1. Cerebrovascular Accident
Roni Eichel M.D.
Department of Neurology
Hadassah Ein-Kerem
03 November 2014

2. Agenda Objectives for this Lesson Cerebrovascular(CV) Anatomy
Pathophisology of CV Accident (CVA)
Main Syndromes of CVA
Management of CVA
Acute Treatment approaches for CVA
Secondary Prevention

3. Objectives of this Lesson
Anatomic and pathophysiological basics of stroke.
To be able to diagnose a stroke and be able to recognize frequent syndromes in stroke patients.
Being familiar with the main preventive and acute treatment approaches in ischemic and hemorrhagic (Intraparynchimal) stroke.

4. Cerebrovascular Anatomy

5. Circulus of Willis

6. Angiography

7. CTA

8. MRA

10. Pathogenesis of Stroke: Ischemia & Hemorrhage
Ischemia: lack of circulating blood deprives the neurons of oxygen and nourishment
Hemorrhage: Extravascular release of blood causes damage by cutting off connecting pathways, resulting in local or generalized pressure injury

11. CBF & Ischemic Thresholds
Normal CBF cc/100 g/minute
Varies in different regions of the brain
CBF 20-30cc/100g/min Loss of electrical activity
CBF 10 cc/100g/minNeuronal death

12. Ischemic Penumbra & Window Of Opportunity
Ischemic zone that surrounds a central core of infarction with CBF of 25% to 50% of normal and loss of auto regulation
Viability of brain tissue is preserved if perfusion is restored within a critical time period

13. Microcellular Mechanisms of Neuronal Injury
Development of microcirculatory disturbances
Formation of micro thrombi
Accumulation of noxious metabolites
Interaction of endothelial cells with PMN leukocytes & platelets
PMNs trigger neuronal necrosis

14. Major Categories of Ischemic Stroke
Thrombosis
Embolism
Hemodynamic Stroke

15. Thrombotic Stroke
Atherosclerosis: the commonest pathology of vascular obstruction leading to thrombosis
Other pathological causes:
Fibro muscular dysplasia
Arteritis (Giant Cell & Takayasu)
Dissection of vessel wall and hemorrhage into atheromatous plaque
Hypercoaguability

16. Embolic Stroke Two most common sources of emboli:
Left sided cardiac chambers
Artery to artery stroke: as in detachment of a thrombus from ICA at the site of a plaque
Embolic strokes can become “hemorrhagic”

17. Embolism

18. Ischemic Stroke Due To Hemodynamic Crisis: “Hypotensive Stroke”
Any event causing abrupt drop in blood pressure results in critical compromise of CBF (cerebral blood flow) and hence cerebral perfusion.
Sites affected by critically low CBF are located at the end of an arterial territory. Hence the term “watershed or boundary zone infarct.”

19. Watershed Infarcts Resulting From Hemodynamic Crisis (Hypotensive Stroke)

20. Selective Vulnerability of Neurons to Global Ischemia
Hippocampus: pyramidal cell layer
Cerebral cortex: Purkinje cell layer
Cerebellar cortex
The increased vulnerability of these neurons is due to the abundance of neurotransmitter glutamate in these neurons
Some neurons are more susceptible to ischemia than others. The more common ones are listed here. The pyramidal cell layer of hippocampus and the purkinje cell layer or the cerebral cortex are most vulnerable to lack of oxygen. This is believed to be due to the fact that these neurons are rich in neurotransmitter glutamate
Now I will review what happens when CBF is restored as it occurs either spontaneously or thru interventional therapy.

