Stroke –the brain attack

A devastating medical emergency

(A NEGLECT EPIDEMIC)
DR GP BURMAN MD (INT. MEDICINE)
DM NEUROLOGY ,PGI, CHANDIGARH
FORMERLY INCHARGE NEURO ,PGI ROHTAK,
MEMBER INTERNATIOAL STROKE(WSO)
ORGANISATION AND WORLD FEDERATION OF
NEUROLOGY
Neglect epidemic-stroke(brain attack)
Second leading cause of death
Prevalace:8-11/ 1000 population
Incidence of its TIA or stroke 50-150/100000/YR
Second episode of TIA or stroke 0.3 -1.55/1000 and
stroke related death 4.4 million in 1990: projected to 7.7
million by2020 and burden of disease would be >6% of
total illness world wide. JUST being non communicable
disease /& due to lack of awareness developing world
pay little attention to stroke (their population is aging &
more are life expectancy therefore incidence &
prevalence would increase every yr.)
 Indian perspective
GBD-(2002)-15.9. Million stroke and 5.5 million stroke related death, in
India-half million CVD related death. Disability adjusted life
yrs(DAILY)lost 8.5 million estimated to be projected from INDIA by2020
due to stroke overall crude prevalence rate would be in India 250/1lac
population
A crude prevalence study on advanced age group (41-60) from east
India -540/100,000, extremely high figure. where as a small
survey conducted by me on 35 -80 yrs of age group prevalence rate
180/100.000,almost similar to EROS study group another small survey
was conducted from Rohtak mainly on urban population showed much
lower incidence and prevalence. A prospective study from Mumbai
showed stroke survival is increased upto 68% but with residual
disability CAUSING a burden on the family ,on the society and on
country as well

DATA: presented in Vancouver WSC 2005

 Here are some the facts:
1 in 6 people will have a stroke in their lifetime.
Every 6 seconds stroke kills someone.
Every other second stroke attacks a person,
regardless of age or gender.
15 million people experience a stroke each year, 6
million of them do not survive.
About 30 million people have had a stroke in next 5
yrs- most will have residual disabilities
•stroke can be prevented.
•Stroke can be treated. 
•Stroke can be managed in the long-term.
 TODAYS DISCUSSION
1. STROKE REDIFINED & DIFF.BETWEEN
STROKE AND TIAS/RISK FACTORS OF AIS
2. CLASSIFACATION / RECOGNITION
3. NEURORADIOLOGICAL DIAGNOSIS &
EXCLUDING STROKE MIMICS (APP.OF
CLINICAL NEUROLOGY+RADIOLOGY
COMBINED)
4. MANAGEMENT PRE & IN HOSPITAL .
5. IV TRHOMBOLYSIS AND BEYOND THB.
 Definition of stroke
Stroke is defined by the World Health
Organization(WHO)
as a clinical syndrome consisting of ‘rapidly
developing clinical signs of focal (at times
global) disturbance of cerebral function, lasting
more than 24 h or leading to death with no
apparent cause other than that of vascular
origin’. A transient ischemic attack (TIA) is
defined as stroke symptoms and signs that
resolve within 24 hours.
 stroke and TIAS to be redefined
Stroke is caused by loss of blood to an area of brain which
IS PERSITENT 24 hours after onset in AIS but study shows
that considerable brain damage – some of which are
irreversible – has occurred almost immediately after a a
vascular episode. CBF <16–18 mL/100 g tissue per minute
cause infarction within an hour; and values 18ml <20
mL/100 g tissue per minute cause ischemia Using high-
resolution microscopy, functional brain imaging(MRS) ADC
Mapping , scientists demonstrated that the structure and
function of cortical neurons and other parenchymal cells are
severely compromised only in one min. after vascular
compromisation during a massive wave of electrical
discharge termed ischemic depolarization. 24 hrs no longer
correct
PATHOPHYSIOLOGY OF STROKE
Brain Damage Occurs Within Minutes
From The Onset Of A Stroke, Study Reveals
Cascade of events.
45yr old MAN NON DM/HTN
•Urgent visit to NC (Dr GP)
•Difficulty ‘getting words out’, right facial
weakness (15 min)
•Loss of vision left eye, 6/7d earlier (2-3 min).
•Smoker, party drinker Hx of elevated lipids
•BP: 143/72, normal pp and systemic exam.
NAD, started recovering after 30 mins
spontaneously.
•Normal neurological exam /normal fundus
Dx: ?........
So, can we predict Mr. x`s 45
future risk now?

Lancet, 2007
 ABCD SCORING SYSTEM
1. Age (≥60 years, 1 point).
2. Blood pressure at presentation (≥140/90 mm Hg, 1 point).
3. C features (unilateral weakness 2 points or speech disturbance without
weakness 1 point).
4. Duration of symptoms (≥60 minutes, 2 points or 10-59 minutes, 1 point).
The calculation of ABCD-2 also includes the presence of diabetes (1 point).

Total scores range from 0 (low risk) to 7 (high risk).

