Familial amyloidosis, Finnish type (FAF) (gelsolin-related amyloidosis) is an autosomal dominant form of systemic amyloidosis characterized by corneal lattice dystrophy and peripheral polyneuropathy. The accumulating protein in FAF consists of fragments of gelsolin, an actin-modulating protein. The gelsolin mutation G654A has been found in both Finnish and Japanese patients. To study the origin of the gelsolin mutation in these patients we performed haplotype analysis in 10 Finnish and 2 Japanese FAF families. Poymorphic DNA markers GSN, D9S103, AFMa061xd9, and AFMa139xb9 revealed a uniform disease haplotype in all the disease-associated chromosomes of the Finnish FAF families, which was different from the one observed in the Japanese families. The present results and the previously detected gelsolin mutation G654T in Czech and Danish FAF patients suggest that nucleotide 654 may represent a mutation hot spot in the gelsolin gene. The DNA markers studied here will be useful in future genealogical analyses of FAF.
We found degeneration of enteric nerve plexuses in two patients with type I familial amyloid polyneuropathy. Amyloid deposition was more severe in the wall of the stomach than in the rectum. Hypomotility of the upper gastrointestinal tract, resulting from both amyloid deposition in the stomach and upper bowel and degeneration of the intrinsic autonomic nerves, may be responsible for anorexia, nausea, and vomiting. Diarrhea and constipation may be caused by degeneration of the enteric nerve plexuses. Gastric biopsy is valuable and safe in the diagnosis to type I familial amyloid polyneuropathy.
Two patients with tactile naming disorders are reported. Case 1 (right hand tactile agnosia due to bilateral cerebral infarction) differentiated tactile qualities of objects normally, but could neither name nor categorize the objects. Case 2 (bilateral tactile aphasia after operation of an epidural left parietal haematoma) had as severe a tactile naming disturbance as Case 1, but could categorize objects normally, demonstrating that tactile recognition was preserved. Case 1 may be the first case of tactile agnosia clearly differentiated from tactile aphasia. CT scans of Case 1 revealed lesions in the left angular gyrus, and in the right parietal, temporal, and occipital lobes. Case 2 had lesions in the left angular gyrus and of posterior callosal radiations. Our findings suggest that tactile agnosia appears when the somatosensory association cortex is disconnected by a subcortical lesion of the angular gyrus from the semantic memory store located in the inferior temporal lobe, while tactile aphasia represents a tactual-verbal disconnection.
Aims Axonal aggregates of phosphorylated (p‐) transactive response DNA‐binding protein 43 kDa (TDP‐43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. Methods Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin‐fixed paraffin‐embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. Results (i) Aggregates of p‐TDP‐43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p‐TDP‐43 in the axons showed two characteristic microscopic features – dash‐like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p‐neurofilaments, but p‐neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p‐ and p‐independent (i)‐TDP‐43, and almost all neurones had lost their nuclear TDP‐43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP‐43‐immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p‐TDP‐43 deposition was evident. Conclusions There are two types of axonal p‐TDP‐43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p‐i‐TDP‐43 in the nuclei of postsynaptic neurones.
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