Acute Stroke Prognosis

November 24th, 2016

Plasticity after Stroke

Lemanic Symposium on Clinical Neurosciences

Centre

Cérébrovasculaire

Patrik Michel, MD, Associate Professor

Head, Stroke Center

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Prognosis isn’t easy :

Nov. 9th 2016 : « Triumph for Trump »

« Clinton has 87% chance of winning »

Nov. 2nd 2016:

Stroke : historic controversy Vascular Neurological

« ... the acute phase

and aetiology are clearly

vascular »

(WHO ICD-11 task force)

« The medical rationale for

stroke being a disease of the

brain is overwhelming »

(World Stroke Organisation and

World Federation of Neurology)

Stroke : historic controversy - 1

4

Vascular Neurological

prognosis

What is stroke ? Acute focal brain ischemia, usually from thrombosis

& clots occluding cerebral or cervical arties

Core

Penumbra

Ischemic stroke : pathogenesis & recovery

Hypoperfusion

Reperfusion

Hyperperfusion

Preexisting

microvascular

disease

Chro

nic

S

ubacute

A

cute

P

re-s

troke

P. Michel, Lausanne

Recanalisation

Obstruction, clot

Collaterals /vasodil.

Atherosclerotic /

hematological /

cardiac disease

Venous outflow

Thrombogenesis / clot formation

Vascular remodelling

Preexisting

lesions and

atrophy

Infarct lesion

Atrophy

Swelling/mass

Haemorrhage

Neuroplasticity & neuronal regrowth

Exictotoxicity

Depolarization

Endog. neuroprotect.

Edema, inflammation

Necrosis/apoptosis

Preexisting

microscopic

damage

Preconditioning

Early infarct

Penumbra

Gliosis

Temperature, metabolics, other organs. Systemic circulation, blood pressure, genetics & proteomics

Macrocirculation Microcirculation Neuron & Glia Macro-brain

Stroke recurrences, other brain & body disease, environment

Age, baseline structure & function, social integration

Exemple: your neighbour, 66y In good health

Treated hypertension

Since 1 hour, acute aphasia, moderate right

sensory-motor deficit, right visual field

decreased

Arrives at 1h20min. In the emergency room

Moderate stroke severity (NIHS Score = 11)

Glucose and labs: ok

CT-based imaging :

What is her likelihood of being

disabled in 3 months, assuming state-

of-the-art stroke care ?

2669562

Stroke prognosis : Controversy - 2 How to measure it ?

« Consensus »: modified Rankin score (mRs) at 3-12m

Rankin Scott Med J 1957

Death (Rankin score 6)

No handicap (Rankin 0-1)

Minor handicap (Rankin 2)

Moderate handicap (Rankin 3-4)

Bedridden (Rankin 5)

Rankin score use for outcome How to measure it ?

Dichotomization 0 1 2 3 4 5 6

« Favorable » « Unfavourable »

0 1 2 3 4 5 6 Shift-analysis

Severity adjusted: Adams CVD 2004. Shift: Saver Arch Neurol 2004

Rankin score 3 months after ischemic stroke CHUV 1/2003-6/2015, n = 3’653

Source: P. Michel & A. Eskandari; 2.2% missing data

0%

10%

20%

30%

40%

1 2 3 4 5 6

39%

20%

13% 9%

4%

15%

0 -

Stroke prognosis : Controversy - 3 What parameters should be measured ?

Epidemiological Radiological

• Age

• Sex

• Handicap

prestroke

• Comorbidities

• Risk factors

Clinical Genetics

Chro

nic

S

ubacute

A

cute

P

re-s

troke

• Severity

• Conscious-

ness

• Stroke

cause

• Delays

• Early stroke

core

• Penumbra

• Arterial

occlusions

• Collaterals

• Chronic

lesions

• Thrombosis

• BBB

• Neurons, glia

• Cytotoxics

• Inflammation

• Endogenous

neuroprotection

• Neuroplasticity

Stroke prognosis : Controversy - 3 What parameters should be measured ?

