An altered GABA-A receptor function in spinocerebellar ataxia type 6 and familial hemiplegic migraine type 1 associated with the CACNA1A gene mutation

Background: Mutations in the CACNA1A gene encoding the voltage-gated calcium channel α1A subunit have been identified in patients with autosomal dominantly inherited neurological disorders, including spinocerebellar ataxia type 6 (SCA6) and familial hemiplegic migraine type 1 (FHM1). In order to investigate the underlying pathogenesis common to these distinct phenotypic disorders, this study investigated the neuronal function of the GABAergic system and glucose metabolism in vivo using positron emission tomography (PET). Methods: Combined PET studies with [11C]-flumazenil and [18F]-fluorodeoxyglucose (FDG) were performed in three FHM1 patients and two SCA6 patients. [18F]-FDG-PET using a three-dimensional stereotactic surface projection analysis was employed to measure the cerebral metabolic rate of glucose (CMRGlc). In addition, the GABA-A receptor function was investigated using flumazenil, a selective GABA-A receptor ligand. Results: All patients displayed a significant decrease in CMRGlc and low flumazenil binding in the cerebellum compared with the normal controls. The flumazenil binding in the temporal cortex was also decreased in two FHM1 patients. Conclusions: Cerebellar glucose hypometabolism and an altered GABA-A receptor function are characteristic of FHM1 and SCA6. General significance: An altered GABA-A receptor function has previously been reported in models of inherited murine cerebellar ataxia caused by a mutation in the CACNA1A gene. This study showed novel clinical characteristics of alteration in the GABA-A receptor in vivo, which may provide clinical evidence indicating a pathological mechanism common to neurological disorders associated with CACNA1A gene mutation

New Porous Carbon Materials as Gas Diffusion Layer for Polymer Electrolyte Fuel Cells

New porous carbon materials are proposed in which washi, the Japanese paper as well as cotton and other cellulose materials are carbonized by new method, retaining their original fibrous structures. Porous carbon sheets thus fabricated are used as gas diffusion layer in fuel cells. Fuel cell testing is conducted and the optimum conditions of fabrication are investigated. Low cost and superior characteristics of new carbon structure are demonstrated based on morphological study and fuel cell polarization data

Reduced gray matter volume is correlated with frontal cognitive and behavioral impairments in Parkinson\u27s disease

Objective: To identify the brain-volume reductions associated with frontal cognitive and behavioral impairmentsin Parkinson\u27s disease (PD).Methods: Forty PD patients without dementia or amnesia (Hoehn and Yahr stage 3) and 10 age-matched controlsunderwent brain magnetic resonance imaging. Cognitive and behavioral impairments were assessed by using theFrontal Assessment Battery (FAB) and Frontal Systems Behavioral Scale (FrSBe), respectively. We applied voxelbasedmorphometry to investigate the correlations of regional gray matter volume with FAB, FrSBe, and physicaldisability.Results: FAB was significantly lower in PD than in controls. FrSBe was significantly higher after PD onset thanbefore, notably in the apathy subscale. FAB and FrSBe were significantly intercorrelated. In PD patients, leftinferior frontal volume was positively correlated with FAB, whereas right precentral volume was negativelycorrelated with FrSBe total score. The brain volumes in both of these regions were not correlated with theUnified PD Rating Scale III.Conclusion: Behavioral impairments in PD tended to coexist with progression of frontal cognitive impairment.Regional atrophy within the frontal lobe was associated with both frontal cognitive and behavioral impairments.However, the specific region responsible for behavioral impairment differed from that for frontal cognitiveimpairment. These associations were independent of physical disability

Frontal assessment battery and frontal atrophy in amyotrophic lateral sclerosis

Objectives: To determine the potential utility of the frontal assessment battery (FAB)in assessing cognitive impairments in amyotrophic lateral sclerosis (ALS), we investigatedthe association between the FAB score and regional gray matter volume, andascertained whether the regional brain alterations related to cognitive impairmentsoccur in relatively mild stage of ALS.Materials and Methods: Twenty-fourALS patients with a Mini-MentalStateExamination score of >23, a normal score on the Self-RatingDepression Scale, little orno disturbance in speech and handling utensils on the ALS Functional Rating Scale(ALSFRS), and normal measures on respiratory tests (respiratory function test and arterialblood gas analysis), and two age-matchednormal control groups (one for FABassessment and the other for brain morphometry) underwent FAB testing and structuralmagnetic resonance imaging. We applied voxel-basedmorphometry to investigatethe relationship between the FAB score and regional brain alteration, andassessed the relationship between the altered regional brain volume and ALSFRS orrespiratory tests.Results: Frontal assessment battery scores were significantly lower in ALS patientsthan in normal controls. Volume reduction in the right orbitofrontal gyrus in ALS wascorrelated with a lower FAB score. There was no correlation between the right orbitofrontalgyrus volume and ALSFRS or respiratory tests.Conclusions: The results suggest that the FAB is an adequate tool for detecting cognitiveimpairments related to frontal lobe pathology in the relatively mild stage of ALS,independent of physical dysfunctions

Correlation of frontal atrophy with behavioral changes in amyotrophic lateral sclerosis

Background: Recent studies have linked cognitive impairment in amyotrophic lateral sclerosis (ALS) to frontotemporal pathology. Aim: We examined possible associations between behavior changes and regional gray matter volume in early ALS and assessed whether the volume changes were independent of physical impairments. Methods: Seventeen ALS patients with Mini-Mental State Examination ≥24, no need for assistance in daily life, normal respiratory tests (respiratory function test and arterial blood gas analytes), and eleven age-matched controls, underwent structural MRI. Behavioral changes were assessed with family-rating Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry to investigate the correlation between FrSBe and gray matter volume and assessed the correlation of volume with ALS Functional Rating Scale (ALSFRS) and respiratory tests. Results: Current FrSBe were significantly higher than retrospective scores assessing the status before onset, most notably in apathy. The volumes of right middle and left medial frontal gyri in ALS were negatively correlated with FrSBe, whereas they were not correlated with ALSFRS and respiratory tests. The volume of right frontal cluster, but not left medial frontal cluster, was significantly smaller than that of controls. Conclusions: Regional atrophy within frontal lobe was associated with behavioral dysfunction in early ALS, this association was independent of physical factors

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer\u27s disease.

Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer\u27s disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [C]PBB3 and [C]DPA713