Prediction of cerebral infarction due to vasospasm following aneurysmal subarachnoid haemorrhage using acetazolamide-activated123I-IMP SPECT

Summary Prediction of cerebral infarction due to vasospasm (VS) following aneurysmal subarachnoid haemorrhage (SAH) was investigated using acetazolamide-activated (A-A) N-isopropyl-p-[¹²³I] iodoamphetamine (¹²³I-IMP) single photon emission computed tomography (SPECT) in 79 SAH patients. A-A SPECT was undertaken twice or more for one each patient by Day 18. Fifty-six (71%) of the 79 patients presented with reduction of cerebral vasodilatory capacity (CVC) on SPECT due to VS by Day 18.Of the 56 patients, 29 showed CVC by Day 8 (Group A), while the other 27 first showed CVC reduction between Day 9 and 18 (Group B). Cerebral infarction on CT was revealed by Day 18 in 15 patients (52%) of Group A and 3 (11%) of Group B.Of the 56 patients, 20 showed reduced CVC in watershed[s] (Type 1), 12 in a sole territory of the intracranial major arterial trunk (Type 2), and 24 in several territories or in a sole territory with distant watershed[s] (Type 3). Cerebral infarction on CT by Day 18 was revealed in one patient (5%) in Type 1, 3 (25%) in Type 2, and 14 (58%) in Type 3.Twelve (71%) of 17 patients belonging to both Group A and Type 3 resulted in cerebral infarction. These results suggest that early and extensive CVC reduction are significant factors responsible for cerebral infarction due to VS following SAH.Cerebral infarction can be reasonably predicted using A-A SPECT in SAH patients.     

Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery

A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) were enrolled in a double-blind placebo-controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography (CT)-visualized infarcts after SAH and surgery. The administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. Of the 213 patients enrolled in the study, 58 were operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not operated on. A follow-up examination with CT scanning, performed 1 to 3 years after the SAH (mean 1.4 years), revealed no significant differences in the overall outcome between the groups. However, nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts visualized by CT scanning in the whole population (p = 0.05), especially in patients without an associated intracerebral hemorrhage on admission CT scan (p = 0.03).     

Correlation of transcranial Doppler sonography findings with timing of aneurysm surgery

Thirty-six patients with a proven first subarachnoid hemorrhage (SAH) from a ruptured supratentorial aneurysm were subjected to repeated transcranial Doppler sonography assessments. Eighteen individuals (Group A) were operated on within 48 hours, while the other 18 (Group B) had surgery between 49 and 96 hours after SAH. The patients represented two clinically comparable groups. In the first 72 hours post-SAH, no increased flow velocities suggestive of arterial narrowing or vasospasm were recorded. There was no significant difference in preoperative flow velocities between the groups. Postoperative flow velocities were significantly lower in patients operated on within 48 hours (p less than 0.001). Two patients, who had surgery on Day 4 post-SAH and who showed the highest recorded postoperative flow velocities, died from cerebral vasospasm and infarction. The results favor a referral system which enables early surgical intervention not only to prevent rebleeds but also aimed at reducing delayed ischemic dysfunction.     

Nimodipine and early aneurysm operation in good condition SAH patients

A prospective open multicenter study on the preventive effect of nimodipine on symptomatic vascular spasm was performed in 120 (consecutive) patients with aneurysmal subarachnoid haemorrhage (SAH). All patients underwent early surgery (i.e. within 72 hours post SAH) and were in neurological grades I-III in Hunt and Hess. Grade IV and V as well as patients with significant intracerebral haematoma are not included. On preoperative CT, SAH was mild in 28 cases, moderate in 56 and severe in 36 cases. 25 patients (21%) were in grade I, 63 patients (53%) in grade II and 32 patients (26%) in grade III. The ruptured aneurysm was located on the anterior cerebral artery complex in 57 patients, on the internal carotid artery complex in 35, on the middle cerebral artery in 24 patients and on the basilar artery in 4 patients. After occlusion of the ruptured aneurysm, the lipophilic calcium channel blocker nimodipine was administered in the following manner: Intraoperative, topical irrigation of the exposed arteries. Intravenous infusion until day 7-14 after SAH followed by peroral medication for another week. Nimodipine was well tolerated and neither significant hypotension nor any other adverse reaction attributable to the drug was observed. Ischaemic cerebral dysfunction of delayed onset with permanent neurological deficit occurred in 2 patients (2%). Another 8 patients showed transient ischaemic symptoms. At 6 months follow-up, 93% of the patients were classified as having made a full recovery, 16% as being minimally disabled, 5% as being moderately disabled and 3% as being severely disabled. Three patients had died. The present study supports the concept that preventive nimodipine treatment may reduce delayed ischaemic deficit in early aneurysm surgery.     

