Hiroki Ohkuma

Incidence and Significance of Early Aneurysmal Rebleeding Before Neurosurgical or Neurological Management

Background and Purpose Rebleeding is a major cause of death and disability in aneurysmal subarachnoid hemorrhage (SAH); however, there has been no report focusing on rebleeding before hospitalization in neurosurgical or neurological institutions. The aim of this study was to clarify the incidence of prehospitalization rebleeding, its impact on the clinical course and prognosis in patients with aneurysmal SAH, and the possible factors inducing it. Methods In 273 patients who were admitted to our institution within 24 hours after the initial SAH bleeding and whose clinical course before admission could be fully evaluated, the patients’ clinical conditions and CT findings on admission, operability, prognosis, and possible factors inducing rebleeding were comparatively evaluated between the patients with and without an episode of prehospitalization rebleeding. Results Of the 273 patients, 37 (13.6%) patients suffered from 39 episodes of rebleeding in the ambulance or at the referring hospital before admission to our hospital. The peak time of rebleeding was within 2 hours (77%), in which the incidence was statistically significant compared with that occurring 2 to 8 hours after the initial SAH bleeding (P <0.01). The group experiencing rebleeding showed more severe Hunt and Hess grades on admission, higher rates of intracerebral hematoma, of intraventricular hematoma, and of subdural hematoma on CT scan on admission, less operability, and poorer prognoses with statistically significant differences compared with the group that did not experience rebleeding. Systolic arterial pressure >160 mmHg was a possible risk factor of rebleeding (odds ratio 3.1, 95% CI 1.5 to 6.8). Conclusions Rebleeding during transfer and at the referring hospital is not rare. To improve overall outcome of aneurysmal SAH, the results obtained in this study should be made available to general practitioners and the doctors devoted to emergency medicine.

Impact of Cerebral Microcirculatory Changes on Cerebral Blood Flow During Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF). METHODS In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm. RESULTS Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF. CONCLUSIONS In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.

Cerebrovascular disorders associated with von Recklinghausen's neurofibromatosis: a case report.

A 28-year-old woman with von Recklinghausens neurofibromatosis (NF-1) had a huge hematoma in the left posterior nuchal region. Carotid and vertebral angiograms revealed marked stenosis at the C3 portion of the left internal carotid artery, slight moyamoya staining, occlusion of the left vertebral artery at the atlas level, and a right internal carotid artery aneurysm. The radiographic, clinical, and histological features of this case are discussed together with a review of 42 similar cases found in the literature.

Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs.

OBJECTIVE Morphological and microcirculatory changes in intraparenchymal vessels after subarachnoid hemorrhage (SAH) have not yet been fully clarified. We conducted this experimental study to investigate the serial morphological changes of intraparenchymal arterioles after SAH. METHODS SAH was produced by injecting autologous arterial blood into the cisterna magna twice at 48-hour intervals in 30 dogs. The dogs were killed 3, 7, or 14 days after SAH, and then perfusion-fixed specimens of both anterior sylvian giri were obtained by using two methods. Microvascular corrosion casts produced by arterial injection of polyester resin were examined using scanning electron microscopy, and the widths of 40 arterioles of each animal were measured. Sectioned slices from the brain surface to 500 microns deep were examined by light microscopy, and external diameter, internal diameters, and wall thickness of the arterioles at depths of 50, 200, and 500 microns from the brain surface were morphometrically evaluated in 40 arterioles of each animal. In control animals receiving cisternal injections of mock cerebrospinal fluid (n = 10) and in healthy control animals (n = 10), the same examination and evaluation were performed. RESULTS Corrosion casts of arterioles showed tapered narrowing with folding after SAH, and the width of the arterioles significantly decreased 3 and 7 days after SAH (P < 0.01). Morphometric examination by light microscopy showed a significant decrease of internal diameter of arterioles associated with a significant increase of wall thickness at any depth from the brain surface 3 and 7 days after SAH (P < 0.05 or P < 0.01). These findings improved 14 days after SAH. Control animals receiving cisternal injections of mock cerebrospinal fluid showed no significant differences compared with healthy control animals. CONCLUSION These results suggest that constriction of intraparenchymal arterioles occurs after SAH and may contribute to delayed cerebral ischemia.

Dissecting Aneurysms of Intracranial Carotid Circulation

Background and Purpose— Clinical features of nontraumatic dissecting aneurysms of intracranial carotid circulation remain unclear because investigation of this disease has been limited to case reports. The aim of this study was to investigate the clinical features of this disease through the use of cooperatively collected cases. Methods— The cases diagnosed as dissecting aneurysms of intracranial carotid circulation on the basis of clinical signs and neuroradiological findings in 46 stroke centers from 1995 through 1999 were collected, and their clinical features were analyzed. Results— Forty-nine cases of dissecting aneurysms of intracranial carotid circulation were collected. Thirty-two patients presented with subarachnoid hemorrhage (SAH), and 17 presented with cerebral ischemia. The ratio of this disease to all intracranial dissecting aneurysms treated in the same institutes for the same period was 19.1%, and the ratio of SAH resulting from this disease to SAH of unverified origin treated in the same institutes for the same period was 6.2%. The predominant site of lesion was the internal carotid artery in 18 of 32 patients (56%) with SAH and the anterior cerebral artery in 13 of 17 patients (76%) with cerebral ischemia. The predominant angiographic findings were that stenosis with dilatation occurred in 20 of 32 patients (63%) with SAH and stenosis without dilatation was seen in 11 of 17 patients (65%) with cerebral ischemia. Poor prognosis was seen in 21 of 32 patients (66%) with SAH, which was due largely to rebleeding seen preoperatively, during operation, and even postoperatively when clipping or wrapping of the aneurysmal bulge was performed. Conclusions— Nontraumatic dissecting aneurysm of intracranial carotid circulation is not as rare as expected. It seems to be one of the important causes of SAH of unverified origin.

