MANAGEMENT OF ISCHAEMIC STROKE

DR. VINIT SURI

MD (Medicine), DM (Neurology)
Sr. Consultant Neurologist
Indraprastha Apollo Hospital
 “ BRAIN ATTACK”
‘ACUTE NEUROVASCULAR SYNDROME’
STROKE IS A MEDICAL EMERGENCY

FAST ACT FAST TIME IS BRAIN

•Face
•Arm
•Speech
•Test
 No. of dead
EVIDENCE OF EFFICACY Odds Or dependent
Ratio Avoided / 1000 pts.

Acute aspirin 0.94 13

Stroke unit treatment 0.78 50

0 – 3 hr IV TPA 0.66 140

0 – 6 hr IA Prourokinase 0.58

Hemicraniectomy 0.33 500

0.5 1.0 2
Treatment Placebo
better better
 PRE-HOSPITAL CARE

• Stroke is a medical emergency and all patients should be

hospitalized urgently. [even if minor stroke – 25-40% deteriorate
over 24-48 hrs] .Avoid wait & watch

• FAST

• Blood sugar estimation and correction of hypoglycemia (<60 mg%)

– Exclude Stroke mimics

• Aspirin to be administered preferably after CT Scan [Aspirin in 1st

48 hrs] unless significant delay.
No harm documented in hemorrhagic stroke.

• Do not lower BP unless Sys > 220 Dias > 120. Do not use sublingual
nifedipine
TRIAGE MANAGEMENT
1. Stabilization • Stabilization of ABC
2. Establish diagnosis
(exclude stroke mimics) • IV access – NS @ 50 ml/hr in
nonparalysed arm
3. Stroke Scale (NIHSS
score)
• Continuous cardiac
4. Imaging – CT /MRI monitoring

5. Investigations
• Oxygen saturation monitoring
6. Thrombolysis – IV / IA for 48-72 hrs

7. Shift to Stroke ICU

TRIAGE MANAGEMENT

1. Stabilization STROKE MIMICS

- Post ictal deficiet
2. Establish diagnosis - Neurogenic migraine
(exclude stroke mimics) - Subdural hematoma
- Brain abscess
3. Stroke Scale (NIHSS
score) - Tumor
- Hypertensive encephalopathy
4. Imaging – CT /MRI - Multiple Sclerosis
- Spinal cord or disc disease
5. Investigations - Bells palsy
- Cerebritis
6. Thrombolysis – IV / IA
 CT helpful but MRI is significantly better, especially
7. Shift to Stroke ICU with DWI establishing infarct beyond 39 minutes
 Absence of DWI restricted pathology – look for an
alternate cause
TRIAGE MANAGEMENT
1. Stabilization NIHSS score
• NIHSS < 10 – 60 – 70% favourable outcome
1. Establish diagnosis at 1 yr.
(exclude stroke mimics)
• NIHSS > 20 4 – 16% favourable outcome at 1
3. Stroke Scale (NIHSS yr.
score) • NIHSS < 10 – IVTPA
> 25 – IVTPA contra indicated
4. Imaging – CT /MRI

5. Investigations

6. Thrombolysis – IV / IA

7. Shift to Stroke ICU

 NIHSS SCORE
1A Level of 0 – Alert 6 Motor function 0 – No drift
conciousness 1 – Drowsy
2 – Obtunded (Leg)
3 – Coma a : Left 1 – Drift before 5 secs
1B Orientation 0 – Answers both correctly b : Right 2 – Falls before 5 secs
questions (2) 1 – Answers 1 correctly
2 – Answers neither correctly 3 – No effort against gravity
1C Response to 0 – Performs both correctly 4 – No movement
commands (2) 1 – Performs 1 correctly
2 – Performs neither 7 Limb Ataxia 0 – No ataxia
1 – Ataxia in one limb
2 Gaze 0 – Normal horizontal 2 – Ataxia in two limbs
movements
1 – Partial gaze palsy 8 Sensory 0 – No sensory loss
2 – Complete gaze palsy 1 – Mild sensory loss
3 Visual fields 0 – No visual field defect 2 – Severe sensory loss
1 – Partial hemianopsia 9 Language 0 – Normal
2 – Complete hemianopsia
3 – Bilateral hemianopsia 1 – Mild Aphasia
4 Facial 0 – Normal 2 – Severe aphasia
movements 1 – Minor facial weakness 3 – Mute or global aphasia
2 – Partial facial weakness
3 – Complete unilateral palsy 10 Articulation 0 – Normal
1 – Mild dysarthria
5 Motor function 0 – No drift
(ARM) 2 – Severe dysarthria
a : Left 1 – Drift before 5 secs
b : Right 2 – Falls before 10 secs
3 – No effort against gravity 11 Extinction or 0 – Absent
4 – No movement Inattention 1 – Mild (loss 1 sensory
modality)
2 – Severe (loss 2 modalities)
TRIAGE MANAGEMENT

