Shiro Kashiwagi

Sphingosylphosphorylcholine Is a Novel Messenger for Rho-Kinase–Mediated Ca2+ Sensitization in the Bovine Cerebral Artery: Unimportant Role for Protein Kinase C

Although recent investigations have suggested that a Rho-kinase–mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase–mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 &mgr;mol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester–induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase–mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.

The effect of EC-IC bypass surgery on resting cerebral blood flow and cerebrovascular reserve capacity studied with stable Xe-CT and acetazolamide test

SummaryCerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were measured by stable xenon computerized tomography (Xe-CT) and acetazolamide test in 15 patients with cerebrovascular disease before and after extracranial-intracranial (EC-IC) bypass surgery for minor stroke, reversible ischemic neurological deficit or transient ischemic attack. All had angiographically shown occlusive lesions of the major arterial trunk. In the present series, global analysis showed that the bypass did not increase the resting rCBF, but did increase the rCRC. We divided the patients into four groups according to the preoperative resting rCBF and rCRC. All 3 patients with normal resting rCBF and reduced rCRC showed postoperative improvement of rCRC. Of 6 patients with reduced CBF and reduced CRC, three had postoperative increase in resting CBF and four had increased CRC. One of two patients with reduced CBF and normal CRC showed only an increase in CRC. We propose that reduced CRC or reduced CBF with reduced CRC are criteria for selection of candidates for bypass surgery. We conclude that Xe-CT with the Diamox test is a useful and simple method for evaluating cerebral hemodynamics. Preoperative grouping with a combination of preoperative resting cCBF and preoperative rCRC is useful for predicting the effect of EC-IC bypass surgery.

Evaluation of Cerebral Perfusion parameters measured by Perfusion CT in chronic Cerebral ischemia: Comparison with xenon CT

Purpose The purpose of this work was to evaluate the usefulness of perfusion CT in the evaluation of patients with chronic cerebral ischemia by comparing it with xenon CT (Xe-CT). Method Cerebral blood flow (CBF) of perfusion CT (CBFper) and time to peak (TTP) were compared with the CBF of Xe-CT (CBFxe) in 18 patients. Cerebral blood volume (CBV) was compared with cerebral vascular reserve (CVR) in 10 of 18 patients who underwent pre- and postacetazolamide Xe-CT. Results CBFper and TTP demonstrated a high correlation with CBFxe in relative values by side-to-side comparisons (r = 0.743, p < 0.0001 and r = −0.760, p < 0.0001, respectively). There was a negative correlation between relative CBV and relative CVR (r = −0.637, p = 0.0025). Visually, territories with delayed TTP corresponded well to those of decreased CBFxe, but these territories tended to be larger in TTP maps. Conclusion Perfusion CT is a useful tool to evaluate chronic hemodynamic disturbance and can be an alternative method for those using acetazolamide challenge.

Cerebral Aneurysms in the Elderly in Yamaguchi, Japan Analysis of the Yamaguchi Data Bank of Cerebral Aneurysm From 1985 to 1995

BACKGROUND AND PURPOSE The number of elderly people is markedly increasing in Japan. We have investigated the epidemiology and management outcome of cerebral aneurysms in elderly patients aged > or = 70 years. METHODS A total of 3100 patients were enrolled in the Yamaguchi Data Bank of Cerebral Aneurysm between 1985 and 1995. Of these, 598 with ruptured cerebral aneurysms and 120 with unruptured cerebral aneurysms were elderly (ie, aged > or = 70 years). RESULTS The number of elderly patients with cerebral aneurysms has markedly increased since 1991, and in 1995 approximately 30% of all patients with cerebral aneurysms were elderly. In cases of ruptured cerebral aneurysms, the proportion of patients with severe neurological grade did not change and that with an unfavourable outcome did not decrease throughout the 11 years. The proportion of patients with severe neurological grade in the elderly group was higher than in the younger group (< 70 years), and the management outcome of elderly patients for each neurological grade on admission was worse than that of younger patients (P < .01). However, the incidence rate of symptomatic cerebral vasospasm and rebleeding was the same for the two age groups. Eventually, 60.4% of all elderly patients with ruptured cerebral aneurysms had an unfavorable outcome. In cases of unruptured cerebral aneurysms, 63.3% of the selected elderly patients were surgically treated, and the surgical morbidity and mortality rates were 26.3% and 4.0%, respectively. These rates were nonsignificantly higher than those for younger patients. CONCLUSIONS The number of elderly patients with cerebral aneurysms has markedly increased in Yamaguchi. Because of the unsatisfactory management outcome of ruptured cerebral aneurysms and surgical outcome of unruptured cerebral aneurysms in elderly patients during the 11-year period, we propose the treatment of unruptured cerebral aneurysms at a younger age and the use of a screening system to detect these subjects.

