[A patient of Charcot-Marie-tooth disease with rigid spine and respiratory failure].

This report describes a case of a 17-year-old girl with Charcot-Marie-Tooth disease (CMT) representing rigid spine and respiratory failure. At age 11, she tended to walk on her toes and had difficulty in getting up from the floor without support. She became aware of flexion limitation of the neck at the age of 12. At 15 years of age, She began to have dyspnea on effort. When she was 17 years old, neurological examination revealed mild weakness of the upper extremities and severe weakness of the distal lower extremities, generalized wasting and areflexia. Superficial sensation was mildly impaired distally, and vibration sensation was severely impaired in the lower extremities. Motor and sensory nerve conduction velocities were mildly reduced, and compound muscle action potential of the tibial and peroneal nerves and sensory nerve action potential on ulnar and sural nerves were absent. Electromyography showed neurogenic changes with denervation potentials. Sural nerve biopsy revealed severe loss of myelinated fibers without any onion-bulb formation. As for family history, her elder sister showed moderate loss of vibration sensation in the lower extremities. On the basis of these findings, she was diagnosed as having CMT type 2, though a mode of inheritance was uncertain. She also had peculiar findings of flexion limitation of the spine (rigid spine), contracture of the hip joint, and fatty degeneration of paraspinal muscles on CT. Percent vital capacity (VC) was 22.5%, and arterial blood gas analysis showed PaO2 of 60.5 mmHg and PaCO2 65.0 mmHg. To our knowledge, this is the first case of CMT accompanied by rigid spine and respiratory failure. Motor and sensory neuropathy combined with rigid spine also have not been reported previously. The relationship between rigid spine syndrome with neurogenic muscular atrophy and CMT type 2C with the clinical characteristics of diaphragm and vocal cord paresis is discussed.

Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15A13-15.

To date, three loci for autosomal recessive hereditary spastic paraplegia (ARHSP) linked to chromosomes 8p12-q13, 16qter, and 15q13-15 have been characterized. We have clinically characterized 13 Japanese ARHSP families and performed genetic linkage analyses. All 13 families were classified as having the "complicated" form, which manifests with mental impairment and thin corpus callosum. Linkage to the 8p12-q13 and 16qter loci was excluded, although 10 of the 13 families showed marker data consistent with linkage to the 15q13-15 locus. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3-centimorgan segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 centimorgans telomeric from D15S994 to D15S659. We have shown that ARHSP with thin corpus callosum, a subtype of recessive spastic paraplegia, maps to chromosome 15q13-15.

Drop in relapse rate of MS by combination therapy of three different phosphodiesterase inhibitors.

Phosphodiesterase inhibitors (PDEIs), when used in combination, synergistically suppress TNFalpha production by various cells and also suppress experimental demyelination at very low concentrations. We conducted a pilot study to determine whether the combination of three PDEIs suppresses the relapse of MS at the usual therapeutic doses. Of the 12 relapsing remitting MS, the mean relapse rate/year dropped remarkably (from 3.08+/-3.32 to 0.92+/-1.86) after PDEI treatment. Seven out of 12 (58.3%) were relapse-free in the follow up period (499+/-142 days). The combination of three PDEIs can be safe and useful strategy for the future treatment of MS. - 58

Hybrid survival motor neuron genes in Japanese patients with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a frequently occurring autosomal recessive disease, characterized by the degeneration of spinal cord anterior horn cells, leading to muscular atrophy. Most SMA patients carry homozygous deletions of the telomeric survival motor neuron gene (SMN) exons 7 and 8. In the study presented here, we examined 20 Japanese SMA patients and found that 4 of these patients were lacking in telomeric SMN exon 7, but retained exon 8. In these 4 patients, who exhibited all grades of disease severity, direct sequencing analysis demonstrated the presence of a hybrid SMN gene in which centromeric SMN exon 7 was adjacent to telomeric SMN exon 8. In an SMA family, a combination of polymerase chain reaction and enzyme-digestion analysis and haplotype analysis with the polymorphic multicopy marker Agl-CA indicated that the patient inherited the hybrid gene from her father. In conclusion, hybrid SMN genes can be present in all grades of disease severity and inherited from generation to generation in an SMA family.

[Screaming during sleep in patients with Parkinson disease].

We studied 12 patients with Parkinson disease who scream while sleeping. All 12 patients showed clinical manifestations and brain images of typical idiopathic Parkinson disease. On average, the screaming began 4.8 years after the onset signs and symptoms of Parkinson disease. In many cases, sleep talking started before the onset of Parkinson disease. All patients reported that the screaming disrupted the sleep of their families, and half of the patients reported that the screams disturbed their own sleep. The screams were incorporated into their dreams. Clonazepam was effective to alleviate this screaming in 8 out of 9 cases. We considered this screaming to be caused by similar mechanisms as rapid eye movement (REM) sleep behavior disorder in which muscle atonia characterizing normal REM sleep is absent. The screams were not accompanied by other abnormal behaviors. We postulate that the screaming is a symptom closely related to that of mid or lower brainstem lesion in Parkinson disease because the neural activity of the locus ceruleus or the pudunculopontine nucleus are responsible for muscle atonia in REM sleep.

[A report of two siblings with both maternal dentato-rubro-pallido-luysian atrophy and paternal Ehlers-Danlos syndrome type III].

The report deals with the first description of two siblings, a 43-year-old woman and 39-year-old man, who have developed cerebellar ataxia, choreoathetosis, dementia, epilepsy, hyperelasticity of the skin, and hypermobility and dislocation of joints. The frequent dislocations of joints sometimes could not be corrected surgically. Their mother and maternal uncle have the same neurological signs and symptoms as the siblings do. However, they do not present with the signs of skin and joints. Gene analysis of peripheral blood lymphocytes from these 4 patients revealed that the CAG repeat length of the dentato-rubro-pallido-luysian atrophy (DRPLA) gene is increased in all four. On the contrary, their father has displayed only hyperelasticity of the skin. From the clinical signs, family history and skin biopsy, we consider that the siblings and their father have Ehlers-Danlos syndrome (EDS) type III. In conclusion, the previously unreported coincidental development of maternal DRPLA and paternal EDS observed in two siblings deserves to be described.

[A family with dentato-rubro-pallido-luysian atrophy (DRPLA): an intergenerational contraction of the CAG repeat].

We describe the relation of the CAG repeat length to the genetic anticipation in a Japanese family with dentato-rubro-pallido-luysian atrophy (DRPLA). The proband, a 21-year-old woman, developed epilepsy at age 19. Her mother has displayed cerebellar ataxia, choreoathetosis, and dementia since age 40, and the grandmother has shown cerebellar ataxia since age 52. So a genetic anticipation was observed. The CAG repeat sizes of peripheral blood lymphocytes from the proband, mother, and grandmother were found to be 61, 59, and 60, respectively. Thus, the mother showed earlier onset but a smaller CAG repeat length as compared to the grandmother. This case is thought to be rare and valuable in respect that the intergenerational contraction of the CAG repeat was shown in spite of the genetic anticipation was observed.

Central motor reorganization after anastomosis of the musculocutaneous and intercostal nerves following cervical root avulsion.

In 4 patients with a complete upper limb palsy due to traumatic cervical root avulsion, surgical anastomosis of intercostal to musculocutaneous nerves was performed to restore function in the biceps brachii muscle. Four to 6 months after the operation, motor unit discharges were recorded from the biceps muscle on the operated side during deep breathing and by cortical magnetic stimulation. The motor unit discharges became independent from respirations gradually over 1 to 2 years. The latencies of the motor potentials evoked by cortical and thoracic root magnetic stimulation decreased gradually over 2 to 3 years. Motor cortex mapping of the reinnervated biceps muscle showed a gradual change over 4 to 33 months from the area of the intercostal muscles to that of the arm area, which was more lateral on the motor cortex. These findings suggest that reorganization of the motor cortex to arm flexor muscles occurs following peripheral nerve anastomosis.

Sweat function in Parkinson's disease.

Sweat function was studied in patients with Parkinson's disease and in normal adults by sympathetic skin response, the bromphenol blue printing method and the silicone mould method. In patients with Parkinson's disease, dysfunction of sweating was classified into two types: one type involved the postganglionic fibres and the other involved the preganglionic fibres or the central nervous system. The latter was observed in patients with milder disease and the former was observed in patients with severe disease. The progressive involvement of sweat function in Parkinson's disease may reflect spread from the central nervous system or preganglionic fibres to postganglionic fibres. In a few patients the results of sweat tests were normal. Ceruletide increased sweating in Parkinson's disease patients, and decreased the prolonged latency of the sympathetic skin response. It is hypothesized that ceruletide facilitates the preserved somatosympathetic reflex of sweating.

A clinicophysiologic study of central and peripheral motor conduction in hereditary demyelinating motor and sensory neuropathy.

Central and peripheral motor nerve conduction were analyzed in 13 patients with hereditary demyelinating motor and sensory neuropathy using central magnetic stimulation and peripheral electrodiagnostic techniques. All patients showed a marked decrease in peripheral nerve conduction velocity. In 11 patients, the central motor conduction time was slightly prolonged but in 2 it was markedly prolonged suggesting dysfunction of the corticospinal tract. These two patients exhibited marked weakness and atrophy of distal muscles without clinical signs of upper motor neuron dysfunction, which was considered to be masked by the lower motor neuron disorder. This study suggests that in some patients with hereditary demyelinating polyneuropathy central as well as peripheral nerve fibers may be affected.

Ceruletide therapy in action tremor following thalamic hemorrhage.

Two men, aged 63 and 71 years, developed a gross action tremor and dysesthesias several months after an intracerebral hemorrhage. CT and MRI showed a small hemorrhage in the posterior region of the lateral nucleus of the thalamus in each patient. The tremor occurred on movement, had frequencies of 2.5-4.5 Hz and the amplitude varied depending on the joint position of the limb. Ceruletide (a cholecystokinin analog) 0.8 micrograms/kg i.m. produced a marked reduction in the action tremor and improved motor function. This effect appeared 10-15 min after the injection, and lasted for up to 4 weeks. It is suggested that ceruletide may be of value in the treatment of action tremors following a thalamic lesion.

Recurrent polyradiculoneuropathy with hyperthyroidism.

A 30-year-old woman, who had had two episodes of distal dominant sensorimotor disorders in the extremities, developed again sensorimotor involvement in the distal portion of all limbs. She was also found to have hyperhidrosis, tachycardia and goiter. Neurological and endocrinological examinations led to a diagnosis of coexistence of recurrent polyradiculoneuropathy and hyperthyroidism. Treatment with thiamazole resulted in improvement of the neurological features as well as of hyperthyroidism. The relationship between polyradiculoneuropathy and hyperthyroidism is discussed.

Central motor conductivity in aged people.

The conductivity of motor neurons in 26 aged females (mean age 79 years) was analyzed by the conventional conduction method and by pulsed magnetic stimulation and compared with that in 14 younger controls. In aged people, slow motor conduction velocities were found in peripheral nerves. Central motor conduction time (CMCT) in relaxed muscle was shorter in the aged people, although CMCT was normal in mildly contracted muscle. These findings coincide with the results studied in Parkinson's disease, although these subjects were not diagnosed as having Parkinson's disease. Aged people generally have an anteflexed posture, slow movements, and poor postural reflexes, and have been reported to have a decrease in the dopamine level which is relatively earlier than that of other transmitters in the basal ganglia. This may account for the present finding that aged people have neurophysiological abnormalities in CNS which are similar to those in Parkinson's disease.

[A case of Japanese encephalitis demonstrating characteristic changes in MRI].

A 40-year-old woman developed high fever and headache. Five days later, she was admitted because of consciousness disturbance and tremulous movements in upper extremities. The paired sera showed more than fourfold elevation in complement fixation titer to Japanese encephalitis virus. She was diagnosed as Japanese encephalitis from the clinical features and serological tests. Magnetic resonance imaging (MRI), which was performed about seven months after the onset, revealed abnormal intensity areas bilaterally in the thalamus, hippocampus, substantia nigra, globus pallidus and white matter around the lateral ventricle. Eight months after the onset, she was left with bradykinesia, disturbance of rightening reflex, emotional lability and impairment of recent memory with a long period of amnesia, including not only her illness and subsequent events but also about several years before her illness. The characteristic memory dysfunction seems to be due to disorder of bilateral hippocampus, where MRI revealed abnormal intensity areas. And disorder of medial thalamic nucleus would be related to emotional liability. The relation between the clinical features and MRI findings is also discussed.