21. Ischemic Stroke Syndrome
Transient Ischemic Attack (TIA)
Neurologic deficit that resolves within 24 hours
Most TIAs resolve < 30 minutes
Approx. 10% of patients will have a stroke in 90 days
Half of these in just 2 days

22. Ischemic Stroke Syndromes
Anterior Cerebral Artery Infarction
Contralateral weakness/numbness greater in leg than arm
Dyspraxia
Speech perseveration
Slow responses

23. Ischemic Stroke Syndromes
Middle cerebral artery occlusion
Dominant Hemisphere (usually the left)
Contralateral weakness/numbness in arm and face greater than leg
Gaze preference toward side of infarct
Aphasia (Wernicke’s -receptive, Broca’s -expressive or may have both)

24. Ischemic Stroke Syndromes
Middle cerebral artery occlusion
Nondominant hemisphere
Contralateral weakness/numbness in arm and face greater than in the leg
Apraxia
Inattention, neglect, or extinction

25. Ischemic Stroke Syndromes
Posterior Cerebral Artery Infarct
Often unrecognized by patient- minimal motor involvement
Light-touch/pinprick may be significantly reduced
Contra lateral hemianopsia

26. Ischemic Stroke Syndromes
Vertebrobasilar Syndrome
Posterior circulation supplies brainstem, cerebellum, and visual cortex
Dizziness, vertigo, diplopia, dysphagia, ataxia, cranial nerve palsies, and b/l limb weakness, singly or in combination
HALLMARK: Crossed neurological deficits: ipsilateral CN deficits with contralateral motor weakness

27. Ischemic Stroke Syndromes
Basilar Artery Occlusion
Severe quadriplegia
Coma
Locked-in syndrome-complete muscle paralysis except for upward gaze

28. Ischemic Stroke Syndromes
Cerebellar Infarction-subset of post. circ. infarcts
Symptoms: “drop attack” with sudden inability to walk or stand, often a/w vertigo, HA, nausea/vomiting, neck pain
Diagnosis: MRI, MRA as bone artifact obscures CT
Cerebral edema develops w/in 6-12 hrs → increased brainstem pressure and decreased LOC
Treatment: decrease ICP and emergent surgical decompression

29. Ischemic Stroke Syndrome
Lacunar Infarction
Infarction of small penetrating arteries in pons and basal ganglia
Associated with chronic HTN present in 80-90%
Pure motor or sensory deficits
Arterial Dissection
Often a/w severe trauma, headache, and neck pain hours to days prior to onset of neuro symptoms
HTN risk factor for spontaneous dissection

30. Hemorrhagic Syndromes
Intracerebral (Intraparynchimal) Hemorrhage
Risk Factor HTN
ICH – sudden onset HA, elevated BP
Progressive focal neurologic deficits over minutes
Patients may rapidly deteriorate
Exertion commonly triggers symptoms
Bleeding localized to putamen, thalamus,
pons-pinpoint pupils, and cerebellum

31. Hemorrhagic Syndromes
Cerebellar Hemorrhage
Sudden onset dizziness, vomiting, truncal ataxia, inability to walk
Possible gaze palsies and increasing stupor
Treatment: urgent surgical decompression or hematoma evacuation

32. Diagnosis-Critical Pathway
History
Last moment patient known to be normal
Initial orders
ECG, Cardiac Enzymes, CBC, Coags, Glucose, Renal function studies, +/- drug screen, Noncontrast CT-head
Review alteplase inclusion/exclusion criteria

33. Diagnostic Tests Emergent noncontrast CT of head
Differentiate hemorrhage vs ischemia
MOST ischemic strokes (-) by CT for at least 6 hrs
Hypodensity indicating infarct seen hrs
Can identify hemorrhage greater than 1cm, and 95% of SAH
If CT (-) but still considering SAH may do L.P.