1. Stabilization
NCCT Head
2. Establish diagnosis
(exclude stroke mimics) I. CT sufficient to exclude
hemorrhage and stroke mimics
3. Stroke Scale (NIHSS
score)
and hence proceed with
thrombolysis
4. Imaging – CT /MRI
ii. Short duration imaging
5. Investigations
iii. Can be used despite
6. Thrombolysis – IV / IA
pacemakers, valve
7. Shift to Stroke ICU replacement, restless patients
MRI
ADVANTAGES :
i) Can detect ischemic areas within 39
minutes of onset
ii) Can differentiate old from acute
infarct
iii) Can detect posterior circulation and
lacunar stroke
iv) Can give information about ischemic
penumbra (DWI + perfusion
mismatch)
v) Can reveal intracranial vessel
disease on MRA
vi) Can detect microbleeds

DISADVANTAGES :
i) Time consuming
ii) Contra-indications (Pacemaker, Post
CABG, Valve replacement)
TRIAGE MANAGEMENT
• CBC, PT, aPTT, LFT, KFT
1. Stabilization
• ECG, Chest X-ray
• Echo, Carotid Doppler
2. Establish diagnosis
(exclude stroke mimics) • Thrombolysis pts – Platelet count, RBS, PT
if on anticoagulants or suspected
3. Stroke Scale (NIHSS coagulopathy
score)
• Pulse oximetry
• Cardiac monitoring (AF, arrhythmia)
4. Imaging – CT /MRI

Special tests :
5. Investigations
• TCD
• Thrombotic profile
6. Thrombolysis – IV / IA
• Collagen profile
• ABG
7. Shift to Stroke ICU
 Stratify patients

•Recanalization therapy

•Stroke ICU General care

RECANALIZATION

• Intravenous
• Intra arterial
• Combined IV + IA
• mechanical
 THROMBOLYSIS IN STROKE

IV TPA :
INCLUSION CRITERIA

 Ischaemic stroke

 Persistent neurological deficit beyond isolated sensory deficit or

ataxia

 CT negative for hemorrhage


Initiation of treatment WITHIN THREE HOURS ( 4.5 hrs)
 THROMBOLYSIS IN STROKE
IV TPA :
EXCLUSION CRITERIA
• > 4.5 hours since onset , Time uncertain
• Oral anticoagulant use or PT > 15sec ( INR > 1.7)
• Heparin use in 48 hours with prolonged PTT
• Platelet count < 1.0 x 105
• Pretreatment BP > 180 systolic, > 110 diastolic
• Prior stroke or head injury in 3 months
• Acute MI in last 3 months
• Major surgery in 2 weeks
• Seizure at onset
• GI or UT hemorrhage within 2 weeks
• Arterial puncture at a noncompressible site within 7 days
• Age > 80 years (?)
• Known AVM / aneurysm
 THROMBOLYSIS IN STROKE

IV TPA - GUIDELINES

DOSAGE :
 0.9 mg / kg (50 mg vial / 20 mg vial) max 90 mg
: 10 % bolus IV over 1 min,followed by 90 % infusion
over 1 hr

 Children : safety unclear : 0.5 mg / kg

Stop transfusion and stat CT Scan Brain if patient becomes

drowsy, vomits, has severe headache or acute hypertension
 THROMBOLYSIS IN STROKE

IV TPA - POST THROMBOLYSIS CARE :

– BP q 15 min x 6 hrs. Treat if systolic > 180,
diastolic > 105
– Avoid central line, arterial line puncture for 24 hrs
– Avoid Ryle’s tube insertion for 24 hrs
– Avoid urinary catheterization during and for ½ hrs post TPA
– Mannitol to reduce oedema
– No antiplatelets, anticoagulants for 24 hrs
– CT after 24 hrs (earlier if neurological deterioration)
INTRA – ARTERIAL THROMBOLYSIS
 INTRA-ARTERIAL THROMBOLYSIS

