Rapid disease progression correlates with instability of mutant SOD1 in familial ALS.

Studies on the clinical course of familial ALS suggest that the duration of illness is relatively consistent for each mutation but variable among the different mutations. The authors analyzed the relative amount of mutant compared with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22 different mutations. Turnover of mutant SOD1 correlated with a shorter disease survival time.

The "pulvinar sign" in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin's lymphoma.

This paper reports a 59 year old woman with paraneoplastic limbic encephalitis associated with diffuse large B cell lymphoma. Her brain magnetic resonance imaging scan showed bilateral posterior thalamic hyperintensities, similar to the "pulvinar sign". Her symptoms included progressive psychiatric disturbance and resembled the initial symptoms of variant Creutzfeldt-Jakob disease (vCJD). Clinicians should consider this treatable disorder in the differential diagnosis of vCJD.

Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient.

A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards.

Isaacs' syndrome successfully treated by immunoadsorption plasmapheresis.

We report a 70-year-old woman with Isaacs' syndrome (acquired neuromyotonia) who showed a marked improvement after immunoadsorption plasmapheresis (IAP). She developed hyperhidrosis in her teens, and slowly progressive symptoms of neuromyotonia for over 50 years. An in vitro investigation of her serum with patch-clamp technique suggested the presence of antibodies against potassium channels. She was treated with IAP, which brought disappearance of her symptoms. Though the symptoms started to recur in 3 weeks, moderate improvement has been maintained by immunosuppressive drug treatment.

HTLV-I-associated myelopathy manifested after renal transplantation.

We report a patient with HTLV-I-associated myelopathy (HAM), who developed symptoms of myelopathy 4 years after cadaveric renal transplantation. Since he was seronegative before the transplantation, it is suggested that HTLV-I infection was transmitted via renal graft transplantation. He has been treated with immunosuppressive agents such as cyclosporin A (CsA), mycophenolate mofetil (MMF), and prednisolone (PSL) to prevent graft rejection. This case suggested that these immunosuppressive agents are poorly effective in suppressing either the onset or progression of HAM/TSP.

[A case of Gerstmann-Sträussler-Scheinker syndrome (P102L) accompanied by optic atrophy].

We report a patient with Gerstmann-Sträussler-Scheinker syndrome (GSS102) who developed optic atrophy. He had been complaining of slowly progressive postural unsteadiness and pain in both legs for 3 years. Visual acuity subacutely worsened in the last half year. His father and two aunts, who already died, had been diagnosed to have dementia. It is uncertain whether they had optic atrophy or not. He was alert but apathetic. Neurological examination revealed cerebellar ataxia, painful dysesthesia and loss of deep tendon reflexes in the lower limbs. Fundoscopic examination revealed bilateral optic atrophy without retinal degeneration, which has never been reported in GSS. A brain MRI showed mild atrophy of cerebellar hemispheres without signal abnormalities of optic nerves. DNA analysis of prion gene revealed point mutation at codon 102 (P102L), which was relatively common mutation in GSS. Other mutations were not found. Only two patients of Creutzfeldt-Jakob disease with optic atrophy have been reported. This case seems to be important to investigate why optic tracts are generally spared in prion disease.

[An autopsy case of Degos' disease with ascending thoracic myelopathy].

Degos' disease is a rare multisystem vasculopathy of unknown etiology. We report a 44-year-old man who presented himself with gait and sensory disturbances mainly due to thoracic transverse myelopathy four years after the appearance of many characteristic umbilicated papules over the trunk and extremities. He did not complain of abdominal pain or discomfort. Laboratory, electrophysiological and imaging studies did not show any characteristic change, except for the increase of protein contents and cell counts in the cerebrospinal fluid. We tried methylprednisolone pulse-dose therapy (1,000 mg/day x 3 days) five times, but this patient's neurological condition worsened stepwise after it, although the appearance of new skin lesion was suppressed. Intravenous infusion of ozagrel sodium and cyclophosphamide (1,000 mg/day) were also ineffective, and this patient died of respiratory failure after showing oculomotor paresis and comatose state. Necropsy revealed Degos' disease-specific vasculopathy in the central nervous system and the gastrointestinal tract, where occlusions of small-sized arteries and veins due to the intimal thickening were evident. The tissue necrosis was macroscopically remarkable in the brainstem and the thoracic spinal cord. The efficacy of steroid therapy for this disease should be investigated more carefully.

Chronic inflammatory demyelinating polyneuropathy accompanied by hepatocellular carcinoma.

We report a patient with chronic inflammatory demyelinating polyneuropathy (CIDP) accompanied by hepatocellular carcinoma (HCC). Due to the remarkable weakness in the lower limbs and loss of the position sense, he could not walk. On neurophysiological examination, he had impaired nerve conduction velocities. Biopsied nerve and muscle specimens demonstrated demyelination of nerve fibers and neurogenic degeneration of muscles. After steroid therapy he showed marked improvement in muscle strength and sensory function.