34. Diagnostic Tests Depending on circumstances, other helpful tests
Echocardiogram – identifies mural thrombus, tumor, valvular vegetations in suspected cardioembolic stroke
Carotid duplex -for known/suspected high grade stenosis
Angiography – “gold standard” identifies occlusion or stenosis of large and small vessels of head/neck, dissections and aneurysms
MRI scan – identifies posterior circulation strokes better and ischemic strokes earlier than CT
Emergent MRI- considered for suspected brainstem lesion or dural sinus thrombosis
CTA/MRA scan – identifies large vessel occlusions – may replace angiography in the future

35. Differential Diagnosis
Ddx of Acute Stroke (not inclusive)
Epidural/subdural hematoma
Hyponatremia
Brain tumor/abscess
Postictal paralysis (Todd paralysis)
Hypertensive encephalopathy
Meningitis/encephalitis
Hyperosmotic coma

36. Differential Diagnosis Cont.
Wernicke Encephalopathy
Drug toxicity (lithium, phenytoin, carbamazepine)
Complicated Migraine
Bells palsy
Multiple sclerosis
Meniere’s disease
Labyrinthitis

37. Special Populations In Stroke
Young Adults (age 15 to 50)
20% of ischemic strokes due to arterial dissection
Often preceded by minor trauma
Cardioembolic etiologies- MVP, rheumatic heart disease, or paradoxical embolism
Migrainous stroke- infarction a/w typical attack
Air embolism-scuba diving or recent invasive procedure
Drugs: heroin, cocaine, amphetamines

38. Special Populations In Stroke
Pregnancy
↑risk during peripartum and up to 6 weeks postpartum
Contributors to risk-preeclampsia/eclampsia, decrease in blood vol. and hormonal status following birth
Specially in risk patients with Pre-Eclampsia, Eclampsia ,HELP-Syndrome, Previous Hypercoagulation states.

39. Ischemic Stroke Management
General Management
A, B, Cs
IV, oxygen, monitor, elevate head of bed slightly
E.D. protocols/Notify stroke team
Treat dehydration and hypotension
Avoid overhydration – cerebral edema
Avoid IVF with glucose – except if hypoglycemic
Fever – worsens neurologic deficits

40. Ischemic Stroke Management
Hypertension
Treatment indicated for SBP > 200 mm Hg or mean arterial pressure > 130 mm Hg
Lowering BP too much reduces perfusion to penumbra converting reversible injury to infarction
Use easily titratable Rx (labetalol or enalaprilat)

41. Management of HTN cont.
Thrombolytic candidates- use Nicardipine or Labetalol to reduce BP < 185/115 to allow tx
Requirements for more aggressive treatment exclude the use of tissue plasminogen activator.

42. Thrombolysis Background
NIH/NINDS study
624 patients, RDBPC trial IV tPA vs placebo
Treatment w/in 3 hrs of onset
At 3 months pts tx’d with tPA were at least 30% more likely to have minimal/no disability…absolute favorable outcome in percent
6.4% of patients treated with tPA developed symptomatic ICH compared with 0.6% in placebo group
Mortality rate at 3 months not significantly different
tPA group had significantly less disability
FDA approved in 1996

43. tPA Dose and Complications
IV tPA –Total dose 0.9 mg/kg, max. 90mg
10% as bolus, remaining infusion over 60 min.
BP and Neuro checks q 15 min x 2 hrs initially
Treatment must begin w/in 3hrs or up to 4.5 hrs (additional exclusion criteria) of symptoms and meet inclusion and exclusion criteria
No ASA or heparin given x 24 hrs after tx

44. Emergent Mngt of HTN during/following rtPA in Acute Stroke
Monitor BP closely
q 15 min x 2 hrs, then q 30 min x 6 hrs, then q 60 min for 24 hr Total
If SBP or DBP mmHg
10 mg labetalol IVP q min, max 150 mg
If SBP > 230 or DBP mmHg
10 mg labetalol may repeat q min, max 150 mg
If BP not controlled by labetalol then consider nitroprusside ( mcg/kg/min), continuous arterial monitoring advised
If DBP > 140 mmHg
Infuse sodium nitroprusside ( mcg/kg/min), continuous arterial monitoring advised