Epidemiological Radiological

• Age

• Sex

• Handicap

prestroke

• Comorbidities

• Risk factors

Clinical Genetics

Chro

nic

S

ubacute

A

cute

P

re-s

troke

• Severity

• Conscious-

ness

• Stroke

cause

• Delays

• Early stroke

core

• Penumbra

• Arterial

occlusions

• Collaterals

• Chronic

lesions

• Thrombosis

• BBB

• Neurons, glia

• Cytotoxics

• Inflammation

• Endogenous

neuroprotection

• Neuroplasticity

1. Epidemiological prognosis Poorer outcome (with or without treatment) if ...

Higher age

Significant pre-stroke handicap

Comorbidities / risk factors

Cardiac disease

Renal failure

Cancer

Diabetes/high admission sugar

Ntaios Neurology 2012; Saposnik Circulation 2011

2. Clinical prognosis Poorer outcome (with or without treatment) if ...

High clinical stroke severity

Especially if no rapid initial recovery

Decreased level of consciousness

Stroke cause

Other than small vessel stroke

Undetermined / rare causes

Delays

Later hospital arrival

Unknown onset (?)

Ntaios Neurology 2012; Saposnik Circulation 2011

3. Radiological prognosis Poorer outcome

(with or without treatment) if ... CBS: Puetz IJS 2008

ASPECTS: Barber Lancet 2000; Puetz Int J Stroke 2009

Clots & outcome: Medlin Stroke 2014; Rotzinger AJNR 2017

Core/penumbra: Zhu Stroke 2013;

TRAIT: Warach Stroke 2016

Large « core » = large irreversible damage

Large penumbra (=salvageable tissue) ?

(Extensive) occlusions in cerebral

arteries

Few collaterals

Rapid and complete recanalisation Dots =

symptomatic

occlusions

Large penumbra = good or bad ? 38 y women, mechanical valve

1. Left stroke: Imaging at 9h

Penumbra=green

Not treated

2. Right stroke 6 months later Imaging at 12h

Clot retrieval

Dr A.Uske * Zhu Stroke 2013

Large penumbra = good or bad ? 38 y women, mechanical valve

1. Left stroke: Imaging at 9h

Penumbra=green

Not treated

2. Right stroke 6 months later Imaging at 12h

Clot retrieval

Dr A.Uske

« Penumbra is a double – edged sword * »

Saving the penumbra is probably the

best neuroprotection

* Zhu Stroke 2013

4. Genetic prognosis Poorer outcome (with or without treatment) if ...

Largely unknown :

Thrombosis markers (?)

BBB (?)

Neurons, glia (?)

Cytotoxics (?)

Inflammation (?)

Endogenous neuroprotection (?)

Neuroplasticity (?)

Lindgren Stroke 2016

5. Treatment and prognosis Better outcome if ...

Stroke unit admission

Acute aspirin

~ 3.5 Full package

Aspirin : Sandercock Cochrane 2005; Stroke Units: Cochrane Langhorne Stroke 2014;

IV rtPA: Emberson Lancet 2014; EVT: HERMES/Goyal Lancet 2016

1.0 2 0.5

Odds Ratio

No added Rx Added Rx

1.26 (1.11-1.47)

0.94 (1.01-1.10)

0-3h i.v. rtPA

Thrombectomy

if proximal occlusion

1.68 (1.24-2.26)

2.71 (2.07-3.55)

Prognosis: which variables to use ?

Clinical

Epidemio-

logical

Radiology

Laboratory Treatment

Genetics

In general, use easily available variables

with high yield

and independence of each other

Prognosis of acute ischemic stroke iSCORE for one year mortality after AIS (11 items)

Age years

Male 5

Severity (Canadian Neurological Scale) 0

≤ 4

5-7

≥ 8

70

40

25

0

Stroke type : non-lacunar

Undetermined

15

20

Risk factor: Atrial fibrillation

Congestive heart failure

5

10

Smoker or previous MI 5

Comorbidities : Cancer

Renal dialysis

15

40

Prestroke dependence (handicap) 20

Admission glucose ≥7.5 mmol/L (≥135 mg/dL) 10

Saposnik, Circulation 2011

Prognosis of acute ischemic stroke ASTRAL-score

Age : for every 5 years 1 Severity : for every NIHSS point 1

Time : onset to door > 3 hours 2 Range of visual field defect 2 Acute glucose >7.3mmol/l or <3.7 mmol/l 1 Level of consciousness decreased 3

