Multiplex families with multiple system atrophy.

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 dentatorubral-pallidoluysian atrophy (DRPLA) was evaluated by polymerase chain reaction. Direct sequence analysis of coding regions in the alpha-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, beta isoform; PP2R2B), SCA17 (TATA box binding protein, TBP) and DRPLA (atrophin 1; ATN1), were excluded, and no mutations in the alpha-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.

Mimics of brain tumor on neuroimaging: part II.

Brain tumor is a distinct pathological entity that differs from other diseases, including cerebrovascular, demyelinating, inflammatory, infectious, and various miscellaneous diseases. Insidious onset and gradual progression of signs and symptoms are common in patients with brain tumors, whereas the onset of cerebrovascular diseases is usually acute or sudden. Patients with demyelinating, inflammatory, or infectious diseases show subacute onset. Differentiation of brain tumors from other disorders is usually possible from the clinically and radiologically characteristic features. However, in some diseases other than brain tumors, an atypical clinical course and/or radiological findings may suggest or simulate those of brain tumors. The diagnosis of brain tumor is confirmed histopathologically, and appropriate therapies are given to the patient based on the histopathological type and grade of the tumor. In order to obtain a specimen for histopathological examination, surgical intervention is required. Other diseases are usually diagnosed clinically and radiologically. Invasive procedures should be avoided in making a diagnosis. Therefore, differentiation of brain tumors from other diseases is a critical issue for neuroimaging. Detailed inspection of images is necessary, and characteristic findings, and additional imaging methods, such as diffusion-weighted imaging, are often helpful for the differential diagnosis. We assess the imaging findings of diseases simulating brain tumors and review the literature.

Mimics of brain tumor on neuroimaging: part I.

Brain tumor is a distinct pathological entity that differs from other diseases, including cerebrovascular, demyelinating, inflammatory, infectious, and various miscellaneous diseases. Insidious onset and gradual progression of signs and symptoms are common in patients with brain tumors, whereas the onset of cerebrovascular diseases is usually acute or sudden. Patients with demyelinating, inflammatory, or infectious diseases show subacute onset. Differentiation of brain tumors from other disorders is usually possible from the clinically and radiologically characteristic features. However, in some diseases other than brain tumors, an atypical clinical course and/or radiological findings may suggest or simulate those of brain tumors. The diagnosis of brain tumor is confirmed histopathologically, and appropriate therapies are given to the patient based on the histopathological type and grade of the tumor. In order to obtain a specimen for histopathological examination, surgical intervention is required. Other diseases are usually diagnosed clinically and radiologically. Invasive procedures should be avoided in making a diagnosis. Therefore, differentiation of brain tumors from other diseases is a critical issue for neuroimaging. Detailed inspection of images is necessary, and characteristic findings, and additional imaging methods, such as diffusion-weighted imaging, are often helpful for the differential diagnosis. We assess the imaging findings of diseases simulating brain tumors and review the literature.

MR features of diseases involving bilateral middle cerebellar peduncles.

BACKGROUND AND PURPOSE: Distribution of lesions or involvement of specific anatomic sites can suggest the diagnosis of disease. The purpose of this study was to investigate what diseases affect both middle cerebellar peduncles (MCPs) and to evaluate other MR features for differential diagnosis. METHODS: MR findings of 27 patients (14 male and 13 female; age range, 4-77 years [mean, 48.5 years]) with bilateral MCP lesions were retrospectively studied. RESULTS: Neurodegenerative diseases were the most frequent diagnoses (n = 11 [41%]: sporadic olivopontocerebellar atrophy, eight; Shy-Drager syndrome, one; spinocerebellar ataxia, two). Also included were metabolic diseases (n = 6 [22%]: adrenoleukodystrophy, two; Wilson disease, two; cirrhosis of the liver, one; and hypoglycemia, one); cerebrovascular diseases, including posterior reversible encephalopathy syndrome (n = 3 [11%]: infarction, one; hypertensive encephalopathy, one; cyclosporin-A encephalopathy, one), demyelinating and inflammatory diseases (n = 4 [15%]: multiple sclerosis, one; acute disseminated encephalomyelitis, one; Behçet disease, one; and HIV encephalopathy, one), and neoplasms (n = 3 [11%]: lymphoma, one; glioma, one; meningeal carcinomatosis, one). All patients showed symmetrical T2 hyperintensity in both MCPs, except for one with malignant lymphoma. Marked atrophy in the posterior fossa was characteristically seen in neurodegenerative diseases. Enlargement of the pons was observed in hypertensive encephalopathy and neoplasms but absent in meningeal carcinomatosis. Lesions were restricted in the posterior fossa in eight patients with neurodegenerative diseases and one with brain stem glioma. Other patients had supratentorial lesions. CONCLUSION: Symmetricity of MCP lesions, morphologic change of the posterior fossa structures, and distribution of other lesions are helpful in the differential diagnosis.

Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation.

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.