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Spinocerebellar ataxia (SCA) 6 is caused by small expansion of a polyglutamine sequence, encoded by CAG trinucleotide repeats, at the C-terminal end of the human CaV2.1 (P/Q-type) Ca2+ channel α12.1 subunit and it manifests itself as slowly progressive cerebellar ataxia. To elucidate the pathogenic mechanisms underlying SCA6, we introduced CAG repeats of various lengths into the Ca2+ channel α12.1 subunit cDNA and expressed them in baby hamster kidney cells stably expressing the auxiliary subunits (α2δ and β4). The occurrence of cell death differed between cells transfected with the normal and mutant Ca2+ channels under the condition of serum starvation plus potassium-induced depolarization, and Cdk inhibition elucidated the differences more clearly. The CaV2.1 (P/Q-type) Ca2+ channel-specific blocker ω-agatoxin IVA abolished the cell-death-preventing effect of the normal Ca2+ channel. Together with our previous finding that the polyglutamine expansion in SCA6 interferes with the Ca2+ channel to reduce Ca2+ influx, these results indicate that impaired function of the mutant Ca2+ channels rendered them unable to prevent cell death. [Copyright &y& Elsevier]

An autopsy case is reported here of a 70-year-old Japanese man with primary central nervous system lymphoma (PCNSL) manifesting subacute mental deterioration and progressive white matter lesions. Brain magnetic resonance imaging (MRI) revealed irregular hyperintense lesions on T2-weighted images of the white matter of the bilateral frontal lobes. The hyperintense lesions then spread to the corpus callosum, internal capsule, globus pallidus and along the pyramidal tract in the brainstem without a mass effect. The U-fibers were also involved in some regions. Neither brain swelling nor a significant atrophy was observed. The clinical manifestations and imaging findings of PCNSL are diverse. Recently, some reports have revealed atypical MR imaging of PCNSL exhibiting diffuse infiltration in the brain parenchyma without mass formation and enhancement of the lesions after the administration of a contrast medium. The authors also encountered an interesting case of PCNSL presenting as progressive white matter lesions without brain swelling. It is now possible to finely observe white matter lesions by brain MRI, particularly in T2-weighted images. Recently the number of immunocompetent elderly patients with PCNSL appears to be increasing in Japan. Autopsy of the present case revealed an intermediate lymphocytic malignant lymphoma. Because imaging and laboratory findings are not completely specific for the diagnosis of PCNSL at present, brain biopsy is more strongly recommended for the final diagnosis of PCNSL even in elderly patients, based on which appropriate treatment is administered. [ABSTRACT FROM AUTHOR]

Background: Immune system function declines with age. We evaluated the effects of supplementation with the probiotic Bifidobacterium longum BB536 on immune function and intestinal microbiota in the elderly., Materials and Methods: In a double-blind study, 45 elderly patients fed by enteral tube feeding (mean [SD] age 81.7 [8.7] years) were given BB536 (n = 23) or a placebo powder (n = 22) for 12 weeks and were observed for an additional 4 weeks posttreatment. At week 4, all patients received an influenza vaccination (A/H1N1, A/H3N2, and B). Clinical data were assessed, including body temperature, bowel movements, fecal microbiota, and immunological biomarkers in blood., Results: BB536 intake significantly increased cell numbers of bifidobacteria in fecal microbiota. There was a tendency toward an increase (P = .085 at week 4 and P = .070 at week 16) of serum IgA in the BB536 group compared with the placebo group. BB536 intake did not significantly affect hemagglutination inhibition (HI) titers in response to the influenza vaccine. Natural killer (NK) cell activity decreased significantly in the placebo group during the intervention but not in the BB536 group. Among those subjects with low NK cell activity (<55%, n = 10 for each group), a significant intergroup difference (P < .05) was observed in the changed values from baseline of NK cell activity at weeks 8 and 12., Conclusions: These results shed new light on the potential of long-term ingestion of BB536 in increasing the cell number of bifidobacteria in intestinal microbiota and modulating immune function in the elderly.

