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We conduct a double-blind randomized placebo-controlled clinical trial (Phase III: confirmatory trial) of intravenous infusion of autologous mesenchymal stem cells for cerebral infarction patients. The objectives of this study were to examine feasibility, safety, and efficacy of cell therapy using auto serum-expanded autologous mesenchymal stem cells derived from bone marrow in the stroke patients. Inclusion criteria is (1) Cerebral infarction onset within 40 days, (2) Supra-tentorial cerebral infarction(NINDS-III 1990) diagnosed by MRI(or CT), MRA (3D-CTA or DSA), ECG, chest X-ray etc., (3) Classified under grade 4 or 5 of mRS (modified Rankin scale), (4) Age between 20 to 80, (5) The written informed consent from subjects and legal representative is provided.

Intravenously administrated mesenchymal stem cells (MSCs) isolated and expanded from human bone marrow have been reported to ameliorate functional deficits in several CNS diseases in both experimental animal models and clinics. Therapeutic mechanisms may include replacement of damaged cells, neuroprotective effects, induction of axonal sprouting, and neovascularization. Here, we review the reparative and protective properties of transplanted MSCs in stroke, describe initial clinical studies on intravenous MSC delivery in stroke patients, and discuss a perspective on the prospects of MSCs for dementia.

Intravenous transplantation of mesenchymal stem cells (MSCs) derived from bone marrow has been reported to ameliorate functional deficits in several CNS diseases. The objectives of this presentation were to show feasibility and safety of cell therapy using auto serum-expanded autologous MSCs in stroke. Twelve (male and female) patients with stroke were enrolled. Cryopreserved MSCs were thawed and injected intravenously into patients over 30 min. Serial evaluations showed no severe adverse cell-related effects. In patients with cerebral infarcts, the intravenous administration of autologous MSCs appears to be feasible and safe, and merits further study as a therapy that may improve functional recovery.

Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow has been reported to ameliorate functional deficits in several CNS diseases in experimental animal models. The objectives of this study were to examine feasibility and safety of cell therapy using auto serum-expanded autologous MSCs in the stroke patients. Twelve (male and female) patients with stroke were enrolled. Cryopreserved MSCs were thawed and injected intravenously into patients over 30 min. Serial evaluations showed no severe adverse cell-related effects. In patients with cerebral infarcts, the intravenous administration of autologous MSCs appears to be feasible and safe, and merits further study as a therapy that may improve functional recovery.

The authors report on a patient with postoperative CSF (cerebrospinal fluid) leakage subsequent to transsphenoidal surgery where cisterno SPECT (single photon emission computed tomography) demonstrated the precise location of a CSF fistula. Seven months after surgery, the patient suffered from CSF rhinorrhea and headache. MRI (Magnetic Resonance Imaging) revealed significant contrast on T1-weighted images resulting from measurements in the right sphenoid sinus, which were hyperintense relative to CSF. On the basis of signal intensity differences, MRI could not distinguish between CSF leakage and postoperative scarring. Therefore, we performed cisterno SPECT at the same time as RI cisternography with intrathecal lumbar injection of 111In-DTPA which revealed dramatic accumulation of the tracer in the right sphenoid sinus. The patient underwent re-operation via a transsphenoidal approach, and the CSF leakage was repaired using fat-in-fibrin glue and the sella floor was reconstructed by hydroxyapatite platinge. These results suggest that cisterno SPECT may be useful in identifying the precise location of CSF fistulae, while other techniques fail to show evidence of CSF leakage.

It has been known that an isolation of Wernicke's area from auditory input results in pure word deafness. In this report, a 73-year-old female case with tentorial meningioma suffering from pure word deafness is reported. The patient initially presented with hydrocephalus, and was treated with a ventriculo-peritoneal(V-P) shunt. A year after the V-P shunt, she suffered from a symptom of deafness. On admission, her repetition and auditory comprehension were severely impaired, while reading and visual comprehension were almost normal. Auditory brain stem response(ABR) revealed normal latency between wave I and V, while wave VI and VII was disappeared. Middle latency response(MLR) showed no wave peak. On MRI, tentorial meningioma compressed bilateral medial geniculate bodies, but not auditory radiation or temporal lobe. 99mTc-HMPAO single photon emission computed tomography(SPECT) showed hypoperfusion in the left temporal lobe, considered as a diaschisis resulting from the isolation of left temporal lobe from auditory input via bilateral medial geniculate bodies.

Transplantation of Schwann cells (SCs) induced remyelination of demyelinated rat dorsal column (DC) axons and improved conduction. To investigate the difference between oligodendrocyte (OL) and SC myelination in conductive functions of axons, we compared normal DCs, demyelinated DCs, demyelinated DCs remyelinated by SC transplantation, and normal dorsal roots. All of the axons was originated from dorsal root ganglion neurons. Dorsal roots of adult rats were demyelinated at T11 by X-ray irradiation and ethidium bromide, and transplanted with SCs (3 x 10(4)) of adult rats. Three weeks later, the spinal cord was removed and pinned in a recording chamber and compound action potentials (CAPs) were recorded, to investigate conduction properties (conduction velocity and response after high frequency stimulation). Normal DCs or dorsal roots were recorded in same manner. Following transplantation of SCs, histological examination revealed SC-like patterns of remyelination in demyelinated DCs. SC transplantation improved significantly conduction properties compared to demyelinated axons, but less than normal DC. Moreover, remyelinated axons by SC transplantation showed as low amplitude of CAP as dorsal roots, but lower conduction velocity than dorsal roots. Though anatomical difference and/or time after transplantation influenced the conduction, these result suggested that SC myelination resulted in lower amplitude of CAP than OL, and SC remyelination might be insufficient for conduction velocity.