Total score in this patient=4(ABCD) very low risk <5%
• further assessed <4hr at clinic
•ABCD2 : 3 Then 7d stroke risk 1-4%
(‘low’) rx in outdoor basis?
•Dual TIA +ve
•Duplex US LICA 50-69% stenos
is :FURTHER CONFIRMED WITH MRA
•DWI positive
•ABCD3 is- 9 then 7d stroke risk up
>25%
•Hospital admission, immediate
medical rx and plan ?CEA
/APD/STATIN
Patients who have had a suspected TIA with an ABCD-2 score of 4 or more and those
presenting with crescendo TIA - that is, two or more TIAs in a week (even if the
ABCD-2 score is 3 or below), are at high risk of stroke and should have specialist
`assessment
ABCD3-I item Risk Score
Age>60 1
SBP>140, DBP>90 1
Clinical syndrome, weakness speech 1 or 2
duration: 10-60, >60 1 or 2
Diabetes 1
Dual TIA 2
Imaging-Carotid stenos is =2
Imaging-DWI +ve = 2
Total =13
INCLUSION OF IMAGING IN RISK POPULATION
•Might guide decision-making in secondary care, esp. hospital admission
•ABCD2+MRI (n=180, AUC 0.780.88)]
•ABCD2-I (meta-analysis, n=4,574, AUC 0.66 0.78) [Giles]
•Valuable validation set, other predictors
Coutts, Int J Stroke 2008; Ay, Stroke 2009; Giles, Stroke 2010

ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in

the Prediction of Short- and Long-Term Risks of Stroke After
Transient Ischemic Attack(STROKE ,DEC.2013) Fukuoka
Stroke Registry Investigator,japan.
 TIAS REDINED
RADIOLOGICAL DEMOSTRATION OF
TISSUE DAMAGE>1HRS (NO MORE TIAS –
MINI STROKE) HIGH CHANCE OF GETTING
A STROKE WITH IN HRS OR DAYS WHEN
CLINICORADIDIOLOGICAL SCORING ARE
HIGH >9-13,more are the scores more are
the risks.
NEWLY TERMED AS "ACUTE
CEREBROVASCULAR SYNDROME" (ACVS)
Risk factors for stroke include the
following:
•Age - as you get older>60 your risk increases. Male SEX (NONMOD.) A family history
of stroke, High blood pressure ,diabetes, cardiac disease with AF ,High cholesterol.
And LDL &, increased level of serum homocysteine and protein c and s South Asians
(Indians, Pakistanis and Bangladeshis), have a higher risk of brain stroke than the rest
of the population of Asia.
The risk of brain stroke can increase due to:
An unhealthy diet containing too much ghees(animal fat) or transfat
A lack of exercise
Tobacco use/smoking/chewing and Drinking too much alcohol many times
(Neurology September2012). 11 1109-1115 adulterated and indigenously prepared
Cns infection : TB /HIV/NCC---vacuities/stroke
•Diabetes/UNDELYING CARDIAC DISEASE

•BOTH VALVULAR AND NON

 Classification of AIS
•OSCSP CLASSIFICATION
•TACI –GLOBAL TERRITORY OF MCA INVOLVED
•PACI- PART OF TERRITORY OF MCA INVOLVED
•LACI-(LACUNAR ANT.CIRCULATION)<2MM
•PCCI –THE INFRACT IS IN THE DISTRIBUTION OF
POSTERIOR CIR.
 Classification of AIS
1.Toast classification
2. Large vessels disease
3. Small vessels oc.(lacunars syndrome)
4. Cardio embolic events with evidence of cardiac
factors(HD &AF)
5. Other determined etiologies like infection and
vacuities(primary Cns /secondary vacuities)
6. Other undetermined when no etiology is evident
after investigation(rcvs)
 Reperfusion injury and
inflammatory responses following
recanalization
it can inflict damage in the form of
edema or hemorrhage. increased
microvascular permeability,
oedema, thrombosis and
parenchymal cell death.
T1 sagittal image without contrast
demonstrating gyriform
hyperintensities. These represent
subacute petechial hemorrhage
.The goal of acute
revascularization should not just
be to open occluded vessels but to
open them quickly.
Learn More Stroke Warning Signs and Symptoms
•200
Updated:Dec 13,2013

         
                                                                                                                                                       