[A case report of the compression syndrome due to hypertrophic neuropathy].

We reported a case of hypertrophic neuropathy of adult onset. The pathological change in the sural nerve was decreased axonal population with onion-bulb formation. On examination, there were enlarged nerve on palpation and she was found to have distal muscle atrophy, weakness and sensory loss. The deep tendon reflexes of extremities were weak. The first clinical feature of this patient was mainly polyneuropathy. The lower limbs were slightly spastic and plantar responses were extensor bilaterally. There was also sensory level at C6 level. After 1.5 years from first examination, she had shown myelopathy. Magnetic resonance imaging (MRI) of the spine showed marked thickening of the nerve roots and it revealed the compression of the spinal cord by enlarged nerve roots from C2 to C6 level. The compression syndrome of the patients with hypertrophic neuropathy was unclear at the onset in this case. MRI study of the spinal cord would be very beneficial to disclose subclinical myelopathy associated with hypertrophic neuropathy, as indicated in this report.

[An MRI study of hereditary spinocerebellar degenerations].

We evaluated magnetic resonance image (MRI) in 21 cases of hereditary spinocerebellar degenerations (SCD) of autosomal dominant trait. By the discriminant formula based on size of the cerebellar vermis and ventral pons, which was reported in our previous study, the patients were classified into three types. Group 1 included the cases with atrophies in the vermis and pons; OPCA type. Group 2 showed vermian atrophy and less significant atrophy in pons; LCCA type. And Group 3 was no significant atrophies both in vermis and pons. Cases in Group 1 were furthermore divided into two groups according to width of the midbrain tegmentum. Group 1A, with normal midbrain tegmentum, was consisted of five cases. Four cases were diagnosed as Menzel type OPCA. Another case showed various clinical symptoms and relatively mild atrophies for his duration of illness. His family members were classified to Group 3. Seven cases in Group 1B showed reduced midbrain tegmentum. Four cases showed ataxia, spasticity, ocular symptoms, bladder dysfunction and amyotrophy with or without fasciculation, and they seemed to be a special type of SCD mimicking Joseph disease. One case showed bulging eyes, ocular movement palsy and dystonia. However, his sister manifested only ataxia with very mild ocular movement disorder. Their MRI demonstrated severe atrophies in the cerebellum, pons and afferent cerebellar peduncli, and this pedigree was thought to be Menzel type OPCA with various associated disorders. Another case was clinically diagnosed as dentate-rubro-pallido-luysian atrophy. Group 2 was consisted of 6 cases who were clinically diagnosed as Holmes type LCCA. MRI demonstrated medial dominant cerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Central motor conduction time (CMCT) in hereditary motor sensory neuropathy type I (HMSN type I)].

The motor system of 13 cases with hereditary motor sensory neuropathy (HMSN) type I were analysed by clinical neurophysiological method. The motor conduction velocity (MCV) and F wave latency in lower motor neurone were markedly delayed. The latency of the muscle evoked potential (MEP) by cortical magnetic stimulation were also markedly delayed. The central motor conduction times (CMCT) were calculated by two methods. CMCT-mag was calculated by subtraction of the MEP by cervical magnetic stimulation from the MEP by cortical magnetic stimulation. CMCT-f was calculated by subtraction of the [(F wave latency -1 + distal latency)/2] from the MEP by cortical magnetic stimulation. There were positive correlation between CMCT-f and CMCT-mag. CMCT of HMSN type I were divided to two groups. CMCT of the first group was markedly delayed. CMCT of the second group was mildly delayed or normal. The former group showed marked weakness in distal muscles clinically. The latter group showed mild or moderate weakness in distal muscles clinically. All these patients did not show any pyramidal tract signs, which could be covered by severe lower motor neurone involvements. The classification of HMSN type I by gene was well known, genetical analysis might be important to these groups in HMSN type I.

[MRI study of hemiballism].