EVIDENCE :
PROACT I STROKE 1998
6 hrs, 6 mg prouk - 67.7 % vs. 14.3% recanalization
(+ heparin) - 10 - 12 % excellent outcome at 3 months
- 15.4 % vs. 7% hemorrhage
PROACT II JAMA 1999
6 hrs, 9 mg prouk - 40 % vs. 25% Rankin < 2 at 3 months
(heparin / no heparin) - 66% vs. 15%recanalization
- hemorrhage 10%
J MUSIC (Japan’s multicentre stroke investigators collaboration)
Inoue Cerebrovascular disease 2005 ; 19 : 225 – 228
Favourable outcome (m Ranking) 51% IATPA vs 34% control

Macleod Cerbrovasc Dis 2005 ; 20 : 12 – 17

15 pts, post circulation stroke within 24 hours, IA prouk vs conservative
Good outcome 4/7 IATPA vs 1/8 control
INTRA-ARTERIAL THROMBOLYSIS

ADVANTAGES OF INTRA-ARTERIAL THROMBOLYSIS

• Better recanalization compared to IV TPA

– IVTPA – 39% FDA approved
– IATPA – 66%
– MERCI device – 69% FDA approved

• Better in severe deficit (NIHSS > 20)

• Presentation between 3 – 6 hours in anterior circulation and 24 hours in

posterior circulation

• Recent history of surgical procedure

• Occlusion of major cervical and or intracranial vessel

INTRA-ARTERIAL THROMBOLYSIS

RECOMMENDATION (AHA / ASA / Adams et al Stroke 2007)

IA thrombolysis is an option for treatment of selected pts who have

major stroke < 6 hrs duration due to occlusion of MCA and who are
not otherwise candidates for IV TPA (Class I Level B)

• IA thrombolysis is reasonable in pts with contra-indications for IV

TPA eg. Recent surgery (Class IIa Level C)

• Availability of intra-arterial thrombolysis should not preclude IV TPA

(Class III Level C)
COMBINATION THERAPY (IV + IA TPA)
 COMBINATION THERAPY

• Initiation of IV thrombolysis followed by IA thrombolysis (specialised centre)

• IMS study (Interventional management of stroke) IMS study Investigators Stroke
2004 ; 35 ; 906-911
– IV TPA 0.5 mg/kg (60 mg max over 30 minutes) within 3 hours of onset,
IATPA at site of occlusion to a total dose of 22 mg over 2 hours of infusion
or till recanalization
– Symptomatic ICH 6.3% (NINDS 6.4%)
– 3 monthly mortality lower (16%) but NS vs placebo (24%) and IV TPA of
NINDS group (21%). IMS group had significantly better outcome at 3
months compared to NINDS placebo group

Recommendation ( AHA / ASA / Adams et al Stroke 2007)

• At present combination IV and IA TPA to restore perfusion cannot be
recommended outside the setting of a clinical trial (Class III Level B)
ENDOVASCULAR INTERVENTION

CLOT EXTRACTION
MERCI (Mechanical Embolus Removal in
Cerebral Embolism TRIAL Smith WS Stroke 2007
i) MERCI device to extract thrombi from
occluded intracranial vessels
ii) Rate of recanalization of MCA in MERCI
was 60% - 68% vs 66% in PROACT II and 39%
with IVTPA

iii) FDA approved

Recommendation (AHA / ASA / Adams et al; 2007)
MERCI device has FDA approval. MERCI device is a reasonable intervention for extraction
of intra-arterial thrombi, the utility of the device in improving outcomes after stroke is
unclear (Class II B, Level B)
Usefulness of other endovascular treatment is not established
STROKE UNIT MANAGEMENT
ANTICOAGULATION AND
ACUTE ISCHEMIC STROKE
UNFRACTIONATED HEPARIN

• International Stroke trial Lancet 1997 ; 349 ; 1569 – 1581

– 5000 u/day vs 25,000 u/day, within 48 hours +_ Aspirin
– Minor benefit in lowering early recurrence negated by increased bleeding
complication (No benefit even in AF)

• Swedish Trial – Roden Julling A I Intern med 2000 ; 248 ; 287 -291
– No benefit

• European trials
- Camerlingo Stroke 2005 ; 36 ; 2415 – 2420 (within 3 hours)
No benefit

- Chemorro A Cerebrovasc Dis 2005 ; 18 ; 402 – 404

No benefit
 LOW MOLECULAR WEIGHT HEPARIN

• Hong Kong trial Kay NEJM 1995 ; 333; 1588 – 1593

Nadoparin x 10 days : No benefit
TOAST TRIAL
• Berg E Lancet 2000 ; 355 ; 1205 – 1210
Dalteparin vs Aspirin : No benefit