Approach to a suspected stroke

STROKE CARE 0-6 HRS(utmost important part is
Clinical approach –Symptom recognition
localisation & confirmation
Beyond F.A.S.T. – Other Symptoms You Should Know
•Sudden numbness or weakness of the leg, arm or face
•Sudden confusion or trouble understanding  
•Sudden trouble seeing in one or both eyes   
•Sudden trouble walking, dizziness, loss of balance or
coordination
 Sudden severe headache with no known cause
•SUDDEN DROP ATTACKS & DROWSINESS- MOST
ALERMING
CLINICAL LOCALISATION&
DIFF.I/C BLEED VS AIS
1.ANT VS POST CIRCULATION
2.ACA VS MCA
3.BLEED VS ISCHEMIC EPISODE
Blood supply-Lateral view
Blood supply-Medial view
Blood supply-Axial view
Anterior cerebral artery infarction
Clinical features
1.Contralateral
a.paralysis of leg and foot with paresis of arm
b.cortical sensory loss over leg and foot
c.presence of primitive reflexes
2.Urinary incontinence
3.Gait apraxia
4.Mutism, delay and lack of spontaneity of
motor acts
5.Apraxia of left sided limbs(with left sided
lesion and corpus callosum involvement)
Middle cerebral artery infarction -
Inferior branch
Clinical features
1.Contralateral hemianopia.
2.Wernicke’s dysphasia ( if left sided )
3.Left spatial neglect ( if right sided )
Middle cerebral artery infarction - superior
branch
Clinical features
1.Contralateral hemiplegia – face and
upper limb more involved than lower
limb.
2. Contralateral hemisensory loss.
3.Conjugate gaze paresis(patient looks
towards the side of lesion.
4.Broca’s dysphasia (if left sided)
Post circulation
Importance of clinical localisation of stroke1.
Careful clinical evaluation in combination
with imaging helps to find out the etiology of
stroke and plan the appropriate treatment.
2. Clinical observations in correlation with
imaging helps to understand neurology /
neurophysiology better.
CTSCAN BRAIN : Decidestroke or
stroke mimic –IMMEDIATE(to rule
out bleed) MRI IS MORE
INFOMATIVE ,MORE SENSITIVE
BUT
TIMECONSUMING/DIFFICULT
FOR A CRITICAL & INJURED PT
ASPECTSCTS), which is also a very valid and useful score. Basically, this score measures 10 regions
wo slices in the middle cerebral territory 10 out of 10,NORMAL BRAIN
Prediction of stroke outcome in relation to
Alberta Stroke Program Early CT Score
(ASPECTS) at admission in acute ischemic
stroke: A prospective study from tertiary care
hospital in north India. Neurology Asia.
2012;17(2):101–107.
 Advanced ct techniques for AIS
INCREASED SENSITIVITY & MORE SPECFIC
INFORMATION OF BRAIN PARENCHYMA AS WELL
ARTERIAL STATUS CAN OBTAINED WITH
CTA.CTA-SI AND CTP IMAGE .THESE TESTS COULD
BE DECISSION MAKING FOR IV TPA VS
ENDOVASCULAR INTERVENTION AND FOR
PREDICTION OF OUTCOME,FOR EXAMPLE OCCULT
DISTAL OCCLUSION WITH UNREMARKABLE LARGE
VESSELS GIVE BETTER OUTCOME WITH LITTLE
CHANCE OF ICH(possible in multislice scan only)
Head CT Angiography AND CTA-SI
A head CT Angiography is a specialized Neuro CT scan which involves fast CT imaging while
simultaneously injecting IV contrast into a vein in the arm. This allows for visualization of specific
vascular anatomy of the organs in the body. It may be used to evaluate vessels & SITE OF
OBS.WITH LENGTH OF OBS for decision to give iv TPA OR ENDOVASCULAR intervention /BOTH
CTA IS MORE SENSITIVE THAN MRA COMPARATIVE TRIAL
KEEPING DSA AS REF.STANDARD.
POOR OUTCOME IN case of TERMINAL ICA OR MI/M2 OCC.
STOP STROKE TRIAL ON 649 PTS) BASIC SCORING SYSTEM
CLOT BURDEN SCORING (CBS)>6 GET GOOD ECANALIZATION
AFTER rtPA where as proximal occ. with lower score <6 fails
to reanalyzes with iv tpa ,- endovascular procedure may be
required. CTA SOURSE IMAGE (CTA-SI) -FORM OF PWI
DONOT REQUIRE POST PROCESSING IS MORE RELIABLE &
MORE PREDICTIVE THAN NCCT ALONE EASILY AVILABLE
AFFORDABLE AND SIMPLE TO PERFORM IN A CRITICAL CASE
.
•MAGNETIC RESONANCE
IMAGING
1.5 TESLA & ABOVE IS REQ.
MIN SEQ-DW1,FLAIR ,T2 ,T1/ADC MAP. IF
TECHNOLOGIST IS EXPERIENCED ENOUGH TO DO A
FAST DPM &OR MRA OR BOTH(PRE TREATMENT
MRI PARAMETERS PREDICT CLINICAL OUTCOME)
Numerous studies have shown that ADCs in ischemic areas are
lower by 50% or more compared with those of normal brain areas,
and they appear as bright areas (i.e., hyperintensities) on DWI
(see the image below). Studies have demonstrated that changes
in the ADC occur as early as 10 minutes following the onset of
ischemia.
Magnetic resonance imaging in acute stroke. Left: Diffusion-weighted MRI in
acute ischemic stroke performed 35 minutes after symptom onset. Right:
Apparent diffusion coefficient (ADC) map obtained from the same patient at the
same time.
Dynamic Contrast-Enhanced MR Perfusion
DCE MR perfusion, also widely referred to as “permeability” MRI, is based on the acquisition
of serial T1-weighted images before, during, and after administration of extracellular low-
molecular-weight MR contrast media, such as a gadolinium-based contrast agent. The resulting
signal intensity–time curve reflects a composite of tissue perfusion, vessel permeability, and
extra vascular-extracellular space 

Dynamic Susceptibility Contrast-Enhanced

MR Perfusion
Because the method is based on a fast echo-planar imaging acquisition, the scanner needs to be
equipped with echo-planar imaging capabilities. Susceptibility changes on the basis of the
injection of an exogenous tracer (gadolinium-based contrast agent) are not strongly field
dependent. Therefore, perfusion measurements can be performed both at 1.5 T and 3 T, but
even a 1-T system, if equipped with echo-planar imaging, can be used. For the sequence, the
maximal temporal resolution should be 1.5 seconds; both 2D and 3D gradient-recalled echo or
spin-echo echo-planar imaging sequences can be used.
DWI has been shown to reveal diffusion abnormalities in almost 50% of patients with
clinically defined transient ischemic attacks (TIAs); it tends to be of higher yield at
increasing time intervals from the onset of stroke symptoms.
clinical experience at the University of North Carolina at Chapel Hill Stroke Center, the following
differential for areas of hyper intensity on DWI was generated :
•Sub acute ischemic stroke - Usually takes 7-14 days for hyper intensity to subside
•Hemorrhagic stroke - Usually bright on T1-WI
•Multiple sclerosis plaque - Also bright on fluid-attenuated inversion recovery (FLAIR) and
T2-WI
•Traumatic brain injury - History of trauma
•Brain abscess/NCC - Ring enhancement on contrast MRI
•Choroid plexus - Usually intraventricular in location, may be bilateral
•Epidermis - Usually extra-axial in location
•Air-bone interface - Commonly bilateral, in the temporal bone
Matched diffusion- and perfusion-weighted abnormalities correlate with the region of
infarction and are indicative of permanent neuronal death. Mismatched diffusion and
perfusion abnormalities with the perfusion abnormality larger than the diffusion abnormality
may be indicative of a region of reversible ischemic penumbra (see the image below).
Magnetic resonance imaging in acute stroke. Left: Perfusion-weighted MRI of a patient who
presented 1 hour after onset of stroke symptoms. Right: Mean transfer time (MTT) map of the same
patient.
 •MRI Findings in Acute Ischemic Changes 
Time MRI Finding Etiology
2-3 min DWI - Reduced ADC Decreased motion of
protons

