1 = Performs one task correctly
2 = Performs neither task correctly
5. Motor (Arm)
5 a. Left arm 5 b. Right arm 6 a. Right leg
0 = No drift; limb holds 90 (or 45)
degrees for full 10 seconds
1 = Drifts; limb holds 90 (or 45)
degrees but drifts down before
full 10 seconds; does not hit bed or
other support
2 = Some effort against gravity, limb
cannot get up to or maintain (if
cued) 90 (or 45) degrees; drifts
down to bed, but has some effort
against gravity
3 = No effort against gravity; limb
falls
4 = No movement
9 = Amputation or joint fusion;
explain
APPENDIX
2. Best gaze
0 = Normal
1 = Partial gaze palsy. Gaze is
abnormal in one or both eyes
but forced deviation or total gaze
paresis is not present
2 = Forced deviation, or total gaze
paresi s is not overcome by
oculocephalic maneuver
6. Motor (Leg)
6 b. Left leg
0 = No drift; leg holds 30-degree
position for full 5 seconds
1 = Drifts; leg fal ls by the end of the
5-second period but does not
hit bed
2 = Some effort against gravity; leg
falls to bed by 5 seconds but has
some effort against gravity
3 = No effort against gravity; leg falls
to bed immediately
4 = No movement
9 = Amputation or joint fusion;
explain
 7. Limb ataxia 8. Sensory 9. Best Language (Fig. 1) 10. Dysarthria (Fig. 2)

0 = absent 0 = Normal; no sensory loss 0 = No aphasia 0 = Normal

1 = Present in one limb
2 = Present in two limbs
9 = Amputation or joint fusion;
explain
1 = Mild to moderate sensory loss;
patient feels pinprick is less sharp
or dull on the affected side; or
there is a loss of superfici al pain
with pinprick, but patient is aware
he/she is being touched
2 = Severe or total sensory loss;
patient is not aware of being
touched in the face, arm or leg
1 = Mild to moderate aphasia; some 1 = Mild to moderate; patient slurs
obvious loss of fluency or facility at least some words and at worst,
of comprehension, without can be understood with some
significant limitation on ideas difficulty
expressed or form of expression. 2 = Severe; patient’s speech is so
Reduction of speech and/or slurred as to be unintelligible
comprehension, however, makes in the absence of or out of
conversation on provided material proportion to any dysphasia, or is
difficult mute/anarthric
2 = Severe aphasia; all communication 9 = intubated or other physical
is through fragmentary expression; barrier; explain
great need for inference,
questioning and guessing by the
listener. Range of information
that can be exchanged is limited;
listener carries the burden of
communication
3 = Mute, global aphasia; no usable
speech or auditory.comprehension

11. Extinction & Inattention

0 = No abnormality
1 = Visual, tactile, auditory, spatial or personal inattention or extinction to
bilateral simultaneous stimulation in one of the sensory modalities *Total score=42
2 = Profound hemi-attention or hemi-inattention to more than one modality.
Does not recognize own hand,or orients to only one side of space

231
APPENDIX
APPENDIX
Figure 1. NIHSS Item 9 - tests for best language (Aphasia)

A. Describe what is happening

in the picture

B. Name the items

C. Read the sentences

FIGURE 2:
NIHSS Item 10 - Read or repeat words

232

B.3.1. Modified Rankin Scale (mRS) for Adults and Children
Score Adults
0 No symptoms at all
No significant disability despite
1 symptoms; able to carry out all
usual duties and activities
Slight disability; unable to carry
out all previous activities, but able
2 to look after own affairs without
assistance
APPENDIX
Children
No symptoms at all
No significant disabilities despite symptoms
behavior appropriate to age and normal further
development
Slight disability; unable to carry out all previous
activities, but same independence as other age-
and sex- matched children (no reduction of levels
on the gross motor function scale)

Moderate disability; requiring some help, but able

Moderate disability; requiring some
to walk without assistance; in younger patients,
help, but able to walk without
3 adequate motor development despite mild
assistance
functional impairment (reduction of 1 level on
gross motor function scale)

Moderately severe disability; unable Moderately severe disability; unable to walk

to walk without assistance and without assistance; in younger patients, reduction
4
unable to attend to own bodily of at least 2 levels on the gross motor function
needs without assistance scale

Severe disability; bedridden, Severe disability; ,bedridden, requiring constant

5 incontinent and requiring constant nursing care and attention
nursing care and attention
6 Dead Dead
Source: Bigi S. et al. Ann Neurol. 2011;70:245-254.

