Single-photon emission computed tomographic investigation of patients with motor neuron disease.

To investigate the correlation between involvement of the CNS in motor neuron disease (MND) and neuroimaging abnormalities, we studied 18 patients with MND by single-photon emission computed tomography (SPECT) and MRI. Patients were divided into four groups according to the results of SPECT. Group 1 consisted of four patients with reduced isotope uptake in the frontal lobe, including the motor area, and in the anterior part of the temporal lobe; group 2 consisted of two patients with reduced isotope uptake in the motor area spreading to the adjacent frontal lobe; group 3 consisted of eight patients with reduced isotope uptake confined to the motor area; and group 4 consisted of four patients without reduced isotope uptake. We found dementia in group 1, borderline dementia in group 2, and no cognitive deficit in group 3 or four. MRI demonstrated enhanced T2-weighted signals along the pyramidal tract in eight patients, but this finding also existed in some control subjects. SPECT appears useful in identifying the location of cortical neuronal degeneration in patients with MND.

Parkinson's disease and myasthenia gravis: adverse effect of trihexyphenidyl on neuromuscular transmission.

A 55-year-old man with idiopathic Parkinson's disease developed myasthenia gravis shortly after taking trihexyphenidyl. The myasthenic weakness waxed and waned with rise and fall in serum levels of trihexyphenidyl, without marked change of anti-acetylcholine receptor antibody titer.

Improvement of abnormal pyruvate metabolism and cardiac conduction defect with coenzyme Q10 in Kearns-Sayre syndrome.

In a patient with Kearns-Sayre syndrome, concentration of coenzyme Q10, a component of the mitochondrial electron transport system, was decreased in serum and in the mitochondrial fraction of skeletal muscle. Serum concentrations of lactate and pyruvate were abnormally high, especially after exercise or oral glucose loading. Levels of folic acid in plasma and CSF were decreased. ECG showed a first-degree atrioventricular block. After administration of coenzyme Q10 60 to 120 mg daily for 3 months, serum levels of lactate and pyruvate became normal, with improvement of atrioventricular block and ocular movements.

Undetectable dystrophin can still result in a relatively benign phenotype of dystrophinopathy.

We present here a 28-year-old male patient with Becker muscular dystrophy whose skeletal muscle showed an absence of dystrophin. He has had progressive and predominantly proximal muscular wasting since 5 years of age, but was able to walk until 26 years of age. He showed hypertrophic calves, cardiomyopathy, and an elevated serum creatine kinase level (934 U/1). A skeletal muscle biopsy revealed advanced chronic myopathic changes. Immunohistochemical examination using anti-dystrophin antibodies against C-terminus showed deficiency of the protein. Rod domain and N-terminus were also absent in almost all muscle fibers, but only in a small part of the sample, they were faintly stained. beta-Dystroglycan and utrophin were present only in a small number of muscle fibers. DNA and RT-PCR analysis showed a frame-shift deletion of exons 3-7 in the dystrophin gene. In such an exceptional case as this one, it is important to investigate the factors which determine the severity of dystrophinopathy.

Focal luxury perfusion with an early-filling vein in relation to neurological symptoms evoked by heat.

A 50-year-old man with a 1-year history of transient attacks of left total hemiparesis was admitted to hospital with a complaint of increasing frequency of attacks. Minimal or moderate left hemiparesis was elicited by elevation of environmental temperature when taking a hot bath or a hot shower. Right carotid angiography revealed an early-filling vein near the right central sulcus. An increase of focal luxury perfusion by elevation of body temperature seemed to cause relative ischaemia in this paracentral gyrus.

Trophic effect of iron-bound transferrin on acetylcholine receptors in rat skeletal muscle in vivo.

Trophic effect of iron-bound transferrin (FeTf) on the total content of acetylcholine receptors (AChRs) and the specific activity of AChRs in innervated and denervated skeletal muscle was investigated in vivo. The right ischiadic nerves of 15 rats weighing 160 g were transected. FeTf (1.2 mg/ml) was injected daily into bilateral crural muscles of rats for the following 11 days. Control groups received injections of saline or no treatment. FeTf significantly increased the total content of AChRs and the specific activity of AChRs in innervated and denervated muscle compared with control groups (P less than 0.001). This result shows that intramuscular injections of FeTf may be useful for the treatment of disorders of neuromuscular transmission.

