Acute stroke treatment

Tim Harrington

Important conceptsAll time loss/wastage results in further neuronal loss/poorer outcome

The rate at which neuronal loss occurs is highly variable

variations in COW and pial collaterals

Penumbra- injured but resurrectable brain

Patient selection is critical and is still controversial

CTP not reliable, MRP not readily available

IV and IA have differing strengths and weaknesses

Variability and reversibility of focal cerebral ischaemia in unanesthetized monkeys

Cromwell RM et alStroke lab, Uni of MassachusettsNeurology October 198131(10):1295-1302

‘neurologic improvement was common after the release of occlusion. …frequent with 30-min and 4-hour occlusions

…was observed even after 16 hours’

CONCEPTS

INFARCT CORE

ISCHAEMIC PENUMBRA

concepts

Core of irreversible injury

Penumbra sustained by peripheral collaterals: potentially salvageable with prompt institution of appropriate therapy

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Aims

Recannalisation

Minimal delay

Minimal Cx- nb sICH

Optimise physiological parameters to minimise cerebral compromise

What do we know?

Most of morbidity and mortality comes from large vessel occlusions -46% of stroke involve large vessel occlusions and these have a poor prognosis (eg Basilar or ICA occlusion have 4.5 fold ↑ risk of death and 3 fold ↓risk of good outcome)-Smith WS et al Stroke 2009

Recanalisation associated with good outcome- 58 vs 25% Rha Stroke 2007

Higher rates of recanalisation with arterial embolectomy than IV tPA especially in the vessels that IV tPA is ineffective

Neuronal loss

32,000 neurones/min Average

Individual rates are highly variable and depend mainly on

quality/quantity of pial and other collateral

other drivers of perfusion such as BP

Time

A protocol that allows up to 4.5hrs does not mean that much time should be used up

Procedural time is often one of the least important delays in achieving recannalisation

TimeA successful acute stroke program will address delays throughout the treatment pathway

Public information re nature of stroke and urgency

Ambulance diversion to stroke centres

Rapid triage and informing of relevant teams

Imaging urgency

Parallel arrangement of consent, ICU, aneasthetics, bloods whilst waiting for other steps

IV Thrombolysis

Almost 20yrs old and still only <20% being treated in western countries- bolus + 1hr infusion

Only requires NCCT for triage

many contraindications- mainly re bleeding risk

not effective in large vessels

newer agents more fibrin specific eg Tenectoplase

Advanced imaging hoping to improve pt selection

IV Thrombolysis38% good outcome in NINDS in strokes selected for small size by clinical stroke score

recannalisation <10% in ICA, <25% in M1

Approx 9% sICH

Tenectoplase- ↑recannalisation, ↑neurological improvement Parsons et al

rtPA approved to 4.5hrs

Patient selection

Time is a poor surrogate for knowing an individual’s pathophysiology

Assessing ‘penumbra’

CTA and CTP whilst not having full validation proving to be useful tools and readily available- adds about 15min to NCCT

NECT

Haemorrhage

Cytotoxic oedema

Dense MCA sign

Lentiform nucleus

Insular stripe

Hyperdense MCA

MRI

DWI measures “water motion”

Ischaemia: normal cellular ion pumps (eg Na-K) fail

Shift of water from extracellular to intracellular space

Cytotoxic oedema

Restricted diffusion

CT perfusion

Can be used to measure perfusion parameters

CBV

CBF

MTT

cerebral blood volume

Volume of blood per unit of brain tissue

4-5mL/100g

cerebral blood flow

Blood flow per unit of brain tissue per minute

50-60mL/100g/min

MEAN TRANSIT TIME

Time difference between arterial inflow and venous outflow

CEREBRAL ISCHAEMIA

Decreased CBF

Cerebral autoregulation

Capillary dilatation

CAPILLARY DILATATION

Increased CBV

Increased MTT

CRITICAL CBF LOSS

Normally 20%

Failure of autoregulation

Reduction in CBV

Reduction in CBF

Imaging the core

MRI DWI

Visible hypo-attenuation of NECT rarely reverses

CBV abnormality on Perfusion

IMAGING THE PENUMBRA

Increased MTT

Normal CBV

CTA

Site of occlusion

length of occlusion

Tandem lesions- ICA source of embolus

Access issues

Level & Access

Level & Access

Imaging Core

CBV or DWI

Poor chance of good outcome if >25ml

Almost no chance of good outcome if >70ml

Severe perfusion changes predicts ICH TTP >14sec

Poor collateral/CTP 2hrs

Poor collaterals/CTP

Poor collaterals/CTP

Good collaterals/CTP at 8hrs

Good collaterals/CTP at 8hrs

Good collaterals/CTP

IA therapy/embolectomy

Stentriever- Solitaire, Trevo, others

Direct aspiration- Penumbra

Combination of above

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What do we know?iv tPA fails to recannalise in most

large vessel occlusions-25% success in M1,10% for ICA

Most patients do not receive iv tPA- at best 20% - time and other exclusions

Imaging can select gps with salvageable brain beyond 3-4.5hr time window Abou-Chebl A Stroke 2010

Efficacy?

Recannalisation rates of 80-90%

Average times to recann. of 40min

Frequent single pass recann-average no of passes 1.8

Outcomes

Miteff F- mRS≤2 in 56% ant circ’n 16pts

Galimanis A et al-623 pts prospective-48.9%

Soize S et al-36pts prospective- 63.9%

STAR- prospective registry multinational -58%

83yo female

SUDDEN COLLAPSE

DYSPHASIA

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Blood volume

Mean transit time

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PROCEDURE TIME: 15 MIN

SINGLE PASS

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IV vs IA

IMS 111 failed but wrong devices used with unacceptable delays

Randomised trials in US , Europe and Aus

Evolving Protocol

Clinical then CT work-up

NCCT,CTA,CTP

IV rTPA in those suitable

Endovascular immediately in those with large vessel occlusion

Treatment selectionIV tPA has limit on size of vessel/thrombus it can dissolve

longer than 8mm embolus has 0 recann

should have occurred within 1hr of injection

Quick and no skill in delivery, can be used after limited imaging( NCCT as per NINDS)

‘drip and ship’ model

Treatment selectionArterial treatment restricted to large vessels

ICA, M1/2,Basilar

these are most morbid strokes

Technical issues/skill important

access difficult in elderly- ?restrict to <80yrs

Not interfered with by prior tPA and not limited by tPA limitations

Treatment synergyIV and IA are not really the competitors they are made out to be

Interested in different vessels

Extend IA- IV vs IV plus IA, similar UK/European studies

IMS 111- poor devices and prolonged delays in IA Rx

Treatment selectionIV thrombolysis- rTPA, tenectoplase

IA

stentriever

aspiration

IA thrombolysis

Thank You