MRI findings of four hemiballism cases are described, and pathophysiology, pathogenesis and treatment of hemiballism are discussed. All cases had no family history. The lesions revealed by MRI and the pathogenesis were different each other. Case 1, a 17 years aged girl with a history of hyperthyroidism and repeated tonsillitis, showed right sided hemiballism which was recovered by prednisolone and haloperidol. Although her involuntary movement was ameliorated by administration of sodium valproate and phenytoin, phenytoin caused allergic agranulocytosis which required prednisolone treatment. T2 weighted MRI at the 31st disease day demonstrated hyperintensities in the left caudate nucleus, putamen, lateral pallidum, perirubral area and substantia nigra. Hyperintensity in the prerubral area suggested involvement of the subthalamic nucleus or its connecting pathway. Fourteen months later, she suffered from convulsion and mental confusion. There were theta wave bursts and delta waves in EEG. No abnormal findings in MRI and positive antinuclear antibody (ANA: X320, speckled type) were observed. Case 2, a 78 year aged woman, suffered from right sided hemiballism. MRI findings at the 58th disease day were the left putaminal infarction and lacunar state in the bilateral caudate nuclei and the deep white matter of the centrum semiovale. There were no abnormal findings in the subthalamic nucleus. Case 3, a 51 year aged man with diabetes mellitus, had right sided hemiballism. X-ray CT at the 8th disease day showed hyperdensity in the left subthalamic nucleus region which could not be observed at the 12th day. Hypointensity in the left subthalamic nucleus region was observed in both T2 weighted and proton density MRI at the 52nd day. Case 4, an 82 year aged woman, had right sided hemiballism which remarkably diminished at the third disease day and disappeared by the fifth day. Any pathogenic lesion concerning to hemiballism was detected by X-ray CT or MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

[The kinesiological, chemical and pathological analysis in pulsed magnetic stimulation to the brain].

Pulsed magnetic stimulation of the human brain and spinal region has been reported recently. Unlike electrical stimulation, magnetic stimulation excites the motor cortex without discomfort to the subject. This method will be used as a new clinical test to study the central motor pathway. Although no deleterious effects have been observed thus far, the safety of this technique is regarded as unproven. We have investigated kinesiological, neurochemical and pathological analysis. Our pulsed magnetic discharge system consists of a high voltage capacitor bank and flat circular coil of insulated copper wire. The high voltage capacitor bank has a maximum voltage of 900 V, a maximum current flow of 8,000 amp and 1,637 uF in condenser capacitance. Sixty four normal wistar rats each weighing 200 g were used in this study. The rats were separated into two groups. Rats in one group received pulsed magnetic stimulation 50 times in 0.5 Hz by a flat circular coil which surrounded the head of rat at 1 cm in front of the interauricular line. The rats were housed in a long circular chamber. Rats in the other group did not receive the pulsed magnetic stimulation in the long circular chamber. The details of kinesiological analysis by Animex II measurement were described in an other paper (Act Neurologica Scandinavica 73; 352-358, 1986). The measurement of monoamines, dopamine (DA), homovalinic acid (HVA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), were made according to the Mefford's method 1 hour and 4 days after the magnetic stimulation. The analysis of the pathological state was also studied 1 hour and 4 days after the magnetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of juvenile-type distal and segmental muscular atrophy of upper extremities (Hirayama disease) with the isolated cervical fusion at the C3-C4 levels].

The case, 29-year-old male, had suffered from muscular weakness and atrophy of the bilateral forearms and hands with tremor of the bilateral fingers for about 13 years. A neurological examination showed normal muscle-stretch reflexes and no sensory disturbances. A cervical spinogram revealed a fusion at the C3-C4 levels and mild spondylotic changes. We clinically diagnosed him as juvenile-type distal and segmental muscular atrophy of upper extremities (Hirayama disease) with the isolated congenital cervical fusion. Magnetic resonance imaging demonstrated an enlargement of the anterior epidural space from the C4-C5 levels to the Th 1-Th 2 levels. This abnormal epidural space showed relatively high signal intensity partially with low signal intensity on the T2 weighted spin-echo image and decreased in signal on the T1 weighted spin-echo image. And the dural sac was shifted backward and narrowed. And the soft discs was slightly protruded at the level of C4-5, C5-6 and C6-7. These findings suggest the over swelling and the delayed blood flow of the internal vertebral venous plexus. In this case, the degeneration of the cervical spine and soft disc derived from the congenital cervical fusion seems to have caused the internal vertebral venous plexus congestion and then have damaged the anterior horn cells.