Surgical manipulation of primate cerebral arteries in established vasospasm

It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation.     

Evaluation of changes in circulating blood volume during acute and very acute stages of subarachnoid hemorrhage: implications for the management of hypovolemia

OBJECT: Circulating blood volume (cBV) is reported to decrease in patients who suffer a subarachnoid hemorrhage (SAH), but little is known about the correlation between changes in cBV, and patient clinical condition and time course after SAH, especially during the very acute stage. To determine appropriate management of patients with SAH, the authors measured cBV by using pulse spectrophotometry immediately after patient admission. They also evaluated whether the timing of surgery influenced changes in cBV. METHODS: Circulating blood volume was measured in a total of 73 patients who were divided into the following three groups: Group A (very acute SAH) consisted of 14 SAH cases, Group B (acute SAH) included 34 SAH cases, and Group C (controls) included 25 other neurosurgical cases. All patients in Group A underwent aneurysm clipping within 6 hours after onset of SAH, whereas all patients in Group B underwent aneurysm clipping within 72 hours after onset. Hypervolemic therapy was not performed in patients with SAH. Before surgery, cBV was significantly lower in patients in Group B than in those in Group C, but there was no significant difference in this parameter when comparing Groups A and C. Although there was a transient drop in cBV in Group B patients for at least 3 days after surgery, there was no significant change in cBV in Group A patients during the study period. None of the Group A patients suffered from symptomatic vasospasm; however, four Group B patients did experience symptomatic vasospasm. CONCLUSIONS: The authors assert that normovolemic fluid management is appropriate for patients who undergo surgery during the very acute stage of SAH, whereas a relatively hypervolemic therapy is necessary for 3 to 5 days after operation to prevent early hypovolemia in patients who undergo surgery during the acute stage of SAH.     

Effect of nimodipine on the outcome of patients after aneurysmal subarachnoid hemorrhage and surgery

The effect of intravenous nimodipine on the incidence of mortality and delayed ischemic neurological deficits of patients after aneurysmal subarachnoid hemorrhage (SAH) and surgery was studied in a prospective double-blind placebo-controlled trial. Upon admission, all of the patients were in Grades I to III according to the classification of Hunt and Hess. Of the 213 patients enrolled in the study, 58 underwent early surgery (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not scheduled for operation. Administration of the drug was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. The dose of nimodipine or matching placebo was 0.5 micrograms/kg/min via continuous intravenous infusion for 7 to 10 days after the SAH and, if the patient was operated on late, for 2 to 3 days after the operation as well. After intravenous treatment, oral administration of nimodipine or placebo was continued for up to 21 days after SAH in a dose of 60 mg every 4 hours. Nimodipine treatment was associated with a significant decrease in mortality rate (p = 0.03) in the early and subacute surgery groups. In the total series the number of deaths due to delayed ischemic deterioration was significantly lower in the nimodipine group than in the placebo group (p = 0.01).     

Neuropeptide Y in the primate model of subarachnoid hemorrhage.

The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p less than 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.     

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.     

Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage

Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe.     

