Komei Kumagai

A new congenital muscular dystrophy with mitochondrial structural abnormalities

We report a new form of congenital muscular dystrophy (CMD) in 4 patients from three unrelated families with probable autosomal‐recessive inheritance. All patients had the clinical characteristics of merosin‐positive congenital muscular dystrophy, but had marked mental retardation. The disease was slowly progressive and 1 patient died from dilated cardiomyopathy at the age of 13 years. In addition to dystrophic changes with necrosis and regeneration in muscle, the most striking finding was mitochondrial depletion in the center of the sarcoplasm. Mitochondria at the periphery of fibers were markedly enlarged (“megaconial” appearance) with complicated cristae, and contained a normal amount of mitochondrial DNA by in situ hybridization. Mitochondrial enlargement may represent functional compensation for mitochondrial depletion in the central sarcoplasm, where myofibrillar degeneration occurred.

Sanfilippo syndrome type C: A clinicopathological autopsy study of a long-term survivor

A 39-year-old Japanese woman with Sanfilippo syndrome type C is reported. Developmental delay was observed during infancy and progressive intellectual deterioration became apparent at 2 years. Her gait became unsteady and she became bed-ridden at 22 years of age. An intestinal fistula was made because of pyloric stenosis possibly caused by accumulation of mucopolysaccharide at 37 years of age. She died of acute cardiac failure at age 39 years. Pathological changes were marked in the heart and brain. Focal necrosis of myocardial fibers with replacement fibrosis and many vacuolated cells were observed between the muscle fibers and there were many vacuolated cells in the pyloric ring. There was severe neuronal loss with gliosis and massive corpora amylacea formation in the cerebral cortex, especially in layers 2 and 3. Ballooning of neurons was less prominent than neuronal loss. There were many vacuolated cells in the mesenchymal tissues; however, this finding was much less prominent than in other types of mucopolysaccharidosis. Our patient survived much longer than others with Sanfilippo syndrome type C of similar severity.

The Clinical Use of Multichannel Surface Electromyography

Surface EMG motor unit action potentials (MUAPs), recorded with “array” or “matrix” types of electrodes, can be seen to propagate from the motor end plates in both directions along the muscle fibers. We attempted to obtain diagnostic information in muscle disease by using the multichannel surface EMG. The subjects examined were 28 normal controls (5–40 years old), seven patients with myopathy and three patients with neuropathy. The tibialis anterior and the biceps brachii muscles were investigated at weak and moderate contraction levels. In normal muscles, the mean muscle fiber conduction velocity increased with muscle force. In four of seven cases with myopathy, the conduction velocities were reduced compared to normal subjects (p<0.01), and there was little or no correlation between the conduction velocity and muscle force. In Duchenne muscular dystrophy, abnormal propagation patterns of MUAPs were obtained. The conduction velocities were within the normal range in the muscles of patients with neuropathy. However, abnormal MUAPs, giant and fasciculation potentials, and diminished discharge patterns of motor units (MUs) were detected during voluntary contraction and at rest in neuropathy.

A comparison survey of seizures and other symptoms of Pokemon phenomenon

On 16 December 1997, many Japanese children developed neurologic problems while watching the animated television series Pokemon. This study included children who visited the outpatient departments of 14 pediatric clinics for other reasons within 2 months after this incident. Volunteering children and parents or guardians were asked to complete questionnaires. We obtained 1,373 replies (including 800 males, 558 females, and 15 children without information on sex; mean age, 6.8 +/- 3.5 years). The majority of children included in this study (80%) watched this program, and 67 (6.1%; 40 males, 27 females) were affected by the program. There were 10 patients with seizures (0.9%; four males and six females). Fifty-seven patients developed other symptoms. Compared with nonaffected children, significantly more affected children reported that they concentrated on watching this program, watched it at a short distance from the screen, and did not watch this program in a brightly lit room. Seizures tended to occur in older children (average = 10.8 years) and in children with a high rate of familial histories of seizures. Symptoms other than seizures occurred more frequently, and autonomic and psychologic factors, such as motion sickness, could be considered possible mechanisms. Children who developed symptoms seemed to have problems in viewing conditions.

Muscle histochemistry in myotubular (centronuclear) myopathy.

We report the clinical and histochemical findings in 7 patients with myotubular (centronuclear) myopathy aged from 2 months to 32 years. The clinical symptoms varied from patient to patient. Three patients developed severe muscle weakness and hypotonia with respiratory distress from infancy, and 4 had muscle weakness from 2-5 years of age with no apparent delay in developmental milestones. In addition to an increased number of fibers with centrally placed nuclei, there were 3 other histochemical characteristics of this disorder, i.e., type 1 fiber predominance, type 1 fiber hypotrophy and type 2B fiber deficiency. Other histological findings included a peripheral halo in the sarcoplasm on NADH-TR staining and an increased number of undifferentiated type 2C fibers, indicating a delay in muscle fiber growth and differentiation due to a probable defective neural supply in the developing muscles.

