Thick Subarachnoid Hemorrhage Research Articles

Sample Size Estimates for Clinical Trials of Vasospasm in Subarachnoid Hemorrhage

Clinical trials for prevention of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) seldom have improved overall outcome; one reason may be inadequate sample size. We used data from the tirilizad trials and the Columbia University subarachnoid hemorrhage outcomes project to estimate sample sizes for clinical trials for reduction of vasospasm after SAH, assuming trials must show effect on 90-day patient-centered outcome. Sample size calculations were based on different definitions of vasospasm, enrichment strategies, sensitivity of short- and long-term outcome instruments for reflecting vasospasm-related morbidity, different event rates of vasospasm, calculation of effect size of vasospasm on outcome instruments, and different treatment effect sizes. Sensitivity analysis was performed for variable event rates of vasospasm for a given treatment effect size. Sample size tables were constructed for different rates of vasospasm and outcome instruments for a given treatment effect size. Vasospasm occurred in 12% to 30% of patients. Symptomatic deterioration and infarction from vasospasm exhibited the strongest relationship to mortality and morbidity after SAH. Enriching for vasospasm by selection of patients with thick SAH slightly decreased sample sizes. Assuming beta=0.80, alpha=0.05 (2-tailed) and treatment effect size of 50%, total sample size exceeds 5000 patients to demonstrate efficacy on 3-month patient-centered outcome (modified Rankin Scale). Clinical trials targeting vasospasm and using traditional patient-centered outcome require very high sample sizes and will therefore be costly, time-consuming, and impractical. This will hinder development of new treatment strategies.

Acute gastric dilatation causing bacterial cerebral aneurysm—Case report

Acute gastric dilatation (AGD) is a very rare entity which can sometimes be life-threatening. We report a case of a patient presenting with a rupture of a BCA during the treatment of AGD. A 24-year-old woman, who had a history of bulimia and vomiting episodes, was transferred in shock with marked abdominal distension. A large nasogastric tube was inserted, and 9 liters of viscous gastric contents were drained out. Her circulation became stable. About 3 months after admission, she became drowsy and presented with a right hemiparesis and aphasia. Computed tomography of the head showed a diffuse thick subarachnoid hemorrhage. Left carotid angiograms revealed an obscurely-shaped aneurysm in the left middle cerebral artery. Trapping of the aneurysm was performed. Thirty-four days after admission, the patient had a residual right hemiparesis and motor aphasia, and was discharged.

Early vasospasm on admission angiography in patients with aneurysmal subarachnoid hemorrhage is a predictor for in-hospital complications and poor outcome.

Early vasospasm (EVSP), defined here as arterial narrowing seen on diagnostic angiography within the first 48 hours of aneurysmal rupture, is a rarely reported and poorly defined phenomenon in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to characterize EVSP in a large database of such patients. We analyzed the relationship of EVSP to clinical characteristics, in-hospital complications, and outcome at 3 months among 3478 patients entered into 4 prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997. Three hundred thirty-nine (10%) of 3478 patients had EVSP. EVSP was significantly more likely in patients with poor neurological grade on admission, history of SAH, intracerebral hematoma, larger aneurysm, thick SAH on cranial computed tomography, and intraventricular hemorrhage. EVSP was not associated with delayed cerebral vasospasm. After adjustment for differences in admission characteristics, EVSP was associated with cerebral infarction (adjusted odds ratios [OR]=1.51; 95% CI, 1.18 to 1.94; P=0.001), neurological worsening (OR=1.41; 95% CI, 1.10 to 1.81; P=0.007), and unfavorable outcome (OR=1.51; 95% CI, 1.15 to 2.00; P=0.003). In addition, there was a trend for patients with increasingly severe EVSP to have unfavorable outcome (OR=1.84 for mild and OR=2.66 for moderate/severe EVSP). EVSP was seen in 10% of SAH patients and was predictive of cerebral infarction and neurological worsening as well as unfavorable outcome at 3 months. EVSP was not associated with late vasospasm. EVSP may be as important as delayed vasospasm in predicting complications and long-term morbidity in SAH patients.