We report a 45-year-old woman admitted to our hospital due to fever, consciousness disturbance, and severe seizures. Based on her signs and symptoms and clinical course, a diagnosis of non-herpetic acute encephalitis was made. She received antibiotic drugs, acyclovir, gamma-globulin, and steroid pulse therapy (methylprednisolone 1 g/day, 3 days). The patient's signs, symptoms and severe seizure showed marked improvement, but she still showed monthly seizure attacks and both anterograde and retrograde amnesia Viral infection and autoimmune response after viral infection may have been involved in non-herpetic acute encephalitis in our patient. Recently, autoantibodies to GluRepsilon2 and VGKC were reported in cases of non-herpetic acute limbic encephalitis (NHALE). In our patient, we detected IgM type autoantibody to GluRdelta2 and epsilon2 in both the CSF and serum, and these antibodies normalized in the CSF with the clinical course. Autoantibodies to GluRdelta2 and epsilon2 may be involved in the clinical symptoms and pathogenesis of non herpetic acute limbic encephalitis. This is the first report of MRI-positive non-herpetic acute encephalitis with autoantibodies to GluRdelta2 and epsilon2.

We report here a 65-year-old man with ptosis, diplopia, and progressive lower limb muscle weakness without nasal symptoms. CA19-9 and CEA were elevated in the serum and cerebrospinal fluid (CSF), but Squamous Cell Carcinoma Antigen (SCC) was not. CA19-9-positive atypical cells were found in the CSF. A right ethmoidal tumor was discovered by paranasal CT and 18F-Deoxyglucose Positron Emission Tomography (FDG-PET) studies. The ethmoidal tumor invaded to the orbits and disseminated into the CSF space through the cribriform plate. Biopsy demonstrated that the paranasal tumor consisted of mucoepidermoid carcinoma. We report here the first case of meningeal carcinomatosis due to mucoepidermoid carcinoma in the ethmoid sinus.

Niemann-Pick disease, type C (NPC) is a neurometabolic genetic disorder that is distinguished from other types of Niemann-Pick disease by its later onset, more insidious progression, variable visceromegaly, and abnormalities of intracellular cholesterol metabolism. We report cases in 18-year-old and 20-year-old brothers who presented with disinhibition and involuntary movement of their hands. Both brothers presented various signs such as dementia, vertical supranuclear ophthalmoplegia (VSO), dysarthria, axial and limb dystonia, hyperreflexia, pathologic reflex, cerebellar ataxia, as reported. They also presented startle response. Brain MRI showed diffuse cerebral atrophy and abdominal CT reveals hepato-splenomegaly in both patients. These cases were suspected to be NPC based on dementia, VSO, cerebellar ataxia, hepato-splenomegaly and foam cells in the bone marrow. Generally, the diagnosis of NPC is based on deficient cholesterol esterification and excessive lysosomal filipin staining in cultured skin fibroblasts. However, culture of fibroblasts obtained from a biopsied skin samples is slow. We have rapidly made the diagnosis of NPC in our patients by filipin staining of foam cells from bone marrow. This diagnostic process using a bone marrow smear is more convenient and rapid than previous methods using cultured skin fibroblasts.

We report a 40-year-old man who noticed difficulty in standing on his tiptoe from approximately 36 years-old. He presented with selective calf muscle weakness on flexion. The serum creatine kinase (CK) level slightly increased to 569IU/l. Muscle computed tomography (CT) revealed selective gastrocnemius and soleus muscle atrophy with fat tissue replacement. A biopsy of the left gastrocnemius muscle revealed a marked variation in muscle fiber size and some necrotic and regenerating fibers. Immunohistochemical analysis using an anti-dysferlin antibody showed a faint and irregular immunostaining of the muscle surface membrane and abnormal immunoreactive depositions in the cytoplasm, although normal dysferlin content was detected by Western blotting. The sequence analysis of all exons of the dysferlin gene revealed no responsible mutations. The case had clinical and pathological findings similar to those of Miyoshi myopathy. The present study indicates that there may be a secondary abonormality of dysferlin derived from some other factors in patients with clinical and pathological findings similar to those of Miyoshi myopathy. The mechanism of dysferlin expression should be elucidated to obtain a conclusive pathogenetic mechanism underlying this disorder.