Inhibition of Integrin αvβ3 Ameliorates Focal Cerebral Ischemic Damage in the Rat Middle Cerebral Artery Occlusion Model

Background and Purpose— Recent studies have shown that selective inhibition of specific subsets of intercellular adhesion molecules protects the brain during ischemia. We studied selective inhibition of integrin αvβ3 with cyclo [Arg-Gly-Asp-d-Phe-Val] (cRGDfV) in the rat middle cerebral artery occlusion model (MCAO). Methods— Rats were treated before and after MCAO with cRGDfV. Physiological parameters, expression of integrin αvβ3, infarction volume, brain water content, Evans Blue exudation, IgG exudation, histology, immunohistochemistry, and western blotting were studied in 4 groups of animals: sham operation (n=13), untreated (n=18), nonfunctioning peptide treatment (n=19), and cRGDfV treatment (n=27). Results— Treatment with cRGDfV reduced infarction, reduced brain edema, reduced exudation of Evans blue and IgG, and prevented fibrinogen deposition. Western blotting showed reduction of phosphorylated Flk-1 (a vascular endothelial growth factor [VEGF] receptor), reduction of phosphorylated FAK (an intracellular kinase phosphorylated in the presence of VEGF), reduction of VEGF, and reduction of fibrinogen in the cRGDfV treatment group. Conclusions— The selective integrin αvβ3 inhibitor cRGDfV improves outcomes in the MCAO model by preserving the blood-brain barrier, which mechanistically may occur in a VEGF- and VEGF-receptor–dependent manner.

Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patients prognosis during the advanced stage.

Comparison of silicon-coated nylon suture to plain nylon suture in the rat middle cerebral artery occlusion model

UNLABELLED A variety of intraluminal sutures have been used in the middle cerebral artery occlusion model (MCAO) of focal ischemia. In the present study we tested commercially available silicon-coated nylon suture in the MCAO model and compared the results to traditional monofilament nylon suture occlusion. Twelve Sprague-Dawley male rats were randomly divided two groups, MCAO with 4-0 nylon suture (Group N, n=6) and MCAO with silicone-coated 4-0 nylon suture (Group S, n=6). Rats were sacrificed 24 h after reperfusion. Assessment included mortality rates, neurological evaluation, and infarct volume. One rat died in each group from subarachanoid hemorrhage. Neurological evaluation demonstrated that Group S tended to have worse neurological outcomes than Group N, although this difference was not statistically significant. On TTC stain Group S had significantly larger infarct volumes than Group N. We conclude that the commercially available silicone-coated occlusion suture provides better occlusion of the middle cerebral artery than the traditional uncoated nylon suture. CLASSIFICATION Disease-related neuroscience (Section 6).

Management of giant serpentine aneurysms of the middle cerebral artery--review of literature and report of a case successfully treated by STA-MCA anastomosis only.

SummaryThirty-eight cases of giant serpentine aneurysms (GSA), including 17 GSA of the middle cerebral artery (MCA), were reviewed in the literature. The treatment possibilities of GSA of the MCA are discussed together with our own case who was a 39-year-old male with a GSA of the right MCA and was treated only by STA-MCA anastomosis. The pathogenetic mechanism of progressive enlargement of the aneurysm is also discussed.

Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVEIt is hypothesized that cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is induced by free radicals released from a subarachnoid clot. This study therefore investigated the effect of a new free radical scavenger, edaravone, in the treatment of patients with aneurysmal SAH. METHODSNinety-one patients with aneurysmal SAH participated in this study and were randomized into a control group (n = 42) and an edaravone-treated group (n = 49). The difference between the 2 groups in terms of incidence of delayed ischemic neurological deficits (DINDs) and cerebral infarction caused by vasospasm, and Glasgow Outcome Scale score at 3 months after SAH were statistically analyzed. RESULTSThe incidence of DINDs was 21% in the control group and 10% in the edaravone-treated group, yet there was no statistically significant difference between the 2 groups (P = 0.118). In patients with DINDs, the incidence of cerebral infarction caused by vasospasm was 66% in the control group and 0% in the edaravone-treated group (P = 0.028), whereas the incidence of poor outcome caused by vasospasm was 71% in the control group and 0% in the edaravone-treated group (P = 0.046). CONCLUSIONWe found a trend toward a lesser incidence of DINDs and a lesser incidence of poor outcome caused by cerebral vasospasm in edaravone-treated patients. It might therefore be suggested that edaravone is a useful agent for the treatment of aneurysmal SAH.