In order to establish the standard therapy for malignant gliomas, the JCOG-Brain Tumor Study Group was organized in 2002 and started a phase II/III study. It is investigating the efficacy of procarbazine+ACNU+radiation compared to ACNU+radiation which is considered to be the standard therapy for malignant gliomas. Patients with astrocytoma grade 3 or 4 are randomized into two groups postoperatively. Patients in Arm A receive intravenous injection of ACNU on day 1 and day 36 of radiotherapy. Those in Arm B receive oral procarbazine for 10 days before injection of ACNU. Procarbazine is reported to reduce O^6-methylguanine-DNA methyltransferase(MGMT) activity and enhance the anti-cancer effect of nitrosoureas. Recently many studies have been started to overcome chemo-resistance. A trial of the individualization of the treatment, the so-called taylor-made therapy, is one of the challenges for treatment. Loss of chromosome 1p and 19q is considered to be closely related to chemo-sensitivity in anaplastic oligodendrogliomas. Procarbazine+CCNU+vincristine (PCV) therapy is very effective in tumors with 1p and 19q losses compared to those without these losses. This is one of the epoch making findings in the field of chemotherapy for malignant brain tumors. MGMT is a DNA repair enzyme which reduces the anti-cancer effect of nitrosourea. In order to overcome this chemo-resistance nitrosourea or drugs which reduce the MGMT activity such as procarbazine or O^6-benzylguanine are used for those tumors expressing MGMT. However, even in Taylor-made therapy prospective randomized studies under good quality control and quality assurance are essential to establish an evidence-based treatment.

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Photon-based fractionated radiotherapy at a dose of 60 Gy has become the standard radiotherapy for malignant brain tumors, mainly gliomas. However, in most cases such treatment still does not provide a satisfactory clinical outcome. According to one large extended study, even with this standard radiotherapy the median survival time of patients with a glioblastoma after diagnosis is 9 to 12 months, and only 23% of patients achieve a glioblastoma size reduction of more than 50%. We therefore compared the effects of different advanced radiation modalities with those of standard radiotherapy. We introduce here four advanced radiation modalities, namely stereotactic conformal radiotherapy (SCRT) with micro multi-leaf collimator (mMLC), intensity modulated radiotherapy (IMRT), particle radiation therapy (carbon beam and proton beam), and boron neutron capture therapy (BNCT). SCRT with mMLC improved dosimetry remarkably even for relatively large tumors even though it is normally contraindicated in ordinary radiosurgery including that employing γ-and x-knives. IMRT is based on a clever concept of infiltrating tumors such as gliomas. The feature of this radiation modality is it applies a dose gradient for each planned target volume by a change in the shape and size of the collimator. It enables irradiation of different doses for contrast enhanced lesions and infiltration of a lesion separately. Particle radiation therapeutics has a very unique "Bragg peak" character. This modality provides a very sharp distribution of dosimetry behind the target compared to photon irradiation. Carbon and proton beams are utilized worldwide in particle radiation. So called "heavy particle radiation" employs carbon beams. Carbon beams have greater high-relative biological effects and a low oxygen enhancing ratio. These characteristics of carbon beams give them a theoretic advantage especially over radioresistant tumors. The three advanced radiation modalities share the concept of spatial targeting for tumors to obtain good tumor control with decreased damage to normal tissue. BNCT involves the unique concept of cell biological targeting. It employs a binary approach with boron compounds and neutron beams. It is based on the principle that if boron compounds were applied selectively to tumor tissue, then neutron α reactions that occur only within tumor cells would be followed by tumor cell death with minimal harm to normal tissue. All four advanced radiation modalities have been studied rigorously of late, and the publication of some promising results should not be too far away.

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Cell replacement therapy is one of the methods used for the regeneration of neuronal functions. Transplantation of fetal dopaminergic (DA) neurons can produce symptomatic relief, however, the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy. In the future, neural precursor cells and embryonic stem (ES) cells are expected to be candidates for use as potential donor cells for transplantation. First, we examined the potential of neural precursor cells derived from a 9-week-old human embryo. Two region-specific differences in neural precursor cells were revealed : 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) The precursors from the mesencephalon gave rise to more TH-positive neurons than those from the telencephalon. Furthermore, the former TH-positive cells were large, multipolar, and GABA-negative, which suggested that these cells were midbrain DA neurons. In contrast, the latter were small, bipolar, and GABA-positive, suggesting that they were interneurons. Embryonic stem (ES) cells are pluripotent cells that can be expanded without losing their potential to differentiate into a variety of cell types from all three germ layers. Previous studies examining, monkey, and human ES cells have revealed that they are also able to differentiate into neural cells. Furthermore, when grafted into the brain, ES cells survive and can differentiate into functional neurons. These data suggest that ES cells might represent a useful donor source for cell transplantation that may be used to treat neurological disorders such as Parkinson's disease. Next, we generated neurospheres composed of neural precursors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, synergistically increased the number of DA neurons in ES cell-derived neurospheres with FGF2 treatment. We analyzed the effect of transplantation of DA neurons generated from monkey ES cells into MPTP-treated monkeys as a primate model of Parkinson's disease. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons, attenuating the MPTP-induced neurological symptoms.