術中著明な血圧低下をきたした後大脳動脈りゅうの１例

A 48-year-old woman was admitted to our emergency center for deterioration of consciousness. On arrival, her level of consciousness was 3 by the Japan Coma Scale and 10 by the Glasgow Coma Scale. Her blood pressure was 144/100 mmHg, and her pulse was regular at 136 beats/min. She was intubated under general anesthesia to lower the systolic blood pressure to 90-100 mmHg. Laboratory analysis showed elevated blood glucose (329 mg/dl), lactic dehydrogenase (311 U/l), creatinine kinase (CK, 410 U/l), and white blood cell count (19600/μl), and a reduced serum potassium (3.1 mmol/l). A computed tomographic scan showed a diffuse thick subarachnoid hemorrhage (SAH), and a chest X-ray revealed cardiomegaly and pulmonary edema. Electrocardiography on admission demonstrated sinus tachycardia and ST segment elevation in leads I, II, aVL, and V3 to V6, and a slightly prolonged QTc interval of 0.45 second. Echocardiography showed that wall motion of the left ventricular apex was significantly reduced, indicating specific “takotsubo” cardiomyopathy. Her cardiac function appeared to be well tolerant for direct surgery. Digital subtraction angiography was performed and disclosed an aneurysm at the P1 segment of the left posterior cerebral artery. Surgical intervention was undertaken by the left pterional approach. While a subarachnoid clot in the prepontine cistern was being evacuated to expose the aneurysm via an opticocarotid triangle, her blood pressure suddenly dropped to 20 mmHg, her heart rate declined to 20 beats/min, and carotid pulsation disappeared. The surgery was discontinued and cardiac resuscitation was conducted by intravenous injection of 1 mg epinephrine and cardiac massage by chest compression. Twenty-five minutes later her cardiac function stabilized, and the aneurysm was successfully clipped. The postoperative course was uneventful, and the electrocardiogram showed inversion of T waves and gradual improvement of echocardiographic abnormalities. An excessive catecholamine secretion related to hypothalamic damage is presumed to be the cause of cardiac dysfunction in the acute phase of SAH. Although evacuation of prepontine clot is a routine surgical maneuver, subtle compression or traction of the perforators from the P1 segment that feeds the hypothalamus might further injure the already affected hypothalamus to result in sudden cardiac arrest. In treatment of patients with SAH associated with cardiac dysfunction, preparation of an intra-aortic balloon pumping would be beneficial.

Ｋｉｓｓｉｎｇ ａｎｅｕｒｙｓｍに類似した両側末梢性前大脳動脈りゅうの１例

A 71-year-old woman presented disturbance of consciousness due to subarachnoid hemorrhage (SAH). A computed tomography (CT) on admission revealed diffuse thick SAH and intracerebral hematoma in the right frontal lobe. Conventional angiography and three-dimensional CT angiography showed symmetrical aneurysms located on the bilateral pericallosal arteries at bifurcation of the callosomarginal arteries. The operation was performed on the next day after onset of SAH. The aneurysms were clipped via the right unilateral interhemispheric approach. Intraoperative findings demonstrated a ruptured right-side aneurysm adhered to a left unruptured aneurysm. Neck clipping was performed with meticulous dissection, especially between both aneurysmal necks. Bilateral distal anterior cerebral artery (BDACA) aneurysms are rarely reported. Surgery of closely located aneurysms requires dissection of all the aneurysmal necks to secure safe and accurate obliteration. Meticulous procedures are nesesary to deal with BDACA similar to kissing aneurysms in the internal carotid artery.

Predictors of cognitive dysfunction after subarachnoid hemorrhage.

Cognitive dysfunction is a common and disabling sequela of subarachnoid hemorrhage (SAH). Although several clinical and radiographic findings have been implicated in the pathogenesis of cognitive dysfunction after SAH, few prospective studies have comprehensively and simultaneously evaluated these risk factors. Between July 1996 and March 2000, we prospectively evaluated 113 of 248 consecutively admitted nontraumatic SAH patients alive at 3 months with a comprehensive neuropsychological evaluation. Summary scores for 8 cognitive domains were calculated to express test performance relative to the entire study population. Clinical and radiographic variables associated with domain-specific cognitive dysfunction were identified with forward stepwise multiple regression, with control for the influence of demographic factors. The study participants were younger (P=0.005), less often white (P=0.006), and had better 3-month modified Rankin scores (P=0.001) than those who did not undergo neuropsychological testing. The proportion of subjects who scored in the impaired range (>2 SD below the normative mean) on each neuropsychological test ranged from 10% to 50%. Predictors of cognitive dysfunction in 2 or more domains in the multivariate analysis included global cerebral edema (4 domains), left-sided infarction (3 domains), and lack of a posterior circulation aneurysm (2 domains). Other variables consistently associated with cognitive dysfunction in the univariate analysis included admission Hunt-Hess grade >2 and thick SAH in the anterior interhemispheric and sylvian fissures. Global cerebral edema and left-sided infarction are important risk factors for cognitive dysfunction after SAH. Treatment strategies aimed at reducing neurological injury related to generalized brain swelling, infarction, and clot-related hemotoxicity hold the best promise for improving cognitive outcomes after SAH.

