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Stroke 2014 SSP
Stroke 2014 SSP
Sixth
Edition
2014
Copyright © 2014 The Stroke Society of the Philippines. All rights reserved.
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
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
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 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!
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.
4
ssP VIsIon
ssP MIssIon
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:
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
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.
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”
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(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.
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.
Mukha: ipakita ang ngipin o mag-smile. Tingnan kung may kaibahan ang
kaliwa at kanang bahagi ng mukha.
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.
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Panel 4. UTAK Slogan (SSP 2009 Lay Education Campaign Winner)
Tandaan: “UTAK”
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
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”.
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:
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:
Stroke – a sudden onset of focal (or global) neurologic deficit due to an underlying vascular
pathology
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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.
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.
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
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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.
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).
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
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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.
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.
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.
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.
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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:
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.
Questions YES NO
Has there been loss of consciousness or syncope? -1 0
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).
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The presence of the following should alert one to consider a condition other than
stroke:
• Trauma
TRANSiENT
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:
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.
iSCHEMiC ATTACK
tool available for stratifying TIA patients in making recommendations for hospital
TRANSiENT
admission (Table 9).
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)
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.
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 Anatomical location/structure involved
Contralateral weakness of leg & foot > arm Motor leg (and arm) area
(cerebral paraplegia, if bilateral ACA occlusion) Sensory area for foot & leg
Cortical sensory loss over toes, foot, & leg Superior frontal gyrus (bilateral)
Urinary incontinence Posterior frontal lobe
Contralateral grasp reflex, paratonia (gegenhalten) Mesiofrontal region (bilateral)
Frontal lobe release signs, abulia (akinetic mutism), amnesia with apathy Corpus callosum
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 Somatic motor area supplied by MCA in frontal lobe
Preferential gaze looking away from the weakness Opposite frontal eye field or projecting fibers
Contralateral hemineglect Non-dominant parietal lobe
Contralateral hemisensory impairment over face, arm, & leg Somatosensory area supplied by MCA in parietal lobe
Global aphasia (if dominant hemisphere is affected) Central language area & dominant parietooccipital cortex
Middle Cerebral Artery (MCA) Homonymous hemianopia (often superior quadrantanopia) Optic radiation deep to second temporal convolution
Proximal Segment
Contralateral weakness of face & arm > leg Somatic motor area (face & arm) in frontal lobe
Contralateral hemisensory loss of face & arm > leg Somatic sensory area (face & arm) in parietal lobe
Preferential gaze looking away from the weakness Opposite frontal eye field or projecting fibers
Expressive (Broca’s) aphasia (if dominant hemisphere is affected) Broca’s area in frontal suprasylvian area
21
OVERVIEW
OVERVIEW
22
TABLE 10. (continued)
Vascular territory involved Signs and Symptoms Anatomical location/structure involved
Signs and symptoms Occipital lobe
Posterior cerebral artery (PCA) Homonymous hemianopia with macular sparing Ventral occipital cortex; infracalcarine
unilateral 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
PCA, bilateral visual hallucinations
(Anton’s syndrome)
PCA-MCA border zone Optic ataxia (inability to reach targets with optic guidance),
oculomotor apraxia, simultagnosia Bilateral occipital-parietal border zones
(Balint syndrome)
Anterior inferior cerebellar artery (AICA) Ipsilateral dysmetria, hearing loss, Horner’s syndrome, choreiform
Lateral pons
Lateral Pontine Syndrome dyskinesia, contralateral thermoanalgesia
Basilar artery Somnolence, peduncular hallucinosis, convergence nystagmus, Midbrain, thalamus, mesial temporal lobes, and
skew deviation, oscillatory eye movements, Colliers sign
(Top of the basilar syndrome) (retraction and elevation of eyelids), vertical gaza paralysis occipital lobes
Basilar artery Quadriplegia, horizontal gaze paralysis, bifacial paralysis, tongue Lower pons
(Locked-in syndrome) and mandibular weakness; awareness is spared
Vertebral artery (VA) Contralateral weakness of leg and arm, hemisensory loss; Medulla and cervical spinal cord
(Dejerine syndrome) ipsilateral tongue paralysis
OVERVIEW
Waist-to-hip ratio 26.5 (18.8-36.0)
TABLE 12. Risk Factors for Stroke among Filipinos: the PNA-DOH RIFASAF Study36
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
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).
