Extracranial-intracranial arterial bypass in the management of symptomatic vasospasm

Delayed neurologic deterioration from vasospasm remains the greatest cause of morbidity and mortality following subarachnoid hemorrhage. The authors performed superficial temporal artery-middle cerebral artery bypass in three patients with symptomatic vasospasm and studied its effects on cerebral hemodynamics. All three patients responded neurologically to the bypass procedure within 24 hours. The average cerebral blood flow in the region supplied by the spastic middle cerebral artery increased from 40 ml/100 g/min to 49 ml/100 g/min after bypass. Angiography disclosed dilatation of donor vessels during the peak of spasm, followed by their decrease in caliber coincident with alleviation of vasospasm. The authors conclude that superficial temporal artery-middle cerebral artery anastomosis for the management of symptomatic vasospasm can increase blood flow in the ischemic region supplied by the spastic artery. This management strategy may lower the incidence of death and disability from vasospasm after subarachnoid hemorrhage.     

Cerebral vasospasm after subarachnoid hemorrhage

Cerebral vasospasm causes permanent neurolological deficit or death occurance in 13% of clinical cases. Peak frequency is from 8-10th day after SAH. The purpose of this study is factor analysis that may have influence on vasospasm development , as well as predictor determination. The study is prospective and analysis 192 patients treated in Institute of Neurosurgery, Clinical Centre of Serbia, Belgrade. The majority of patients were admitted in hospital in first four days after SAH, and 184 had GCS over 7. Univariate methods of factor analysis were used, and for significance of predictors influence testing multivariante regression analysis was used. Vasospasm occurred in 22,40% of all cases. No relationships have been found between sex, age, previous hypertension, timing of surgery, appearance of hydrocephalus and intracerebral hematoma, hypertermia or mean arterial blood pressure, with occurrence of cerebral vasospasm. Factors with significantly associated with the occurance of vasospasm were: hearth disease, hypernatriemia, Hct, clinical grade on admission as well as preoperative clinical grade and Fisher CT scan grade. In the first four days after SAH, Fisher scan grade, preoperative clinical grade and Hct, appeared as predictors. After four days, clinical grade on admission and hypernatiemia, showed as poredictors.     

N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage

BackgroundThis study investigated the ability of NAC to prevent cerebral vasospasm in a rabbit model of SAH.MethodsTwenty-one, male New Zealand white rabbits were randomly divided into 3 groups of 7 rabbits each: group 1 (control), group 2 (SAH only), group 3 (SAH + NAC treatment). NAC (150 mg/kg, single dose, IP) was administered just before SAH and continued until 72 hours after SAH in group 3.Animals were killed 72 hours after SAH. Tissue MDA levels, SOD, and GSH-Px activities were measured, and basilar artery cross-sectional areas, arterial wall thickness, and endothelial apoptosis in a cross section of basillary artery were determined in all groups.ResultsIntraperitoneal administration of NAC was found to be markedly effective against developing a cerebral vasospasm following a SAH in rabbits. It could significantly reduce elevated lipid peroxidation and increase the level of tissue GSH-Px and SOD enzymatic activities. Also, NAC treatment was found to be effective in increasing the luminal area and reducing wall thickness of the basilar artery. The morphology of arteries in the NAC treatment group was well protected. NAC markedly reduced apoptotic index and protects the endothelial integrity.ConclusionsThis study demonstrates, for the first time, that NAC treatment attenuates cerebral vasospasm in a rabbit SAH model. NAC treatment has significant neuroprotective effect and markedly prevents cerebral vasospasm after SAH. In conclusion, the NAC treatment might be beneficial in preventing cerebral vasospasm after SAH, thus showing potential for clinical implications.     

Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage

OBJECT: Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis. METHODS: Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration. Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.     