Intraaneurysmal GDC Embolization for Ruptured Aneurysm in the Acute Stage

This report focused on our treatment protcol and results on the intraaneurysmal GDC embolization for ruptured aneurysm in the acute stage. Clinical materials of this study consist of 39 patients who were treated with intraaneurysmal GDC embolization within 72 hours after the onset of subarachnoid hemorrhage from March 1997 to May 1999. Patients with cerebral aneurysms are always examined as a possible candidate for neurosurgical clipping. If the patient had any difficulties and/or problems on neurosurgical clipping (high age 24, poor grade 12, surgically difficult location 11, systemic disease 2), the patient was treated by intraaneurysmal GDC embolization. GDCs were inserted as tight as possible. Then, spinal drainage was set in patients with thick subarachnoid hemorrhage. Tissue plasminogen activator was administered via the drainage in patients with thicker subarachnoid hemorrhage. Two patients experienced rerupture during peritherapeutic period. Symptomatic vasospasm was observed in 2 patients (5.1%). Good outcome was obtained in 31 out of 34 surviving patients. Symptomatic complication caused by distal embolism occurred in 1 patient, parent artey occlusion in 3 patients. In conclusion, intraaneurysmal GDC embolization is thought to be sufficient regarding prevention of rerupture, incidence of vasospasm, and clinical outcome.

Intra-aneurysmal GDC Embolization for Ruptured Aneurysm in the Acute Stage

This study focused on our experiences in intraaneurysmal embolization for ruptured aneurysm in the acute stage. Clinical materials of this study consist of 37 patients who were treated with intra-aneurysmal GDC embolization within 72 hours after the onset of subarachnoid hemorrhage from December 1995 to July 1998. Patients with cerebral aneurysms are always examined as possible candidates for neurosurgical clipping. If the patient had any difficulties and/or problems on neurosurgical clipping (high age 22, poor grade 15, surgically difficult location 9, systemic disease 3), the patient was treated by intra-aneurysmal GDC embolization. GDCs were inserted as tight as possible. Then, spinal drainage was set in patients with thick subarachnoid hemorrhage. Tissue plasminogen activator was administered via the drainage in patients with thicker subarachnoid hemorrhage. One patient experienced rerupture during peritherapeutic period. Symptomatic vasospasm was observed in three patients (8.1%). Good outcome was obtained in 26 out of 30 surviving patients. Symptomatic complication caused by distal embolism occurred in two patients. In conclusion, intra-aneurysmal GDC embolization is thought to be sufficient regarding prevention of rerupture, incidence of vasospasm, and clinical outcome.

Management of subarachnoid hemorrhage patients who presented with respiratory arrest resuscitated with bystander CPR.

The sudden death rate from aneurysmal subarachnoid hemorrhage (SAH) is 10%. Since 1989, 26 SAH patients who were witnessed to collapse into coma with respiratory arrest and required cardiopulmonary resuscitation (CPR) at the scene survived to reach the hospital and be diagnosed. Although reports on hospital management of grade V SAH suggest improved outcome, no report has previously addressed the issue of respiratory arrest after acute SAH. We analyze our experience with this unique subgroup of aneurysmal SAH patients. This is a retrospective analysis of 26 consecutive SAH patients who collapsed at the scene and required CPR for respiratory arrest and survived to reach the hospital and be diagnosed. Statistical analysis was performed using the t test and Mann-Whitney rank-sum test. All patients were grade V on arrival at the emergency department. Twenty-one patients received mouth-to-mouth resuscitation only, and 5 received chest compressions as well. The mean duration of bystander CPR was 12 to 15 minutes. CT scan showed diffuse, thick SAH in all patients, an associated subdural hemorrhage in 2, and an intraparenchymal hemorrhage in 4. After CT scan, an intracranial pressure (ICP) monitor was placed in 24, and 2 were taken to emergency surgery for subdural and intracerebral hemorrhage. ICP was elevated in 24 patients (mean, 54 mm Hg), and a ventriculostomy was placed in all 24. ICP was unresponsive in 12, and all suffered brain death. ICP lessened to < 25 mm Hg in 12, and all underwent angiography. All 12 had an aneurysm and underwent emergency surgical clipping. Time to surgery from SAH was < or = 11 hours in all 12 patients. All were managed with calcium channel blockers and hyperdynamic therapy in addition to aggressive control of ICP. The outcome at 12 months in the 14 surgical cases was normal in 3 patients (21%), good in 2 (14%), vegetative in 1 (7%), and death in 8 (57%). Aneurysmal SAH patients that present with respiratory arrest present as grade V patients with elevated ICP. Bystander CPR coupled with early retrieval, diagnosis, and therapy can lead to 20% functional survival in what used to be sudden death from aneurysmal SAH.