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
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.
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.
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
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
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.
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.
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
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.
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
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).
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
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
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.
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.
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).
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).
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
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
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.
C. Recommendations
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.
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.
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).
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).
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.
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).
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).
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
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.
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
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
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
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.
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.
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
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58
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PREVENTION
PREVENTION
Stroke. 1998;29:1389-1392.
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cerebral artery. J Neurol Neurosurg Psychiatry. 2004;75:1300-1303.
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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.
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
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.
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
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
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.
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
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.
Strength
Circuit training increase independence in ADLs 1-3 sets of 10-15 repetitions of 8-10
exercises involving the major
weight machines muscle groups
Free weights
isometric exercise 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.
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
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
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
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
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
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
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
• 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
ISCHEMIC
CARDIOEMBOLISM NOT CARDIOEMBOLISM HEMORRHAGIC
SUSPECTED SUSPECTED
(Thrombotic, Lacunar)
TREATMENT
74
GUiDELiNES FOR MANAGEMENT OF MiLD STROKE (continued)
ISCHEMIC
DELAYED MANAGEMENT AND SECONDARY PREVENTION
CARDIOEMBOLISM NOT CARDIOEMBOLISM HEMORRHAGIC
SUSPECTED SUSPECTED
(Thrombotic, Lacunar)
• Give antiplatelets (e.g., • Request • Long-term strict
ASA, clopidogrel, cilostazol, echocardiography and/or BP control and
triflusal, dipyridamole, refer to cardiologist monitoring
extended-release • Novel oral anticoagulants • Consider contrast CT
dipyridamole + ASA (NOACs) are preferred scan, 4-vessel cerebral
combination) (see Chapter 4) over dose-adjusted angiogram, MRA or
• Control/treat risk factors warfarin. CTA if the patient is:
• Recommend carotid • if anticoagulation is a. < 45 years old
ultrasound (UTZ) to contraindicated, give ASA b. normotensive
document extracranial 160-325 mg. The addition c. has lobar iCH
stenosis; if UTZ reveals of clopidogrel to ASA d. has uncertain cause
>70% stenosis, refer to a therapy is reasonable. of iCH
neurologist/neurosurgeon/ e. suspected to have
vascular surgeon for aneurysm, AVM, or
decision-making regarding vasculitis
carotid endarterectomy
(CEA) or stenting.
• Recommend transcranial
Doppler (TCD) studies or
CT or MR angiography
(CTA/MRA) to document
intracranial stenosis.
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.
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)
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.
• 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)
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.
B. Neuroprotection
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
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).
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).
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.
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.
“The use of drugs with neurorestorative and neuroprotective properties in acute stroke
remains as a matter of preference of the attending physician.”
82
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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
e. How to Anticoagulate
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
• 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
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.
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.
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
ECASS II: Second European 800 patients with acute No significant difference was
Australasian Cooperative ischemic stroke < 6 hours seen in the rate of favorable
Acute Stroke Study were randomized to rt-PA 0.9 outcome at 3 months between rt-
mg/kg or placebo. PA- and placebo- treated group.
TREATMENT
(Lancet 1998; 352: 1245-1251)
ACUTE
ATLANTIS A: Alteplase 142 patients with acute No significant difference was
Thrombolysis for Acute ischemic stroke < 6 hours seen on any of the planned
Non-interventional were randomized to rt-PA 0.9 efficacy endpoints at 30 and 90
Therapy in ischemic mg/kg or placebo. days between groups. The
Stroke risk of symptomatic iCH was
increased with rt-PA treatment
(Stroke 2000; 31:811 – 816) particularly in patients treated
between 5 to 6 hours.