B.3.2. Modified Rankin Scale (mRS) Questionnaire Algorithm*

Could you live alone without any help from another person?
(i.e. can bathe, use the toilet, get/prepare meals, shop, manage finances)

Are you able to do everything that you were

Can you walk without help
doing just before your stroke, even if slower or
from another person?
not as much?

Are you completely back Are you bedridden or

mRS 2 to the way you were just in need of constant mRS 3
before your stroke? supervision?

mRS 0 mRS 1 mRS 4 mRS 5

mRS Qualifiers mRS score

Remaining symptoms ≥1, not 0
Inability to do all previous activities ≥2, not 1
Dependence on others in ADL ≥3, not 2
Inability to walk without assistance ≥4, not 3
Bedridden, requiring constant nursing care ≥5, not 4
(If in doubt between 2 alternatives, choose the worse grade)
* modified from: Bruno A, et al. Stroke. 2010;41:1048-1050.
233

234
Appendix C. International Classification of Headache Disorders, 3rd Edition (ICHD-3) Diagnostic Criteria: Migrainous Infarction
Migrainous infarction
A. Migraine attack fulfilling
criteria B and C
B. Occurring in a patient with B. Acute ischemic stroke has
migraine with aura and
typical of previous attacks
except that one or more
aura symptoms persists for
>60 minutes
C. Neuroimaging
demonstrates ischemic
infarction in a relevant area
D. Not better accounted
for by another ICHD-3
diagnosis.
International Headache Society. Cephalagia. 2013 Jul;33(9):629-808.
APPENDIX
Versus Headache Attributed to Stroke
Headache attributed to:
Transient ischemic Non-traumatic intracerebral Non-traumatic subarachnoid
Ischemic stroke
attack (TIA) hemorrhage (ICH) hemorrhage (SAH)
A. Any new headache fulfilling A. Any new headache A. Any new headache fulfilling A. Any new headache
criterion C fulfilling criterion C criterion C fulfilling criterion C
B. Transient ischemic B. ICH in the absence of head B. SAH in the absence of
been diagnosed attack (TIA) has been trauma has been diagnosed head trauma has been
diagnosed diagnosed
C. Evidence of causation C. Evidence of causation
demonstrated by at least one C. Evidence of causation demonstrated by at least two C. Evidence of causation
of the following: demonstrated of the following: demonstrated by at least
1. headache has developed by both of the 1. headache has developed in two of the following:
in very close temporal following: close temporal relation to 1. headache has developed
relation to other 1. headache has other symptoms and/or in close temporal
symptoms and/or clinical developed clinical signs of ICH, or has relation to other
signs of ischemic stroke, simultaneously led to the diagnosis of ICH. symptoms and/or
or has led to the diagnosis with other 2. headache has significantly clinical signs of SAH,
of ischemic stroke symptoms and/ improved in parallel or has led to the
2. headache has significantly or clinical signs with stabilization or diagnosis of SAH.
improved in parallel of TIA improvement of other 2. headache has
with stabilization or 2. headache 3. symptoms or clinical or significantly improved
improvement of other resolves within radiological signs of ICH in parallel with
symptoms or clinical 24 hours 4. headache has at least one stabilization or
or radiological signs of of the following three improvement of other
ischemic stroke D. Not better accounted characteristics: 1) sudden 3. symptoms or clinical
for by another ICHD- or thunderclap onset; 2) or radiological signs
D. Not better accounted for by 3 diagnosis. maximal on the day of of SAH
another ICHD-3 diagnosis its onset; 3) localized in 4. headache has sudden
accordance with the site of or thunderclap onset
the hemorrhage
D. Not better accounted for
D. Not better accounted for by by another ICHD
another ICHD-3 diagnosis.
 APPENDIX
Appendix D. Gugging Swallowing Screen (GUSS)

1. Preliminary Investigation/Indirect Swallowing Test

Yes No

Vigilance (The patient must be alert for at least 15 minutes) 1 0

Cough and/or throat clearing (voluntary cough) 1 0

(Patient should cough or clear his/her throat twice)

Saliva Swallow:
• Swallowing successful 1 0
• Drooling 0 1

• Voice change (hoarse, gurgly, coated, weak) 0 1

SUM =
(score 1-4: investigate further; 5: continue with part 2) (5)

