No abstract

We report a case of frontotemporal dementia and parkinsonism linked to chromosome 17 of 5 years' duration in an 81-year-old man whose brother had died at age 86 years with dementia. In this patient, we found frontal and temporal neuronal loss, glial-predominant tau deposits, progressive supranuclear palsy-like straight tubules, accumulation of 4-repeat-predominant Sarkosyl-insoluble tau, and a novel exon 1 (Arg5His) tau gene mutation. This mutation decreased microtubule-promoting capacity and increased fibrillation of tau in vitro. Thus, we consider that the Arg5His mutation is an authentic tau gene abnormality responsible for the patient's tau pathology and late-onset dementia.

Background: Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance. Objective: To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects. Design: Clinical and genetic study. Setting: Four departments of neurology in Japan. Patients: Eight patients in 4 families with parkinsonism, cerebellar ataxia, and autonomic failure with age at onset ranging from 58 to 72 years. Two siblings in each family were affected with these conditions. Main Outcome Measures: Clinical evaluation was performed according to criteria by Gilman et al. Trinucleotide repeat expansion in the responsible genes for the spinocerebellar ataxia (SCA) series and for dentatorubralpallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the ␣-synuclein gene was performed. Results: Consanguineous marriage was observed in 1 of 4 families. Among 8 patients, 1 had definite MSA, 5 had probable MSA, and 2 had possible MSA. The most frequent phenotype was MSA with predominant parkinsonism, observed in 5 patients. Six patients showed pontine atrophy with cross sign or slitlike signal change at the posterolateral putaminal margin or both on brain magnetic resonance imaging. Possibilities of hereditary ataxias, including SCA1 (ataxin 1, ATXN1), SCA2 (ATXN2), Machado-Joseph disease/SCA3 (ATXN1), SCA6 (ATXN1), SCA7 (ATXN7), SCA12 (protein phosphatase 2, regulatory subunit B, ␤ isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the ␣-synuclein gene were found. Conclusions: Findings in these multiplex families suggest the presence of familial MSA with autosomal recessive inheritance and a genetic predisposition to MSA. Molecular genetic approaches focusing on familial MSA are expected to provide clues to the pathogenesis of MSA.

We assess diffusion-weighted MR images in the differential diagnosis of intracranial brain tumors and tumor-like conditions. Heavily diffusion-weighted (b = 1100 or 1200 s/mm2) axial images were obtained with single-shot echo-planar technique in 93 patients with pathologically confirmed various intracranial tumors and tumor-like conditions with diffusion gradient perpendicular to the images. We compared signal intensity of the lesions with those of gray and white matter, and cerebrospinal fluid (CSF). In 29 cases (31.1%) the lesions were isointense to gray and/or white matter. However, 5 cases (5.4%) showed extremely increased signal intensity: two epidermoid cysts; two chordomas; and one brain abscess. The entire portion of a tumor was markedly hyperintense in 10 cases (10.8%): four malignant lymphomas; four medulloblastomas; one germinoma; and one pineoblastoma. A CSF-like hypointense signal was seen in many cystic tumors, and cystic or necrotic portions of tumors. A neurosarcoid granulation was the only solid lesion showing characteristically a hypointense signal like CSF. The combination of markedly hyperintense and hypointense signals was seen generally in hemorrhagic tumors. Diffusion-weighted echo-planar MR imaging is useful in the differential diagnosis of brain tumors and tumor-like conditions, and suggests specific histological diagnosis in some cases.

We have studied brain tissues from three patients with corticobasal degeneration (CBD) histologically, ultrastructurally and immunohistochemically. Ballooned neurons in the cerebral cortex and severe degeneration of the substantia nigra were observed in them all and weakly basophilic neurofibrillary tangles (NFTs) were distributed widely in the basal ganglia and brain stem. Ultrastructural examination demonstrated that the NFTs comprised characteristic 15-nm-wide straight tubules, which showed positive immunohistochemical staining with an antibody against tau, but not ubiquitin. Tau-immunoreactive neuronal cell bodies without NFTs also were found in the cerebral cortex and subcortical nuclei, predominantly in the brain stem, and the greatest number of tau-positive glial inclusions occurred in the cerebral gray and white matter of the pre- and post-central gyri. These inclusions comprised tubular structures with diameters of about 15 nm and were localized in the oligodendroglial cellular cytoplasm and processes. These findings indicate that there is a close cytoskeletal pathological relationship between CBD and progressive supranuclear palsy.