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 1927Moniz - angiography 1937Dandy describes the clipping of intracranial aneurysm 1949Robertson described post-mortem lesions after aneurysmal SAH. Brain 72:150, Ecker & Reimenschneider angiographic spasm

Time Course After aneurysmal subarachnoid hemorrhage Delayed onset Rarely present before Day 3 Peak Day 6-7

Significance 1970’sDoes it exist? Time course in humans Kwak, NiizumaSurg Neurol 11:257, 1979 Niizuma, Kwak Surg Neurol 11:263, 1979 Cause of death or disability in 13.5% in co- operative study J. Neurosurgery 73:18-36, 1990

Vasospasm and SAH Relationship to the amount of subarachnoid hemorrhage Fisher CT Grade –I2/11 angiographic spasm, 0/11 –II0/7 –III23/24 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 Diagnosis Hypervolemic-hypertensive therapy Calcium channel blockers Cerebral angioplasty Intracisternal thrombolytic therapy

Diagnosis 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: , 1998 Eskridge et al Neurosurgery 42: , 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) mild/no spasmsevere –Placebo42%23% –rt-PA69%15% –Findlay et al Neurosurgery 37: , 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: ET A, ET B1, ET B2 Neurosurgery 43: , 1998

Endothelin Receptors ET A localized to smooth muscle mediates vasoconstriction ET B1 Localized to vascular endothelial cells Mediates endothelium-dependant vasodilation action of ET ET B2 Similar localization and action to ET A

Endothelin and Vasospasm 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 Day1-3 Hyponatremia Fever Oxygenation Hydrocephalus Medications Rebleed/unsecured aneurysm

Approach to Patient with Delayed Neurological Deficit Day3-10 Vasospasm Vasospasm Vasospasm Hydrocephalus Fever/pneumonia