Perioperative management protocols for children with moyamoya disease

Abstract Protocols for prevention of cerebral ischemic attacks caused by hyperventilation resulting from crying, as observed in perioperative pediatric moyamoya patients, were evaluated. The first protocol involved the use of sedation when staff were setting up the intravenous lines, performing neuroimaging studies, and controlling postoperative pain. The second involved the use of wound-handling techniques designed to ease postoperative wound care; these included steristrip closure, use of paraffin gauze and not using adhesive tapes. We compared 14 and 11 surgical cases handled before and after the protocols were introduced, respectively. The number of patients with perioperative cerebral infarction decreased from 2 to 0. Appropriate sedation reduced the incidence of transient ischemic attacks from 28.6% to 3.7%. The average postoperative hospital stay was similarly reduced, from 21.3 days to 16.1 days, as a consequence of the reduced incidence of complications. It is concluded that the perioperative risks can be minimized when invasive procedures are managed according to our protocols.

Brain perfusion studies by xenon-enhanced CT using washin/washout study protocols.

Very short inhalation times and short total examination times are desirable in cerebral blood flow measurements by xenon enhanced CT to minimize the possibility of flow activation and--more importantly for practical purposes--the probability of patient motion due to the effects of xenon. We have investigated washin/washout procedures and have compared them with conventional washin scanning protocols by simulation and in clinical studies. Examination protocols with only 3 min of inhalation and up to eight scans, all taken at 1 min intervals, provide flow estimates with smaller SDs than would be obtained for washin studies taken with the same total radiation dose. Compared with a standard 8 min washin procedure, a 3 min washin/5 min washout study using the same dose yields an SD reduction by a factor of 1.3 for low flow areas and of 1.8 for high flow gray matter. A 3 min washin/3 min washout study, employing only 78% of the dose of an 8 min washin study, will still provide an SD reduction factor of 1.7 in gray matter. These results have been confirmed qualitatively by studies carried out both in volunteers and in patients.

The effect of sodium bicarbonate on CBF and intracellular pH in man: Stable Xe‐CT and 31P‐MRS

The effects of sodium bicarbonate on cerebral blood flow (CBF) and intracellular pH were studied in five normal volunteers. CBF and intracellular pH were measured by stable xenon computed tomography and phosphorus‐31 magnetic resonance spectroscopy (31P‐MRS) respectively. Each patient received 7% sodium bicarbonate (3.5 ml/kg body weight) infused intravenously for 15 minutes. Before and after this injection, CBF, intracellular pH and physiological parameters were measured. CBF and PaCO2 were significantly increased. On the other hand, hematocrit and intracellular pH were decreased. These result suggests that three factors are thought to contribute to increase CBF during administration of sodium bicarbonate in humans: 1) arterial dilatation in response to carbon dioxide 2) an decrease of hematocrit 3) intracellular acidosis.

Revascularization with split duro-encephalo-synangiosis in the pediatric Moyamoya disease—surgical result and clinical outcome

Dural arteries are potential donor arteries for cortical revascularization. In this report, a technique of indirect anastomosis using a split dura is presented. At surgery, the dura near the branches of the middle meningeal artery was split into outer and inner layers, and the split surface of the outer layer was attached to the cortical surface (split duro-encephalo-synangiosis; split DES). This procedure, combined with standard encephalo-duro-arterio-synangiosis, was applied to 25 hemispheres in 18 patients with pediatric Moyamoya disease (mean age, 6 years). Postoperative superselective angiograms demonstrated effective cortical revascularization through the dural arteries in addition to the supply from the scalp arteries. All the patients were symptom free by 1.5 years after surgery. Postoperative reversible ischemic neurological deficit and infarction were seen in three (12%) and one (4%), respectively. The follow-up period ranged from 1 to 12 years (mean, 6.5 years). Thirteen of 16 (81%) patients led normal lives and three were mildly handicapped due to mental retardation that existed preoperatively. The split DES is a useful technique to extend the area of revascularization of ischemic hemispheres in Moyamoya disease.

Intracranial pressure monitoring using a programmable pressure valve and a telemetric intracranial pressure sensor in a case of slit ventricle syndrome after multiple shunt revisions

A case of hydrocephalus showing slit ventricle syndrome after multiple shunt revisions was treated with a programmable pressure valve, and intracranial pressure was monitored with a telemetric sensor. High pressure setting produced positive and normal values of intracranial pressure in this patient. We report our experiences.

Regression of rnoyamoya vessels and hemodynamic changes after successful revascularization in childhood movarnova disease

Successful revascularization improves ischemic symptoms in the pediatric patients with moyamoya disease. However, it is not clear whether the revascularization prevents future intracranial hemorrhage from the residual moyamoya vessels. The purpose of this study is to investigate perioperative morphological and hemodynamic changes in the moyamoya vessels. Four pediatric patients (age < 15 years old) with bilateral moyamoya disease were selected for this study. To quantify the number of moyamoya vessels, T1‐weighted transverse images at the level of the basal ganglia and the thalamus were selected and characteristic flow voids in the lentiform nucleus were counted. Resting CBF and cerebrovascular reserve capacity (CRC) were measured pre‐ and 1 year after surgery using Xenon‐CT CBF method with acetazolamide test. The ratio of deep CBF/kortical CBF was calculated as an index of hemodynamic stress distribution. The one‐year follow‐up studies showed that 1) the number of moyamoya vessels decreased on the operative side, but did not change on the nonoperative sides in all cases; 2) the ratio of deep CBFkortical CBF decreased on the operative sides, but did not change in the non‐operative sides; and 3) the CRC increased on both sides. This observation suggests the possibility that revascularization surgery may be effective for preventing the future risk of intracranial hemorrhage.