Patient background of the Pokemon phenomenon: Questionnaire studies in multiple pediatric clinics

Many children in Japan developed various neuropsychological problems, including seizures, while watching the program Pocket Monster, televised on 16 December 1997. To examine the basis for this incident, we have performed a survey of volunteering children and their parents who visited our pediatric clinics for other reasons from 8 January to 28 February 1998. Children and their parents filled out questionnaires. Among the total of 662 children surveyed, the great majority (603, 91.1%) was found to have watched the Pocket Monster program and 30 individuals (5.0% of viewers) complained of variable degrees of neuropsychological abnormalities. These included seizures (two cases), headache (nine cases), nausea (eight cases), blurred vision (four cases), vertigo (two cases), dysthymia (two cases) and vomiting (one case). Nearly half (14) of these children developed symptoms during or immediately after watching the program, while the remainder did so later. Representative cases are reported and other statistical aspects are discussed.

Adrenoleukomyeloneuropathy presenting as cerebellar ataxia in a young child: a probable variant of adrenoleukodystrophy

A child aged 5 years 7 months was diagnosed as suffering from adrenoleukomyeloneuropathy (ALMN). The first sign was ataxia, and high intensity lesions were observed in the cerebellar hemispheres on T2-weighted brain MRI. His condition progressed rapidly to a vegetative state in 1 year. When aged 7 years 3 months adrenal insufficiency supervened and his skin turned dark. Rectal biopsy revealed linear cytoplasmic inclusions in macrophages in the rectal membrane. At the age of 8 years 2 months, an analysis of very long-chain fatty acids of sphingomycin in plasma led to the final diagnosis. At the age of 10 years, cerebellar and cerebral atrophy were prominent and diffuse high intensity lesions were noted in the cerebellum and cerebrum. An onset below 9 years of age has not previously been documented in ALMN.

Professor Norimitsu Yoshikura (1902–1988). A leading Japanese authority in paediatric neurology

Dr. Norimitsu Yoshikura, Professor of Pediatrics, Surugadai Hospital, Nihon University School of Medicine, was born in Tokyo on 18th January, 1902. He first graduated from the Faculty of Literature, Waseda University, and thereafter from the Jikei University School of Medicine in 1933. He was a member of the committee of the Japanese Pediatric Neurology Association from 1964 to 1976, and an honorary member of the French Neurological Society. In 1966 he was president at the 6th annual meeting of the Japanese Society of Child Neurology. He retired from

An autopsy case of atypical adrenoleukomyeloneuropathy in childhood

Adrenoleukomyeloneuropathy (ALMN) usually occurs in adulthood, it being extremely rare in childhood. We reported a quite atypical clinical case of ALMN as a variant of adrenoleukodystrophy (ALD). The onset was at 5 years 7 months and ataxia was the major symptom. His condition progressed rapidly to a vegetative state within 1 year. At the age of 11 years and 11 months he died of pneumonia and an autopsy was performed. We herein reported the neuropathological findings in this rare case. The autopsy revealed marked atrophy with diffuse demyelination and astrogliosis throughout the cerebrum, cerebellum and brainstem. Massive degeneration of the pyramidal tracts and loss of neurons were also seen in the spinal cord. The adrenal cortex showed marked atrophy with a striated cytoplasm in ballooned cells. These findings include pathological characteristics of both ALD and adrenomyeloneuropathy (AMN), suggesting ALMN. However, diffuse demyelination with gliosis in the cerebrum and cerebellum is quite atypical for ALMN. They might explain his atypical clinical course, especially the early onset of the disease with ataxia and rapid deterioration.

Adrenoleukomyeloneuropathy presenting with spino-cerebellar ataxia in a young child

Cockayne syndrome complicated by acute subdural hemorrhage Hide0 Shimoizumi “jb, Mika Matsui a, ‘, Shigeko Ito “24 Masutomo Miyao ‘jb and Shigeichi Kobayashi b (” Tochigi Prefectural Hospital and Welfare Center for the Crtppled. Tochigi; b Department of Pediatrics. Jichi Medical College, Tochigi, Japan) We describe a patient with Cockayne syndrome who developed an acute cerebral hemorrhage as a late complication with rapid clinical deterioration. Case report: A lZyear-old boy was the term product of an uncomplicated pregnancy and delivery. He was referred to an institution for handicapped children at 1 year 2 months of age because of his motor delay. He was diagnosed as having Cockayne syndrome on the basis of stunted growth, special facial features, rigid muscle tone and skin photosensitivity. He began to walk at 2 years of age, but became unable to walk after 3 years 6 months of age. He was referred to our hospital at 6 years of age. On examination he was found to be a cachectic dwarf (BH 86.5 cm, -6.5 SD) with microcephalus (HC 44.0 cm, 5.1 SD), multiple joint contractures, deafness and retinal pigmentary abnormalities. He could sit without aid but showed cerebellar ataxia, rigidity and hyperreflexia. Cranial CT showed atrophy of the cerebrum, cerebellum and brain stem, and calcification in the basal ganglia and paraventricular parenchyme. MRI showed changes compatible with leukodystrophy. NCVs were abnormally slow. At 12 years of age, he developed acute renal failure and hypertension after some febrile illness. CT demonstrated bilateral acute subdural hemorrhage. His neurological status deteriorated rapidly. After this episode he responded poorly to external stimuli. Conclusion: Subdural hemorrhage could be a serious complication in the late stage of Cockayne syndrome.