Sei Sugata

Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure

The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

Immunoreactivity of Wnt5a, Fzd2, Fzd6, and Ryk in glioblastoma: evaluative methodology for DAB chromogenic immunostaining

The aim of this study was to determine the influence of Wnt5a and its receptors on the survival of glioblastoma patients and to determine reliable evaluation methods for immunohistochemistry. Diagnostic specimens from 41 histopathologically confirmed primary glioblastoma patients whose Gd-enhanced tumors had been totally removed were immunohistochemically stained for Wnt5a, Fzd2, Fzd6, and Ryk. The immunoreactivity was evaluated using the following methods: (A) grayscale optical density after color deconvolution, (B) percentage of stained cells, (C) density of stained cells, (D) staining amount (multiplication product of B and C), and (E) staining rank. The data sets of A to E were statistically evaluated by correlation matrix analysis and regression analysis. The influence of the expression of the markers on survival was analyzed using a proportional hazard model. The results of color deconvolution (A) were well correlated with the results of the staining rank (E). In the semiquantitative results (B, C, and D), the staining amount (D) tended to show a better correlation with results of color deconvolution (A). Among all data sets, color deconvolution (A) demonstrated the most preferable fit in a proportional hazard model, and the expression of Fzd2 and Fzd6 was associated with poor prognosis in glioblastoma patients.

TLR4, IL-6, IL-18, MyD88 and HMGB1 are highly expressed in intracranial inflammatory lesions and the IgG4/IgG ratio correlates with TLR4 and IL-6.

We determined distribution of plasma cells and IgG4/IgG index and factors associated with the index in intracranial inflammatory lesions. Specimens of nine patients were analyzed immunohistochemically using antibodies against CD45, CD68, CD3, CD4, CD8, CD20, CD138, lambda chain, kappa chain, IgG, IgG4, IL‐1α, IL‐6, IL‐18, toll‐like receptor (TLR) 2, TLR4, high‐mobility group box 1 (HMGB1), tumor necrosis factor‐alpha (TNF‐α), myeloid differentiation factor 88 (MyD88), and anaplastic lymphoma kinase (ALK). The relationship between all the factors was assessed using Spearmans rank correlation coefficient (ρ). Negative ALK staining was observed in all the patients. Plasma cells were detected in eight patients with varying degrees. The highest number of neutrophils, but no plasma cells, was observed in a patient with the shortest history of inflammation. IgG4/IgG index was independent of the number of plasma cells. The index was relatively highly correlated with IL‐6 (ρ = 0.7271) and TLR4 expression (ρ = 0.7246). IL‐6 expression was highly correlated with TLR4 expression (ρ = 0.8042). IL‐18 was maximally expressed in all the patients. TLR4 expression was strong, but TRL2 expression was weak. Positive HMGB1 staining was observed in all the patients, predominantly in the nuclei, but also in the cytoplasm in four patients. The cytoplasmic expression strongly correlated with IL‐1α expression (ρ = 0.9583). The cytoplasmic colocalization of HMGB1 and IL‐1α was histologically confirmed in cells with collapsing nuclei by the double‐staining method. The IgG4/IgG indexes varied case by case. IL‐6 and TLR4 expressions may influence IgG4/IgG index. The nuclei of cells with both IL‐1α and HMGB1 expressions in the cytoplasm collapse in the cell death stage. The cooperative high expression of TLR4, IL‐6, IL‐18, MyD88 and HMGB1 suggest their critical roles in the inflammation circuit.

Pineal mixed germ cell tumor with a synchronous sellar lesion in the sixth decade

Intracranial germ cell tumors (GCTs) typically affect children and adolescents. We here report on a 59-year-old male patient presenting with diplopia, polydipsia and polyuria. On clinical examination, slight restriction of the upward gaze was seen on the left side. Computed tomography demonstrated calcifications in the pineal region and enhanced neurohypophysis. Magnetic resonance imaging displayed a heterogeneous pineal mass of 3-cm diameter, which was multicystic with an enhanced cyst wall, and also swelling of the pituitary stalk. The pineal lesion of the tumor, which included calcifications and keratinaceous components, was totally excised using an occipital transtentorial approach. Histopathological examination showed it to be a mixed GCT with germinoma and mature teratoma components. Postoperative chemoradiotherapy provided complete disappearance of the suprasellar lesion. To our knowledge, this is the first case of mixed bifocal GCT in an older adult reported in the literature, although a few cases of tumors with a single histological component have been reported. Hence, our case further underlines the possibility of the occurrence of GCTs in older adults and advocates the consideration of GCTs in the differential diagnosis of such cases for appropriate management.

Improvement in treatment results of glioblastoma over the last three decades and beneficial factors

