Familial amyotrophic lateral sclerosis: a SOD1-unrelated Japanese family of bulbar type with Bunina bodies and ubiquitin-positive skein-like inclusions in lower motor neurons.

We describe a new family with adult onset amyotrophic lateral sclerosis (FALS), in which the disease was characterized clinically by relatively rapid progression of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed in one patient showed no mutations. Autopsy of another patient demonstrated degenerative changes restricted to the upper and lower motor neuron systems; no evident changes were observed in the posterior column, Clarke's column or spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive skein-like inclusions in the lower motor neuron was of considerable interest. Cases of FALS with such pathological features are quite rare in the literature. Identification of the gene responsible for the disease is desirable in order to shed further light on the molecular pathology of not only familial, but also sporadic, ALS.

Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes.

We report two sporadic cases of tauopathy with unusual neuropathological features. The ages of the patients at death were 86 and 74 years, and the disease durations were 4 and 3 years, respectively. The former patient showed progressive dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was responsible for the amyotrophy), and the latter showed progressive parkinsonism and dementia. The essential brain pathologies were similar to each other; although ballooned neurons and astrocytic tau lesions (astrocytic plaques) were present in the affected cerebral cortex, the most striking finding was focal, much heavier accumulation of tau in the subcortical white matter. Moreover, double-labeling immunostaining, as well as Gallyas-Braak electron and AT8 immunoelectron microscopic studies strongly suggested that in the affected subcortical white matter, the accumulation of tau occurred mainly in the astrocytic processes. In the latter patient, for whom frozen brain tissue was available, immunoblotting of insoluble tau revealed a pattern compatible with that obtained from brain affected by typical corticobasal degeneration (CBD), and gene analysis of tau revealed no mutations, with a H1 haplotype. Finally, in both cases, the pathological diagnosis of CBD was considered to be appropriate. However, the tau pathology affecting the subcortical white matter astrocytes was very unusual for the disease.

Primary lateral sclerosis: a rare upper-motor-predominant form of amyotrophic lateral sclerosis often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions? Report of an autopsy case and a review of the literature.

We report the autopsy findings of an 82-year-old woman who exhibited slowly progressive upper motor neuron signs (pseudobulbar palsy, muscle weakness and positive Babinski's sign) in the absence of lower motor neuron signs, which were followed by progressive dementia and frontotemporal atrophy, and who died 7 years and 4 months after onset of the disease. In this patient, the upper motor neuron system, including the precentral cortex and descending pyramidal tract, was severely degenerated, but the lower motor neurons and innervated skeletal muscles were well preserved. A few lower motor neurons were found to contain cytoplasmic inclusion bodies characteristic of amyotrophic lateral sclerosis (i.e., Bunina bodies and ubiquitin-positive skeins). However, fragmentation of the Golgi apparatus was not evident in the anterior horn cells examined. Therefore, it was considered that the lower motor neurons were also involved, but that the rate of degeneration of these neurons was very slow in the disease process. Marked frontotemporal lobar degeneration characterized by microvacuolation, and ubiquitin-positive neuronal inclusions and dystrophic neurites in cortical layer II were also observed, the precentral cortex being the most severely affected area. Similar ubiquitin-positive structures were also observed in the neostriatum. Finally, a survey of the literature based on this patient's clinical and pathological features led us to conclude that the rare clinical syndrome of primary lateral sclerosis is, in general, a rare upper-motor-predominant form of amyotrophic lateral sclerosis that is often accompanied by frontotemporal lobar degeneration with ubiquitinated neuronal inclusions.