Dr André Peeters Service de Neurologie 1200 BRUXELLES · Acute ischemic stroke thrombolysis...

Acute ischemic stroke

thrombolysis outside

the license

Dr André

PeetersService de NeurologieCliniques Universitaires Saint-Luc / U.C.L.1200 BRUXELLES

Patient JG (♀

86

)

• Medical

history

– AHT, R/ , Emconcor

2.5 mg, Lasix

40 mg

– AF paroxystic

R/ Apocard

150 mg (refuses OAC)

– basocellular

carcinoma, surgery

D-3

• Actual

condition

– 09:30 left

hemiparesis

– 11:12 admission : NIHSS 6

• Ancillary

tests

– INR: 0.90, platelets

232.000

– MRI: exclusion ICH, occlusion R ACM, DWI/PWI mismatch

Contra-indications:

Situations

with

a high risk of haemorrhage

such

as:known

haemorrhagic

diathesis; concomitant oral

anticoagulants; manifest

or

recent severe

or

dangerous

bleeding; known

history

of or

suspectedintracranial

haemorrhage; suspected

subarachnoid

haemorrhage

or

condition

after

subarachnoid

haemorrhage

from

aneurysm; history

of CNSdamage; within

10 days

of traumatic external

heart

massage, obstetrical

delivery, recent puncture

of a non-compressible

blood-vessel; severeuncontrolled

arterial

hypertension; bacterial

endocarditis, pericarditis;

acute pancreatitis; documented

ulcerative

gastrointestinal

disease

duringthe last 3 months, oesophageal

varices, arterial

aneurysms, arterial/venous

malformations; neoplasm

with

increased

bleeding

risk; severe

liverdisease, including

hepatic

failure, cirrhosis, portal hypertension

and active

hepatitis; major surgery

or

significant trauma in past 3 months; symptomonset

more than

3 hours

or

unknown; minor neurological

deficit

or

symptoms

rapidly

improving

before

infusion

start; severe

stroke;seizure

at onset

of stroke; evidence

of ICH on

CT-scan; symptoms

of subarachnoid

haemorrhage; heparin

within

previous

48 hours

and elevated

thromboplastintime; history

of stroke

and concomitant diabetes; prior stroke

within

last 3

months; platelet

count

<100,000/mm3; systolic

blood

pressure

>185 or

diastolic>110 mmHg, or

aggressive

management necessary

to reduce

BP to these limits;

blood

glucose <50 or

>400mg/dL; for

age

18–80 years

only.

IV Thrombolysis : off-label

• Recent

(major) surgery

– relative small

or low

risk

procedure

– accessible site

– amenable

to conservative R of bleeding

complications

Stroke 2007;38:2612-2618


• Mild

or rapidly

improving

symptoms

– substantial

number

have poor

outcomes

– mild

symptoms

can

be

very

disabling

– observational

studies: IVT associated

with

good outcome

Stroke 2007;38:2612-2618

Patient JG (♀

86

)

• IV thrombolysis

at

12:30 (DNT: 78 min)

• Evolution

– 13:30 NIHSS 3

– Frontal hematoma

– D5 leaves

the hospital, NIHSS 0

– Outpatient

clinic

after

6 weeks

• hematoma

entirely

recovered

• R/ dabigatran

2 x 100 mg


• > 80 years

– Stroke 2000;31:370-375

– Neurology

2005;65:1795-1798

– J Neurol

Neurosurg

Psychiatry

2006;77:375-377

– J Neurol

Neurosurg

Psychiatry

2007;78:690-693

– Cerebrovasc

Dis. 2008;25:129-135

– Stroke 2010;41:1833-1835

– K Lees (Vista)

Stroke 2010, 41:2840-2848


• > 80 years

– no increased

risk

of symptomatic

intracranial

hemorrhage

– chance of favorable outcome

at

3 months

is

50 % less

– in-hospital

†

D7 : 13 % (80 plus) versus 11 % (< 80)