2. Direct Swallowing Test*

In the following order: 1 2 3

SEMISOLID LIQUID SOLID

DEGLUTITION
• Swallowing not possible 0 0 0
• Swalllowing delayed (>2 sec) (solid textures >10 sec) 1 1 1
• Swallowing successful 2 2 2

COUGH (involuntary)
(before, during, or after swallowing–until 3 minutes
later)
• Yes 0 0 0
• No 1 1 1
DROOLING
• Yes 0 0 0
• No 1 1 1

VOICE CHANGE (before & after swallowing; patient

should say “O”)
• Yes 0 0 0
• No 1 1 1
(5) (5) (5)
1-4: Investigate 1-4: Investigate 1-4:
SUM = further further Investigate
5: Continue 5: Continue further
Liquid Solid 5: Normal

* materials: aqua bi, flat teaspoon, food thickener, bread

235
APPENDIX
Appendix D. Gugging Swallowing Screen (GUSS) (Continued)

3. Evaluation
Results Severity Code Recommendations
20 Semisolid/ Slight / No Normal diet
liquid and dysphagia Regular fluids (First time under supervision of the speech
solid texture with a and language therapist [SLT] or a trained stroke nurse)
successful minimal risk
of aspiration

15-19 Semisolid and Slight Dysphagia diet (pureed and soft food)
liquid texture dysphagia Liquids very slowly – one sip at a time
successful with a Functional swallowing assessments (e.g., Fiberoptic
and solid low risk of Endoscopic Evaluation of Swallowing [FEES],
unsuccessful aspiration Videofluoroscopic Evaluation of Swallowing [VFES])
Refer to SLT
10-14 Semisolid Moderate Dysphagia diet, beginning with:
swallow dysphagia Semisolid textures such as infant food and additional
successful with a risk of parenteral feeding
and liquid aspiration All liquids must be thickened
unsuccessful Pills must be crushed and mixed with thick liquid
No liquid medication
Further functional swallowing assessments
Refer to SLT
Supplementation with nasogastric tube (NGT) or
parenteral
0-9 Preliminary Severe NPO
investigation dysphadia Further functional swallowing assessment
unsuccessful with a Refer to SLT
or semisolid high risk of
swallow aspiration
unsuccessful
Trapl M, et al. Stroke. 2007;38:2948-2952.

Appendix E. Stages of Pressure Sores

Stage I The skin is not broken; The skin appears red on people with lighter skin
color, and the skin does not briefly lighten (blanch) when touched. In
people with darker skin, the skin may show discoloration, and it does not
blanch when touched. The site may be tender, painful, firm, soft, warm or
cool compared with the surrounding skin.
Stage II The outer layer of skin (epidermis) and part of the underlying layer of
skin (dermis) is damaged or lost. The wound may be shallow and pinkish
or red. The wound may look like a fluid-filled blister or a ruptured blister.

Stage III The ulcer is a deep wound: The loss of skin usually exposes some fat.
The ulcer looks crater-like. The bottom of the wound may have some
yellowish dead tissue. The damage may extend beyond the primary
wound below layers of healthy skin.

