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 Surg 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– I 2/11 angiographic spasm, 0/11– II 0/7– III 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

• 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 42:1256-1264, 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)

mild/no spasm severe– Placebo 42% 23%– rt-PA 69% 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

• 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

• 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