Involvement of the central nervous system in myotonic dystrophy.

To investigate the etiological factors responsible for intellectual impairment and mood changes in patients with myotonic dystrophy (DM), we evaluated 14 patients with DM by means of neuropsychological evaluation and magnetic resonance images (MRI). There were significant differences between patients and controls in regard to the Barthel index, Zung's depression scale, attention, verbal fluency and digit span. All patients had ventricular enlargement and white matter abnormalities on MRI. However, the severity was variable and there was no difference in neuropsychological testing between patients with mild ventricular dilatation and those with severe dilatation. On the other hand, significant differences were present between patients with mild white matter lesions and those with severe white matter abnormalities in regard to verbal fluency and attention. Neuropathologic examination of an autopsied brain showed an increase in the interfascicular space of the white matter which produced pallor on myelin staining. The present findings suggested that the white matter abnormalities were the cause of cognitive impairment among patients with DM.

[A case of lead neuropathy--importance of subclinical entrapment of nerves in lead neuropathy].

The patient was a left handed 25-year-old man who had worked in a vinyl chloride resin factory since July 1987 using lead stearate as a stabilizer. During the two years preceding hospitalization, he had been admitted three times for colicky abdominal pain with constipation and nausea. Anemia and proteinuria without causative diseases were pointed out. Because of progressive muscle weakness of hands which began since January 1989, he was admitted to our neurologic clinic on October 2 1989. Neurological examination showed severe atrophy of both small hand muscles without sensory disturbances. Left hand was predominantly affected, especially in interossei muscles. Laboratory findings are as follows; RBC 3.25 million/cu.mm: Hb 9.7 g/dl:blood lead concentration 100 micrograms/dl: urinary coproporphyrin 4503 micrograms/l: urinary delta-ALA 138 mg/l: and urinary lead excretion after 1 g CaEDTA infusion: 3938 micrograms/day. Electromyography of extensor carpi radialis, flexor carpi ulnaris and opponens showed increased polyphasic, long duration MUPs. Electromyography of dorsal interossei showed fibrillation. Nerve conduction study showed mildly decreased motor and sensory conduction velocities and markedly reduced amplitude of compound muscle action potentials (CAMPs). Investigation by inching method revealed conduction block of left ulnar nerve across elbow. After CaEDTA chelating therapy, 1 g once a week, steady improvement of muscular weakness was observed within a few months. Serial nerve condition studies revealed constant recovery of nerve conduction velocities, amplitude of CMAPs and diminution of conduction block across the left elbow. Conduction block across left elbow without sensory disturbances implies that subclinical cubital tunnel syndrome might have existed in this patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of spinal muscular atrophy with marked calf hypertrophy and adolescent onset].

We report on a 41-year-old male patient with spinal muscular atrophy (SMA). He had slowly progressive muscular weakness and hypertrophic calves since 14 years of age. The upper arms were slightly, and the thighs moderately atrophic, but the calves were remarkably hypertrophic. There was muscle weakness of both the upper and lower limbs, being more proximal in distribution. He had a positive Gowers' sign and his gait was slightly waddling. Serum creatine kinase level was elevated (518IU/l). Electromyogram revealed a neurogenic pattern. Muscle biopsy of the left biceps brachii showed chronic neurogenic changes. Immunohistochemical examination and Western blot analysis using anti-dystrophin antibodies showed no abnormality. DNA analysis with multiplex PCR proved no deletion in the dystrophin gene, while deletions of exons 7 and 8 of the telomeric copy of survival motor neuron gene were detected. In 1978, Pearn et al. described a new variant syndrome of SMA, characterized by adolescent onset, gross hypertrophy of calves, and a slowly progressive clinical course. The present case is compatible with this syndrome. Therefore, it is suggested that this syndrome, mimicking Becker muscular dystrophy, is not an independent clinical entity, although the phenotype of this syndrome is different from that of typical SMA.

[A family with facioscapulohumeral muscular dystrophy and hereditary long QT syndrome].