2-3 min PWI - Reduced CBF, CBV, MTT Decreased CBF

0-2 h T2-WI - Absent flow void signal Slow flow or occlusion

0-2 h T1-WI - Arterial enhancement Slow flow

2-4 h T1-WI - Subtle sulcal effacement Cytotoxic edema

2-4 h T1-WI - Parenchyma enhancement Incomplete infarction

8h T2-WI - Hyper intense signal Cacogenic and Cytotoxic

edema

16-24 h T1-WI - Hypo intense signal Cacogenic and Cytotoxic

edema
5-7 d Parenchyma enhancement Complete infarction
 Limitation of DPM
EPITHET TRIAL(3-6 hrs)
Merci Rescue –DPM excellent outcome
negative result of a phase III desmetoplase
trial within 9 hours in MRI selected patients
A suitable way seems to be the application of diffusionDefuse
and perfusiontrial
magnetic
resonance imaging (DWI and PWI MRI) before iv rtpa. Several studies were able to
show that systemic thrombolysis can be delivered not only safely between 3 to 6
hours in patients with a significant DWI/PWI mismatch, which resembles penumbral
tissue but is more effective than otherwise unselected thrombolysis and
significantly improves outcome even in the 3 to 6 hours interval
A 48 yr old lady ,known NIDDM well controlled, non
HTN (140/85)presented with aphasia ,left horizontal
gaze deviation and rt hemi paresis of unknown onset
time & NCCT showed mild atrophic changes of brain
woke up in morning with stroke with CT –ve, RBS 140)
Is she a suitable candidate for iv thrombolysis ,if so
why? If not why?
IS PLAIN CT SUFFICIENT FOR HER?
IS IV THROMBOLYSIS IS ADEQUATE FOR HER? Any plan
beyond that?
New DRAGON Score Predicts Ischemic Stroke Outcome(2012)
Dense Cerebral Artery or Early Infarct Signs on
Computerized Tomography
 Rankin Scale (M) >1, Prestroke status
Age
• Younger than 65 years (0 points)
• Age 65 to 79 years (1 point)
• 80 years or older (2 points None of the people
Glucose Level on Admission with DRAGON scores
• <8 mmol/L (144 mg/dL) (0 points) of 8 to 10 had good
• >8 mmol/L (144 mg/dL) (1 point) outcomes. A poor
Onset to Treatment Time outcome was defined
• 90 minutes or less (0 points) as being dead,
• More than 90 minutes (1 point bedridden,
incontinent, or
National Institutes of Health Stroke requiring constant
Scale nursing care.(1330 pts)
• 0 to 4 (0 points) cutoff<7
• 5 to 9 (1 point)
• 10 to 15 (2 points)
• More than 15 (3 points)
 Clinico radiological scoring
DRAGON SCORE( CT)
AGE,NIH STROKE SCALE,SERUM GLUCOSE
LEVEL,PRESTROKE DISABILITY,EARLY INFRACT SIGNS,
HYPERDENSE MCA SIGNS ON CT
DRAGON SCORE(MRI)
2 radiological variables :M1/M2 occlusion on MRA &
DW1 ASPECTS(Dw imaging in Albert stroke
programme)
<7 for MRI VIABLE(score more poorer prognosis-
mRS)
Figure 2. Approximate timeline of stroke-induced responses in the brain parenchyma.
Figure 3. Hypothetical scenarios for progression of ischemic brain injury after stroke.
WHAT ELSE CAN BE DONE ? APPLICATION
OF A VALID & SENSITIVE DIAGNOSTIC
TOOL AT BED SIDE AS WELL AS FOR
MONITORING PURPOSE?
Neurosonology  extra cranial and trans cranial color dopler study
schematic image of the sectional
planes for the temporal and
foramen magnum acoustic
windows

The middle cerebral artery

(MCA), anterior cerebral artery
(ACA) and posterior cerebral
artery (PCA) are imaged via the
temporal window (a). The
intracranial vertebral arteries
(VA) and the basilar artery (BA)
are imaged via the foramen
magnum window (b).
 Tran cranial DOP-US - clinical
applications in cerebral ischemia
Diagnosis of extra cranial and intracranial stenosis and occlusion.
Detection and monitoring of vasospasm following aneurismal
Subarachnoid Hemorrhage.
Detection of Patent Foramen Ovale (PFO) and Right to Left Shunts (RLS).
Detection and counting of emboli.-ARTERY TO ARTERY OR CARDIAC
Evaluation of the brain vasomotor reserve.
Support for brain death diagnosis.
Monitoring during thrombolysis treatment for acute stroke patients,
identifying the point in time at which recanalization occurs
only neurologist or highly trained
person can do dedicated brain DOP STYDY.
TCD is the most available bedside tool that is used to
determine cerebral arterial occlusion and to
continuously monitor recanalization during
thrombolysis treatment. TCD has a sensitivity of 91%
and a specificity of 93% to determine complete
recanalization of the middle cerebral artery (MCA) in
tpa-treated patients. Furthermore, continuous clot
exposure to ultrasound Doppler signal enhances tpa
activity, and clot degradation with ultrasound
irradiation is 18 times greater than that with tPA
alone.
•Flow velocities:
Intracranial ICA, MCA, ACA ≥130 cm/sec
VA ≥80 cm/sec
BA ≥ 90 cm/sec
PCA ≥110 cm/sec                                
•MFV MCA/MFV extra cranial ICA >3 (Lindegaard ratio)
•MFV BA/MFV extra cranial VA >2
•Changes in the Doppler waveform: decrease of plasticity index (PI), signs of
turbulence, fluttered envelope
•A rapid early rise in flow velocities