Role of computed tomography in the management of vasospasm after subarachnoid hemorrhage

The role of computed tomography (CT) in the management of vasospasm from subarachnoid hemorrhage was evaluated in 242 consecutive cases with CT performed within 7 days after hemorrhage. Only 20% of these cases did not show a detectable subarachnoid hemorrhage on CT. Subsequent angiograms showed vessel narrowing in 56% of the cases; associated clinical deterioration was noted in 34% of the cases. On later CT, clear ischemic areas were detected in 20% of the cases. A strict correlation between the amount of cisternal blood and the subsequent development of vasospasm was observed: although absent or thin cisternal depositions were rarely associated with vasospasm, consistent or thick depositions were frequently linked to vasospasm (72% of the cases) and to ischemic disturbances (51% of the cases), as well as to clear ischemic areas on later CT (30% of the cases). Regarding the morphology of the cisternal blood collection, the risk of developing vasospasm was at its lowest (42%) for depositions only in the frontal interhemispheric fissure and was at its highest (79%) for depositions in multiple cisterns. The site of cisternal deposition corresponded closely to the area of ischemia on later CT. The persistence of subarachnoid blood more than 72 hours after hemorrhage probably increases the risk of vasospasm, although our data are not conclusive. The definition of a CT scan "at risk" for vasospasm--based on the previous findings--gives practical advantages: proper selection of patients in regard to timing of operation, closer observation and the possibility of prophylactic treatment in patients "at risk," and more adequate evaluation of different therapeutic modalities for vasospasm. With regard to the last point, the incidence of vasospasm was not statistically different between two groups of patients uniformly "at risk": the first group submitted to early operation and the second awaiting operation.     

Diffusion-perfusion mismatch in symptomatic vasospasm after subarachnoid hemorrhage

Diffusion-weighted and perfusion-weighted magnetic resonance (MR) imaging were investigated as a method to detect diffusion-perfusion mismatch in the early stages of vasospasm in 17 patients with acute subarachnoid hemorrhage after aneurysm clipping. Single photon emission computed tomography (SPECT) with N-isopropyl-p-[(123)I]iodoamphetamine was also performed. Diffusion-perfusion mismatch was clearly identified in the 3 patients who manifested clinical deterioration. Perfusion-weighted imaging showed increased mean transit time, normal cerebral blood flow, and increased or normal cerebral blood volume. SPECT revealed no earlier signs of vasospasm. Diffusion-perfusion mismatch was clearly demonstrated in the early stages of vasospasm, so may be useful for early identification of ischemia in vasospasm and initiating appropriate treatment.     

Transcranial Doppler in the evaluation of vasospasm after subarachnoid hemorrhage

Flow velocities (F.V.) in 65 patients admitted for subarachnoid hemorrhage (S.A.H.) were measured 4-7 times a week by Transcranial Doppler (T.C.D.). Patients were classified into 4 T.C.D. groups according to the highest mean flow velocity recorded in the M.C.A. during hospitalization: Group 1 (18 patients) with F.V. below 100 cm/s (normal), group 2 (19 patients) with F.V. between 100-150 cm/s (starting spasm), group 3 (23 patients) with F.V. between 150-200 cm/s (major spasm) and group 4 (5 patients) with F.V. over 200 cm/s (critical spasm). Based on clinical, radiological and ultrasound data as well as patient outcome (good results with no specific problems or with transient deficit, permanent deficit and pre- or postoperative death), the authors analyse the value of T.C.D. in the evaluation of vasospasms following S.A.H. The review involves 49 patients with surgically treated aneurysms (including two associated A.V.M.s), 9 patients who had suffered a S.A.H. of unknown origin and 7 patients who had died prior to surgery. T.C.D. is a non-invasive method of following post-S.A.H. spasms and the close correlation between the angiography and the T.C.D. makes pre-operative control angiographies unnecessary. A correlation between clinical status and T.C.D. was only observed in extreme cases where F.V. exceeded 200 cm/s or increased by 100 cm/s or more within 3 days (6 patients out of 65). M.C.A. spasm can, however, be underestimated by the T.C.D. approach in cases where there is an associated spasm of the infraclinoidal carotid artery. In these cases, classical Doppler evaluation of the cervical portion of the I.C.A. is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)     

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and-Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as a predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and-Cw4 exert protective influence against DIND.     