Risk factors for ischemic lesions following aneurysmal subarachnoid hemorrhage

OBJECT: The aim of this study was to test whether enoxaparin treatment (40 mg subcutaneously once daily) reduces the risk of cerebral infarction after subarachnoid hemorrhage (SAH) and to investigate predictive risk factors for permanent ischemic lesions visible on follow-up computerized tomography (CT) scans obtained 3 months after SAH. METHODS: After undergoing surgery for a ruptured aneurysm, 170 patients were randomized in a prospective, double-blind, placebo-controlled trial to test the effect of enoxaparin on the occurrence of ischemic lesions, which were demonstrated on follow-up CT scans available for 156 patients. The presence of lesions correlated highly with an impaired outcome, as assessed using both the Glasgow Outcome and modified Rankin Scales (p < 0.01). Lesions occurred in 101 (65%) of the 156 patients. In half of the patients (51 patients) no lesion was visible on the CT scan obtained on the 1st postoperative day in 51 patients. On univariate analysis, the presence of lesions at 3 months post-SAH was not associated with enoxaparin treatment but did correlate with several clinical, radiological, and prehemorrhage variables. Significant independent risk factors for lesions consisted of an impaired initial clinical condition (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.03-6.73), amount of subarachnoid blood (OR 6.51, 95% CI 2.27-18.65), nocturnal occurrence of SAH (that is, between 12:01 a.m. and 8:00 a.m.; OR 4.32, 95% CI 1.28-14.52), fixed symptoms of delayed ischemia (OR 5.21, 95% CI 1.02-26.49), duration of temporary artery occlusion during surgery (OR 1.66 per minute, 95% CI 1.20-2.31), and body mass index (OR 1.13/kg/m2, 95% CI 1.01-1.28). CONCLUSIONS: The presence of ischemic lesions can be predicted by the severity of bleeding, delayed cerebral ischemia, excess weight, duration of temporary artery occlusion, and occurrence of nocturnal aneurysm rupture.     

Plasma endothelin and big endothelin concentrations and serum endothelin-converting enzyme activity following aneurysmal subarachnoid hemorrhage

OBJECT: Pathogenesis of delayed ischemia after aneurysmal subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET)-1 with its powerful and long-lasting vasoconstricting activity. In this prospective study the author investigated the correlations between serial plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 molar concentration ratio and serum endothelin-converting enzyme (ECE)-1 activity, and ischemic complications after SAH. METHODS: To measure plasma ET-1 (51 patients), big ET-1 immunoreactivity (22 patients), and serum ECE-1 activity (13 patients), blood samples were obtained on admission, in the morning after aneurysm surgery, and during the 2nd week after hemorrhage in 51 consecutive patients (28 men and 23 women, with a mean age of 50.8 years) with aneurysmal SAH. Mean plasma concentrations of ET-1 in patients with SAH (mean +/- standard deviation: on admission, 4.2 +/- 2 pg/ml; after surgery, 4.3 +/- 2.2 pg/ml; and during the 2nd week after SAH, 3.7 +/- 1.9 pg/ml) differed from those in healthy volunteers (2.9 +/- 1.2 pg/ml; p < 0.01). Plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 ratio did not change significantly with elapsed time following SAH; however, serum ECE-1 activity during the 2nd week after SAH was higher in patients with SAH than that in controls (162 +/- 43 compared with 121 +/- 56 pg/ml, respectively; p = 0.028). Plasma ET-1 concentrations (p < 0.05) and the ET-1/big ET-1 ratios (p = 0.063) were higher but plasma big ET-1 concentrations were lower (p < 0.05) in patients who experienced symptomatic delayed cerebral ischemia, compared with other patients with SAH. In addition, in cases in which follow-up computerized tomography scans or magnetic resonance images demonstrated permanent ischemic lesions attributable to vasospasm, patients had higher ET-1 concentrations than did other patients with SAH. CONCLUSIONS: The plasma ET-1 concentration correlates with delayed cerebral ischemia after SAH, suggesting that an increased ET conversion rate in the endothelium predicts ischemic symptoms. Increased serum ECE-1 activity during the 2nd week may reflect the severity of endothelial injury to cerebral arteries.     

Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing

The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% +/- 2.66% (mean +/- standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% +/- 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 +/- 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 +/- 0.03 mm was observed by Day 3 post SAH (p less than 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 +/- 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p less than 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH.     