The interhemispheric approach has been selected for clipping of the anterior communicating artery aneurysm located high above the sphenoidal plate, and in a posterior direction. However, this approach is sometimes complicated with postoperative hemorrhagic infarction due to excess brain retraction combined with damages of the cortical bridging veins. We have devised a modification in this approach to eliminate these complications. Our newly devised methods include the following; 1) Small bifrontal craniotomy performed, 2) Continuous ventricular drainage performed to minimize the effect of compression by the spatula during resection of interhemispheric fissure, 3) Bifrontal dural incision made along the frontal skull base, 4) Mobilization of the major cortical vein in the operated field, if necessary, by resection of the overlying arachnoid membrane with or without sacrificing its small tributaries, 5) Gradual dissection of the olfactory nerves according to the process of operation. We analysed the incidence of operative complications in thirteen consecutive cases with this approach. Major frontal ascending veins were carefully preserved in all cases. None showed hemorrhagic infarction, regardless of the cortical venous drainage patterns. The degree of smell preserved in 10% of the examined 11 cases was more than unilateral. In conclusion, this method is useful for the elimination of perioperative complications even in the acute stage of subarachnoid hemorrhage.

Twenty-two hydrocephalic patients with a ventriculoperitoneal shunt using a continuously variable flow resistance valve (Orbis-Sigma valve system; Cordis Corporation, USA) were reviewed to discuss usefulness of the shunt system. We divided the cases into two groups according to the demonstration of the cortical sulci in computed tomography (CT) as follows; A: progressive hydrocephalic cases mimicking simple brain atrophy, B: acute or subacute hydrocephalic cases with evidence of increased intracranial pressure. Patients in Group A had begun to present slowly progressive loss of activity, dementia and gait disturbance of various degrees after a long quiescent period following primary central nervous system injury. CT findings of these cases showed they were mimicking simple brain atrophy. Although the period of their deterioration was very long, ranging from 1 month to nine years, clinical signs improved in all cases after the shunt. None showed complications. Group B cases consisted of those with signs of increased intracranial pressure such as consciousness disturbance, nausea and vomiting. These cases showed poor demonstration of the cortical sulci in CT. Eleven out of thirteen cases showed satisfactory clinical improvement, though the size of the ventricle showed a slight decrease following shunt procedure. Only one case showed unilateral subdural effusion. In conclusion, this shunt system is useful for the management of ventricular enlarged cases mimicking simple brain atrophy as well as acute hydrocephalic cases. Troublesome consequences such as subdural effusion and hemorrhage rarely occur even in cases with low cerebrospinal pressure.

We have examined the total number of admitted cases to clarify the pathogenesis of hyponatremia during the management of neurosurgical patients. We experienced 32 cases of hyponatremia during the past year by measuring the sodium balance and atrial natriuretic peptide (ANP) level. According to these two factors, we divided the cases into three groups. The first group shows normal ANP levels in spite of hyponatremia. Low administration of the sodium was thought to be the cause in these cases. The second group shows the elevated ANP levels with a positive sodium balance. Elevated circulatory volume due to the inadequate level of antidiuretic hormone and mild heart and/or kidney failures cause these conditions. Water restriction and/or diuresis were effective methods in the management of the cases. The last group shows the elevated ANP levels with a negative sodium balance. There is a statistically significant negative correlation between sodium balance and the ANP level. Marked natriuresis due to the elevated ANP causes the decrement of the circulatory volume in these cases. Pathogenesis of the last group is very important in the management of neurosurgical patients in an acute state, especially in subarachnoid hemorrhage cases. The decrement of the systemic circulatory volume would jeopardize the patient's neurological condition. In this group, water restriction that has been commonly recommended is contraindicated. Satisfactory water and sodium replenishment seems to be the best recommended treatment for this group.

We report on a case of hypertensive intracerebral hematoma associated with a severe paralytic ileus during a continuous injection of nicardipine hydrochloride. The patient (63 year-old male) had been admitted with a left hemiparesis. On the second day of admission, the patient received a continuous intravenous injection of nicardipine hydrochloride following the failure to get a constant reduction of systemic blood pressure. The initial dose of the drug was 2 micrograms/kg/min. It was administered for 22 days and the average daily dosage was 187mg. On the eighth day following the beginning of the drug administration, he complained of abdominal distention. Abdominal X-ray photogram revealed a marked air collection in the colon. Despite various forms of treatments, the abdominal distention continued for 20 days until cessation of the drug administration. The paralytic ileus in this case was most likely caused by the following; 1) a relatively large amount of the drug was administered via the continuous intravenous route, 2) unexpected accumulation of the drug in the digestive tract may occur due to the dysfunction of the liver and the kidney, 3) clearance of the drug in humans may be lower than the expected value obtained from animal experiments.