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Treatment Of Acute Ischemic Strokes Dr Sanjith Aaron Dept. of Neurology Christian Medical College, Vellore

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Page 1: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Treatment Of Acute Ischemic Strokes

Dr Sanjith Aaron

Dept. of Neurology

Christian Medical College,

Vellore

Page 2: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

1. Pathophysiology

2. Assessment

3. Treatment

Page 3: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

1. Pathophysiology

2. Assessment

3. Treatment

Page 4: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Stroke mechanisms:

1. Embolic

2. Atherosclerosis

3. Low-flow

4. Lacunar

Page 5: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine
Page 6: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Distant source – Cardiac

Artery to artery - Carotids

Embolic

Atrial Fibrillation

Rheumatic Heart Disease

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Atherosclerosis

Thrombus developing

on an atherosclerotic

plaque – Plaque

rupture

Diabetes

Hypertension

Smoking

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Low-flow /

Hemodynamic strokes

Sudden drop in blood

pressure

Watershead infarcts

•Cardiac arrhythmia

•Myocardial infarction

•B P medications

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Lacunar

Penetrating vessels

Lipohyalinosis

Atheromatous

Diabetes

Hypertension

Page 10: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

• Progression of a large Ischemic stroke

Page 11: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine
Page 12: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra Large Infarct

Within 4 - 6 hours

30000 brain cells die

per second

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1. Pathophysiology

2. Assessment -

3. Treatment

Clinical / Imaging

Page 14: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

• Level of consciousness

• Orientation

• Comprehension

• Gaze

• Visual fields

• Facial motor function

• Limbs motor function (R and L scored independently )

• Limb ataxia (cannot be tested in presence of paresis)

• Sensory function

• Language

• Articulation

• Extinction or inattention (neglect)

Clinical

NIH Stroke Scale (NIHSS)

Composed of 11 items adding up

to a total score of 0 to 42

The higher the score – the more severe

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NIH Score Good Outcome at 3 Months

The higher the stroke

severity - as measured by

the NIH Score –

The worse the outcome

Especially in the elderly

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Imaging assessment

Page 17: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

3 P s

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CORE

Penumbra

Which vessel is

occluded (Pipe)

How much brain is already

Infarcted (Parenchyma)

Is there any more tissue

at risk (Penumbra)

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CORE

How much brain is already

Infarcted (Parenchyma)

Page 20: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CT vs MRI

CT Scan – Fast

Easily available

Differentiate hemorrhage better

MRI Scan – Pick up early Ischemia (15 mts)

Posterior circulation pick up better

Page 21: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

60 Minutes into stroke – CT Vs MRI

Page 22: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Diffusion restriction

Seen within 15 minutes DWI ADC

Page 23: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Loss of the insular ribbon sign refers to a loss

of definition of the gray-white interface in the

lateral margin of the insular cortex ("insular

ribbon")

Dense MCA sign

Plain CT Scan – Hyperacute phase

Page 24: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Sulci and gyri ironed out

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ASPECTS score = < 7 predicts

1. Worse functional outcome at 3 months

2. Increased chance of symptomatic

haemorrhage.

ASPECTS score of 10 is Normal

Lower the ASPECTS – The more area damaged

Page 27: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CT - Established infarct

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CORE

Which vessel is

occluded (Pipe)

How much brain is already

Infarcted (Parenchyma)

Page 29: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

For successful treatment Vessel

imaging is essential

Page 30: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra

Which vessel is

occluded (Pipe)

How much brain is already

Infarcted (Parenchyma)

Is there any more tissue

at risk (Penumbra)

Page 31: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

MR Perfusion Study

Cerebral Blood Volume

MTT

53 yrs Male –with R

Hemiplegia - 5 hours

Page 32: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

25yrs Smoker

Wake-up stroke

Right hemiplegia

R - Neglect

Global aphasia

Large

penumbra

Page 33: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

1. Pathophysiology

2. Assessment

3. Treatment

Page 34: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Treatments available for acute

ischemic stroke

Page 35: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra

Recanalization and

restoration of cerebral

blood flow

Acute stDefinitive therapy - Reperfusion

Page 36: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra

Recanalization and

restoration of cerebral

blood flow

Intra-venous thrombolysis

rtPA (Tissue Plasminogen

activator)

Acute stDefinitive therapy - reperfusion

Page 37: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Intravenous Thrombolysis

rtPA (Tissue Plasminogen activator)

Page 38: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Which patient can benefit form this

therapy?