Derex L, Nighoghossian N. Nat Rev Neurol 2009;5:506Uyttenboogaart M et al. Age Ageing 2007;36:577


• Prospective studies

in > 80 years

– IST-3 (presented

at

ESC Lisbon

22-25 May 2012)

• Inclusion < 6 h

• 1617/3035 patients aged

> 80 years

– TESPI (Thrombolysis

in Elderly

Stroke Patients in Italy)


• > 80 years, –

with

↑

age, ↑

risk

of dementia

& microbleeds

• National Inpatient

Sample

Database

–

35.557 patients, 207 with

dementia

received

IVT–

no increased

risk

of ICH or death

• «

Add

life to years

> add

years

to life

»

Neurology 2011;76:1575–1580

Contra-indications:

Situations

with


such

as:known

haemorrhagic



or

recent severe

or

dangerous

bleeding; known

history

of or



subarachnoid

haemorrhage

or

condition

after

subarachnoid

haemorrhage

from

aneurysm; history


10 days


heart





arterial




ulcerative

gastrointestinal

disease


varices, arterial



with

increased

bleeding

risk; severe


hepatic


and active


or


more than

3 hours

or


deficit or

symptoms

rapidly

improving

before

infusion

start; severe

stroke;seizure

at onset

of stroke; evidence

of ICH on

CT-scan; symptoms

of subarachnoid


within

previous

48 hours

and elevated


of stroke


within

last 3

months; platelet

count


blood

pressure

>185 or


aggressive


to reduce

BP to these limits;

blood

glucose <50 or

>400mg/dL; for

age

18–80 years

only.

IV thrombolysis

Lancet 2004;363:768-74

> 4,5 tim> 4,5 timNNT 3

NNT 7

NNT 14

off-label !


• Wake-up

stroke

–

about 25% AIS awaken

with

their

deficits–

stroke onset

defined

as last-seen-normal time

–

early

morning

peak

occurrence AIS •

CT

• MRI (PRE-FLAIR)

–

retrospective

study

thrombolysis

in WUS patients •

Treated

WUS (n=46) outcome

> non-treated

WUS (n=34)

and similar

to < 3h-treated

patients

Stroke 2009;40;827-832

PRE-FLAIR

Lancet Neurol 2011; 10: 978–86

PRE-FLAIR

Lancet Neurol 2011; 10: 978–86

moderate sensitivity

(62%) but

good

specificity

(78%) in the identification

of patients

in the < 4.5 h window

«

Selecting

patients by tissue-window

rather

than

by time window

»

Contra-indications:

Situations

with


such

as:known

haemorrhagic



or

recent severe

or

dangerous

bleeding; known

history

of or



subarachnoid

haemorrhage

or

condition

after

subarachnoid

haemorrhage

from

aneurysm; history


10 days


heart





arterial




ulcerative

gastrointestinal

disease


varices, arterial



with

increased

bleeding

risk; severe


hepatic


and active


or


more than

3 hours

or


deficit or

symptoms

rapidly

improving

before

infusion

start; severe

stroke;seizure

at onset

of stroke; evidence

of ICH on

CT-scan; symptoms

of subarachnoid


within

previous

48 hours

and elevated


of stroke


within

last 3

months; platelet

count


blood

pressure

>185 or


aggressive


to reduce

BP to these limits;

blood

glucose <50 or

>400mg/dL; for

age

18–80 years

only.

IV Thrombolysis: BP & INR

• Usefulness

BP count before

IVT (Stroke. 2007;38:1639-1640)

– unsuspected

platelet

count 100 000 was

found

in 0.3%

• Usefulness

clotting

test < IVT

(Neurology 2009;73;1957-1962)

– Unsuspected

coagulopathy

was

found

in 0.4 %

– Coagucheck


• Use of oral anticoagulants

– INR < 1.7

– 7 studies

with

3631 patients -

6.6% on warfarin

• risk

of symptomatic

ICH is

increased

• no difference

in mortality

or functional

outcome

Int Stroke J 2011;6:568

Patient GD (1)

