Kikuo Ohno

A new surgical treatment of moyamoya disease in children: A preliminary report

A new operative method, encephalo-duro-arterio-synangiosis, for the surgical treatment of pediatric moyamoya disease has been developed. The rationale of the operation is to help promote the natural tendency of this disease to develop cerebrovascular collaterals. The method is to transplant a scalp artery with a strip of galea, leaving the distal as well as the proximal arteries intact, to a narrow linear dural opening made under an osteoplastic craniotomy. A representative case is described and the operative procedure is outlined. Our new method is compared with other surgical treatments of this disease.

Brain edema during ischemia and after restoration of blood flow. Measurement of water, sodium, potassium content and plasma protein permeability.

The left cerebral hemisphere of Mongolian gerbils was used to elucidate the mechanisms of brain edema which develop during cerebral ischemia and after restoration of cerebral blood flow following temporary ischemia. Water content was measured by the tissue-drying method. Sodium and potassium ion concentration was measured by flame photometry. Passage of 131I-albumin (RISA) from blood to the cerebral parenchyma was measured on a gamma scintillation counter. Our findings indicate that pure cytotoxic edema develops during ischemia and during a short period after restoration of cerebral blood flow. Vasogenic edema, which is accelerated by the leakage of plasma constitutents from blood due to blood-brain barrier damage, developed after restoration of the cerebral blood flow. After less than 1 hr of ischemia, restoration of the cerebral blood flow drastically reduced the degree of brain edema. However, restoration of the cerebral blood flow greatly worsened the brain edema following more than 3 hr of ischemia.

Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil

We measured the regional cerebral blood flow in both hemispheres of Mongolian gerbils subjected to permanent left carotid artery ligation, using [3H]nicotine as the tracer. At 1, 3 and 6 h post-ligation, neurological signs were recorded and a stroke index score was tallied for each animal. In conscious control gerbils, mean cerebral blood flow on the left side was 1.10 +/- 0.08 (S.E.M.) ml X g-1 X min-1 at the cerebral cortex, 0.58 +/- 0.02 at the hippocampus and 0.69 +/- 0.04 at the diencephalon. Animals with a stroke index score exceeding 10 were considered symptomatic. We noted a close relationship between regional cerebral blood flow and the stroke index score. In symptomatic animals, regional cerebral blood flow in the ischemic hemisphere at 1, 3 and 6 h post-ligation was less than 0.21 ml X g-1 X min-1 at the cortex and diencephalon, and less than 0.09 ml X g-1 X min-1 at the hippocampus. We suggest that unilaterally ligated gerbils manifesting a stroke index score greater than 10 represent a good experimental model for the study of ischemia.

Accumulation of CD133-positive glioma cells after high-dose irradiation by Gamma Knife surgery plus external beam radiation

OBJECT Recent evidence suggests that a glioma stem cell subpopulation might contribute to radioresistance in malignant gliomas. To investigate this hypothesis, the authors examined recurrent malignant gliomas for histopathological changes after high-dose irradiation with Gamma Knife surgery (GKS) and external beam radiation therapy (EBRT). METHODS Thirty-two patients with malignant gliomas (Grade 3 in 8 patients, Grade 4 in 24) underwent GKS in combination with EBRT. Serial MR and L-[methyl-(11)C] methionine PET images were employed to assess remnant or recurrent tumors after GKS. Twelve patients underwent surgical removal after GKS and EBRT. Histological sections were subjected to immunohistochemistry for MIB-1, factor VIII, and stem cell markers, nestin and CD133. RESULTS The site of GKS treatment failure was local in 16 (76.2%) of 21 patients with glioblastomas showing progression; in 9 of these 16 patients, the recurrence clearly arose within the target lesion of GKS. Histopathological examination after GKS and EBRT showed variable mixtures of viable tumor tissues and necrosis. Viable tumor tissues exhibited high MIB-1 indices but reduced numbers of tumor blood vessels. There was marked accumulation of CD133-positive glioma cells, particularly in remnant tumors within the necrotic areas, in sections obtained after GKS plus EBRT, whereas CD133-positive cells appeared very infrequently in primary sections prior to adjuvant treatment. CONCLUSIONS The results indicate that CD133-positive glioma stemlike cells can survive high-dose irradiation, leading to recurrence, despite prolonged damage to tumor blood vessels. This could be an essential factor limiting the effectiveness of GKS plus EBRT for malignant gliomas.