Onset of symptoms <4.5 hours before

beginning treatment

Page 39: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Exclusion criteria

Significant stroke / head trauma < three months

Previous intracranial hemorrhage / Symptoms

suggestive of subarachnoid hemorrhage

Intracranial neoplasm

Active internal bleeding / Acute bleeding diathesis

Anticoagulant use with an INR >1.7

Heparin within 48 hours with elevated aPTT

Current stroke already involving >33 % MCA

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Relative exclusion criteria

Major surgery or trauma in the previous 14 days

Gastrointestinal or urinary tract bleeding in the

previous 21 days

Pregnancy / Recent MI (<3 Months) Complicated by

pericardititis

Consider IA / Mechanical devices if available

Page 41: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

0

1

2

3

4

5

6

7

8

50 60 70 80 90 100 110 120 130 140 150 160 170 180

Minutes from Stroke Onset to Start of Treatment

Od

ds R

ati

o f

or

Fa

vo

rab

le

Ou

tco

me a

t 3 M

on

ths

Relationship of Time to Thrombolyse and

Odds Ratio of Favorable Outcome

Benefit for rt-PA

No Benefit for rt-PA

Tpa can be given up to 4.5 hours

Page 42: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Needle Time NNT

(In minutes)

0 to 90 4.5

91 to 180 9

181 to 270 14

271 to 360 21.4

Lancet. 2010;375(9727):1695

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Sonothrombolysis

Page 44: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Ultrasound enhanced

thrombolysis

(Sonothrombolysis )

Page 45: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Sonothrombolysis – 42 Male .Needle time 4 Hours

Page 46: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Drawbacks of IV thrombolysis

Page 47: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

73%

30 - 40% 14%

Stroke. 1995;26(4):581.

Recanalization rates

at 8 and 24 hours after

thrombolysis

Site of occlusion

Page 48: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Contraindications for IV Tpa

• Patient on anticoagulation

• Pregnancy

• Post surgery

• Patient presenting beyond window period

of 4.5 hours – having a salvageable

penumbra

Page 49: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

31 year old lady

8 months pregant

Known Rheumatic heart disease

Mitral Stenosis – on Warfarin

L Hemiplegia –

Time of onset -- 4 hours( not very certain)

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Potential

infarct area

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• Pregnancy

Tpa -relatively contraindicated

• Patient on warfarin

INR awaited

• Time of onset not very clear

IV Tpa window 4.5 hrs

• Proximal M1occlusion

IV Tpa 15 – 20% chance

Page 52: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Mechanical thrombectomy

--- The PENUMBRA Suction device

Page 53: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine
Page 54: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Angio –

MCA (M1) Cut off PENUMBRA suction

device catheter

Page 55: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Mechanical thrombectomy

Pre Post

Page 56: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Other Mechanical thrombectomy devices

Solitaire device

Merci

Page 57: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Solitaire™ FR Revascularization Device

Page 58: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Five multicenter open-label randomized controlled trials

•MR CLEAN

•ESCAPE

•SWIFT PRIME

•EXTEND-IA

•REVASCAT

Second-generation mechanical thrombectomy devices is superior to standard IV Tpa. – in strokes caused by a proven large artery occlusion in the proximal anterior circulation

Page 59: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

2015 American Heart Association/American

Stroke Association Focused Update of the 2013

Guidelines for the Early Management of Patients

With Acute Ischemic Stroke -- Regarding

Endovascular Treatment

Page 60: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra

Recanalization and

restoration of cerebral

blood flow

Collateral flow –Maintain/

Augmentation

For thrombolysis

Systolic < 185 mmHg

Diastolic < 110 mmHg

If no thrombolysis

Diastolic <120mmHg

Systolic < 220mmHg

Never

reduce BP

abruptly

Page 61: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

60 yr male –

Chronic smoker /diabetic

Newly diagnosed

hypertension – treated by a

GP - Ampodipine 5mg BD

R – Hemiparesis.

Recovered

Made to walk on 3rd day

Recurrence of weakness

Page 62: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

CORE

Penumbra

Recanalization and

restoration of cerebral

blood flow

Collateral flow –Maintain/

Augmentation

Neuroprotection

Page 63: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Citicoline

Cytidyl diphosphocholine

Edaravone

Free Radical Scavenger

Cerebrolysin® peptide that stimulates

neurotrophic regulation

Page 64: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Surgical intervention

Page 65: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

16h

Can treat with 3% Saline / Mannitol

Keep the neurosurgeon informed

No Aspirin / Clopodigrel / Warfarin / Heparin

Page 66: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

16h 24h

Page 67: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

48h:

hemicraniectomy

16h 24h

Page 68: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

48h:

hemicraniectomy

16h

Cranioplasty after 4

months

24h

Page 69: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Early secondary preventive measures

Page 70: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

Antiplatlet agents

Single antiplatlet Double antiplatlet

agents Aspirin

Clopidogrel

Cilazitazole

Dipyridamole

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Anticoagulants : Warafarin /Acitrom

Newer oral anticoagulants ?

Cardiac Emboli

Carotid atherothrombus

Intracranial thrombus

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Carotid disease Symptomatic Stenosis - 70 to 99 %

1. Recent

2. Nondisabling ischemic stroke

3. Life expectancy of at least five

years

Carotidendarterectomy (CEA)

Preferred over stenting)

Medical Rx High dose statins

Double antiplatlets

>70% stenosis Maximum benefit if CEA done < 2 weeks

50 -69% stenosis : benefit only if CEA done < 2 weeks

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Acute Stroke

Important medical emergency

Brain Stroke = Brain Attack (Heart Attack)

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??

Thank You

Page 75: Treatment Of Acute Ischemic Strokes - cmcmac.in CME pdfs/DR SANJITHMEDICINE CME 2106.pdf · Tpa -relatively contraindicated •Patient on warfarin ... Citicoline Cytidyl diphosphocholine

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