The advantages of using TCD for cerebral vascular disorder

Noninvasive
Bedside examination
Cost-effective
High sensitivity and specificity
Comfortable, and easily repeatable examination
Enables early detection
Management of
acute ischemic
stroke
Pre hospital care
in hospital care
at discharge / follow up for 90 days
Acute management of AIS
Narrow therapeutic time window
•Early intervention critical for stroke
care
•Prehospital personnel 35-70% of
stroke patients arrive by ambulance
Unique position: first medical
professional to come in contact with
stroke patient
COUNTDOWN STARTS AS AND WHEN STROKE
SYMPTOMS APPEAR - GO F-A-S-T
 Pre Hospital recognition
Rapid recognition of symptoms and diagnosis
•In people with sudden onset of neurological symptoms a
validated tool, such as FAST/LAPSS/MASS (Face Arm Speech
Test), should be used outside stroke centre to screen for a
diagnosis of stroke or TIA.
.
Patients should be transported rapidly to the
closest NEURO INSTITUTE, if no such centers
exist, the most appropriate institution that
provides emergency stroke care
HISTORY OF STROKE PATIENT + blood sugar test = LAPSS OR MASS
History (4 items) onset/duration of symptoms
Age /history of seizure disorder
baseline functional status (m-RS)

•Exam (3 items): identifies unilateral weakness /facial weakness

arm drift /grip strength

•Finger stick blood glucose (1 item)

 Treat Stroke in the Field: Lessons from the NIH FAST-MAG Trial
IF YOU CANNOT DO IT AT PERIPHERAL LEVEL
LITTLE YOU CAN DO AT CENTRAL LEVEL

RECOGNITION
MONITORING OF BP
ECG AND QUICK BLOOD SUGAR TESTING ,IV ACCESS N/S
AND 10% D/W DEPENDING ON BP AND BS REPORT
QUICKE TRANSPORTATION TO STROKE CARE CENTRE
AWARENESS CREATION : SERIOUS DISEASE ,NOT TO
ADOPT FOR desi /alternative medicine ,Chiropractic
massage etc
 1. Blood Pressure Control?BEFORE SCAN > (220/110)
• RIGHT trial, glyceryl trinitrate
• PIL-FAST trial, Lisinopril
• For severely hypertensive patients (FAST-BP), glyceryl trinitrate
• Injection labetolol
• DO` S MONITORING ,DON`T DOWN BP DRASTICALLY WITH S/L NIFEDIPINE OR
DON`T USE MANITOL /DEXTROSE OR DISPRINE AS A ROUTINE TILL IMAGING ,BS
IF POSSIBLE (China Antihypertensive Trial in Acute Ischemic Stroke
(CATIS 2013)-4000 pts
• No anti-htn drug. vs. anti-htn drug in mod.-sever htn –no
difference.
2. Neuroprotection ?
Magnesium fast-mag, phase 3 is going on

3. THROMBOLYSIS - TO BE PLANNED & DISCUSSED WITH RELATIVES

 Magnesium Sulfate
FAST-MAG, phase 3 trial is going on

Therapies targeting the neural parenchyma- show great

promise as synergistic complements to reperfusion
therapies for acute ischemic stroke. As demonstrated
with magnesium sulfate, neuroprotective agents can be
started in the field hyper acutely, before hospital arrival,
before brain imaging, and reperfusion therapy,
potentially IT will be freezing the ischemic penumbra
and delivering to hospital-based specialist a greater
volumes of salvageable brain to save
 FAST-MAG, phase 3 IS GOING ON/PRELIMINARY RESULT
First “golden hour” (<1 hr) stroke treatment trial
•First acute (<3 hr) neuroprotective stroke treatment trial The
1700 stroke patients
trial involved within 2 hours of symptom onset, who were
randomly assigned to a loading dose (4 g over 15 minutes) of magnesium sulfate or matched
saline placebo in the ambulance. Upon arrival in the hospital emergency department, a
maintenance infusion of 16 g of magnesium sulfate or matched placebo was given over 24
hours.
•First trial of neuroprotective drugs before recanalization
therapies
•First prehospital stroke RCT
This is the first time a stroke therapy has been tested in a
prehospital setting in a phase 3 pivotal trial"It shows it is
feasible. This will help with the design and planning of studies
looking at the delivery of other agents in the field."
 In hospital care
Patient History
The single most important piece of historical information is
the time of symptom onset. symptom-free or known to be
“normal.”
Establishing onset time may require confirming the patient’s,
bystander’s, initial assessment. Creative questioning to
establish time anchors potentially allows treatment of patients
initially identified as “onset time unknown.” These include
inquiring about prestroke or post stroke cellular phone use
(and identifying the corresponding call time stamp) or use of
television programming times to determine onset time.
Patients with “wake-up” strokes may identify a time point
when they were ambulatory to the bathroom or kitchen.
An organized protocol for the emergency evaluation
of patients with suspected stroke is
recommended (Class I; Level of Evidence B). The goal
is to complete an evaluation and to begin
Thrombolytic treatment within few minutes of the
patient’s arrival in an ED. Designation of an acute
stroke team that includes neurophysicians, nurses,
and laboratory/radiology personnel encouraged with
ventilators` support stand by. Patients with stroke
should have a careful clinical assessment, including
neurological Neuro- radiological
examination. (Unchanged from the previous
guideline)
The use of a stroke rating scale, preferably the
NIHSS, is recommended (Class I; Level of
Evidence B). (Unchanged from the previous
guideline)
A limited number of hematologic,
coagulation, and biochemistry
tests are recommended during the
initial emergency evaluation, and
only the assessment of blood
glucose must precede the
initiation of intravenous rtPA
(Class I; Level of Evidence
B). (Revised from the previous
guidelines)
Tested Item Title Responses and Scores
0—Alert
1—Drowsy
IA Level of consciousness 2—Obtunded
3—Coma/unresponsive
0—Answers both correctly
1B Orientation questions (2) 1—Answers 1 correctly
2—Answers neither correctly
0—Performs both tasks correctly
1C Response to commands (2) 1—Performs 1 task correctly
2—Performs neither
0—Normal horizontal movements
2 Gaze 1—Partial gaze palsy
2—Complete gaze palsy
0—No visual field defect
1—Partial hemianopia
3 Visual fields 2—Complete hemianopia
3—Bilateral hemianopia
0—Normal
1—Minor facial weakness
4 Facial movement 2—Partial facial weakness
3—Complete unilateral palsy

