Yoshiaki Wada

Selective loss of Purkinje cells in a patient with anti-glutamic acid decarboxylase antibody-associated cerebellar ataxia

Anti-glutamic acid decarboxylase antibody is associated with the development of progressive cerebellar ataxia and slowly progressive insulin-dependent diabetes mellitus. Previously, the neurophysiological characteristics of IgG in the cerebrospinal fluid of a patient with anti-glutamic acid decarboxylase antibody-associated progressive cerebellar ataxia and slowly progressive insulin-dependent diabetes mellitus were reported. Using a voltage-gated whole-cell recording technique, it was observed that the IgG in the cerebrospinal fluid of the patient selectively suppressed the inhibitory postsynaptic currents in the Purkinje cells. The patient died from aspiration pneumonia. Postmortem examination showed almost complete depletion of the Purkinje cells with Bergmann gliosis. Therefore, the main cause of cerebellar ataxia observed in this case may be attributed to the near-complete depletion of the Purkinje cells. In this paper, the pathomechanisms underlying Purkinje cell damage are discussed.

A quantitative Golgi study of basal dendrites of hippocampal CA1 pyramidal cells in senile dementia of Alzheimer type.

Basal dendrites of hippocampal CA1 pyramidal cells in senile dementia of Alzheimer type (SDAT) were studied quantitatively by the Golgi impregnation method. The present data suggested that basal dendrites of the pyramidal cells were decreased in number in SDAT, and that the dendritic decrease was associated with a decrease in size of their cell bodies.

Radiation myelopathy: significance of gadolinium-DTPA enhancement in the diagnosis

SummaryWe described two cases of chronic progressive radiation myelopathy (CPRM), in which magnetic resonance imaging (MRI) was of great value for the diagnosis. Gadolinium-DTPA (Gd-DTPA) enhancement delineated precise lesions responsible for Brown-Séquard syndrome caused by CPRM in both cases. This safe, sensitive procedure will be a requisite study in patients who are suspected of CPRM.

Pattern of epitopic reactivity of the anti-Hu antibody on HuD with and without paraneoplastic syndrome

Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/PSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90–101 or aa 171–206. Some anti-Hu samples reacted with the deletion fragments containing aa 223–234, aa 235–252, or aa 354–373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90–101 and aa 171–206 are the major epitopes with which all anti-Hu serum samples react, and aa 223–234, aa 235–252, and aa 354–373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.

Peripheral neuropathy with predominantly motor manifestations in a patient with carcinoma of the uterus.

SummaryAn autopsy case of a 56-year-old woman who had carcinoma of the corpus uteri and peripheral neuropathy with predominantly motor manifestations is described. The neurological abnormalities included subacute weakness of the limbs and loss of deep reflexes, which improved after the surgical removal of the uterine carcinoma. Neuropathologically, peripheral nerves mainly presented features of axonal degeneration with a mild loss of myelinated fibres. Anterior horns of the spinal cord showed central chromatolysis of the motor nerve cells and many spheroids without neuronal loss. Axonopathy of peripheral nerves was considered to be the main pathological process in this paraneoplastic syndrome.

Marked hypertrophy of the cauda equina in a patient with chronic inflammatory demyelinating polyradiculoneuropathy presenting as lumbar stenosis.

Sirs: Hypertrophy of peripheral nerves and enlargement of nerve roots have been reported in some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) [4]. We report a patient with CIDP who suffered from intermittent claudication as a rare manifestation of enlargement of the cauda equina. A 63-year-old male was admitted to our hospital in 2001 complaining of difficulty in walking and recurrent pain in the legs. The patient had noticed slight atrophy of the muscles in the left hand in 1980. In 1996, he noticed numbness of both feet. In March 1999, intermittent claudication appeared: he noticed tingling pain in the lower thigh, which worsened after ambulation for several hundred meters and ameliorated after a rest. He was diagnosed as having lumbar stenosis by an orthopedist. However, his condition continued to worsen and he could not walk without assistance after six months. Physical examinations showed severe wasting of muscles and distal dominant sensory loss. Drop foot was observed. Hypertrophic peripheral nerve trunks were not found. Tendon reflexes were absent without pathological reflexes. Routine laboratory tests including serum autoantibodies against gangliosides and DNA analysis for P0, connexin 32 and PMP 22 genes were normal. Cerebrospinal fluid (CSF) contained a markedly elevated protein (952 mg/dl). Motor nerve conduction velocity of the right median nerve was extremely slowed (28.6 m/s) with marked dispersion of action potentials. Compound muscle action potentials of both lower extremities and all sensory nerve action potentials were not detectable. Needle electromyography showed typical findings of reinnervation without evidence of ongoing denervation. MRI of the lumbar spine showed marked enlargement of the cauda equina and spinal nerve roots (Fig. A, C). The spinal subdural space was occupied with enlarged cauda equina (Fig. A). Patchy enhancement of these hypertrophic tissues was observed (Fig. B). The biopsy specimen of the right sural nerve showed severe depletion of myelinated fibers with onion-bulb formations (Fig. D). Electron microscopy showed myelinated fibers surrounded by several layers of Schwann cells (Fig E). The patient was diagnosed as having definite CIDP [7]. Initial treatment with oral prednisolone was ineffective. The patient received three courses of intravenous immunoglobulin therapy (IVIG, 0.5 g/kg), which ameliorated the weakness of the muscles and the intermittent claudication. A diagnosis as a lumbar stenosis was initially raised when the patient complained of the slowly progressive onset of leg pain and gait disturbance including intermittent claudication. However, absence of tendon jerks and a distal weakness in the upper limbs hinted at a more diffuse neuropathy, and subsequent examinations fulfilled the criteria for the diagnosis of CIDP. Apparent effects of IVIG treatment also supported the diagnosis of CIDP. Hypertrophy of peripheral nerves and spinal nerve roots is a well-known presentation of CIDP. However, CIDP presenting initially with symptoms of lumbar stenosis is rare; only eight cases have been reported so far [2, 3, 5, 6, 8]. Among these patients, two underwent nerve biopsy and the biopsy specimens showed marked onion-bulb formations [3, 5]. Therefore, the pathomechanism of nerve root hypertrophy may be attributed to repeated segmental demyelination and remyelination along with onion-bulb formations. Neurogenic intermittent claudication is one of the characteristic symptoms of lumbar stenosis in which hypertrophy of osseous and soft tissue structures surrounding the lumbar canal causes entrapment of the cauda equina nerve roots [1]. As in our patient, the structures around the lumbar canal were intact in contrast to marked hypertrophy of the cauda equina, that is, occupation of lumbar canal by hypertrophic nerve roots caused relative narrowing of lumbar canal, which led to symptoms similar to “true” lumbar stenosis. In conclusion, this case is of particular interest because it shows that “apparent” lumbar stenosis associated with marked hypertrophy of nerve roots can develop during the course of CIDP.

“Quadriceps myopathy”: a clinical variant form of becker muscular dystrophy

SummaryA 26-year-old male with “quadriceps myopathy” is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45–48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy.