Eishun Nitta

Germanium intoxication with sensory ataxia

Sensory ataxia in inorganic germanium intoxication is rare. A 63-year-old housewife had taken inorganic germanium preparations at a dosage of 36 mg a day for about 6 years (total dose about 80 g). She subsequently developed difficulty in writing and gait disturbance with peripheral neuropathy and renal involvement. Germanium, which is not usually detected in the non-germanium user, was accumulated in her hair and nails, permitting a diagnosis of inorganic germanium intoxication. The peripheral neuropathy and renal injury were not reversible after discontinuing the preparation. Pneumonia and sepsis then supervened and the patient died. Autopsy findings showed degeneration and loss of the dorsal root ganglion cells and degeneration of the dorsal column of the spinal cord. Two previously reported cases presented with ataxia. These patients took germanium for long periods and/or large quantities like our case. It was supposed that sensory ataxia was induced by chronic and dose dependent toxicity of inorganic germanium.

An autopsy case of an aged patient with spinocerebellar ataxia type 2

We report the case of a woman who developed limb clumsiness in her fifties and gait disturbance in her sixties. She was bedridden after bone fractures at age 75 and showed disorientation, slow eye movement, gaze palsy, ataxic speech, muscle atrophy and weakness, and areflexia with pathological reflex. She died of respiratory failure at age 85. This patient was diagnosed genetically as having spinocerebellar ataxia type 2 (SCA2), and the number of expanded CAG repeats was 41. At autopsy, the brain weighed 965 g, and the brainstem, cerebellum, frontal convexity and spinal cord were atrophic. Neuronal loss and gliosis were severe in the pontine nucleus, inferior olivary nucleus, cerebellar cortex, gracile and cuneate nuclei and moderate in the substantia nigra, cerebellar dentate nucleus, anterior horns of the spinal cord and dorsal root ganglia. Axonal loss was observed in the middle and inferior cerebellar peduncles, pyramidal tract and posterior column of the spinal cord. Senile plaques and neurofibrillary tangles (NFTs) were diffusely found in the cerebrum (plaque stage C; NFT stage IV). Expanded polyglutamine‐immunoreactive inclusions in the neuronal cytoplasm were widely distributed in the CNS, and neuronal intranuclear inclusions were observed in the pontine nucleus and cerebral cortex. This patient in this autopsy case is a late‐onset and aged patient with SCA2, and this is the first report of SCA2 combined with Alzheimers disease (AD) pathology. Neuropathological findings in this patient, except for AD pathology, were consistent with those of reported SCA2 cases. However, the olivo‐ponto‐cerebellar system of this patient was relatively preserved and the cerebellar dentate nucleus was more involved as compared with previously reported cases. These results suggest that age at onset or the number of CAG repeat expansions could correlate with the distribution pattern of SCA2 neurodegeneration.

Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy)

AbstractAutosomal recessive distal myopathy or Nonaka distal myopathy (NM) is characterized by its unique distribution of muscular weakness and wasting. The patients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between markers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refine the localization of the NM gene, we conducted homozygosity and linkage disequilibrium analysis for 14 patients from 11 NM families using 18 polymorphic markers. All of the patients from consanguineous NM families were found to be homozygous for six markers located within the region between markers D9S2178 and D9S1859. We also provided evidence for significant allelic associations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S2181-D9S1804), present in 60% of NM chromosomes and in 0% of parent chromosomes. On the basis of the data obtained in this study, the majority of NM chromosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S1791.

[Cervical epidural β2-microglobulin amyloidoma presenting with acute paraplegia 5 months after introduction of hemodialysis].

A 66-year-old man was admitted to our hospital with acute paraplegia. He has suffered from hypertension with renal dysfunction for 7 years. Five months before admission, hemodialysis was introduced to him because of chronic renal failure due to renal sclerosis. One week before hospitalization, he noticed dizziness, sensory disturbance below the chest, and a urinary difficulty. Two days prior to admission, he could not walk independently. Spinal MRI revealed a mass at the 7th level of the cervical spine, showing low intensity on T(1)-weighted image and surrounding hypointensity with inner mixed intensity on T(2)-weighted image. An urgent surgery removed the cervical epidural mass and the following pathological evaluation established the diagnosis of β2-microglobulin amyloidoma. Hemodialysis-related amyloidoma generally emerges after a long duration of hemodialysis, demonstrates an insidious onset of symptoms, and is very rare. The current case indicates that we need to be aware of the possibility of β2-microglobulin amyloidoma even in patients with a short history of hemodialysis with a rapid presentation.

A case of body lateropulsion to the left in acute cerebral infarction of the right medial parietal lesion

A 68-year-old right-handed woman with acute-onset inability to stand was admitted to our department. Although left hemiparesis was minor, the neurological examination on admission showed marked body lateropulsion (BL) to the left when she stood or stepped with eyes open and feet closed. Neither ataxia nor sensory disturbance was present. Brain MRI and 3D-CT angiography revealed infarction of the right posterior cingulate and the precuneus due to dissection of the right anterior cerebral artery. BL improved on day 10 and she was discharged without sequelae on day 26. BL caused by cerebral lesions is rare, and we should recognize that infarction of the posterior cingulate and/or the precuneus can cause BL.

A case of multiple sclerosis with bilateral intermediate uveitis

We describe a case of 20-year-old woman with visual impairment in her left eye. Her left visual acuity was 0.07 and an ophthalmoscopic examination demonstrated bilateral intermediate uveitis (IU). A neurological examination on admission revealed lower nasal quadrantanopsia in her left eye and an exaggerated right patellar tendon reflex. A T2-weighted MRI showed multiple high-intensity lesions in the bilateral periventricular region, corpus callosum, medulla. A short T1 inversion recovery MRI also showed a swollen left retrobulbar optic nerve and posterior thoracic cord lesion at Th 9 level. The latter longitudinal length was approximately 20 mm. Laboratory investigation demonstrated no abnormalities including an anti-aquaporin-4 antibody. A cerebrospinal fluid examination revealed an increased IgG-index (1.21) with oligoclonal IgG babds. Initially, a diagnosis of retrobulbar optic neuritis with IU was made. She received subtenon corticosteroid injection with intravenous methylprednisolone pulse and oral prednisolone therapy. An immediate improvement of her visual symptoms and MRI abnormalities was observed. Approximately 1 year later, a new high-intensity lesion in the right internal capsule was present on a follow-up T2-weighted brain MRI, established a diagnosis of multiple sclerosis (MS) based on the McDonald criteria in 2010. Previous reports in Japan demonstrated few cases of uveitis in patients with MS and this is the first report of MS with IU in Japan.