Cerebrovascular disorders: stroke

What is stroke? • Suddenly (acutely) developing neurological deficit of vascular origin that lasts longer than 24 hours • 80-85% ischemic

Stroke subtypes Haemorrhagic stroke~20%

Other 5%

Unknown 30%

Atherothrombotikuc stroke 20%

Cardiogen Small artery disease embolisation 20% 25%

Ischemic stroke ~ 80% Albers G et al. Chest. 2001; 119 (suppl): 300S.

Prognosis of stroke • • • •

Slight disabilities Moderate disabilities Severe disabilities Deceased Grau AJ, et al. Stroke 2001

57 % 9% 18 % 15 %

Transient ischamic attack (TIA) • Sudden onset of (any kind) focal neurological sign that disappears within 24 hours • anything (weakness, numbness, dizziness, aphasia, visual disturbance (amaurosis fugax), double vision

TIA symptoms • Sudden onset, usual duration is 5-20 min. • Carotid artery symptoms: – Ipsilateral monocular visual loss (amaurosis fugax) – Contralat. paresis, sensory loss – Aphasia, agnosia, apraxia (dominant hemisphere) – Combination of the above

TIA symptoms • Vertebrobasilar arteries: – Binocular visual loss – Vertigo, ataxia – Dysarthria, dysphagia (TGA) – diplopia

Risk after TIA 1707 TIA’s patients, 90 days follow up • 428 (25.1 %) hospital readmission (for several reasons) • 216 recurrent TIA – (12.7 %). • 44 cardiovascularis events (2.6 %)

• 45 death (2.6 %),

Clinical groups - TIA • 10% of all cerebrovasc. disorders • 10% of all stroke patients have a history of prior TIA • 1/3 of persons who had TIA will develop stroke within 5 years

EPIDEMIOLOGY of STROKE

Stroke • A leading cause of serious, long-term disability (25-50% of stroke victims remains handicapped) • 730.000 new or recurrent strokes occur per year in the US • 40.000-50 000 /year hospital admission due to stroke in Hungary (a new stroke in every 13th minute…!) • Third leading cause of death after cardiovascular diseases and cancer

Distribution of mortality in Hungary

Stroke hearth+periph.art. other 1970 1980 1990 2000 0%

20%

Józan Péter: Agyérbetegségek, 1998. 4: 2-6, KSH 2001

40%

60%

80%

100%

Stroke mortality (1970-1997) 300

Russia 250

BULGaRIA 200

PORTUGAL Hungary.

150 100

Sveden France

50

6 19 9

4 19 9

2 19 9

0 19 9

8 19 8

6 19 8

4 19 8

2 19 8

0 19 8

8 19 7

6 19 7

4 19 7

2 19 7

19 7

0

0

Józan Péter: Agyérbetegségek, 1998. 4: 2-6

Epidemiology • Season differences: more frequent in winter and in spring • Daily differences: most frequent at daybreak • Sexual differences: Men> 2x> Women (stroke rates rise rapidly in menopausa)

Autoregulation of the brain circulation CBF 100 90 80 70 60 50 40 30 20 10 0

Normal Hypertension

0

50

75 100 125 150 175 200 225 250

Tension (Hgmm)

Thrombolysis in acute ischemic stroke
In 90% of the cases occlusion of the intra/extracranial arteries can be detected
Without reperfusion the majority of the ischemic damage is irreversible
80-85%-of all strokes are ischemic

CORE

Penumbra

PENUMBRA Infarktus

H:min 0:00

0:35

2:15

2:45

3:15

3:45

4:15

5:00

5:35

6:00 hours

Intravenous (or intra-arterial) administration of thrombolytic agents can achieve recanalization and improve outcome in carefully selected patients with acute ischemic stroke

Thrombolysis • Iv. rt-PA (0.9mg/kg) with 10% of the dose in iv. bolus, followed by infusion lasting 60 min – within 3 hours of onset of ischemic stroke • Iv. administration of streptokinase is dangerous • Intra-arterial treatment of acute MCA occlusion in 6 hour time window is rec. (using prourokinase) – not registered • Acut basilar occlusion may be treated with intraarterial therapy – not registered