45. IV Thrombolysis Criteria in Ischemic Stroke
Inclusion criteria
Time since onset well established to be < 4.5 hrs
Clinical diagnosis of ischemic stroke

46. Criteria for IV Thrombolysis cont.
Exclusion criteria
Minor/rapidly improving neurologic signs
Evidence of intracranial hemorrhage on pretreatment noncontrast head CT
History of intracranial hemorrhage
High suspicion of SAH despite normal CT
GI or GU bleeding within last 21 days

47. Criteria for IV Thrombolysis cont.
Exclusion criteria
Known bleeding diathesis
Platelet count < 100,000 /mm3
Heparin within 48 hours and has an elevated PTT
Current use of anticoagulation or PT > 15 seconds or INR > 1.7 for time window any use of anticoagulation prior to strokes excludes

48. Criteria for IV Thrombolysis cont.
Exclusion criteria
Intracranial surgery, serious head trauma or previous stroke within 3 months
Major surgery within 14 days
Recent arterial puncture at non compressible site
Lumbar puncture within 7 days
Seizure at onset of stroke

49. Criteria for IV Thrombolysis cont.
Exclusion criteria
History of ICH, AVM or aneurysm
Recent MI
Sustained pretreatment systolic pressure > 185 mmHg or diastolic pressure > 110 mmHg despite aggressive treatment to reduce BP to within these limits
Blood glucose < 50 or > 400 mg/dL

50. Endovascular Intervention
Up to 8hrs from symptom unset in anterior circulation
Up to 24hrs in cases of basilar occlusion
STENT RETRIEVERS over 90% recanalization rate

51. Drug Therapy in Ischemic Stroke and secondary prevention
Majority of pts not thrombolytic candidates
Antiplatelet agents-cornerstone for 2° prevention
Antiplatelet agents
ASA: ↓ risk 20-25% vs placebo
mg dose and will not interfere with tPA therapy
Dipyridamole: alone (200mg BID) ↓ risk 15%
Plavix: (75 mg qd) 0.5% absolute annual risk reduction when compared to ASA
Good Rx for pts who cannot tolerate or fail ASA

52. Anticoagulants and secondary prevention
Heparin/Coumadine: proven only for patient with AF, PAF
Pts may expect fewer strokes but benefit is paid by increased ICH
Similar results with LMWH
Use of UFH, LMWH, or heparinoids to tx a specific stroke subtype or TIA cannot be recommended based on available evidence.
NOAC- New Oral Anticoagulation Drugs
Abixaban , Rivaroxaban, Dagibatran

53. TIA Management
Admit-Evaluate for cardiac sources of emboli or high grade stenosis of carotid arteries
Rx: ASA
UFH-for high risk of recurrence
Known high grade stenosis in appropriate distribution of symptoms, cardioembolic source, Crescendo TIAs, TIAs despite antiplatelet therapy
Urgent Carotid EndArterectomy (CEA) for TIAs that resolve in < 6 hrs and a/w > 70% stenosis of carotid artery
CEA after ischemic stroke and a/w =>70% stenosis of symptomatic carotid artery

54. Treatment for Prevention
Healthy Live Style
3-4 per week aerobic activity at least 30 min.
Statin treatment with target level of LDL under 70.

55. ICH Management
Treat HTN >180 mm Hg systolic or > 110 mm Hg diastolic using labetalol or nitroprusside
Reduce gradually to prehemorrhage levels
Elevate HOB to 30°
Hyperventilation-target PaCO mm Hg
Osmotherapy
Mannitol ( g/kg IV), and lasix (10 mg IV)– target serum osmolality ≤ 310 mOsm/kg
Hyperventilation/osmotherapy used for signs of progressive ↑ ICP
i.e. mass effect, midline shift or herniation
Steroids – not recommended

56. ICH Management cont. ICP Monitoring considered if GCS < 9
Surgery – controversial
Depends on neuro status of pt, size and location of hemorrhage
Best benefit in cerebellar hemorrhage