Heparin-induced thrombocytopenia and thrombosis following subarachnoid hemorrhage. Case report

The authors present a case of heparin-induced thrombocytopenia and thrombosis (HITT) that occurred after aneurysmal subarachnoid hemorrhage (SAH), and they review the relevant literature. An immune-mediated syndrome, HITT is characterized by moderate thrombocytopenia and paradoxical vascular thromboses. Although it has been estimated in prospective studies that HITT occurs in between 1 and 3% of patients receiving heparin, it is underrecognized in the neurosurgical literature. In the present case, a 49-year-old woman underwent clipping of a right posterior communicating artery aneurysm after suffering a Hunt and Hess Grade III SAH. She had an uncomplicated postoperative course with good clip positioning and no vasospasm observed on a cerebral angiogram obtained on Day 7. On Day 23, the patient developed a right hemiparesis and experienced a grand mal seizure. A head computerized tomography scan revealed a hemorrhagic infarct in the left middle cerebral artery distribution. Repeated cerebral angiograms did not show vasospasm. She was thrombocytopenic (platelet count as low as 46 x 10(9)/L on Day 28 compared with 213 x 10(9)/L on Day 1) and had been receiving heparin flushes to maintain intravenous catheter patency. An assay for HITT-associated antibodies was positive. The heparin flushes were discontinued and the platelet count recovered (121 x 10(9)/L). She improved neurologically, but was left with a significant right hemiparesis at discharge. This patient had assay-proven heparin-induced thrombocytopenia despite minimal exposure to heparin. Because there was no evidence of vasospasm or other factors to account for her delayed hemorrhagic infarction, an HITT-related disorder seemed most likely. Despite a large body of literature describing HITT in nonneurosurgical patients, only three previous neurosurgical cases have been published. This case report may serve to heighten awareness of this disorder.     

Fatal bleeding from arterial dissection after clipping of a ruptured aneurysm--case report

A 67-year-old man died of subarachnoid hemorrhage (SAH) resulting from dissection of the distal part of the anterior cerebral artery (ACA). A saccular aneurysm in the anterior communicating artery had ruptured and was successfully clipped on Day 0. The patient recovered consciousness after surgery but his condition deteriorated due to another SAH on Day 1. A second surgical procedure disclosed bleeding from a laceration in the opposite wall of the ACA distal to the clipped aneurysm. Histological examination of the autopsy specimens revealed damage to the internal elastic lamina and inflammatory infiltration of leukocytes. The fatal dissection may have resulted from atherosclerosis, hemodynamic stress caused by hypertension, or trauma due to surgical manipulation.     

Unruptured aneurysms and postoperative volume expansion.

After a ruptured aneurysm has been clipped in patients with multiple aneurysms, the question often arises whether to use volume expansion and/or hypertensive treatment to prevent delayed cerebral ischemia (vasospasm). There is understandable concern regarding the possible rupture of unprotected aneurysms under additional hemodynamic stress. In a series of 199 patients with aneurysmal subarachnoid hemorrhage who underwent early surgery, 31 were left with one or more unprotected aneurysms postoperatively. All patients were treated with prophylactic volume expansion based on a previously reported protocol. Mean central venous pressure during treatment was 10.3 cm H2O and mean arterial blood pressure 141/76 mm Hg; volume expansion was continued for 7 to 10 days. Eight patients developed symptoms of delayed cerebral ischemia and required additional volume expansion and induced hypertension. After institution of hypertension, four of these patients experienced a reversal of their symptoms, while four others developed cerebral infarcts. One patient died from massive cerebral infarction following vasospasm refractory to all measures. No patient suffered rupture of an unprotected aneurysm during hypervolemic treatment. It is concluded that the benefit of prophylactic hypervolemic hypertension in postoperative aneurysm patients warrants its use even in patients with unprotected aneurysms.     

