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Cerebral Vasospasm post Subarachnoid Hemorrhage Pathophysiological bases for its Treatment General considerations Pathophysiology Treatment Cerebral Vasospasm post Subarachnoid Hemorrhage Pathophysiological bases for its Treatment General considerations Pathophysiology Treatment Prof. Dr. Leónidas Quintana Chief of Neurosurgery Service – Van Buren Hospital Cathedra of Neurosurgery Valparaíso University School of Medicine, Chile

AT THE WILLIS CIRCLE THE CEREBRAL VASOSPASM IS REALLY A “SPASM” ? Ecker A. AT THE WILLIS CIRCLE THE CEREBRAL VASOSPASM IS REALLY A “SPASM” ? Ecker A. , Riemenschneider P. A. : Arteriographic demonstration of spasm of the intracranial arteries with special reference to saccular arterial aneurysms. J. Neurosurg. 1951, 8: 660 -667.

PATHOPHYSIOLOGY OF CEREBRAL VASOSPASM Oxy Hb Sonobe M, Suzuki J : Vasospasmogenic substance produced PATHOPHYSIOLOGY OF CEREBRAL VASOSPASM Oxy Hb Sonobe M, Suzuki J : Vasospasmogenic substance produced following subarachnoid hemorrhage and its fate. Acta Neurochir(Wien) 44: 97 -106, 1978

1 Asano T, Tanishima T et als: Possible participation of Free Radical Reactions initiated 1 Asano T, Tanishima T et als: Possible participation of Free Radical Reactions initiated by clot lysis in the Pathogenesis of Vasospasm after Subarachnoid Hemorrhage. In Cerebral Arterial Spasm. Proceedings of the Second International Workshop, pp 190 -201(Wilkins. RH ed), Baltimore: Williams&Wilkins, 1980.

Quintana L, Konda R, Ishibashi Y, Yoshimoto T, Suzuki J. : The Effect of Quintana L, Konda R, Ishibashi Y, Yoshimoto T, Suzuki J. : The Effect of Prostacyclin on Cerebral Vasospasm- An Experimenta Study. Acta Neurochirurgica 62, 187 -193, 1982.

CAM 2 Inflammation Chaichana KL, Pradilla G, Huang J, Tamargo RJ: Role of inflammation CAM 2 Inflammation Chaichana KL, Pradilla G, Huang J, Tamargo RJ: Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage. World Neurosurg 73: 22 -41, 2010.

3 Endothelial Dysfunction 3 Endothelial Dysfunction

4 Cortical Spreading Depression Cortical Spreading Ischemia Intracranial Hypertension due to global increase CBV 4 Cortical Spreading Depression Cortical Spreading Ischemia Intracranial Hypertension due to global increase CBV during aneurysm rupture, and difusse decrease of CBF Regional or focal decrease of CBF at microcirculation level (real “spasm”) Membrane failure Na+/K+ pump Ca++ pump ATP dependent

DELAYED ISCHEMIC DEFICIT SECONDARY TO CEREBRAL VASOSPASM THE “REAL VASOSPASM” Ischemia: K e , DELAYED ISCHEMIC DEFICIT SECONDARY TO CEREBRAL VASOSPASM THE “REAL VASOSPASM” Ischemia: K e , Na i , Ca i Pre-clipping Microcirculation Delayed Ischemic Deficit During ischemia Vasospasm Narrowing due to ultrastructural alterations > 50% stenosis Post-clipping Sundt Th M Jr, Davis DH: Reactions of cerebrovascular smooth muscle to blood and ischemia: Primary versus Secondary Vasospasm. In: Cerebral Arterial Spasm. Wilkins RH (ed), Baltimore, Williams&Wilkins, pp 244 -250, 1980.

TREATMENT OF CEREBRAL VASOSPASM Level Microcirculation Delayed Ischemic Deficit 1 -Haemodynamic Management- Induced Hypertension, TREATMENT OF CEREBRAL VASOSPASM Level Microcirculation Delayed Ischemic Deficit 1 -Haemodynamic Management- Induced Hypertension, Hypervolemia 2 -Calcium Antagonists Level Willis Circle Angiographycal Symptomatic Vasospasm 1 -Prophylaxis: Early Surgery with cisternal washing, Fenestration of Lamina terminalis, drainage of basal cisterns, evacuation of ICH (Modern concept of Integrated Management of the Disease SAH) 2 -Therapeutic Management: Endovascular Angioplasty

“HAEMODYNAMIC THERAPY” Disautoregulation during SAH Takeuchi H, Handa Y et als: Impairment of cerebral “HAEMODYNAMIC THERAPY” Disautoregulation during SAH Takeuchi H, Handa Y et als: Impairment of cerebral autoregulation during the development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. Neurosurgery 28: 4148, 1991. CBF= CPP ( MAP - ICP) n x r 4 8 x v x L The “triple H therapy” is recommended for prevention and treatment of the ischemic complications due to cerebral vasospasm. It´s recommended to perform more clinical trials to establish it´s real efficacy. ( evidence level III-V, grade C ) Circulation 90: 2592 -2605, 1994.

CALCIO ANTAGONISTS Nimodipine is strongly recommended for diminishing the bad results at the outcome, CALCIO ANTAGONISTS Nimodipine is strongly recommended for diminishing the bad results at the outcome, due to DID secondary to vasospasm. (Evidence level I-II; strenght of recommendation A) Circulation 90: 25922605, 1994. *Nimodipine improved the evolution of SAH due to ruptured aneurysm (good vs other and good or moderate vs other) in a ratio 1, 86: 1 and 1, 67: 1 *Nimodipine decreased the probability of deficit and/or mortality due to vasospasm in a ratio of 0, 46: 1 *Nimodipine decreased the probability of ischemic complications at CT scan in a ratio of 0, 58: 1

TOPICAL NIMODIPINE I. V. NIMODIPINE ACTION OF NIMODIPINE ON CEREBRAL CORTICAL ARTERIES OF 1 TOPICAL NIMODIPINE I. V. NIMODIPINE ACTION OF NIMODIPINE ON CEREBRAL CORTICAL ARTERIES OF 1 mm: 40% VASODILATION ARTERIES OF 160 -300 u : 100% VASODILATION ARTERIES OF < 100 u : 200% VASODILATION Quintana L. : Acción de la Nimodipina en el Déficit Isquémico Retardado de la HSA (Action of Nimodipine on Delayed Ischemic Deficit of SAH), Rev. Chil. Neurocirug, Vol. 2 (3), 239 -250, 1988.

MECHANICAL & PHARMACOLOGICAL ANGIOPLASTY MECHANICAL & PHARMACOLOGICAL ANGIOPLASTY

THANK YOU VERY MUCH !!! Prof. Dr. Leónidas Quintana Chief of Neurosurgery Service – THANK YOU VERY MUCH !!! Prof. Dr. Leónidas Quintana Chief of Neurosurgery Service – Van Buren Hospital Cathedra of Neurosurgery Valparaíso University School of Medicine, Chile