ATLANTIS B: Alteplase 613 patients with acute No significant difference in
Thrombolysis for Acute ischemic stroke within 3–5 functional recovery at 90
Non-interventional hours were randomized to days between groups. Risk of
Therapy in ischemic t-PA or placebo. symptomatic intracerebral
Stroke hemorrhage was increased in
t-PA.
(JAMA 1999; 282:2019 –
2026)
J-ACT: Japanese Alteplase 103 patients within 3 hours of 36.9% achieved an mRS of 0-1
Clinical Trial ischemic stroke were given at 3 months; symptomatic iCH
0.6 mg/kg iv rt-PA as single occurred in 5.8%.
(Stroke 2006;37:1810-1815) arm, open-label study.
Data is comparable with
published data using iv rt-PA.
ECASS III: European 821 patients with acute Significantly more patients in rt-
Australasian Cooperative ischemic stroke within 3 to PA-treated group had favorable
Acute Stroke Study 4.5 hours were randomized to outcome at 3 months (52.4% vs
rt-PA 0.9 mg/kg or placebo. 45.2 %, p = 0.04). The incidence
(N Eng J Med 2008; 359: of intracranial hemorrhage was
1317–1329) higher with rt-PA, but mortality
did not significantly differ
between the 2 groups.
(continued on next page)
89
TABLE 4 (continued)
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.
(1) Definition/Formulae:
(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
90
Rationale for Permissive Hypertension:
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.
• 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
TREATMENT
92
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
TREATMENT
TABLE 6. Phase III Clinical Trials on BP lowering in Acute ICH
ACUTE
TRIAL DESIGN RESULT
INTERACT II: intensive 2,388 patients with spontaneous There was no difference in the
Blood Pressure Reduction iCH within 6 hours and SBP > rate of primary outcome of
in Acute Cerebral 150 – 220 mm Hg randomized death and disability between
Hemorrhage Trial–2 to receive intensive treatment 2 treatment groups at 90 days.
to lower SBP to < 140 mm Hg vs.
(N Eng J of Med 2013; 368: guideline based to SBP < 180 mm Pre-specified ordinal analysis
2355-2365) Hg using drugs of physician’s showed significantly lower
choice for 1 week. mRS scores with intensive
treatment (OR for greater
disability=0.87, 95% Ci, 0.77 –
1.00, p= 0.04).
ATACH II: 1,280 patients with acute iCH ongoing
Antihypertensive randomized to receive intensive (Clinicaltrials.gov
Treatment on Acute treatment to lower SBP to < 140 identifier NCT01176565)
Cerebral Hemorrhage–2 mm Hg versus guideline-based
management to SBP < 180 mm Hg
(Neurocritical Care 2011; 15 within 24 hours of randomization
(3): 559 – 576) using iv Nicardipine.
o Unlike SAH, isolated ICH does not have the same propensity to cause
cerebral vasospasm, thus BP lowering can be somewhat more aggressive.
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.
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
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
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
TREATMENT
96
TABLE 7. Locally Available Sedatives and Narcotics
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
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
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.
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)
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
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.
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
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)*
• 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
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
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.
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
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.
108
CHAPTER V
Guidelines for Stroke Prevention in Nonvalvular
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).
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
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
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%
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
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.
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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)
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
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:
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
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.
Level A).
ATRIAL
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:
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
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.
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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).
1. The absence of available antidote for NOACs is a major concern and the
ATRIAL
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.
U/g (may be repeated once or twice but no kg (may be repeated once or twice but no
ATRIAL
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
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
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).
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.
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
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
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
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%
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
126
I. Hypertensive Intracerebral Hemorrhage (HICH)
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.
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
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
129
Patient suspected to have SAH
Repeat CTA/MRA
(+) Aneurysm Normal
in 7-14 days
TABLE 5. Radiologic Grading Scale for Subarachnoid hemorrhage (Fisher Grading System)
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.
as CT and MRI perfusion studies are useful to identify potential regions of brain
ischemia.
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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
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
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.
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
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).
134
Suspected intracranial vascular malformation
Caput medusa
Yes No appearance?