Plasma Concentrations of Brain Natriuretic Peptide in Patients with Acute Ischemic Stroke

Background: Acute blood pressure (BP) elevation and cardiac abnormalities are known to follow ischemic stroke. Brain natriuretic peptide (BNP), which is produced in response to such cardiovascular alterations, is expected to play a hemodynamic role. We measured plasma BNP concentrations in patients with cerebral infarction (CI) to determine the implications of BNP in acute ischemic stroke. Methods: Eighty-eight patients with CI, 59 with essential hypertension, 44 with spontaneous intracerebral hemorrhage, 22 with asymptomatic atrial fibrillation (Af), and 20 age- and sex-matched healthy volunteers were recruited in the study. CI patients were divided into 2 subgroups either having Af (27 patients) or not (61 patients). BNP levels were repeatedly measured in 58 patients with CI. BNP levels were compared between ischemic subgroups categorized by size of infarction. Correlation was investigated between BNP levels and hemodynamic parameters. Results: BNP levels in CI patients were significantly higher, but they decreased in the subacute period. BNP levels in CI patients without Af were correlated with mean arterial blood pressure (MAP) on admission or the degree of reduction in MAP at day 1, while in CI patients with Af BNP levels showed negative correlation with MAP on admission. Follow-up serum sodium levels in CI patients with Af were negatively correlated with BNP levels on admission. Conclusions: This study suggests the hemodynamic implications of BNP in acute ischemic patients.

Preoperative evaluation of neurovascular compression in patients with trigeminal neuralgia by use of three-dimensional reconstruction from two types of high-resolution magnetic resonance imaging.

OBJECTIVE To assess the value of three-dimensional (3-D) images reconstructed from 3-D constructive interference in steady state (3-D-CISS) and 3-D fast inflow with steady-state precession (3-D-FISP) images for the visualization of neurovascular compression in patients with trigeminal neuralgia. METHODS Twenty-four consecutive patients with trigeminal neuralgia underwent preoperative 3-D-FISP and 3-D-CISS imaging. 3-D reconstruction of nerves and vessels was performed with the use of a volume-rendering method. We compared the 3-D reconstructed images with intraoperative findings. RESULTS 3-D-CISS and 3-D-FISP images scanned from the same position clearly delineated the trigeminal nerve and vessels. 3-D reconstructed images showed the spatial relationship between the trigeminal nerve and causative vessels. The responsible arteries were identified from the 3-D reconstructed images, which closely simulated the microscopic operative view. CONCLUSION 3-D reconstructions from two types of high-resolution magnetic resonance images (3-D-CISS and 3-D-FISP) are very useful for creating preoperative simulations and in deciding whether to perform surgery in patients with trigeminal neuralgia.

A Randomized Controlled Trial of Hydrocortisone Against Hyponatremia in Patients With Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Hyponatremia is common after aneurysmal subarachnoid hemorrhage (SAH). It is caused by natriuresis, which induces osmotic diuresis and decreases blood volume, contributing to symptomatic cerebral vasospasm (SCV). Hypervolemic therapy to prevent SCV will not be efficient under this condition. We conducted a randomized controlled trial to assess the efficacy of hydrocortisone, which promotes sodium retention in the kidneys. Methods— Seventy-one SAH patients were randomly assigned after surgery to treatment with either a placebo (n=36) or 1200 mg/d of hydrocortisone (n=35) for 10 days and tapered thereafter. Both groups underwent hypervolemic therapy. The primary end point was the prevention of hyponatremia. Results— Hydrocortisone prevented excess sodium excretion (P=0.04) and urine volume (P=0.04). Hydrocortisone maintained the targeted serum sodium level throughout the 14 days (P<0.001), and achieved the management protocol with lower sodium and fluid (P=0.007) supplementation. Hydrocortisone kept the normal plasma osmolarity (P<0.001). SCV occurred in 9 patients (25%) in the placebo group and in 5 (14%) in the hydrocortisone group. No significant difference in the overall outcome was observed between the 2 groups. Conclusions— Hydrocortisone overcame excess natriuresis and prevented hyponatremia. Although there was no difference in outcome, hydrocortisone supported efficient hypervolemic therapy.