Stage IV The ulcer shows large-scale loss of tissue: The wound may expose muscle,
bone or tendons. The bottom of the wound likely contains dead tissue
that is yellowish or dark and crusty. The damage often extends beyond
the primary wound below layers of healthy skin.
236
 APPENDIX E. Braden Scale For Predicting Pressure Sore Risk
SEVERE RISK: Total score <9; HIGH RISK: Total score 10-12; MODERATE RISK: Total score 13-14; MILD RISK: Total score 15-18
RISK FACTOR SCORE/DESCRIPTION
SENSORY 1. COMPLETELY LIMITED – unresponsive 2. VERY LIMITED – responds only to 3. SLIGHTLY LIMITED – responds to 4. NO IMPAIRMENT
PERCEPTION to painful stimuli, due to decreased level painful stimuli; cannot communicate verbal commands but cannot always – responds to verbal
of consciousness or sedation discomfort except by moaning or communicate discomfort or need to commands; has no sensory
OR restlessness be turned deficit which limits ability
limited ability to feel pain over most of OR OR to feel or voice pain or
body surface. has sensory impairment which limits has some sensory impairment discomfort.
the ability to feel pain or discomfort which limits ability to feel pain or
over of body. discomfort in 1 or 2 extremities.
MOISTURE 1. CONSTANTLY MOIST– skin is kept 2. OFTEN MOIST – often (but not 3. OCCASIONALLY MOIST – requiring 4. RARELY MOIST – Skin is
moist almost constantly by perspiration, always) moist; linen must be changed extra linen change approx. once a usually dry; requires linen
urine, etc. Dampness is detected at least once a shift. day. changing only ro utinely.
everytime patient is moved or turned.
ACTIVITY 1. BEDFAST – confined to bed. 2. CHAIRFAST – ability to walk is 3. WALKS OCCASIONALLY – walks 4. WALKS FREQUENTLY–
severely limited or nonexistent. for very short distances, with or Walks outside the room at
Cannot bear own weight and/or must without assistance; spends majority least twice a day and inside
be assisted into chair/wheelchair. of each shift in bed or chair. room at least once every 2
hours during waking hours.
MOBILITY 1. COMPLETELY IMMOBILE – does not 2. VERY LIMITED – occasional slight 3. SLIGHTLY LIMITED – frequent 4. NO LIMITATIONS –
make even slight changes in the body or changes in body or extremity position though slight changes in body or makes major and frequent
extremity position without assistance. but unable to make frequent or extremity position independently. changes in position
significant changes independently. without assistance.
NUTRITION 1. VERY POOR – never eats a complete 2. PROBABLY INADEQUATE – rarely 3. ADEQUATE – eats over half of 4. EXCELLENT – eats most
meal. Rarely eats > 1/3 of any food. Eats eats complete meal and generally eats most meals. Eats a total of 4 servings of every meal. Usually eats
≤ 2 servings of protein per day; takes only about any of the food. Protein of protein per day. Occasionally a total of ≥4 servings of
fluids poorly, & does not take a liquid intake includes only 3 servings of meat refuses a meal, but will usually take meat & dairy products.
dietary supplement or dairy products per day. Occasionally a supplement if offered Occasionally eats between
OR will take a dietary supplement OR meals. Does not require
is NPO and/or maintained on clear OR is on tube feeding or TPN regimen supplementation.
liquids or IV for > 5 days. receives less than optimum amount of which probably meets most of
liquid diet or tube feeding. nutritional needs
FRICTION 1. PROBLEM - requires moderate 2. POTENTIAL PROBLEM – moves 3. NO APPARENT PROBLEM – moves
AND to maximum assistance in moving. feebly or requires minimum in bed and in chair independently
SHEAR Complete lifting without sliding against assistance. During motion, skin and has sufficient muscle strength
sheets is impossible. Frequently slides probably slides to some extent against to lift up completely during move.
down in bed or chair, requiring frequent sheets, chair, restraints, or other Maintains good position in bed or
repositioning with maximum assistance. devices. Maintains relatively good chair at all times.
Spasticity, contractures, or agitation position in chair or bed most of the
leads to almost constant friction. time but occasionally slides down.
TOTAL SCORE Total score of 12 or less represents HIGH RISK

237
APPENDIX
 Working Group for the SSP Handbook of Stroke:
Guidelines for Prevention, Treatment, and Rehabilitation, 6th Edition
Raquel M. Alvarez, MD, FPNA Betty D. Mancao, MD, FPARM
Ma. Leticia C. Araullo-de Jesus, MD, FPNA Ana Merly A. Migo, RN
Abdias V. Aquino, MD, FPNA Maria Victoria G. Manuel, MD, FPNA
Mina N. Astejada MD, FPNA Manuel M. Mariano, MD, FAFN
Alejandro C. Baroque II, MD, FPNA Dante D. Morales, MD, FPCC
Ralph Louie P. Bautista, MD Jose C. Navarro, MD, FPNA
Allan A. Belen, MD, FPNA Jose Leonard R. Pascual, V, MD, FPNA
Ester S. Bitanga, MD, FPNA Anthony N. Piano, MD, FPNA
Anabelle R. Borromeo, PhD, RN Ma. Isabelita C. Rogado, MAN, RN
Anabelle E. Chua, MD, FAFN Artemio A. Roxas, Jr., MD, FPNA
Carlos L. Chua, MD, FPNA Maria Cristina Z. San Jose, MD, FPNA
Ma. Epifania V. Collantes, MD, FPNA Arturo F. Surdilla, MD, FPNA
Louie Paul P. Eugenio, RN Loreto P. Talabucon, Jr., MD, FPNA
Pedro Danilo J. Lagamayo, MD, FPCR Marilyn A. Tan, MD, FCNSP
Lina C. Laxamana, MD, FPNA Maricar P. Yumul, MD, FPNA
Johnny K. Lokin, MD, FPNA
and the Working Group of the SSP Handbook, 5th Edition