Using readily available information in the emergency room

in previously independent patients

AUC 0.85 in derivation cohort (Lausanne, N=1’968)

Ntaios et al, Neurology 2012

Exemple: your neighbour, 66 years ASTRAL-score

Age : for every 5 years 1 13 Severity : for every NIHSS point 1 11

Time : onset to door > 3 hours 2 0 Range of visual field defect 2 2 Acute glucose >7.3mmol/l or <3.7 mmol/l 1 0 Level of consciousness decreased 3 0

Using readily available information in the emergency room

in previously independent patients

Example your neighbour : score of 26

Ntaios et al, Neurology 2012

Exemple: your neighbour, 66 years ASTRAL - score of 26

100%

80%

60%

40%

20%

0% Pro

b. of

unfa

vora

ble

outc

om

e

0 5 10 15 20 25 30 35 40 45 50 55

Examples: probability

of unfavorable outcome

Score 23 20%

Score 31 50%

Score 38 80%

Ntaios et al, Neurology 2012

Example your neighbour :

28% chance of dependency or death at 3 months

ASTRAL prognostic score validation

25

External validation :

Athens & Vienna (N=2’312, AUC 0.90)

European (thrombolysed) (N=36’131, AUC 0.79)

China (N= 3’755, AUC 0.82)

Ntaios et al, Neurology 2012; Chinese: Liu Stroke 2013;

5 year Athens: Papavasileiou Stroke 2013. Thrombolysis: Cooray/SITS Stroke 2016

Scores vs physicians: Ntaios Eur J Neurol 2016

Scores do better than doctors :

Major disability correctly predicted

Physicians in 57%

Score: 86%

Prognostication in acute stroke is easier .....

... if you know

where the patient comes from

where he/she is now,

and in which direction he/she goes.

Admission 6 hours 24 hours 7 days

NIH

S

S

41 40

38 37 36 35 34 33 32 31 30 29 28 27 26 25 24 23 22 21 20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0

42

39

Further course of stroke severity predicts outcome N=3’443 consecutive AIS patients

ATRAL 1/2003 – 6/2014. Graphic: Ivo Meyer, CHUV Worsening: Ntaios NeurocritCare2013; Improvement: Cuendet, in prepartion

Stroke recurrences over 12 months Depend on vascular disease, stroke mechanism etc.

--Lacunar --Unknown

--Multiple

--Cardiac --Atheroslerosis

--Dissection --Rare

0 50 100 150 200 250 300 350

0.9

00.9

20.9

40.9

60.9

81.0

0

Association of Stroke Recurrence with Stroke Mechanism

Time

Surv

ival

Atherosclerosis

Cardiac

Lacunar

Dissection

Unknown

Other

Multiple

Zachariadis et al, in preparation

Prognosis for stroke recurrences

Recurrence Score (12m)

History of cerebrovascular events 1

Antiplatelet pretreatment 1

Stroke mechanism

Small vessel disease 0

Cardiac/athersclerotic/multiple causes/dissection 1

Other determined / rare 3

No early ischemic changes on acute CT 1

Chronic infarct(s) on imaging 1

Active cancer 2

* ischemic, haemorrhagic, retina

Zachariadis et al, in preparation

Stroke : historic controversy

30

Vascular Neurological

Lemanic Symposium on Clinical Neurosciences

Acute stroke prognosis Summary

Predictors to be used :

Vascular and neurological

From the patient’s past, present and future

Prognosis is quite reliable, better with scores

Major lack of gentic/proteomic predictors,

including neuroplasticity

(Acute) stroke treatment makes a (huge)

difference ....

www.attaquecerebrale.ch (avi)

Suspicion of acute stroke ? Swiss campaign for early recognition of stroke and TIA

Prognosis of intracerebral haemorrhage FUNC-score on admission

ICH-volume (cm3) <30 4

30-60 2

60 0

Age <70 2

70-79 1

≥80 0

Location Lobar 2

Deep 1

Infratentorial 0

GCS admission ≥9 2

<9 0

Pre-ICH cognitive

impairment No 1

Yes 0

Rost Stroke 2008

Similar: « ICH-score »: Hemphill Stroke 2001; Cheung Stroke 2003

0-11 points

Combined

clinical and

radiological

information