• Medical

history

– AF, R/ Sintrom, Lanoxin, Emconcor

– TIA 08/2006

– AIS 12/2006, R/ IA thrombolysis (20 mg rt-PA)

• Actual

condition

– 15:15 loss

of consciousness

– 15:35 admission : conscious, GCS 14/15, no motor

deficit

– 16:20 mydriasis

R, anarthria, hemiplegia

L, NIHSS 18

• Ancillary

tests

– INR: 2.25

– Brain

CT

Patient GD (2)

• Evolution (24 H)–

GCS 4 → 14/15, recovers

L hemiplegia

and R mydriasis

– Oculomotor

palsy

and ataxia

• Evolution (3M)–

Oculomotor

palsy, mRS

2

Contra-indications:

Situations

with


such

as:known

haemorrhagic



or

recent severe

or

dangerous

bleeding; known

history

of or



subarachnoid

haemorrhage

or

condition

after

subarachnoid

haemorrhage

from

aneurysm; history


10 days


heart





arterial




ulcerative

gastrointestinal

disease


varices, arterial



with

increased

bleeding

risk; severe


hepatic


and active


or


more than

3 hours

or


deficit or

symptoms

rapidly

improving

before

infusion

start; severe

stroke;seizure

at onset

of stroke; evidence

of ICH on

CT-scan; symptoms

of subarachnoid


within

previous

48 hours

and elevated


of stroke


within

last 3

months; platelet

count


blood

pressure

>185 or


aggressive


to reduce

BP to these limits;

blood

glucose <50 or

>400mg/dL; for

age

18–80 years

only.


• Prior stroke and diabetes

–

SITS-ISTR and VISTA (prospective)

–

29,500 patients •

5,411 (18.5%) had

DM

• 5,019 had

prior

stroke (17.1%)

• 1,141 (5.5%) had

both

–

Outcomes

from

thrombolysis

are better

than

the controls among

patients with

DM, prior

stroke, or both

Neurology 2011;77:1866–1872

IV Thrombolysis : off-label•

Early

infarct

signs

> 1/3 MCA territory

– IST-3 (presented

at

ESC Lisbon

22-25 May 2012)

JAMA. 2001;286:2830-2838


• Seizure

– exclusion criterion

in RCT (postictal

Todd’s

paralysis

= stroke mimic)

– however, if AIS is

confirmed, these

patients can

be

thrombolysed

Stroke 2007;38:2612-2618


• Cervical artery

dissection

– 180 patients (14 retrospective

series

/ 22 case reports)*

• safety

& outcome

similar

to non-CAD

– 16 ICAD / 625 IVT

• outcome

less

favorable ?**

– ↑

re-occlusion rates in tandem-occlusion

* Stroke. 2011;42:2515-2520

** Int J Stroke 2012;7:7-13

Stroke 2007;38;2270-2274


• Intracranial

aneurysm

(and arteriovenous malformation)

– Is this

aneurysm

an incidental

finding? (AIS not due to vasospasm)

• Yes

consider

IVT

• No consider

thrombectomy

Stroke 2007;38:2612-2618


• Intracranial

aneurysm

(and arteriovenous malformation)

– Brain

imaging

is

ment to exclude

ICH/SAH > to show AIS (EIS)

• subtle

SAH, cortical CVT, traumatic

lesions

(fall

due to stroke)

Stroke 2007;38:2612-2618

AJNR 2010;31:1355– 62


• Recent

myocardial

infarction

?

• Cardiac

thrombus ?

Stroke 2007;38:2612-2618

IVT off-label : conclusions

1. More experience

in off-label use of IVT

2. In relatively

safe

situations: informed

consent → IVT

3. In relatively

high

risk

situations: informed

consent → IAT

Acknowledgements: J De Keyser 10th Symposium BSC 12 Dec 2011

Dr André Peeters Service de Neurologie 1200 BRUXELLES · Acute ischemic stroke thrombolysis...

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