Before thrombolysis CT, no contrast

Before thrombolysis CT, no contrast

Before thrombolysis MRI T2

Before thrombolysis: diffusion MRI

Before thrombolysis MRI angiography

After 6 hours of thrombolysis: recanalisation

After 6 hours of thrombolysis MRI T2

After 2 days of thrombolysis CT, no contrast

How to decrease consequences of stroke Primary prevention Acut stroke treatment

Secundary prevention

Rehabilitation

Risk factors Age Stroke risk/year Age groups 0 - 14 15 - 24 25 - 34 35 - 44 45 - 54 55 - 64 65 - 74 75 - 84 85 +

1 / 30 000 1 / 10 000 1 / 9000 1 / 5000 1 / 1000 1 / 300 1 / 100 1 / 50 1 / 30

strong association with the age

Risk factors of stroke Non - modificable Age, Gender, Race, Heredity Modificable Medical Conditions Behaviors Hypertension Cardiac disease Atrial fibrillation Hyperlipidemia Diabetes mellitus Carotid stenosis

Cigarette smoking Alcohol abuse Physical inactivity

Hypertension is the most important risk factor of stroke!
Metaanalysis

of 14 large randomized controlled trial showed, that decrease of diastolic blood pressure by 5-6 Hgmm decreases the relative risk of stroke by 42%
Do not decrease the blood pressure in acute stroke! (200/100, 150/100 in hemorrhage)

Hypertonia megelızése 40 év alatt két évente vérnyom ásmér és
40 év felett évente, 50 felett f élévente vérnyomásm érés
Hypertonia esetén 140/85 Hgmm alá kell a vérnyomást beállítani az életmód módosítás ával ill. gyógyszerrel (I. szintő evidencia)


Primary prevention

Red wine from Villány …?

Primary prevention

Primary prevention

Primary prevention

Aspirin in primary stroke prevention

Recurrence of stroke Ischemic stroke First year in 5 years Myocardial infarction Vascular death

(%) 6-12 30-40 15 15

Aspirin: 300-100 mg/day

Clopidogrel

Dipiridamol plusz Aspirin

Oral anticoagulation

relative risk reduction for stroke of 60-65%, with a target international normalised ratio of 2.0-3.0

BMJ 2002;324:656

Cholesterol lowering therapy in secondary prevention of stroke

secondary prevention of stroke

Carotid endarterectomy (or stent?)

Clinical manifestations of atherothrombosis Ischaemic stroke Myocardial infarction

Transient ischaemic attack Angina: • Stabil • Instable

Peripherial vessel diseases

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.

Small artery occlusive stroke • 15-20% of thrombotic stroke • Lipohyalinosis, local arteriosclerosis of small penetrating arteries • Etiology: long standing hypertension or diabetes • Typical localisation:basal ganglia, thalamus, pons, internal capsule • Infarction are smaller than 1,5 cm in diameter • Gradual progression

Lacunar infarction

Symptoms • Pure motor paresis (internal capsule, pons) • Pure sensory deficit (thalamus, corona radiata • Dysarthria-clumsy hand (pons, internal capsule) • Ataxic hemiparesis (internal capsule) • Multiple infarction are associated with vascular dementia

Cerebral embolism • 20% of ischemic stroke • Younger patients • Acute onset, maximal severe deficit, quickly improvement • Recurrent stroke (more than one vascular territory) • Cortical infarction • Cardiac diseases in the anamnesis

Cerebral embolism Intracardial thrombus

Vegetation on the aortic valve

Etiology • Atrial fibrillation (most important risk factor of stroke in elderly women • AMI –stroke complicates 2-4%, usually in the first 4-5 weeks (mural thrombus) • ventricular aneurysm • Valve disorders • Prosthetic valve • Infective endocarditis • Intracardial tumors • Cardiac procedures (angiography, bypass, PTCA)

Hemodynamic stroke • Global reduction of the CBF • Cardiac dysfunction, hypotension, hypoxia, hypoglycemia, severe carotid artery stenosis • Multifocal ischemic lesions (cortex, anterior-posterior watershed infarction