Abstract Background. The purpose of this study is to elucidate the trend of glioblastoma outcome and scrutinize the factors contributing to better outcome over three decades. Methods. Survival time and the influencing factors were retrospectively analyzed in 223 newly diagnosed primary glioblastoma patients during 1980–2010. Appraised factors included age, sex, tumor site, year of surgery, extent of resections, use of surgery supporting system, Karnofsky Performance Status (KPS), chemotherapy, conventional external beam radiotherapy (EBRT), and CyberKnife stereotactic radiotherapy (CK-SRT) use. Results. The median survival time (MST) in all patients was 13.6 months. The MSTs for 4 periods were 9.8 (1980–1990), 13.7 (1991–2000), 12.9 (2001–2005), and 15.8 months (2006–2010), respectively (p = 0.0047). Total resection, subtotal resection, partial resection, and biopsy had MSTs of 31.8, 13.9, 11.4, and 7.0 months, respectively (p < 0.0001). Regarding chemotherapy, MSTs of the temozolomide base group and nimustine hydrochloride (ACNU) base group were 16.9 and 14.6 months, respectively, whereas the MST of patients without chemotherapy was only 9.8 months (p < 0.0001). The MSTs for 40-Gy EBRT plus CK-SRT and 60-Gy EBRT were 19.1 and 10.7 months, respectively (p < 0.0001). But in sub-selected patients, treated during 2001–2010, whose resection rate was total resection or subtotal resection, EBRT was completed and postoperative KPS was greater than or equal to 70, the MST with and without CK-SRT was 26.6 and 18.3 months, respectively (p = 0.1529). According to the Cox proportional hazards model, degree of resection, KPS, ACNU use, temozolomide use, bevacizumab use, EBRT dose, and CK-SRT use were good prognostic factors. Use of neuronavigation and use of intraoperative magnetic resonance imaging were related to higher resection rate, but not determined as prognostic factors. Conclusions. We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

Neuroprotective effect of levetiracetam on hippocampal sclerosis-like change in spontaneously epileptic rats

The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration.

Hippocampal cell loss and propagation of abnormal discharges accompanied with the expression of tonic convulsion in the spontaneously epileptic rat

Spontaneously epileptic rats (SER) are double mutants with both tonic convulsion and absence-like seizures from the age of 8 weeks. Hippocampal CA3 neurons in SER display a long-lasting depolarizing shift accompanied by repetitive firing (attributed to abnormalities of the Ca(2+) channels) with a single stimulation of the mossy fibers. In the present investigation, we examined if the seizure discharges of SER were correlated with the hippocampal abnormality of SER using electrophysiological and histological methods. In CA1 neurons of seizure-susceptible mature SER, higher-voltage (<8-11 V) stimulations induced a long depolarization shift (in 25% of neurons) with repetitive firing (in 12.5% of neurons). However, the tremor rat, one of the parent strains of SER, did not exhibit such abnormal firing in the CA3 region of the hippocampus. The number of CA3 neurons in SER was significantly (p<0.01) lower than that in tremor rats and Wistar rats, although no significant difference was established in the hilus. Sprouting of mossy fiber was observed in the dentate of mature SER; however, negligible staining was spotted in the dentate of both mature tremor and Wistar rats. Interestingly, expression of the brain-derived neurotrophic factor was higher in the hilus, CA3, and granular cell layer of dentate gyrus in SER than normal Wistar rats. The expression levels of TUNEL, bax, and Caspase-3 did not show significant changes between the SER and Wistar rats. SER exhibited hippocampal sclerosis-like changes which did not have enough potential for epileptogenesis. Repetitive tonic seizures and vulnerable CA3 neurons of SER could be involved in the induction of sclerosis-like changes in the hippocampus.

Huge Arachnoid Cyst of the Posterior Fossa with Cerebellar Tentorium Dysplasia Associated with Juvenile Polyposis

We report an infant with a huge arachnoid cyst of the posterior fossa with dysplasia of the cerebellar tentorium and meningeal sinus and associated juvenile polyposis. Neuroimaging studies disclosed a huge median cystic lesion extending posterosuperiorly over the cerebellum. The cerebellar tentorium was raised to the parietal area; the vermis was normoplastic. Cystography showed no direct communication with the 4th ventricle or subarachnoid space. We discuss the differential diagnosis of median cysts of the posterior fossa and the association of juvenile polyposis.

Use of a guide wire system to insert guiding catheters

In patients with severe arteriosclerosis or anatomical variations such as a bovine arch, the insertion of a guiding catheter for carotid artery stenting is difficult. The authors use a guide wire system as an anchor and advance the guiding catheter to an area proximal to the stenotic structure. This method is useful and safer than others for carotid artery stenting.

Electrophysiological mapping of the temporal branch of the facial nerve.

BACKGROUND Minimized frontal and frontolateral approaches have been proposed for the clipping of aneurysms and for removal of deep-seated supra- and parasellar lesions. To avoid postoperative facial nerve palsy, anatomical studies have been conducted; however, only one electrophysiological investigation has been reported. We studied the course of the facial nerve in the temporal region and identify the optimal pterional keyhole craniotomy from the perspective of facial nerve protection. MATERIALS AND METHODS We stimulated the temporal branch of the facial nerve in nine healthy volunteers and identified its course electrophysiologically. Electromyographic (EMG) responses were recorded from the superior orbicularis oculi, corrugator, and frontal muscles. The course of the temporal branch of the facial nerve was identified by tracking the stimulation points that elicited the best EMG responses. RESULTS AND CONCLUSION The distances from the tragus to the canthus, the tragus to the point where the facial nerve crosses over the zygomatic arch, the tragus to the first nerve bifurcation, the tragus to the second nerve bifurcation, and from the orbit to the middle rami were 80.8 ± 1.8 mm, 40.2 ± 1.6 mm, 58.1 ± 2.8 mm, 79.1 ± 3.4 mm, and 16.4 ± 0.9 mm, respectively. We found that the temporal branch of the facial nerve innervates each muscle in posterior-anterior direction. Based on these results, we prefer the pterional keyhole approach and incise the skin at a site posterior to the temporal branch of the facial nerve.