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Standard anterior temporal lobectomy is accepted as a recommended surgical treatment of intractable temporal lobe epilepsy, since its efficacy and safety have been well established. While the presence of a localized lesion in preoperative MRI is one of the most important factors for favorable seizure outcome, diagnosis and treatment of extrahippocampal foci would be essential for further improvement of seizure outcome. A variety of surgical approaches to the medial temporal structures with less resection of temporal neocortices have been proposed to presumably prevent cognitive decline. To date, however, there is no evidence to support the superiority of a single approach to others on cognitive outcome. Important surgical points common to all approaches are 1) reliable access to the inferior horn of the lateral ventricle, and 2) prevention of injury to the crus cerebri and intracisternal vasculature, which can be accomplished by making the resection procedure predominantly subpial and confining manipulation of the hippocampal vessels to within the hippocampal sulcus.

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The craniovertebral junction is the greatest mobile region in the whole spinal column replete with complex anatomical structures and it is often associated with instability. Therefore, one must consider the stability of this region in addition to decompression of the nervous system in the pathology of the craniovertebral junction. This review will summarize the evidence-based findings and the standard surgical approaches in surgical disorders of the craniovertebral junction at present. The future of this area will also be discussed.

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We sought to determine the prevalence and rupture rate of unruptured cerebral aneurysms based on a long-term follow-up study of individuals receiving a checkup of the brain and we discussed how to handle these figures. Subjects were 156 cases in which a cerebral aneurysm was noted out of 9,641 individuals who underwent MRA from July 1993 to December 2003. The prevalence of unruptured cerebral aneurysms was 1.6%, which is lower than the figure in previous reports; aneurysms 3-7 mm in size accounted for 78.7% of the aneurysms noted. During observation of 121 cases in which preventive measures were not taken, rupture was noted in 6 cases (mean observation period of 4.7 years); the cumulative rupture rate per the Kaplan-Meier method was 1.9% in 1 year (4.6% in 3 years, 8.5% in 5 years). In addition, the aneurysm was smaller than 7 mm in 5 of the 6 cases in which rupture occurred. According to research by the ISUIA in 2003, the rupture rate is related to the size of the aneurysm; their research stated that aneurysms from 7 to 10 mm in size ruptured with a probability of 0.7% per year and that aneurysms smaller than 6 mm had a low risk of rupture at an annual rate of about 0.1%. Along with our research, however, aneurysms in Japanese are often smaller than those in Europeans and Americans; our research suggests that while these aneurysms are smaller, they may have a higher probability of rupturing.

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The author presents a new surgical technique of hippocampal transection which can preserve postoperative verbal memory, even in left temporal lobe epilepsy without hippocampal atrophy on preoperative MRI images. A small corticotomy is performed in the superior temporal gyrus along the sylvian veins. The temporal stem is accessed by aspirating the gray matter of the superior temporal gyrus along the arachnoid membrane of the sylvian fissure. After resection of the temporal stem, the hippocampus and amygdala are exposed. Intraoperative ECoG is recorded to determine the extent of hippocampal transection. After the tough membrane of the alveus is cut with microscissors, a ring transector with 2 mm diameter is inserted through the slit, and the horizontal connections of the stratum pyramidal are disconnected. The medial part of the hippocampus, composed of CA4 and dentate gyrus, and the lateral deep pyramidal cell layer descending to the subiculum are disconnected using a ring transector with 4 mm diameter. After hippocampal transection is completed, ECoG is repeated to confirm complete cessation of epileptic discharges. If epileptic discharges exist in the anterior temporal basal area, cortical excision is performed through the anterior wall of the inferior ventricle. Epileptic discharges of the surface areas are treated by ordinary multiple subpial transection(MST). Over more than 4 years, 28 patients with unilateral temporal lobe epilepsy(left 17, right 11) underwent hippocampal transection. Out of 20 patients with>1 year follow-up, 16(80%) are seizure-free, 2 have rare seizures, and 2 are significantly improved.

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Two cases of idiopathic normal pressure hydrocephalus with rapid aggravation were presented. The first case with gait disturbance, mental disturbance and urinary incontinence was admitted to our hospital, and was bedridden in two weeks from the onset of symptoms. A ventriculoperitoneal shunt was carried out six weeks after the onset. The second case had chronic renal failure and was undergoing the peritoneal dialysis, and presented with both gait and mental disturbance. The duration from the onset of symptoms to admission was one and a half months. A ventriculoatrial shunt was performed four months after the onset. In both cases, the clinical symptoms gradually improved, and the ventricular size was decreased. A prompt and appropriate diagnosis is important to get a favorable response in cases with rapid aggravation.

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