6: Stroke

Question 1

Stroke

Answer 1

• 70% Ischaemic: not enough blood
• 30% hemorhagic (intracerebral/subarachnoidal bleeding)

Question 2

Stroke mimics

Answer 2

• TIA ( Transient Ischaemic Attack) -> precursor before real stroke
• Seizure (takes longer)
• Migraine

Question 3

TIA; Transitoric ischemic attack:

Answer 3

• Neurological deficit < 24h long
• No tissue loss on MRI
-> Risk of stroke after TIA bigger

Question 4

Warning sign for a stroke: ABCD2 Scheme

Answer 4

• Age: > 60 y 1, < 60 y 0
• Blood pressure: syst. >140 or diast. >90 mmHg 1, otherwise 0
• Clinic: Hemiparesis 2, Aphasia/Dysarthria without paresis 1
• Duration: => 60 min 2, 10-59 min 1, < 10 min 0
• Diabetes: yes 1, no 0

Question 5

Symptoms

Answer 5

– B – Balance: Vertigo, gait problems
– E – Eyes: visual defect (typical: homonymous hemianopia)
– F – Face: central facial palsy
– A – Arm: arm paresis / numbness
– S – Speech: Language,speech problem
– T – Time: acute onset
CAVE: Ischemia and hemorhage cannot be differentiated based on clinical picture

Question 6

Epidemiology

Answer 6

– Incidence: 16’000 new strokes per year in CH
- 15Mio / year
– 50% of patients remain disabled
– Prevalence: World-wide (2019) 101.5 Mio
– Chronic stroke twice as frequent as cardiac insufficiency
– Mortality: second most frequent cause of death world-wide (1/3 dies)

Question 7

Pathophysiology & imaging

Answer 7

• occlusion
• reduced perfusion
• early/late cytotoxic edema (less intracellular space, cells swell)
• vasogenic edema (BBB brakes down)
• necrosis

Penumbra: disfunctional after stroke but survived <- target for therapy -> can be supplied by collateral arteries
= ischemic damage - ischemic cellular damage

CT: can rule out ischaemia but not hemorhage
MRI
DSA

Question 8

Etiology

Answer 8

• stenosis/occlusion of large artery
• Cardio-embolic
• Lacunar/mikrovascular
• Cryptogenic

Macrovascular:
– Occlusion/stenosis of the internal carotid artery
– Occlusion/stenosis of the vertebral artery
– Occlusion/stenosis of an intracranial artery or branch
• occlusion = direct interruption of blood supply
• stenosis = thromboembolism („white thrombus“) and distal occlusion
• hemodynamic ischemia = Reduced blood supply

Microvascular:
– Occlusion of small perforating arteries in center of brain
– Lacunar ischemia (<15mm diameter)
-> MRI (CT would not see it)

Cardioembolic:
Thrombus due to blood not moving in the heart (“red thrombus“)
– Atrial fibrillation
– Scar after myocardial infarction
– Cardiac insufficiency
– Aneurysm of the myocardium
– Persisting foramen ovale (PFO)

Question 9

Investigating the etiology:

Answer 9

– Heart: EKG, Holter-EKG, Echocardiography
– (Pre)cerebral arteries: Doppler/Duplex-Sonography: extracranial, CTA, MRA
– Cerebrospinal fluid chemistry
– Angiography
– Thrombophilia investigation
– Immunological investigations

Question 10

Treatment of risk factors:

Answer 10

arterial hypertension:
– ACE-Inhibitor / AT-receptor antagonists
– diuretics
– Betablocker
– Ca-Antagonist

Diabetes:
– Metformin
– Orale antidiabetics or insulin

Hypercholesterinemia:
– Statins, Ezetimib, Bempedoinsäure
– PCSK-9 inhibitor

Question 11

Karotis-Endarterektomie (CEA) oder Stenting (CAS):

Answer 11

Symptomatische Stenosen >70%:
– CEA oder CAS bei operativem Risiko < 6% (< 2% für Tod oder schweren Insult)

Asymptomatische Stenosen > 60%:
– CEA oder CAS bei operativem Risiko < 3% (< 1% für Tod oder schweren Insult)
– Konservative Behandlung bevorzugt, insbesondere bei älteren Patienten

Question 12

Risk of stroke and outcome are determined by:

Answer 12

• Non-modifiable risk factors (age, sex, comorbidites..)
• Modifiable risk factors (smoking, hypertension, diabetes…)
• Type, location and duration of vascular occlusion
• Treatment success

Question 13

Stroke treatment

Answer 13

• Intravenous Thrombolysis: rtPA

• Mechanical Thrombectomy
-> treatment still not optimal

Newer strategies:
• Strategy to improve clot dissolution

• To prevent hemorrhagic transformation

• To improve tissue reperfusion

Question 14

Animal models

Answer 14

ideal model:
• perfect copy of clinical situation
• easy to perform
• low ethical concerns and costs
• maximum reproducibility
-> there is no perfect model

Induce stroke in models:
• inject thrombin/vasoconstriction
• Cut artery
• Put something in artery

• global model
• global & focal
• focal (high mortality, irreversible changes, easy intervention)
• transient (non-invasive, reperfusion injury)
• thrombin model
• thromboembolic (low mortality, technically challenging)
• endothelin-induced/lacunar (low mortality, limited control, spont. recanalization)
• photothrombosis (no craniectomy, reperfusion not possible)

Question 15

In vitro models disadvantages

Answer 15

• can’t assess physiological factors such as: blood flow, blood pressure, stress, immune system
• interventions restricted/ not possible
• functional readouts restricted/ not possible

Question 16

Animal models (good or bad?)

Answer 16

Do animal models really reflect reality?
…no but rodent-models can predict clinically relevant issues quite well:
- genetic background
- targeted gene knock-out
- age/ sex/ environment/ no comorbidities
- planed pre-stroke assessment
- very high-resolution imaging tools
- choice of model depending on research question

Stroke animal models…
- contributed to understanding of mechanisms
- necessary for development of new therapies
- Will never cover all aspects of human disease
- Must be chosen carefully depending on research question
- Should be used with best experimental standards only