Inherited prion disease with A117V mutation of the prion protein gene: a novel Hungarian family.

Three members of a family with inherited prion disease are reported. One additional family member had a progressive neurological disease without details. Two developed symptoms of ataxia, dementia, myoclonus, rigidity, and hemiparesis, and one had a different phenotype with the combination of lower motor neuron deficit, parkinsonism, intellectual decline, and ataxia. In this last patient cell loss of the anterior horn motor neurons and chronic neurogenic muscle atrophy was evident. Immunostaining for the prion protein disclosed unicentric and multicentric plaques, and coarse and fine granular positivity. Genetic analysis of the prion protein gene of the propositus showed a 117 codon alanine to valine mutation and homozygous 129 valine/valine genotype.

A three-sister sibship of Gerstmann-Sträussler-Scheinker disease with a CJD phenotype.

OBJECTIVE: To describe a rare phenotypic variant of P102L Gerstmann-Sträussler-Scheinker disease (GSS). BACKGROUND: Classic GSS is characterized by an early age at onset, prominent cerebellar signs with a slowly evolving dementia, and a neuropathology including multifocal PrP-positive plaques and variable but usually modest spongiform change. METHODS: Clinical, neuropathologic, immunohistochemical, and molecular genetic analysis of three sisters in a Hungarian family was performed. RESULTS: The clinical course of all three sisters was indistinguishable from sporadic Creutzfeldt-Jakob disease (CJD). Neuropathologic examination revealed spongiform changes, PrP (prion)-positive unicentric "kuru" or multicentric plaques, and abundant beta-A4-positive senile plaques. Molecular genetic analysis of the PRNP gene showed the heterozygous codon P102L mutation of classic GSS, with the methionine encoding allele of a heterozygous codon 129 coupled to the mutant 102 allele. CONCLUSION: The authors report the second recorded example of a sporadic CJD phenotype occurring in association with the P102L GSS genotype, and the first instance in which the phenotype was the rule rather than the exception, or was associated with prominent beta-A4 plaque formation.

No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study.

Schizophrenia is clinically and neuropsychologically characterized by severe cognitive and functional impairment suggesting the presence of a neurodegenerative process in the brains of affected individuals. A variety of neuroanatomical changes have been described such as loss and disorientation of neurons in grey and white matter and cortical atrophy. However, the neuropathological basis for schizophrenia is still unclear. In the present study we monitored the density of GFAP-positive astrocytes in brains of 33 schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal cortex and subiculum) and white matter (premotor cortex, subventricular zone of the third ventricle and next to inferior horn) structures were measured bilaterally. The overall finding was that there is no evidence for increased astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore, degeneration is unlikely to be the main neuropathological mechanism in schizophrenic brains.

Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study.

The planum temporale of the temporal cortex was investigated post-mortem in 24 schizophrenic patients and 24 age- and sex-matched control subjects. Schizophrenic patients demonstrated a 20% volume reduction of the left planum temporale (p = 0.032), whereas on the right side, there was a trend for increase in male schizophrenics (+22%, p = 0.17), while in female patients the volume was moderately decreased (-6%, p = 0.74). The mean anterior-posterior diameter of the planum temporale was significantly reduced in the left hemisphere (-20%, p = 0.008), but unchanged on the right side. The asymmetry coefficients (Galaburda et al. (1987) Neuropsychologia 25, 853-868) for the planum temporale cortex volume (p = 0.02) and anterior-posterior diameter (p = 0.002) but not for mean area (p = 0.61) were significantly different between schizophrenics and control subjects. These data support the idea of disturbed cerebral laterality in schizophrenia. The implications of methodology and patient samples are discussed.

Cholinergic fiber aberrations in nucleus basalis lesioned rat and Alzheimer's disease.

Innervation density and morphological aberrations of cholinergic fibers were studied with choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry in 30-35 month-old aged rats and rats with long-term bilateral lesions of the magnocellular basal nucleus (MBN). In addition, AChE histochemistry was performed on human cortical sections derived from autopsy brains of normal aged and Alzheimer's disease (AD) patients. A limited but variable number of morphological alterations were observed in ChAT-immunoreactive fibers in the cortex and the hippocampus of the aged control rats. The aged MBN-lesioned rats displayed a severely reduced number of cholinergic fibers in the denervated areas of the neocortex, whereas the surviving fibers showed a strongly increased number of aberrations. Fiber anomalies were also observed in the cortex of the aged human subjects and Alzheimer patients, the latter showing a higher incidence of such aberrations. Only a part of these distended profiles were seen in close association with senile plaques as detected in the AChE-stained material. These findings suggest that experimental MBN lesions combined with aging share with AD the induction of large quantities of fiber malformations. Implications of possible mechanisms in both conditions are discussed.

Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study.

The sylvian fissure is known to be one of the most asymmetric structures of the human brain. Sylvian fissure length was measured in post-mortem brains of 35 schizophrenic patients and 33 matched non psychiatric control subjects. The schizophrenics showed a significantly reduced length of the left sylvian fissure (-16%, p less than 0.0001) compared to the control subjects, while the right sylvian fissure length was unchanged. Sylvian fissure asymmetry (left/right ratio) was more reduced in male schizophrenics (-24%, p less than 0.001) than in female patients (-16%, p less than 0.03). This finding is consistent with several post-mortem and MRI studies showing left temporal lobe pathology in a significant proportion of patients and may indicate that schizophrenia is a disorder of early neurodevelopment causing impaired cerebral lateralization.

Contribution to the background of Mollaret's meningitis.

An epidermoid cyst of the 3rd ventricle was verified by necropsy in a man of 60 with three episodes of Mollaret's aseptic leukocytic-endothelial meningitis. The authors accept the interpretation as macrophages of the "endothelial" cells. They bring forward evidence for the blastomatous nature of partly cornified epithelial cells present in their case. They suggest that cholesterin containing debris entering the subarachnoid space from the tumour cysts provoke an aseptic "chemical" meningitis of short course.

Frontal lobe angioma associated with aneurysm.

On autopsy of a 70-year-old hypertensive male a large arteriovenous angioma in the rostral part of the left cingular gyrus, surrounded by remains of old hemorrhages, and a multilobular saccular aneurysm at the junction of the left anterior cerebral and the communicating arteries were found. The vessels of the angioma and its feeding artery as well as the aneurysm were thrombosed. More recent thrombosis obliterated the venous drainage of the angioma and the oral part of the superior sagittal sinus. Both congenital weakness of the arterial wall and increased circulatory demand might have been responsible for this combined condition.