0—No drift
Motor function (arm) 1—Drift before 5 seconds
5 a. Left 2—Falls before 10 seconds
b. Right 3—No effort against gravity
4—No movement
Tested Item Title Responses and Scores
0—No drift
Motor function (leg) 1—Drift before 5 seconds
6 a. Left 2—Falls before 5 seconds
b. Right 3—No effort against gravity
4—No movement

7 Limb ataxia
8 Sensory
9 Language
10 Articulation
0—No ataxia
1—Ataxia in 1 limb
2—Ataxia in 2 limbs
0—No sensory loss
1—Mild sensory loss
2—Severe sensory loss
0—Normal
1—Mild aphasia
2—Severe aphasia
3—Mute or global aphasia
0—Normal
1—Mild dysarthria
2—Severe dysarthria

Extinction or 0—Absent
11 1—Mild (loss 1 sensory modality lost)
inattention 2—Severe (loss 2 modalities lost)
 All patients( URGENTLY REQ)
  Noncontrast brain CT or brain MRI with mandatory diffusion scan
  Blood glucose and o2 saturation measurements
  Serum electrolytes/renal function tests*l/lipid gram

  Complete blood count, including platelet count*/PT/INR Although it is desirable to know the results
of these tests before giving intravenous recombinant tissue-type plasminogen activator, fibrinolytic therapy
should not be delayed while awaiting the results unless (1) there is clinical suspicion of a bleeding
abnormality or thrombocytopenia, (2) the patient has received heparin or warfarin, or (3) the patient has
received other anticoagulants (direct thrombin inhibitors or direct factor Xa inhibitors).

Markers of cardiac ischemia*/biomarkers for stroke can be sent before fibrinolytic infusion
  
  ECG*
  Hepatic function tests
  Toxicology screen
  Blood alcohol level
  Pregnancy test
  Arterial blood gas tests (if hypoxia is suspected)
  Chest radiography (if lung disease is suspected)

Lumbar puncture (if subarachnoid hemorrhage is suspected and CT scan is negative for blood

  Electroencephalogram (if seizures are suspected) can be done bedside

The initial evaluation of a potential stroke patient is
similar to that of other critically ill patients:
•Immediate stabilization of the airway, breathing, and circulation
(ABCs).

•The overall goal is not only to identify Stroke patients with

possible cause of stroke but also to exclude stroke mimics
(conditions with strokelike symptoms) of non-vascular region.

•Identify other conditions that require immediate

intervention, and determine potential causes of the stroke
for secondary prevention.

•Importantly, early implementation of stroke treatment pathways

and/or stroke team notification should occur at this point.
The diagnosis of acute ischemic stroke is often
straightforward. The sudden onset of a focal neurologic
deficit in a recognizable vascular distribution with a common
presentation - such as hemi paresis, facial weakness and
aphasia - identifies a common syndrome of acute stroke. But
differential diagnostic problems remain because there are
several subtypes of stroke and also because some non-
vascular disorders may have clinical pictures that appear
identical to strokes. This talk will briefly review the
differential diagnosis of stroke starting with stroke sub-types.
Stroke “mimics,” non-vascular conditions that simulate
Stroke like picture
 l
n
er

STROKE MIMICS CLINICAL MANIFESTATION

v
o
us
sy
st
Lack of objective cranial nerve findings, neurological findings in a
Psychogenic e
nonvascular distribution, inconsistent examination
m
.

Seizures focal onset History of seizures, witnessed seizure activity, postictal paralysis

History of diabetes, low serum glucose, decreased level of

Hypoglycemia consciousness

Migraine with aura
(complicated History of similar events, preceding aura, headache
migraine/hemiplegic migraine)

Headache, delirium, significant hypertension, cortical

Hypertensive blindness, cerebral edema, seizure, reversible weakness
encephalopathy/ RCVS/PRES Drop attack

Wernicke’s encephalopathy History of alcohol abuse, ataxia, ophthalmoplegia, confusion

History of drug abuse, endocarditis, medical device implant with

CNS abscess fever
Gradual progression of symptoms, other primary malignancy,
CNS tumor seizure at onset