• TOPAS Diener HC Stroke 2000 ; 32 ; 22 -29

Certoparin : No benefit

• TAIST Bath DM Lancet 2001 ; 358 ; 702 -710

Aspirin vs Tinazaparin : No benefit

• TOAST JAMA 1996 ; 279 ; 1265 – 1272

IV Danaproid : No benefit, increased hemorrhage

• TRACE Woessror R Thromb Haemost 2004 ; 91 ; 690 – 693

subcut Enoxaparin : No benefit
Recommendation (AHA / ASA / Adams et al Stroke 2007)

• Early administration of Heparin or LMWH were associated with increased risk

of bleeding (Symptomatic HTN or systemic bleed). No benefit on reducing risk
of early recurrence nor early neurological worsening. No benefit in subgroups
with AF, VB stroke, Arterial dissection

• Urgent anticoagulation with the goal of preventing early recurrent stroke,

halting neurological worsening or improving outcomes after ischemic stroke is
not recommended for patients with AIS (Class III, Level A)

• Initiation of anticoagulation therapy within 24 hours of IV TPA is not

recommended (Class III, Level B)
ANTIPLATELET AGENTS AND
ACUTE ISCHEMIC STROKE
SINGLE ORAL ANTIPLATELET AGENTS

CAST (Chinese Acute Stroke Trial) collaborative group

Lancet : 1997 ; 349 ; 1641 – 49
• IST (International Stroke Trial) collaborative group
Lancet : 1997 ; 349 ; 1569 – 81
• NS reduction in death or disability with Aspirin initiated within 48 hours of AIS
in either trial
• Modest but S benefit with combined results (7/1000 reduced early
recurrence , 10/1000 reduced death, dependency)
• Use of Clopidogrel, Dipyridamole in the setting of acute stroke has not been
adequately evaluated

COMBINATION ANTIPLATELET AGENTS

• Aspirin – Clopidogrel has been used in ACS, with no significant evaluation in
AIS
Recommendations (AHA / ASA / Adams et al Stroke 2007)

• Oral administration of Aspirin (Initial dose of 325 mg) within 24 – 48 hours

of stroke onset is recommended (Class I, Level A). New with addition of
dose

• Aspirin should not be considered as substitute for IVTPA (Class III, Level B)

• Aspirin as adjunctive therapy within 24 hours of TPA is not recommended

(Class III, Level A)

• Administration of Clopidogrel alone or in combination with Aspirin is not

recommended (Class III, Level C)

• Outside the setting of clinical trials IV Antiplatelet Glycoprotein Iib/IIIa is

not recommended (Class III, evidence B)
NEUROPROTECTION
 NEUROPROTECTION
• Aim : Slow down or halt the ischemic cascade for a limited period of time allowing prolongation of
reperfusion therapy time window

• Trials Outcome
Nimodepine Calcium channel blocker Not approved
Fosphenytoin Na channel blocker Not approved
Selfolol NMDA antagonist No efficacy in phase III trials
Trilazed Lipid peroxidation inhibitor Worsened outcome
Lubeluzole Ion channel and nitric Not approved
oxide blocker
Clomethiazole GABA agonists Phase III halted due to no
efficacy
Repinotan 5HT1A receptor agonists Halted due to poor phase IIb
results
ONO2506 Astrocyte modulting Phase II trials unfavorable
NXY – 050 SAINT 1 & 2 – no benefit

RECOMMENDATIONS (AHA / ASA / Adams et al; 2007)

• No neuroprotective intervention can be recommended for stroke management
(Class III level A)
 TEMPERATURE

• Increased body temperature in AIS (first 24-48hrs) is associated with increased

morbidity and mortality secondary to increased free radical production (Hajat
stroke 2000:31:410-414, Castillo stroke 1998, 29: 2455-2461)

• Fever secondary to cause of stroke (Infective endocarditis) or complications

(Pneumonia, UTI)

• Lower body temperature by antipyretics or cooling device will logically

improve neurological outcome (Dippel DW stroke 2001, 32:1607-12)

• Hypothermia has not shown any significant benefit

• Recommendations (AHA/ASA/Adams et al stroke 2007) Source of fever should

be treated and antipyretics should be administered to lower temperature in
febrile patients (class I , level C)
 AIRWAY, SUPPLEMENTAL OXYGEN AND VENTILATORY SUPPORT

