Yuzo Tanabe

A Subtype of Diabetes Mellitus Associated with a Mutation of Mitochondrial DNA

BACKGROUND Several families have been described in which a mutation of mitochondrial DNA, the substitution of guanine for adenine (A-->G) at position 3243 of leucine transfer RNA, is associated with diabetes mellitus and deafness. The prevalence, clinical features, and pathophysiology of diabetes with this mutation are largely undefined. METHODS We studied 55 patients with insulin-dependent diabetes mellitus (IDDM) and a family history of diabetes (group 1), 85 patients with IDDM and no family history of diabetes (group 2), 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and a family history of diabetes (group 3), and 5 patients with diabetes and deafness (group 4) for the mutation. We also studied the prevalence and characteristics of diabetes in 39 patients with a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes who were known to have the mutation and 127 of their relatives (group 5). RESULTS We identified 16 unrelated patients with diabetes associated with the A-->G mutation: 3 patients from group 1 (6 percent), 2 patients from group 3 (2 percent), 3 patients from group 4 (60 percent), and 8 patients from group 5 (21 percent). We also identified 16 additional subjects who had diabetes and the mutation among 42 relatives of the patients with diabetes and the mutation in groups 1, 2, 3, and 4 and 20 affected subjects among the 127 relatives of the patients in group 5. Diabetes cosegregated with the mutation in a fashion consistent with maternal transmission, was frequently (in 61 percent of cases) associated with sensory hearing loss, and was generally accompanied by impaired insulin secretion. CONCLUSIONS Diabetes mellitus associated with the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan.

L-arginine improves the symptoms of strokelike episodes in MELAS.

Based on the hypothesis that mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) are caused by impaired vasodilation in an intracerebral artery, the authors evaluated the effects of administering l-arginine, a nitric oxide precursor. Patients were administered l-arginine intravenously at the acute phase or orally at the interictal phase. l-Arginine infusions significantly improved all strokelike symptoms, suggesting that oral administration within 30 minutes of a stroke significantly decreased frequency and severity of strokelike episodes.

Electrophysiological subtypes and prognosis of childhood Guillain–Barré syndrome in Japan

Guillain–Barré syndrome (GBS) is classified into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), but little is known about the incidence of the subtypes and the prognosis of childhood GBS. To elucidate the features and long‐term prognosis, clinical and electrophysiological data for 31 Japanese GBS children were reviewed. By electrodiagnostic criteria, children were classified as having AIDP (35%) or AMAN (48%), or were unclassified (16%). The AMAN children invariably had normal sensory nerve potentials. Between the two groups, age, sex, and clinical disability did not differ significantly, but the AIDP children more frequently had cranial and sensory nerve involvement, and the AMAN children more frequently had preceding gastroenteritis. By 6 months after onset, all the AIDP and 80% of the AMAN children had regained the ability to walk; by 2 years, all but one of the AMAN children could walk. In Japanese childhood GBS, the proportion of AIDP and AMAN appears to be similar. Recovery is generally favorable in both subtypes, but some of the AMAN children experienced delayed recovery. Muscle Nerve, 2006

MRI changes and deficits of higher brain functions in preterm diplegia

Goto M, Ota R, Iai M, Sugita K, Tanabe Y. MRI changes and deficits of higher brain functions in preterm diplegia. Acta Pædiatr 1994;83:506–11. Stockholm. ISSN 0803–5253

Epilepsy in Peroxisomal Diseases

Summary: Purpose: To clarify the electroclinical manifestation of epileptic seizures and the evolution of epilepsy in patients with peroxisomal diseases.

A comparative magnetic resonance imaging study of the corpus callosum in neurologically normal children and children with spastic diplegia

To determine the extent of brain damage in children with spastic diplegia, we analyzed the true midsagittal magnetic resonance imaging findings for the corpus callosum in 43 children with spastic diplegia and in 69 neurologically normal children. In the normal children, the thicknesses of the genu, midbody, splenium and the entire corpus callosum were found to increase with age, while the ratios of the thickness of the splenium and of the midbody to the length were constant, regardless of age. Both ratios were significantly reduced in diplegic children and the ratio for the splenium was highly correlated with the extent of motor impairment. Assessment of the morphometric changes in the corpus callosum using magnetic resonance imaging may contribute to the determination of the extent of brain damage in diplegic children.

A Case of Acute Disseminated Encephalomyelitis Presenting Hypersomnia With Decreased Hypocretin Level in Cerebrospinal Fluid

A 12-year-old girl was diagnosed as having acute disseminated encephalomyelitis and manifested hypersomnia as the main clinical feature. Magnetic resonance imaging (MRI) revealed lesions in the bilateral hypothalamus in addition to other multifocal brain lesions involving the cerebral white matter, brain stem, and basal ganglia. The level of hypocretin in cerebrospinal fluid was decreased in this patient. Corticosteroid treatment resulted in improvement of the hypersomnia and resolution of MRI lesions in the hypothalamus and other regions. This case suggests that the arousal state control mechanism related to the hypocretin peptide/receptor system may be impaired in some patients with acute disseminated encephalomyelitis. (J Child Neurol 2002;17:537-539).

Neuroradiological findings in children with congenital myotonic dystrophy

We studied seven children with congenital myotonic dystrophy, aged 2.1–8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neonatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow‐up computed tomography scans taken at intervals of one to six years. Also, in T2‐weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxial episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopmental outcome and the extent of the periventricular hyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia.

Muscle fiber growth and necrosis in dystrophic muscles: a comparative study between dy and mdx mice

Histopathological and morphometric studies of murine dystrophic muscles in the early postnatal period were performed. In dy mice, obtained by in vitro fertilization, scattered necrotic fibers were noted at 10 days of age followed by poorly compensated regeneration leading to muscle fiber loss, marked variation in fiber size, and fibrous and adipose tissue proliferation. In mdx mice, clusters of necrotic muscle fibers seen at 10-15 days were followed by well compensated regeneration with little fibrosis. There appeared to be no delay in muscle fiber growth and fiber type differentiation in both dy and mdx mice up to 10 days of age since there was no distinct difference in muscle fiber size, fiber type differentiation and the incidence of myosatellite cells between dystrophic muscles and those from age-matched control mice. Muscle fibers appeared to undergo necrosis only when they had reached a certain stage of maturation since at early stages of development or regeneration they rarely became necrotic. The difference in clinical symptoms between dy and mdx mice may result from differences in their regenerative response to necrosis.

Adolescent case of Alexander disease: MR imaging and MR spectroscopy.

A 17-year-old male was diagnosed as having Alexander disease from the clinical manifestations (psychomotor deterioration and megalencephaly), neuroradiologic findings (frontal dominant leukodystrophy), and elevation of alpha B-crystallin and heat shock protein 27 in the cerebrospinal fluid. He exhibited increased attenuation on computed tomography and T1 and T2 shortening on magnetic resonance imaging in the bilateral basal ganglia and thalamus. Some paramagnetic substances might be deposited in the basal ganglia and thalamus in the late stage of Alexander disease, at least 8 years after onset.