We describe a family with facioscapulohumeral muscular dystrophy (FSHD) and hereditary long QT syndrome (LQT) for three generations. The proband, a 50-year-old woman, had noticed difficulty in raising the upper extremities since the age of 40. At the age of 48, she was admitted to our hospital because of arrhythmia attack. She, her mother, and one of her three children were diagnosed as having LQT. These three individuals and the proband's two siblings were clinically diagnosed as having FSHD which was confirmed by genetic analysis using EcoR1. FSHD is an autosomal dominant disorder and the gene locus is mapped to chromosome 4q35-ter, but the gene has not been isolated. LQT is a group of disorders which cause syncope and sudden death from ventricular arrhythmia in an autosomal dominant fashion. Four loci for this syndrome (LQT1-4) have been known, and three of the genes have been shown to encode ion-channels. Genetic analysis of the proband failed to detect any of previously known mutations in the LQT1, LQT2, and LQT3 genes. The locus for LQT4 has been mapped to chromosome 4q25-7. There have so far been no report of FSHD associated with LQT. Although the pathogenesis is unclear, we speculate that these two diseases are linked each other on chromosome 4q.

[Pharmacokinetics and toxicity of intrathecal administration of recombinant interleukin 2].

In order to contribute to the development of adoptive immunotherapy against malignant brain tumors, the pharmacokinetics and toxicity of intrathecally administered recombinant interleukin-2 in dogs and human patients were analyzed. The pharmacokinetics showed that a high concentration of IL-2 was maintained in the intrathecal cavity in both dogs and human (t1/2 = 1.41 and 1.68 hours, respectively) after administration. However, no activity of IL-2 was detected in the cerebrospinal fluid after the systemic administration of rIL-2 in one dog. No meningitis, ventriculitis or degeneration of neurons was seen histopathologically in dogs 3 weeks after the intrathecal administration of rIL-2 (200 units). A high concentration of IL-2 in the tumor cavity was maintained for a very long time (t1/2 = 14.8 hours) after the intratumoral administration of rIL-2 in one of the patients. Although low-grade fever and mild headache were sometimes observed after the intrathecal administration of rIL-2 in patients, there was no other side effect mentioned. Intrathecal or intratumoral administration of rIL-2 appeared to be an valuable procedure which should be evaluated in conjunction with adoptive immunotherapy against malignant brain tumors.

Beneficial effect of interferon-beta treatment in patients with multiple sclerosis is associated with transient increase in serum IL-6 level in response to interferon-beta injection.

In order to predict the clinical benefit of interferon-beta (IFN-beta) to patients with multiple sclerosis (MS), the following markers were investigated; (1) chronological change of cytokines (IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta) after administration of IFN-beta, (2) untoward effects of IFN-beta such as headache and arthralgia, (3) backgrounds of the patients such as age and relapse rate, (4) efficacy of IFN-beta therapy assessed by the change of relapse rate and progression of disability. Chronological blood sampling was performed 0, 10, and 24 h after injection of IFN-beta. The increase of serum IL-6 level in response to IFN-beta administration was associated with headache, arthralgia, relapse rate before treatment, and disability score at the initiation of the therapy. Significant association of change of serum TNF-alpha with age and headache was also observed. The important finding in this study was that patients with a transient increase in IL-6 in response to IFN-beta showed a slow disease progression. This result suggests that this transient increase in the serum IL-6 predicts favorable response to IFN-beta treatment.

Evaluation of the effect of CDP-choline on poststroke hemiplegia employing a double-blind controlled trial. Assessed by a new rating scale for recovery in hemiplegia.

A double-blind study was conducted in order to evaluate the effect of CDP-choline on functional recovery of hemiplegia. A standardized 12-grade scale (Hemiplegia Function Test) was utilized for the evaluation. The results indicate that for the upper limbs, doses of 1,000 and 250 mg of CDP-choline were superior to placebo at 8 weeks. The higher dose showed an effect at 4 weeks equal to that at 8 weeks while the effect of the lower dose was slower but reached the same level of effect as the higher dose at 8 weeks. Similar results were obtained for the lower limbs but the effectiveness was not statistically significant. The lesser effect for the lower limbs could be attributed to the relatively small number of patients in the early stages of recovery in the present series. No significant differences were found for the effects on subjective symptoms, neurological signs and overall judgment of the physicians. The findings suggest that CDP-choline promotes natural recovery in hemiplegia.