Intracerebral hemorrhage • 10-14% of all strokes, typical age 50-70 years • Overall mortality vary between 25-60% • Etiology: history of hypertension:72-81% • The chronic hypertension is associated with fibrinoid degeneration of small arteries of the brain (Charcot-Bouchard microaneurysm)

Etiology • Vascular malformations (aneurysm, AVM, cavernous angioma) – Leading cause of stroke in younger age group (female predominance) – Typical lobar hemorrhage (temporal-frontal) – Cavernous angiomas are often located in the sub cortical white matter and in the pons – Clinical presentation: seizures (30-70%), ICH (10-30%), progressive neurological deficit (35%)

Etiology of ICH • Intracranial tumors – Less than 10% of ICH (glioblastoma, metastases)

• Bleedind disorders: hemophylia, ITP, leukemia) • Anticoagulant (10%) and fibrinolytic treatment – Slowly progressive course is typical, large volume hematomas, high mortality

• Cerebral amyloid angiopathy (selective deposition of amyloid in cerebral vessels (cortexleptomeninges) – Elderly, nonhypertensive patients, reccurent lober ICH or SAV – Association with histopathological features of Alzheimer’s disease, progressive dementia

Etiology of ICH • Granulomatosus angitis (vasculitis) – Monocular inflamation in the wall of intracranial arteries

• Hemorrhagic transformatio of cerebral infarction (cerebral embolism) • Trauma: hematoma occurs in surface of brain, often multiple • Sympathomimetic agents (amphetamines, cocain) – Subcortical white matter localisation

Clinical manifestation • Sudden onset, followed by progression • Symptomes of elevetad ICP (haedache, womiting, depressed level of consciousness • Focal neurological deficit, rarely seizures • Size of hematoma: – – – –

small:5cm - fatal

Anatomical forms of ICH • • • • • • • • •

Putaminal: 35% , mortality: 37% Caudate: 5%, mortality: 10% Thalamic: 10-15%, mortality: 30% Lobar: 25% mortality: 30% Cerebellar: 5-10% , mortality: 20% Pontin: 5%, paramedian:mortality: 80% Mesencephalic: rare Medullary: rare, mortality: 100% Intraventricular: secondary form (caudate, thalamic, putaminal, lobar), primary form: sunependymal malformation

Subarachnoid haemorrhage • Incidence: 15/100.000/year • 6-10% of all strokes • Etiology: a)intracranial aneurysm (75%), b) arteriovenosus malformation (5%) c)other • Pathogenesis: – Classification of aneurysm: morfological: 1. saccular, 2. fusiform, 3. dissecting – Size: 25 mm (giant) – Origin: congenital (90%)-arise from defects in the muscular layer of cerebral arteries?, degenerative changes? Both ? – Other origin: arteriosclerotic, septic-mycotic, traumatic, neoplastic – Location_ arterial bifurcation of the circle of Willis

Clinical symptoms of SAV • A: unruptured aneurysm: – Anterior comm. artery- visual field defects – Posterior comm. artery- oclulomotor nerv palsy – Middle cerebral artery- aphasia, hemiparesis, seizures

• B: ruptured aneurysm: – – – –

Sudden oncet headache, often extremly severe, womiting Meningeal sign Neurological deficit Depressed level of consciousness

Hunt –Hess clinical score • Grade 0: unruptured aneurysm • Grade I: asymptomatic or mild headache • Grade II: moderate or severe headache, nuchal rigidity, cranial nerve palsy • Grade III: drowsiness, mild deficit • Grade IV: stupor, moderat to severe hemiparesis, vegetative disturbances • Grade V: deep coma, decerebrate rigidity, moribund state

Potential complications of SAV • Rebleeding (10-30%) (prevention of rebleeding: endovascular occlusion of the aneurysm, as soon as possible) • Delayed ischaemia related to vasospasm 3-14 days • Cerebral oedema • Acut obstructive hydrocephalus • Delayed communicating hydrocephalus • Intracerebral, subdural haematoma