Synaptic scaffolding molecule (S-SCAM) membrane-associated guanylate kinase with inverted organization (MAGI)-2 is associated with cell adhesion molecules at inhibitory synapses in rat hippocampal neurons

Synaptic scaffolding molecule (S‐SCAM) is a synaptic protein, which harbors five or six PSD‐95/Discs large/ZO‐1 (PDZ), a guanylate kinase and two WW domains. It interacts with NMDA receptor subunits, neuroligin and β‐catenin, and is involved in the accumulation of neuroligin at excitatory synapses. In this study, we have demonstrated S‐SCAM is localized at inhibitory synapses in rat primary cultured hippocampal neurons. We have identified β‐dystroglycan (β‐DG) as a binding partner for S‐SCAM at inhibitory synapses. WW domains of S‐SCAM bind to three sequences of β‐DG. We have also revealed that S‐SCAM can interact with neuroligin 2, which is known to be exclusively localized at inhibitory synapses. The WW domains and the second PDZ domain of S‐SCAM are involved in the interaction with neuroligin 2. β‐DG, neuroligin 2 and S‐SCAM form a tripartite complex in vitro. Neuroligin 2 is detected in the immunoprecipitates by anti‐β‐DG antibody from rat brain. S‐SCAM, β‐DG and neuroligin 2 are partially co‐localized in rat hippocampal neurons. These data suggest that S‐SCAM is associated with β‐DG and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin–neuroligin complex.

Saccular Aneurysms of the Distal Anterior Cerebral Artery

We report a series of 42 consecutive patients with aneurysms of the distal anterior cerebral artery (ACA). Of these, 36 patients had one aneurysm, 5 had two aneurysms, and one had three aneurysms. Thirty patients had a ruptured distal ACA aneurysm; among these patients, the size of the aneurysm was less than 5 mm in diameter in 20, 6 to 10 mm in 7, and larger than 11 mm in 3. Eighteen patients (42.9%) had multiple aneurysms, and distal ACA aneurysms were responsible for a subarachnoid hemorrhage in 10. Thirty-four patients underwent direct surgery, and 30 of these had excellent outcomes 3 months after surgery. The treatment of patients with distal ACA aneurysms is often technically difficult, because of their broad neck configuration and the coexistence of other aneurysms. Nevertheless, the present study emphasizes that distal ACA aneurysms tend to bleed, irrespective of their size, and that excellent outcomes are obtainable by direct surgery.

Immunohistochemical detection of progesterone receptors and the correlation with Ki-67 labeling indices in paraffin-embedded sections of meningiomas

Female sex steroids may play a role in the proliferation of meningiomas. We investigated the progesterone receptor (PgR) immunoreactivities and the Ki-67 labeling indices in the formalin-fixed, paraffin-embedded sections of meningiomas from 39 patients. After autoclave pretreatment of the sections (which were immersed in a citrate buffer), the sections were incubated with the monoclonal antibody for the PgR and the MIB-1 monoclonal antibody for the Ki-67 antigen. In the meningiomas studied, the immunoreactivity for the PgR was moderately to strongly positive in 51%, weakly positive in 21%, and negative in 28%. The nuclear staining for the PgR was clear, and no tumors were positive for the estrogen receptor. The Ki-67 labeling indices of the PgR-positive meningiomas (mean +/- standard deviation, 2.35 +/- 2.12%) were significantly lower than those of the PgR-negative meningiomas (6.53 +/- 4.83%) (P < 0.05). Two meningiomas that had recurred more than once showed high Ki-67 labeling indices and negative immunostaining for the PgR. These findings indicate that the PgR status may be closely related to the growth potentials of the meningiomas. Our results confirm that the immunodetection of the PgR and the Ki-67 antigen on the paraffin sections of meningiomas provides a practical tool for estimating the biological behavior of the meningiomas.