Drug /alcohol toxicity Lithium, phenytoin, carbamazepine

 Within 6 Hours After 6 Hours
Condition Total Number (%)† 6 (9.7%) 8 (17.0%)
• Toxic/metabolic 12 (11.0%) 6 (9.7%) 6 (12.8%)
• Space occupying 10 (9.2%) 3 (4.8%) 7 (14.9%)
lesion
• Syncope/presyncop 10 (9.2%) 9 (14.5%) 1 (2.1%)
e
• Acute confusional 7 (6.4%) 3 (4.8%) 4 (8.5%)
state
• Vestibular 7 (6.4%) 3 (4.8%) 4 (8.5%)
dysfunction
• Acute 6 (5.5%) 4 (6.5%) 2 (4.3%)
mononeuropathy
• Functional/medicall 6 (5.5%) 4 (6.5%) 2 (4.3%)
y unexplained
symptoms
• Dementia 4 (3.7%) 2 (3.2%) 2 (4.3%)
• Migraine 3 (2.8%) 2 (3.2%) 2 (4.3%)
• Spinal cord lesion 3 (2.8%) − (0%) 3 (6.4%)
• Other 3 (3.7%) 2 (3.2%) 1 (2.1%)
Total 109 (100%) 62 (100%) 47 (100%)
INTRAVENOUS THROMBOLYSIS USING rtPA
The ENS ,EFNS (EAN) AAN AHA/ASA have
produced evidence-based reviews of the
management of stroke and recommend that:
Alteplase(rtPA) should only be administered within a well-organised
stroke service ,TIME WINDOW 4.5 Hrs.
Staff in such a service should be trained in delivering thrombolysis and
in monitoring for any associated complications.
Care should be provided by nursing staff trained in acute stroke and
thrombolysis.
There should be immediate access to imaging and re-imaging and staff
appropriately trained to interpret the images.
Protocols should be instituted for the delivery and management of
thrombolysis, including post-thrombolysis follow up for avoiding
complication
Pooled, patient level analysis
8 trials- NINDS 1 and 2 (Iconic
trial)A new discovery of AIS care
ATLANTIS A and B SITS-MOST
ECASS 1, 2, and 3
8670 patients :IV TPA Only
EFFECTIVE &Only standardized
FDA approved Rx For AIS.
 Trial based on radiological data vs. cl.data

In EPITHET, borderline significant attenuation of infarct growth with alteplase

given 3 to 6 hours after stroke onset in patients with mismatch calculated using a
standard volumetric method. In this method, the diffusion-weighted imaging (DWI)
lesion volume is subtracted from the perfusion-weighted imaging (PWI) volume. In the
coregistered mismatch patients, of whom 45 received alteplase and 43 received
placebo, the primary outcome measure of geometric mean infarct growth was
significantly attenuated by a ratio of 0.58 with alteplase compared with placebo (1.02
vs 1.77; 95% confidence interval [CI], 0.33 – 0.99; P = .0459).
Journal of stroke 2011

showed significant outcome in 90 days follow-up

with favovourable Rankin`s shift
 The Basics:
• blood pressure (BP) to < 185/110 mm Hg before rtPA
• Maintain BP below 180/105 mm Hg for at least 24 hours
after rtPA
• Airway support if necessary
• Treat hyperthermia
• No O 2 if not hypoxic
Though data do not exist guiding antihypertensive selection in acute ischemic stroke, elevated
BP should be lowered to < 185 mm Hg/< 110 mm Hg before rtPA is given and maintained
below 180/105 mm Hg for at least 24 hours after starting therapy; these recommendations
also apply to patients undergoing recanalization procedures (including intra-arterial
fibrinolysis). In cases of decreased consciousness or bulbar dysfunction, airway support and
ventilatory assistance are recommended. Sources of hyperthermia should be identified and
treated and, in nonhypoxic patients, supplemental oxygen is not recommended.
Supportive Care/Addressing
Complications (Revised)
The Basics:
• Cardiac monitoring
• Oxygen and hypovolemia correction
• Lower BP in those not receiving fibrinolysis; medication
only if BP > 200 mm Hg/120 mmHg
• Pre-existing hypertension→ Restart medication
• Treat glucose abnormalities
rtPA is recommended in eligible patients
in the 3- to 4.5-hour window. Eligibility
criteria are similar to those for the 3-
hour window except for the exclusion of
patients over 80 years old, those on oral
anticoagulants, those with a baseline
NIHSS score > 25, those with imaging
evidence of ischemic damage to more
than one third of the middle cerebral
artery (MCA) territory, and those with a
history of both stroke and diabetes
mellitus. Physicians should be prepared
to manage potential side effects such as
bleeding and angioedema.
 Thrombolysis for Acute Stroke in Pediatric age group(2-17)

The excellent work by Janjua et al provides us with the first national register of
thrombolysis in children. It is a retrospective study that analyzes 20% of all
community hospital admissions in the United States. Over a 4-year period, 2904
pediatric patients with stroke were included in the study, with 2% of them receiving
intravenous or intra-arterial thrombolysis, established 3 facts about thrombolysis in
children: firstly, no symptomatic intracranial hemorrhage was reported in the tPA
group; secondly, mortality and dependency were more frequent in the tPA group at
discharge, but the difference was not significant, and thirdly, patients of the tPA group
needed longer stay .

Thrombolysis in Pediatric Stroke (TIPS)

Thrombolysis in Pediatric Stroke (TIPS) is a five-year multi-center international safety and
dose-finding study of intravenous (IV) tPA in children with acute ischemic stroke (AIS) to
determine the maximal safe dose of intravenous Tissue Plasminogen Activator (IV-tPA) among
three doses (0.75. 0.9, 1.0 mg/kg) for children age 2-17 years within 4.5 hours from onset of
acute AIS –REPORT WILL BE AVILABLE IN NEXT YR.
 Limitation of iv thrombolysis

