Hiroyuki Nakashima

Long-term results of surgically treated Moyamoya disease

Various surgical procedures have been tried for patients with Moyamoya disease. The most effective treatment, however, is still controversial. We retrospectively evaluated the long-term results of 71 patients (26 men and 45 women) with Moyamoya disease surgically treated in our institute. They consisted of 56 pediatric patients (younger than 15 years) and 15 adult patients. Symptoms in all patients were due to cerebral ischemia. We did 123 operations on 119 hemispheres: 18 superficial temporal artery--middle cerebral artery (STA-MCA) anastomoses, six STA-MCA anastomoses with indirect bypass (IB), 41 encephalo-duro-arterio-synangiosis (EDAS), 29 encephalo-duro-arterio-myo-synangiosis (EDAMS) and 29 ribbon EDAMS. Average follow-up periods for each procedure were: 7 years for STA-MCA anastomosis, 6.2 years for STA-MCA anastomosis with indirect bypass, 11 years for EDAS, 5.6 years for EDAMS and 2.6 years for ribbon EDAMS, respectively. The results of each procedure were satisfactory because the preoperative transient ischemic attacks disappeared. Analysis of follow-up angiograms shows excellent filling of the ACA and MCA territory in the patients undergoing ribbon EDAMS. However, long-term follow-up study shows that about 10% of the patients had severe difficulty in social or school life because of intellectual impairment.

Histological signs of immune reactions against allogeneic solid fetal neural grafts in the mouse cerebellum depend on the MHC locus

SummaryUsing an immunocytochemical method, we examined the immunological responses of adult mice to intracerebellar syngeneic and allogeneic fetal mouse brainstem transplants (embryonic days 12–14). Syngeneic grafts and major histocompatibility complex (MHC)-compatible and non-MHC-incompatible allogeneic grafts survived well, showing no histological signs of rejection even 6 months after transplantation, and with no expression of MHC antigens being observed in any of the grafts. However, most cases of both MHC- and non-MHC-incompatible allografts showed rejection responses, such as marked neovascularization, cellular infiltration and necrosis, two weeks to one month after transplantation. In animals showing rejection, Class I MHC antigens were found on grafted neuronal tissue. An increased number of reactive astrocytes was also observed in the grafts. High levels of Class I antigen expression and prominent gliosis correlated with vigorous cellular infiltration. A quantitative analysis of T cell subsets in the animals showing rejection revealed that the L3T4/Lyt-2 ratio was 1.02±0.21 (mean ± S.D.), indicating that helper/inducer and cytotoxic/suppressor T cells appeared equally in the rejection of MHC- and non-MHC-incompatible allografts. We consider that in these experiments, the brain was not completely an immunologically privileged site, and that MHC- and non-MHC-incompatible intraparenchymal neural transplants were not shielded from host immune surveillance.

Long-term follow-up study of patients with unilateral Moyamoya disease

Although a number of cases of unilateral Moyamoya disease have been reported, the natural history of this disease remains unclear. The clinical features of 17 patients initially diagnosed with unilateral Moyamoya disease at our hospital are reported. Age at onset was 3-45 years (mean, 13.5). Of these 12 cases had onset of symptoms in childhood and five had onset in adulthood. Seven were male and 10 were female. An ischemic attack was the initial episode in ten of the 12 pediatric cases, two of the five adult cases presented with intraventricular hemorrhage. Of the 12 pediatric patients six developed contralateral lesions between 4 and 34 months (mean, 20) after the diagnosis of a unilateral lesion. The remaining six pediatric patients and all adult patients did not develop lesions on the normal side. The mean age at onset for patients later developing contralateral lesions was 6.2 years. The pediatric cases remaining unilateral was 7.7 years. The normal hemisphere of three of the pediatric patients has remained unchanged on repeated follow-up angiograms for over 10 years. Young children tended to develop the vascular pathology bilaterally. However, there were some pediatric cases whose normal or atypical sides remained unchanged without development of bilateral lesions.

Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery

Six aneurysms in five patients with acute aneurysmal subarachnoid hemorrhages were treated with direct thrombosis using cellulose acetate polymer within 4 hours of rupture. The aneurysms involved the internal carotid and posterior communicating arteries (two patients), the anterior choroidal artery (one patient), the bifurcation of the basilar artery (one patient), and the middle cerebral artery (two patients). Four patients underwent aggressive volume expansion after direct thrombosis with cellulose acetate polymer. The aneurysms remained thrombosed until operations on the necks were performed 2 to 7 weeks after the subarachnoid hemorrhages. Three patients were given intrathecal tissue plasminogen activator. One patient, who remained at neurological Grade V, was not treated surgically and died from cardiac failure. Five aneurysms in the remaining four patients were successfully clipped. These preliminary data suggest that immediate aneurysmal thrombosis, then aggressive preoperative prophylactic volume expansion and/or administration of intrathecal tissue plasminogen activator, can help prevent new bleeding and reduce delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhages.

The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents

This study examines the effect of a novel immunosuppressive agent FK-506 (FK) on the survivability of embryonic (E14) rat ventral mesencephalic tissue after intracerebral grafting to the lateral ventricle of adult mice. The recipient mice were given FK in doses of 10 mg/kg or 1 mg/kg for 2 weeks postgrafting, at which time they were sacrificed and histologically processed except for one group of animals on the high dose (10 mg/kg). In this group most animals died from side effects of the drug during the following days. Only the mice receiving the high dose of FK displayed healthy grafts without signs of rejection.