External Reviewers
Veeda Michelle M. Anlacan, MD, FPNA
Ma. Teresa A. Cañete, MD, FPNA
Vincent Paul E. de Guzman, MD, FPNA
Alejandro F. Diaz, MD, FPNA
Claro B. Ison, MD, FPCR
Roland Dominic G. Jamora, MD, FPNA
Herminigildo H. Gan, MD, FPNA
Robert N. Gan, MD, FPNA
Adriel E. Guerrero, MD, FPCC
Manolete Renato C. Guerrero, MD, FPNA
Geraldine Siena L. Mariano, MD, FPNA
Marilyn H. Ortiz, MD, FCNSP
Rosalina E. Picar, MD, FPNA
Louie C. Racelis, MD, FAFN
Bonifacio S. Rafanan Jr., MD, FPARM
Ignacio V. Rivera, MD, FCNSP
Amado M. San Luis, MD, FPNA
Cymbeline B. Perez-Santiago, MD, FPNA
Theodor S. Vesagas, MD, FAFN

The SSP would like to thank the following organizations for allowing the integration of
their guidelines in the SSP Handbook of Stroke, 6th Edition:
The Philippine Neurological Association (PNA) and the PNA Stroke Council
Critical Care Nurses Association of the Philippines, Inc. (CCNAPI)
Philippine Academy of Rehabilitation Medicine (PARM)
Philippine Society of Parenteral and Enteral Nutrition (PHILSPEN)

Editor-in-Chief:
Artemio A. Roxas, Jr., MD, FPNA

Asst. Editor:
Ralph Louie P. Bautista, MD

Support Staff:
Marilou L. Olpindo
Catherine R Mayordomo, PTRP
Desiree M. Buenaventura
238
 BOARD OF TRUSTEES
Officers 2013-2014

President: Artemio A. Roxas Jr., MD

1st V-President: Maria Cristina Z. San Jose, MD
2nd V-President: Manuel M. Mariano, MD
Secretary: Ma. Epifania V. Collantes, MD
Treasurer: Betty D. Mancao, MD
P.R.O.: Raquel M. Alvarez, MD

Members: Past Presidents:

Ma. Leticia C. Araullo-De Jesus, MD Joven R. Cuanang, MD
(Founding President, 1995-2004)
Alejandro C. Baroque II, MD
Romulo U. Esagunde, MD Abdias V. Aquino, MD
(2005-2006)
Pedro Danilo J. Lagamayo, MD
Annabelle Y. Lao-Reyes, MD Ester S. Bitanga, MD
(2007-2008)
Johnny K. Lokin, MD
Orlino A. Pacioles, MD Jose C. Navarro, MD
Peter P. Rivera, MD (2009-2010)

Maria Socorro F. Sarfati, MD Carlos L. Chua, MD

(2011-2012)

SSP CHAPTERS AND CHAPTER PRESIDENTS

Central Luzon Chapter Jeremias G. Bautista, MD

Pampanga Chapter Ciela V. Balagtas, MD
La Union - Pangasinan Chapter Raymond L. Espinosa, MD
Philip Manuel M. Oliva, MD
Baguio-Benguet Chapter Ma. Socorro F. Sarfati, MD
Southern Mindanao Chapter Orlino A. Pacioles, MD
Iloilo Chapter Joel M. Advincula, MD
Olongapo Chapter Arturo Martin P. Arkoncel, MD
Dumaguete Chapter Brenda V. Diputado, MD
Northern Mindanao Chapter Arturo F. Surdilla, MD
239
 SSP Corporate Members

Boehringer Ingelheim

EVER Neuro Pharma

Hi-Esai Pharmaceutical, Inc.

LRI-Therapharma

Natrapharm, Inc.

Otsuka Pharmaceuticals

Servier

List of Additional Topics available at the SSP website: http://www.strokesocietyphil.org

1. 2010 Philippine National Guidelines on Physical Activity

2. Food Selection Guide by the Philippine Society of Parenteral
and Enteral Nutrition (PHILSPEN)
3. 2012 National Nursing Core Competency Standards
4. Stroke Nursing Certification Program (SNCP)
-list of topics in the Didactic Phase

Artworks
Back Cover**:
“Stroke: Know the Facts”
Mr. Bjorn Michael Bedayo
(De La Salle - College of St. Benilde)

Inside Back Cover**:

“Stroke ay agapan, upang kapansanan ay maiwasan”
Mr. Barry Barrera

**with modifications from SSP

240
back cover