1.Beyond 4.5 hrs –chance of recanalization less,

increased chance of sICH
2.When onset of symptoms is uncertain but other
parameters favorable- to give or not to give? the
decision is very crucial
3.Partial recanalisation-incomplete thrombolysis OR
failed thrombolysis WITH IV TPA(if selection is not
proper ,major arterial occ.) are another problem
4.Systemic factors may be barrier
 Beyond iv thrombolysis
1. enhanced Thrombolysis with appl. of high frequency
TCD(clout bust phase 1&2 trial published ,Showed
success)
2. Low FR. 1- MHz tcd probe –better penetration
through skull-risks of sICH (abandoned –German
trial)
3. Endovascular ultrasound 170khz thrombolysis+ia
tpa on clot-nonrandomized trial /better
recanalization/more sICH
4. combined iv +ia thrombolysis proximal occlusion
/M1 occ.
5. Iv micro bubble +dus enhanced thrombolysis with
alteplase
 Sonotrombolysis technique
Tran cranial ultrasound as an adjunctive therapy to Tpa with approved
labeling administered over 60 minutes Ultrasonic head frame with
active insonation for 120 minutes CLOTBUST-Hands Free: pilot safety
study of a novel operator-independent ultrasound device in patients
with acute ischemic stroke +iv tpa : safety is confirmed
(stroke2014,jan)

Phase 3, Randomized, Placebo-Controlled, Double-

Blinded Trial of the Combined Lyses of Thrombus
With Ultrasound and Systemic Tissue Plasminogen
Activator (tPA) for Emergent Revascularization in
Acute Ischemic Stroke (CLOTBUST-ER) –report
pending till date.
Endovascular intervention
&MECHANICAL THROMBOTECTOMY

Pros and cons(benefit vs. risks)

MERCI TRIAL
PROACT TRIAL
MR- RESCUE
IMS –III TRIAL
Endovascular Interventions
The Basics:
• Give IV rtPA, even if considering intra-arterial management
• Early intra-arterial fibrinolysis in select patients at qualified facility
• Outcomes with mechanical thrombectomy devices not fully established but can
be useful in achieving recanalization in select patients
• Stent retrievers preferred to coil devices; Penumbra System® vs stent retrievers
not yet characterized
• Emergent intracranial angioplasty and/or shunting not recommended
The Bottom Line: Two mechanical embolectomy trials in acute stroke published in
2012, SWIFT [3] and TREVO 2, [4] support the use of stent retriever devices over the
use of the Merci Retriever®.
 Hawaii ISC — Results of the Interventional
Management of Stroke III (IMS-III) trial show no
benefit of endovascular therapy after the use of
intravenous (IV) thrombolysis over IV thrombolysis
alone in the treatment of moderate to severe acute
ischemic stroke with major arterial occlusion .
IMS-III was a phase 3, randomized, open-label international trial comparing a
combined intravenous and intra-arterial stroke treatment with standard intravenous
tPA alone. The planned target for patient enrollment was 900 patients, randomly
assigned in a 2:1 ratio to combined vs. standard therapy within 3 hours of stroke
onset.
Endovascular therapy included a choice of catheters and devices or intra-arterial tPA
based on the lesion characteristics, the experience and training of the investigator, and
the specified use of devices. At the outset, only 1 device was USED, the Concentric
Merci retriever
Use of mechanical techniques to restore blood flow was not studied earlier in a
randomized trial so the clinical efficacy of these treatments remain unproven
Trials of Neuroprotective Agents
TILL DATE
Neuro protective agents tested >100
RCTs performed 114 centers
Patients enrolled 21,445
Neuro protective agents approved 0
Time windows: 4-48 hours
till end of 2013 : NO APPROVAL OF ANY AGENT
 COMBINING ANTITHROMBOTIC AND
THROMBOLYTICS WITH NEUROPROTECTION
AL(albumin)IAS TRIAL( phase3 2013 –report pending)
AR(aspirin iv)TIS TRIAL (TERMINATED PREMATURELY)
FAST MAG as Neuroprotection to penumbra before and after thrombolysis
Argatroban With tPA for Acute Stroke (ARTSS-2)
Final report pending(2015)
CLEAR-ER TRIAL The Combined Approach to Lyses Utilizing Eptifibatide and rt-PA in
Acute Ischemic Stroke - Enhanced Regimen (CLEAR-ER) is an NIH funded, multicenter,
randomized, double-blind trial to determine the safety of the combination of medium
dose rt-PA (0.6 mg/kg total) plus Eptifibatide (bolus 135 mcg/kg and 2 hour infusion at
0.75 mcg/kg/min) compared to standard dose rt-PA (0.9 mg/kg) in patients with acute
ischemic stroke that can have the rt-PA initiated within 3 hours of symptom onset.)
study were presented at the International Stroke Conference (ISC) 2013 
(Gpllb/llla inhibitors and direct thrombin inhibitors +iv rtPA)
Phase 3 trial pending)
 Heparin vs. aspirin

Use of SC unfractionated heparin versus

aspirin was tested in IST. Heparin given SC
afforded no additional benefit over aspirin
and increased bleeding rates. Several trials
of LMWHs have also shown no consistent
benefit in AIS. Furthermore, trials generally
have shown an excess risk of brain and
systemic hemorrhage with acute
anticoagulation. Therefore, trials do not
support the routine use of heparin or other
anticoagulants for patients with
atherothrombotic stroke
 Conclusion
•Iv TPA is gold std. To be given within 4.5 hrs of AIS

•Care should be started at field as fast as possible avoiding unusual delay just
for getting a scan of brain using an outdated machine ,unnecessary waiting for
the reports ONLY BS report is good enough ,recognition is most important.
,primary health care staffs ,doctors and ambulance drivers should know the
basics of FAST/LAPSS ,TRANSLATED INTO LOCAL LANGUAGE.

•Door to computed tomography (CT) & IV Therapy recommended to ≤30

minutes for imaging and door to needle in ≤60 minutes(DNT) from arrival in
the ED.

•Public and professional awareness to recognize early stroke symptoms and

all elderly (60 yrs+) should know & scrutinize their own risk factors and to get
a mandatory health insurance(cashless service) so that cost of rx will not
matter.