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).
• volume: in mL/cc
• age: in years
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• 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
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
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136
Suspected intracranial vascular malformation
Symptomatic
Asymptomatic/
incidental findings
A
No
Does the patient have poor clinical status?
S-M Grade S-M Grade S-M Grade
Yes i - ii iii iv - v
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,
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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
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
Angio,
Developmental Thickened veins interspersed in
contrast CT/ Observation
Venous Anomaly parenchyma
MRI
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17. Kirkpatrick PJ, Turner CL, Smith C, et al. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH):
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NEUROIMAGING
CHAPTER VII
Neuroimaging in Acute Stroke
PeRfUsIon CT IMaGInG
CT anGIoGRaPHY
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).
A B
C D
142
NEUROIMAGING
FIGURE 3. Hyperdense Middle Cerebral Artery (MCA)
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.
A B
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)
143
NEUROIMAGING
NEUROIMAGING
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.
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.
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).
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
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
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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.
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.
FIGURE 9.B
FIGURE 9.C.
149
NEUROIMAGING
FIGURE 9.D.
FIGURE 9.E.
FIGURE 9.F.
FiGURE 11.
FiGURE 12.
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.
FiGURE 14.
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.
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
Occipital
horn of
lateral ventricle
3rd ventrical
Midbrain
Quadrigeminal cistern
Chiasmatic
cistern
Cerebellum Mastoid
air cells Temporal lobe
4th ventricle
Cerebellum
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
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.
Shoulder-hand
Metacarpophalangeal (MCP) Flaccid or
syndrome (CRPS Triple-phase bone scan
joint compression test; skin spastic
type i) Stellate ganglion block
color changes
Biceps tendinitis Positive Yergason test result Flaccid or Tendon sheath injection of
spastic lidocaine
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:
Venlafaxine 37.5-75mg/day 225 mg/day (XR) off-label treatment for neuropathic pain
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.
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
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
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
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).
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
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
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
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
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
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.
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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).
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
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patients with progressive neurological deterioration despite intensive and
therapeutic levels of anticoagulant (Class IIb, 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).
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.
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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,
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little is known about SIY in the Philippines due to few published studies.
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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.
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.
175
C. Etiology
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.
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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
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with subcortical infarcts and leukoencephalopathy, TREX1 mutation disorders,
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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
E. Management
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aura (Class IIa, level B).
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
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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.
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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
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
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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:
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
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).
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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
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
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.
187
TABLE 1. Secondary Movement Disorders in Stroke4
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.
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.
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.
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
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
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
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).
SPECIAL
TOPICS
recurrence in general (Class IIa, level A).
References
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
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.
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).
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).
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
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]).
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.
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.
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
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.
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
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
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
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
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
205
4. Percutaneous Endoscopic Gastrostomy (PEG)/Nasogastric Tube (NGT) insertion
Table 11. PARM Recommendations for PEG/NGT insertion for stroke patients
F. Post-Stroke Spasticity
TABLE 12. PARM Recommendations for management of post-stroke spasticity
206
I. Acute Post-Stroke Rehabilitation
Go to II, III, or IV Go to II Go to II
STROKE
REHAB
5. Skin assessment and pressure ulcers
6. Mobility and need for assistance of movement
7. Deep-vein thrombosis (DVT) risk assessment
207
II. Inpatient Rehabilitation
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
Go to IV
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
Arrange primary-care
Yes
follow-up. Provide
home rehabilitation
program.
Determine optimal environment for community-
based rehabilitation
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.
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.
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
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).
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.
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).
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.
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.