Immunological reaction and blood-brain barrier in mouse-to-rat cross-species neural graft

Pieces of brainstem tissue from mouse embryos were transplanted into the cerebellar vermis of 49 adult rats, which had or which had not been treated with Cyclosporin A (10 mg/kg/day). With no treatment of immunosuppressants survival rates of xenografts were low. However, when Cyclosporin A was administered, the rates increased from 40% (4/10) to 67% (8/12) 2 weeks after grafting and from 25% (3/12) to 60% (9/15) 4 weeks after grafting, although immunological reactions of varying severities were noted in all of the surviving grafts. The present immunocytochemical study elucidated the composition of cell infiltrations frequently seen in the grafts. The results showed that a large number of cytotoxic/suppressor T lymphocytes appeared, while the numbers of helper/inducer T lymphocytes were relatively small. In addition, increased staining of astrocytes and microglia was observed in areas of cell infiltration. These activated cells might play a certain role in the process of graft rejection in the brain. Formation of the blood-brain barrier in the xenografts was examined by means of peroxidase cytochemistry and immunohistochemistry. In brains containing surviving grafts limited leakage of peroxidase, following its injection into the host systemic circulation 30-75 min prior to sacrifice, was detectable at the graft-host interface and at the operation scar near the pial surface. In brains containing rejected grafts extensive extravasation of peroxidase was detected. The severity of the immunological reaction was correlated with the intensity of the rupture in the blood-brain barrier. The findings suggested that the immunological reaction contributed to the transendothelial permeability changes in the vessels of brains containing rejected grafts.

Spinal atypical teratoid/rhabdoid tumor in an infant.

Atypical teratoid/rhabdoid tumor of the central nervous system in infancy and childhood was established as an entity based on histological, immunohistochemical, and cytogenetic studies. We report the case of a 7-month-old girl who presented with progressive paraplegia and hypesthesia of her legs. Imaging studies revealed a spinal cord mass occupying the entire spinal canal below the T7 level. Through a T12-L3 laminectomy, the intramedullary tumor was partially debulked. Histologically, the tumor specimen had rhabdoid cells, and immunostaining showed vimentin and cytokeratin positivity. No abnormality of chromosome 22q was detected with the fluorescence in situ hybridization method.

The importance of venous hypertension in the formation of dural arteriovenous fistulas: a case report of multiple fistulas remote from sinus thrombosis

Various hypotheses have been reported concerning the pathogenesis of dural arteriovenous fistulas (DAVFs). However, it is still controversial whether sinus thrombosis or venous hypertension has a greater influence on the formation of DAVFs. We present a rare case of multiple DAVFs that developed after sinus thrombosis. Chronic venous hypertension secondary to sinus thrombosis in the left transverse-sigmoid sinus induced the multiple DAVFs, including one in the right cavernous sinus, which was remote from the occluded sinus. This case indicates the importance of venous hypertension in the formation of DAVFs.

Effect of external stenting and systemic hypertension on intimal hyperplasia in rat vein grafts.

OBJECTIVE Overdistention of vein grafts in arterial circulation and systemic hypertension are thought to be influential risk factors contributing to vein graft failures. This study tested the effects of external stenting in preventing systemic hypertension and overdistention of the rat vein graft in the long term. METHODS Jugular vein grafts were interposed into the carotid artery of normotensive (n = 39) and two-kidney, one-clip hypertensive (n = 30) rats. Jugular vein grafts wrapped with 1.5-mm-diameter polyester stents were used in normotensive (n = 26) and hypertensive (n = 25) rats. The vein grafts were harvested at 1, 2, 4, 8, 12, and 24 weeks after the grafting procedure. The neointimal area and wall thickness were measured by computerized planimetry, and Ki-67 immunohistochemistry was used to detect replicative smooth muscle cells in the graft wall. RESULTS In each group, intimal hyperplasia was apparent at 1 week and increased gradually to 24 weeks. The number of Ki-67-positive cells was most increased at 2 weeks after the grafting procedure and gradually decreased thereafter. The numbers of Ki-67-positive cells and the extent of intimal hyperplasia were not significantly different between normotensive and hypertensive rats. Both neointima formation and cell proliferation in the graft wall were significantly reduced by external stenting as compared with the results with unstented grafts. CONCLUSION Systemic hypertension by itself is not a risk factor for intimal hyperplasia and experimental vein graft failure in the long term. External stenting is effective against intimal hyperplasia, and it is possible to reduce the subsequent atherosclerotic change of the vein graft wall and improve the long-term patency of the vein graft with external stenting.

Intraparenchymal allografts in the mouse brain in relation to immunocytochemical identification of T lymphocyte subsets

In a study of intracerebellar allografts of mice brainstem anlagen (embryonic day 12-14), we examined immunocytochemically the expression of two different types of T lymphocytes in and around the grafts. Helper/inducer and cytotoxic/suppressor T cells were identified with anti-L3T4 and anti-Lyt-2 monoclonal antibodies, respectively. Allografts into major histocompatibility complex (MHC)-compatible recipients showed no histological signs of rejection such as marked neovascularization and cellular infiltrates even 6 months after transplantation, but those into MHC-incompatible recipients generally had rejection reactions within one month after transplantation. In the latter cases, the L3T4/Lyt-2 ratio for the T lymphocytes in the infiltrates of the grafts was 1.03 +/- 0.14 (mean +/- S.D.), suggesting that both helper/inducer and cytotoxic/suppressor T cells may play important roles in the mediation of intraparenchymal brain allograft rejection.