Prospective study on the prevention of cerebral vasospasm by intrathecal fibrinolytic therapy with tissue-type plasminogen activator.

The authors have evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in patients with a diffuse thick subarachnoid hemorrhage (SAH). The present study examined 105 patients who underwent direct surgery within 48 hours of SAH and whose computerized tomography (CT) findings were classified as Fisher CT Group 3. Patients showing diffuse thick subarachnoid blood clots on CT with greater than 75 Hounsfield units (HU) were included in the tPA therapy group and those with below 75 HU comprised the control group. The surgical method was the same in both groups, and both groups had cisternal drainage instituted. On the day following the operation, the tPA group was given an intrathecal injection of tPA (2 mg), and this was continued for several days until all of the cisterns exhibited low density on CT scans. Follow-up angiography showed that 26 cases (87%) in the tPA group had no vasospasm, three (10%) had moderate vasospasm, and one (3%) had severe vasospasm. All four patients showing spasm on angiography were asymptomatic, and there were no cases of delayed ischemic neurological deficits (DIND). In contrast, there were 11 cases (15%) with DIND in the control group. In the tPA group, there was one case of SAH caused by drainage catheter removal, one with a small epidural hematoma, and one with subgaleal fluid accumulation; all of these were treated conservatively with favorable results. Overall, there were no infectious complications related to cisternal drainage and intrathecal injection of tPA. These results indicate that multiple intrathecal injections of small doses of tPA are effective and safe in preventing vasospasm. On the basis of this experience, the authors conclude that injection of 2 mg of tPA daily for 5 days (a total of 10 mg) is effective in preventing the development of vasospasm.

Cerebral Blood Flow as a Prognostic Indication in Subarachnoid Hemorrhage

In an investigation of the changes in cerebral blood flow (CBF) in subarachnoid hemorrhage, CBF was monitored in 14 patients who underwent surgery within 3 days of the onset of hemorrhage. On admission, one patient was neurological grade I, one was grade II, seven were grade III, and five were grade IV. Computed tomography showed diffuse, thick subarachnoid hemorrhage with or without intracerebral hematoma in all patients, strongly indicating the possibility of cerebral vasospasm. CBF monitoring was performed by the thermal diffusion technique, in which a small flow probe, 7 mm in diameter and 4 mm in height and containing a Peltier stack, is used. The probe was implanted in the subdural space in the frontotemporal region during surgery. Epidural intracranial pressure was also monitored. Local CBF was measured continuously for 7 to 19 days after surgery. Immediately after surgery, CBF was low in grade IV patients (mean, 25 ml/100 g/min), whereas a variety of CBF rates were observed in grade III patients. Minimal decreases in CBF were noted in the grades I and II patients (mean, 41 ml/100 g/min). The sequential changes in CBF were well correlated with outcome. The two grades I and II patients, who had no appreciable decrease in CBF, had excellent outcomes. In the five (of seven) grade III patients who showed good or excellent recovery, CBF was maintained with only a slight decrease. In two grade III patients, substantial depression of CBF occurred several days after the onset of subarachnoid hemorrhage; one had a poor outcome, and one died. Good recovery of CBF was observed in one grade IV patient, who showed excellent postoperative recovery. The remaining four patients, had moderate to substantial decreases in CBF, with poor postoperative results, including two deaths. These observations indicate that a decrease in CBF due to vasospasm or other causes can be detected early through CBF monitoring. In addition, the outcome of subarachnoid hemorrhage can be predicted on the basis of sequential changes in CBF.