218
CHAPTER XIII
Guidelines on the Establishment and
Operation of Stroke Units
Sixth
Edition
2014
Guidelines on the establishment and operation of stroke Units
• 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
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
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
1. Personnel
a. Physicians
b. Nurses
222
c. Physiatrists
d. Occupational therapists
e. Speech pathologists
f. Nutritionists
g. Social workers
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:
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
229
APPENDIX
230
B2. National Institutes of Health Stroke Scale (NIHSS)
Ia. Level of
Ib. LOC Questions Ic. LOC Commands 2. Best gaze
Consciousness (LOC)
0 = Alert, keenly responsive 0 = Answers both questions correctly 0 = Performs both tasks correctly 0 = Normal
1 = Not alert, but arousable by 1 = Answers one question correctly 1 = Performs one task correctly 1 = Partial gaze palsy. Gaze is
minor stimulation to obey, 2 = Answers neither question 2 = Performs neither task correctly abnormal in one or both eyes
answer or respond correctly but forced deviation or total gaze
2 = Not alert, requires repeated paresis is not present
stimulation to attend, or is 2 = Forced deviation, or total gaze
obtunded and requires strong paresi s is not overcome by
or painful stimulation to make oculocephalic maneuver
movements (not stereotyped)
3 = Responds only with reflex
motor or autonomic effects or
totally unresponsive, or totally
unresponsive, flaccid, areflexic
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)
fIGURe 2:
NIHSS Item 10 - Read or repeat words
232
APPENDIX
B.3.1. Modified Rankin Scale (mRS) for Adults and Children
Score Adults Children
0 No symptoms at all No symptoms at all
No significant disability despite No significant disabilities despite symptoms
1 symptoms; able to carry out all behavior appropriate to age and normal further
usual duties and activities development
Slight disability; unable to carry
Slight disability; unable to carry out all previous
out all previous activities, but able
activities, but same independence as other age-
2 to look after own affairs without
and sex- matched children (no reduction of levels
assistance
on the gross motor function scale)
234
APPENDIX C. International Classification of Headache Disorders, 3rd Edition (ICHD-3) Diagnostic Criteria: Migrainous Infarction
Versus Headache Attributed to Stroke
B. Occurring in a patient with B. Acute ischemic stroke has B. Transient ischemic B. iCH in the absence of head B. SAH in the absence of
migraine with aura and been diagnosed attack (TiA) has been trauma has been diagnosed head trauma has been
typical of previous attacks diagnosed diagnosed
except that one or more C. Evidence of causation C. Evidence of causation
aura symptoms persists for demonstrated by at least one C. Evidence of causation demonstrated by at least two C. Evidence of causation
>60 minutes 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:
C. Neuroimaging in very close temporal following: close temporal relation to 1. headache has developed
demonstrates ischemic relation to other 1. headache has other symptoms and/or in close temporal
infarction in a relevant area 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
D. Not better accounted or has led to the diagnosis with other 2. headache has significantly clinical signs of SAH,
for by another iCHD-3 of ischemic stroke symptoms and/ improved in parallel or has led to the
diagnosis. 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.
Yes No
Saliva Swallow:
• Swallowing successful 1 0
• Drooling 0 1
SUM =
(score 1-4: investigate further; 5: continue with part 2) (5)
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
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.
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 Geraldine Siena L. Mariano, MD, FPNA
Ma. Teresa A. Cañete, MD, FPNA Marilyn H. Ortiz, MD, FCNSP
Vincent Paul E. de Guzman, MD, FPNA Rosalina E. Picar, MD, FPNA
Alejandro F. Diaz, MD, FPNA Louie C. Racelis, MD, FAFN
Claro B. Ison, MD, FPCR Bonifacio S. Rafanan Jr., MD, FPARM
Roland Dominic G. Jamora, MD, FPNA Ignacio V. Rivera, MD, FCNSP
Herminigildo H. Gan, MD, FPNA Amado M. San Luis, MD, FPNA
Robert N. Gan, MD, FPNA Cymbeline B. Perez-Santiago, MD, FPNA
Adriel E. Guerrero, MD, FPCC Theodor S. Vesagas, MD, FAFN
Manolete Renato C. Guerrero, MD, FPNA
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
Boehringer ingelheim
LRi-Therapharma
Natrapharm, inc.
Otsuka Pharmaceuticals
Servier
ARTWORKS
Back Cover**:
“Stroke: Know the Facts”
Mr. Bjorn Michael Bedayo
(De La Salle - College of St. Benilde)