Contemporary management of subarachnoid hemorrhage and vasospasm: the UIC experience

BACKGROUND: Cerebral vasospasm is a well-known and serious complication of aneurysmal subarachnoid hemorrhage. The means of monitoring and treatment of vasospasm have been widely studied. Each neurosurgical center develops a protocol based on their experience, availability of equipment and personnel, and cost, so as to keep morbidity and mortality rates as low as possible for their patients with vasospasm. METHODS: At the University of Illinois at Chicago, we have developed algorithms for the diagnosis and management of cerebral vasospasm based on the experience of the senior authors over the past 25 years. This paper describes in detail our approach to diagnosis and treatment of aneurysmal subarachnoid hemorrhage and vasospasm. Our discussion is highlighted with data from a retrospective analysis of 324 aneurysm patients. RESULTS: Over 3 years, 324 aneurysms were treated; 185 (57%) were clipped, 139 (43%) were coiled. The rate of vasospasm for the 324 patients was 27%. The rate of hydrocephalus was 32% for those patients who underwent clipping, and 29% for those coiled. The immediate outcomes for those who underwent clipping was excellent in 35%, good in 38%, poor in 15.5%, vegetative in 3%, and death in 8% of the patients. For those who underwent coiling the immediate outcome was excellent in 64%, good in 14.5%, vegetative in 2.5%, and death in 14.5% of the patients. These statistics include all Hunt and Hess grades.For those patients who underwent clipping, 51% were intact at 6 months follow-up, 15% had a permanent deficit, 10% had a focal cranial nerve deficit, and 2% had died from complications not directly related to the procedure. For those patients who had undergone coiling, 75% were intact at 6 months follow-up, 12.5% had a permanent deficit, and 12.5% had a cranial nerve deficit, with no deaths. CONCLUSIONS: The morbidity and mortality of cerebral vasospasm is significant. A good outcome after aneurysmal subarachnoid hemorrhage is dependent upon careful patient management in the preoperative, perioperative, and postoperative periods. The timely work-up and aggressive treatment of neurological deterioration, whether or not it is because of vasospasm, is paramount.     

Cerebral vasospasm in subarachnoid hemorrhage

Opinion statement The treatment of vasospasm after subarachnoid hemorrhage remains a formidable challenge. The prompt recognition of this complication is essential to prevent ischemic damage. Initial orders should include adequate fluid and sodium supplementation to avoid volume depletion. Prophylactic hypervolemia is not effective in reducing the incidence of vasospasm and may be deleterious. Oral nimodipine (60 mg every 4 hours for 21 days) should be started on admission because it protects against delayed ischemic damage. Increasing blood flow velocities on serial transcranial Doppler studies are reliable indicators of early development of vasospasm. When symptomatic vasospasm occurs, hemodynamic augmentation therapy should be instituted. Crystalloids and colloids may be used to promote hypervolemia. Colloids may provide additional benefit by producing hemodilution. However, the rheological benefits of hemodilution may be offset by reduced oxygen carrying capacity when hematocrit drops below 28%. Hypertension may be induced by administering inotropic drugs and, in certain cases, cardiac output optimization using dobutamine also is necessary. When aggressive medical therapy fails to reverse ischemic deficits, prompt endovascular intervention is indicated. Focal vasospasm of larger vessels may be effectively treated with angioplasty and the benefits of this procedure are durable. Diffuse vasospasm involving smaller arterial branches may be treated with intra-arterial infusion of vasodilators, such as papaverine, verapamil, or nicardipine. Unfortunately, these dilatory effects tend to be short-lasting. In refractory cases, hypothermia may be considered, although value of this strategy remains largely unexplored.     

Depression of circulating blood volume in patients after subarachnoid hemorrhage: implications for the management of symptomatic vasospasm

The result of 42 blood volume determinations made with autologous red blood cells labeled with chromium-51 are reported. The subjects consisted of 11 control patients and 25 patients with recent subarachnoid hemorrhage (SAH). The mean red blood cell volume (RBCV) and the total blood volume (TBV) for female patients after SAH were significantly lower than corresponding control values (P less than 0.01). No depression of blood volume was found in males as a group. Seventy-two per cent of females had below-normal RBCV and 50% had below-normal TBV. Fifteen patients demonstrated angiographic vasospasm or signs of cerebral ischemia. Only 1 patient with asymptomatic vasospasm had a below-normal RBCV or TBV, whereas 6 of 7 patients with symptomatic vasospasm had a subnormal RBCV or TBV. The mean RBCV and mean TBV for female patients with symptomatic vasospasm were significantly lower than corresponding control values (P less than 0.02) and lower than values for female patients with asymptomatic vasospasm (P less than 0.05). The data suggest that volume status may be the important differential between asymptomatic and symptomatic vasospasm. Delayed ischemic deficits can be expected to develop in patients who have both spasm of the intracranial vessels and decreased TBV. Patients with normal blood volume are far less likely to experience cerebral ischemia, even if vasospasm develops.     

Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation

Cerebral vasospasm is a common, formidable, and potentially devastating complication in patients who have sustained subarachnoid hemorrhage (SAH). Despite intensive research efforts, cerebral vasospasm remains incompletely understood from both the pathogenic and therapeutic perspectives. At present, no consistently efficacious and ubiquitously applied preventive and therapeutic measures are available in clinical practice. Recently, convincing data have implicated a role of inflammation in the development and maintenance of cerebral vasospasm. A burgeoning (although incomplete) body of evidence suggests that various constituents of the inflammatory response, including adhesion molecules, cytokines, leukocytes, immunoglobulins, and complement, may be critical in the pathogenesis of cerebral vasospasm. Recent studies attempting to dissect the cellular and molecular basis of the inflammatory response accompanying SAH and cerebral vasospasm have provided a promising groundwork for future studies. It is plausible that the inflammatory response may indeed represent a critical common pathway in the pathogenesis of cerebral vasospasm pursuant to SAH. Investigations into the nature of the inflammatory response accompanying SAH are needed to elucidate the precise role(s) of inflammatory events in SAH-induced pathologies.     

Effect of high-dose methylprednisolone on vasospasm after subarachnoid hemorrhage.

The effects of high-dose methylprednisolone (MP) on vasospasm following subarachnoid hemorrhage (SAH) were investigated. In a double hemorrhage canine model, administration of high-dose MP (10 mg/kg, every 12 hours) reduced angiographic narrowing of the basilar artery and prevented morphological changes in the arterial wall. In addition, increased platelet aggregation observed from days 4 to 7 in untreated SAH dogs was inhibited by the MP treatment. An in vitro experiment showed that MP inhibited platelet aggregation dose-dependently. High-dose MP had a nonspecific vasodilatory effect on the smooth muscle of the basilar artery. In another SAH model with dysautoregulation of cerebral blood flow (CBF), intravenous MP administration markedly attenuated the decrease in both blood pressure and CBF caused by exsanguination. These results indicate that MP has beneficial effects in normalizing CBF dysautoregulation following SAH. High-dose MP has several advantages for preventing and improving the multiple pathological status in cerebral vasospasm following SAH.     

Efficacy of intrathecal liposomal fasudil for experimental cerebral vasospasm after subarachnoid hemorrhage

OBJECTIVE: To investigate the safety and efficacy of liposomal fasudil in a sustained-release form for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: Eighteen rats were divided into three groups, each of which received 2.5 mg/kg of liposomal fasudil, 5 mg/kg of liposomal fasudil, or drug-free liposomes after SAH. Next, experimental SAH was induced in 15 dogs by injection of autologous arterial blood into the cisterna magna twice after baseline vertebral angiography. In six dogs, 0.94 mg/kg of liposomal fasudil was injected into the cisterna magna (treatment group). In four dogs, drug-free liposomes were similarly injected (placebo group), and the remaining five dogs were not treated with liposomal injection after SAH (control group). Angiography was repeated on Day 7, and cerebrospinal fluid was collected before the dogs were killed. RESULTS: A high dose of liposomal fasudil caused no significant changes in mean arterial blood pressure and did not induce seizures during the observation period. Gross and microscopic examination of the brains revealed no abnormalities, but severe vasospasm was noted in the rat basilar artery, mainly in the group treated with drug-free liposomes. Likewise, in the canine placebo and control groups, significant vasospasm occurred in the basilar artery on Day 7. In the treatment group, vasospasm in the basilar artery was significantly ameliorated (P < 0.01). In vivo, 90% of fasudil was released from liposomes in the cerebrospinal fluid. CONCLUSION: A single injection of intrathecal liposomal fasudil is safe and effective for the prevention of vasospasm in experimental SAH.