Transcript carotid disease - The Toronto Brain Vascular Malformation

Cerebral Vasospasm
M. Christopher Wallace M.D.
The Toronto Western Hospital,
University Health Network
University of Toronto
Postgraduate Lecture Series
Division of Neurosurgery
Friday October 20, 2000
Subarachnoid Hemorrhage
• Delayed presentation
• Headache, no deficit
• Minimal subarachnoid
blood
Cause of Subarachnoid
Hemorrhage?
Post surgical CT
Post-op Angiography
Comparison Angiograms
Post surgical CT’s
History
• 1927
Moniz - angiography
• 1937
Dandy describes the clipping of
intracranial aneurysm
• 1949
Robertson described post-mortem
lesions after aneurysmal SAH.
• Brain 72:150, 1949
• 1951
Ecker & Reimenschneider
angiographic spasm
Time Course
• After aneurysmal subarachnoid
hemorrhage
• Delayed onset
• Rarely present before Day 3
• Peak Day 6-7
Significance
• 1970’s Does it exist?
• Time course in humans
• Kwak, Niizuma
• Niizuma, Kwak
Surg Neurol 11:257, 1979
Surg Neurol 11:263, 1979
• Cause of death or disability in 13.5% in cooperative study
• J. Neurosurgery 73:18-36, 1990
Vasospasm and SAH
• Relationship to the amount of subarachnoid
hemorrhage
• Fisher CT Grade
–I
– II
– III
2/11 angiographic spasm, 0/11
0/7
23/24 clinical vasospasm
– Fisher, Kistler, Davis Neurosurgery 6:1 1980
Etiology
• Reversible?
• Smooth muscle contraction vs
morphological change in vascular wall
• Weir, Findlay, MacDonald
– Demonstration of role of oxyhemoglobin leads
to documented contraction of smooth muscle
– Delayed thickening of intima and adventitia day
28
Etiology
• Fresh serum and platelet rich plasma are
vasoreactive
• Washed rbc’s are inert
• Contractility of rbc’s linked to incubation
with plasma
• Trapped rbc’s in subarachnoid space
– day 7
Treatment of cerebral vasospasm
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Diagnosis
Hypervolemic-hypertensive therapy
Calcium channel blockers
Cerebral angioplasty
Intracisternal thrombolytic therapy
Diagnosis
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Clinical suspicion: patient/time period
Transcranial doppler
Cerebral angiography
Neurological deficit
Hypervolemic-hypertensive
therapy
• Prophylactic use of euvolemia in patients
with aneurysmal hemorrhage post-therapy
• Kosnik & Hunt
J Neurosurg 45:148, 1976
• Kassell, Peerless et al
Neurosurgery 11:337, 1982
– Reversal of deficit in 43/58 patients
– Use of colloids and inotropes
– Clinical detection of deficit and angiographic proof of spasm
Calcium channel blockers
• Use of nimodipine 60mg q4h x 3 weeks
• Reduces morbidity/poor outcomes but does
not alter the incidence of angiographic
spasm….?mechanism
• Allen NEJM 308:619, 1983
• Petruk J Neurosurg 68:505, 1988
• Pickard Br Med J 298:636, 1989
Cerebral angioplasty
• Mechanical vs chemical (papaverine)
• Early, minimal deficit, radiological
contraindications
• Permanence
• Risk of rupture
• ?prophylaxis
• Polin et al Neurosurgery 42:1256-1264, 1998
• Eskridge et al Neurosurgery 42:510-516, 1998
Intracisternal thrombolytic
therapy
• Cisternal clot removal
• Laboratory evidence
• Prospective study failed to demonstrate efficacy
– N=100, high risk patients in main centre (p=0.02)
– Placebo
– rt-PA
mild/no spasm
42%
69%
severe
23%
15%
– Findlay et al Neurosurgery 37:168-176, 1995
Endothelin and Vasospasm
• Isolated from endothelial cells, 1988
• Three isoforms: ET-1, -2, -3, 21 AA
• Prepro ET-1 gene, conversion to proendothelin
then Big-ET
• ET-1 most vasoactive
• Vasoconstriction, elevates arterial pressure,
bronchoconstriction
• Endothelin receptors: ETA, ETB1, ETB2
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Neurosurgery 43:863-876, 1998
Endothelin Receptors
ETA
 localized to smooth muscle
 mediates vasoconstriction
ETB1
 Localized to vascular endothelial cells
 Mediates endothelium-dependant vasodilation action of
ET
ETB2
 Similar localization and action to ETA
Endothelin and Vasospasm
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Documented in CSF after aneurysmal SAH
Marker vs mediator
Likely not over expression of ET1
Potential for therapy with selective
agonists/antagonists to receptors
Approach to Patient with
Delayed Neurological Deficit
Post-op
• Hemorrhage
• Ischemia
Vessel occlusion
Clipping or coiling error
Post temporary clipping
Approach to Patient with
Delayed Neurological Deficit
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Day1-3
Hyponatremia
Fever
Oxygenation
Hydrocephalus
Medications
Rebleed/unsecured aneurysm
Approach to Patient with
Delayed Neurological Deficit
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Day3-10
Vasospasm
Vasospasm
Vasospasm
Hydrocephalus
Fever/pneumonia