A) Supplemental oxygen
i) Routine supplemental oxygen not required for stroke patients (Ronning
OM Stroke 1999 ; 30:2033-2037)
ii) Supplemental oxygen used for :
a) Hypoxia : SO2 < 95%
b) Reduced level of consciousness
c) Bulbar dysfunction
B) Elective intubation – Prognosis poor with 50% dead within 30 days of
stroke (Bushnel CD Neurology 1999 ; 52; 1374-1381)
i) Increased ICP or malignant brain edema
ii) Poor airway – altered sensorium or bulbar dysfunction
iii) GCS < 8
C) Hyperbaric oxygen – No benefit except in symptoms secondary to air
embolism (Rusynlek stroke 2003; 34; 571-574)
 HYPERTENSION

• Caution in treating hypertension in AIS unless medical indication

(aortic dissection, ARF, pulmonary edema, ACMI,HT
encephalopathy)
• Recommendation (AHA/ASA/Adams et al stroke 2007)
• BP Target
– Nonthrombolysis : Sys >220, Dias >120 (class I, level C new
recommendation)
– Thrombolysis : Sys >185, Dias >110
• Withold or reduce antihypertensive medication for 24- 48 hrs
• Hypotension – neurological deterioreation if Sys <100,
Identify cause eg: Volume depletion, blood loss, aortic dissection,
myocardial ischemia or arrhythmias
HYPERGLYCEMIA AND STROKE
• Experimental evidence supports a causal relationship between hyperglycemia
and adverse outcome after stroke

• Baird TA Stroke 2003 ; 34 ; 2208 – 2214 – hyperglycemia (Blood sugar > 140
mg / dl) in 72 hours post AIS was associated with larger infarct on MRI and
worse stroke outcome

• Metanalysis of 35 control trials of 8478 pts using GKI infusion – reduced

mortality by 15%
Malmberg J AM Coll Cardiol 1995 ; 26 ; 57 – 65

• GIST – UK Trial Gray, Lancet Neurol 2007 ; 6 ; 397 – 406

Compared GKI vs NS in first 24 hours – No significant change in outcome

Recommendations (AHA/ASA/Adams et al stroke 2007)

• Correct hyperglycemia > 140 mg / dl with desired level of 80 – 140 mg / dl
during 1st 24 hours (class II A level C)
• No indication for intensive GKI infusion
 GENERAL CARE

• Bed rest – Early mobilization when considered stable

• Frequent turning or alternative pressure mattresses
• Measures to avoid falls
• Nasogastric feeding if abnormal swallow test , impaired gag
reflux, dsyphonia, cranial nerve palsy, high NIHS score, impaired
cough
• Bedside swallowing test – 60 ml liquid, watch for cough, wet
voice
• (Food trial Lancet 2005;365;755-772)
No benefit of dietary supplements, Initiation of NG feeds within
7 days or later, NG feeds vs PEG
• Recommendation (AHA/ASA/Adams et al Stroke 2007)
assessment of swallowing before starting or drinking is
recommended (new)
 DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

• Pulmonary embolism accounts for 10% deaths post stroke

• Pulmonary emboli arise from venous thrombi in paralysed limb or pelvis
• Higher risk in older, prolonged immobilization, severe stroke

PREVENTION
• Early mobilization
• Anticoagulation
i) SC Heparin or LMWH (most effective)
ii) No efficacy or safety difference in Heparin vs LMWH Counsell Cochrane
database syst review 2001;4;CD000119
iii) Low dose warfarin for long term Ridher NEJM 2003;349;2164-67
• Aspirin also helpful though less effective Antiplatelet trialists collab; BMJ 1994;
308;235-246
• External compression stockings can be used if anticoagulation is
contraindicated (Class IIa level B)
• IVC filter device if recurrant events despite anticoagulation or anticoagulation
is contraindicated
DECOMPRESSIVE HEMICRANIECTOMY AND DUROPLASTY – FOR
MALIGNANT MCA-INFARCT

Hemicraniectomy doubled the chances of survival from

29% to 78% - absolute risk reduction 48% (HS)

– Number to treat 2 to avoid 1 fatality

– 10 HC – 5 pts will escape death, at 1 yr 1 pt will have

mild disability, 1 will have moderate disability and 3 will
have moderate to severe disability
 URGENTLY TRIAGE AND SHIFT TO STROKE ICU
Aspirin ?

CT head vs multimodal MRI

IV TPA < 4.5 hour IA TPA STROKE ICU

MERCI DEVICE CARE > 4.5 hr)
(4.5 – 6 hr)
• General care
• Aspirin
• Heparin in DVT
preventive dose
• Manage complications