Nimodipine and chronic vasospasm in monkeys: Part 1. Clinical and radiological findings

The efficacy of the calcium channel blocker nimodipine in the prevention of chronic cerebral vasospasm (VSP) and delayed ischemia after subarachnoid hemorrhage (SAH) in monkeys was examined in a blind, randomized, placebo-controlled trial. The primate model developed in this laboratory reliably induces chronic cerebral vasospasm and can induce pathologically proven delayed ischemic neurological deficits (DINDs). With standard microsurgical procedures, an average 6.4-ml autologous hematoma was placed directly against the major anterior cerebral vessels in the right basal subarachnoid spaces of 24 monkeys. The monkeys were randomized to one of four groups and were treated orally q8h for 7 days with nimodipine (3, 6, or 12mg/kg)or placebo. An additional 2 monkeys underwent the surgical procedure without clot placement. Drug administration began between 14 and 20 hours after clot placement. Indices monitored before and after SAH included neurological status, angiographic cerebral vessel caliber, and cerebral blood flow. Significant VSP (25 to 100% reduction in vessel caliber) was present on Day 7 on the clot side in 83% of the animals (P less than or equal to 0.001). There was no significant difference (P greater than 0.05) in the incidence of VSP among the four groups. Similarly, there was no significant difference (P greater than 0.05) in the mean vessel caliber reduction after SAH among the four treatment groups. There was no VSP present on Day 7 in the sham-operated animals. One animal receiving high dose nimodipine (12 mg/kg p.o. q8h) developed a DIND on Day 5 after SAH. A second animal in the 12-mg/kg group developed a transient neurological deficit between Days 4 and 7.     

Preventive effect of synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm in rabbits.

The effect of the synthetic multiserine protease inhibitor FUT-175 on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. The SAH in rabbits was simulated by a single injection of autologous arterial blood into the cisterna magna, and, for 7 days, the caliber of each basilar artery was examined several times via angiogram. In 10 SAH rabbits, the peak of the arterial narrowing was observed on Day 2. In this model, the effect of intravenous administrations of FUT-175 was examined. Twenty-seven SAH rabbits were randomly divided into three groups, and 3 doses of 1, 2, or 3 mg of FUT-175 were administered intravenously. Angiographic arterial narrowing on Day 2 in nontreated SAH rabbits (Control) was 35% compared with 21, 5, and 14% in rabbits treated with a total of 3 (Group A; n = 9), 6 (Group B; n = 13), and 9 mg (Group C; n = 5) of FUT-175, respectively. There were statistically significant differences in the arterial calibers between Group A and the Control on Days 1 and 2, between Group B and the Control from days 1 to 4, and between Group C and the Control from days 1 to 4. In three other rabbits, after vasospasm reached its maximum on Day 2, no vasodilatory effect was observed when a total of 6 mg of FUT-175 was administered intravenously. The results indicate that the inhibition of the plasma serine protease cascades at an early stage of SAH prevents the development of cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Supraorbital eyebrow minicraniotomy for anterior circulation aneurysms

BACKGROUND: We report our experience with the minimally invasive supraorbital approach to aneurysms of the ipsilateral anterior cerebral circulation. METHODS: A prospective review of all patients who underwent operations to clip aneurysms in Newcastle between 1993 and 2002. RESULTS: Fifty-six aneurysms were clipped via minicraniotomy in 47 patients. Six patients presented with acute subarachnoid hemorrhage (SAH), 40 patients were admitted for elective clipping, and 1 patient presented with an SAH, had the responsible aneurysm clipped and was readmitted later for elective clipping of a further aneurysm. Bilateral supraorbital craniotomies were performed in 3 patients. In 6 patients, multiple aneurysms were clipped via a single craniotomy. All aneurysms were well visualized with the microscope. Endoscopic assistance was not found necessary. All were successfully clipped. Two aneurysms ruptured while being clipped. There was no direct mortality from surgery. One patient died later from a separate posterior circulation aneurysm. One patient had a significant long-term deficit but remained independent, and 1 had 3 seizures over the 12 months after surgery. This represents a 4% morbidity at 1 year. CONCLUSION: Selected anterior cerebral circulation aneurysms can be clipped with low morbidity, using an ipsilateral minicraniotomy preserving the orbital rim, and without using an endoscope. The types of aneurysm selection criteria and operative equipment used are described.     

Surgery in the prevasospastic interval

Summary The result of surgery in the prevasospastic interval, between Day 3 and 7 after SAH, for patients with poor neurological conditions was compared with that of the early period within Day 1 or 2 after subarachnoid haemorrhage (SAH). There were no significant differences in incidence of the postoperative ischaemic syndrome or in the final result.