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Biomedical subjects

S Kumada

Publications and source records attributed to S Kumada.

At least 19 recordsLinked to original sources
PubMed2006

Fixation-sensitive myoclonus in Lafora disease.

The authors report a patient with Lafora disease, whose myoclonus was suppressed by passive eye closure. Neurophysiologic studies disclosed that fixation was the most important enhancer of myoclonus. Magnetoencephalographic studies of visual evoked fields revealed abnormal activation of the visual corticocortical pathway via the insular cortex not seen in controls. The authors hypothesize that abnormal activation of the insular cortex may be involved in triggering the mechanism of fixation-sensitive myoclonus.

Adolescent↗
PubMed2001

Lethal form of chondrodysplasia punctata with normal plasmalogen and cholesterol biosynthesis.

We present a male autopsied case of chondrodysplasia punctata with abnormal face, symmetrical proximal limb shortness, severe psychomotor developmental delay, respiratory muscle weakness, and death at the age of 2 years. Although his clinical manifestations were similar to those of rhizomelic chondrodysplasia punctata (RCDP), biochemical studies using skin fibroblasts did not document the peroxisomal dysfunction described in RCDP. In addition, the sterol profile, for which abnormalities have recently been reported in cases of X-linked dominant form chondrodysplasia punctata (CDPX2), was normal both in the liver and in the fibroblasts. This patient may represent a new lethal form of chondrodysplasia punctata.

Calcinosis↗
PubMed2001

Mutation screening for Japanese Lafora's disease patients: identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene.

The progressive myoclonus epilepsy of Lafora type (LD) is an autosomal recessive disorder caused by mutations in the EPM2A gene. We demonstrated recently that EPM2A encodes a dual-specificity phosphatase that is primarily associated with polyribosomes. In the present study, we screened for mutations in the EPM2A gene in 4 Japanese LD families and identified a novel mis-sense mutation, Ala46Pro (136G-->C), in heterozygous condition in one patient. In addition, sequence analyses in the patient and control DNA samples identified 4 single nucleotide polymorphisms (SNPs) (75G/A, 120G/T, 159C/G, 171C/T) in the coding region and a novel insertion/deletion polymorphic site (-483[T](11/10)[A](2/3)) and a SNP (-547A/G) in the putative regulatory region of the EPM2A gene. None of the sequence variants, however, co-segregated with the LD phenotype. Haplotype analysis for the 6q24 region in the affected families revealed lack of homozygosity at the EPM2A locus. Our studies suggest that EPM2A is not involved in the disease phenotype of the 4 families studied and that locus heterogeneity for LD may exist in Japanese population also. A simple test described for the detection of Ala46Pro mutation present heterozygously in Japanese population (allele frequency 0.026) can be used for screening this novel allele in a larger sample size.

Adolescent↗
PubMed2001

Neurodegenerative features in developmental brain disorders.

The authors examined the occurrence of neurofibrillary tangles (NFT), senile plaques, spheroids in Goll's nucleus, grumose or foamy spheroid bodies (GFSB) in the basal ganglia, and hyaline inclusions in the brainstem nuclei in 62 patients under 40 years of age with non-progressive developmental brain disorders. Five cases had demonstrated NFT, which tended to be confined to the subcortical nuclei, whereas no senile plaques were identified in any case. Spheroids in Goll's nucleus were significantly increased in three cases of congenital brain anomalies and five cases of perinatal hypoxic ischemic encephalopathy. The GFSB-positive subjects were clinicopathologically divided into two subgroups consisting of four cases of congenital malformations, which were also associated with severe respiratory failure, and six cases of perinatal brain disorders in which the basal ganglia were severely affected. Eosinophilic intracytoplasmic inclusions, unlike the hyaline inclusions of the Lewy type, were found in the substantia nigra and/or locus ceruleus in two subjects. It is speculated that a variety of mechanisms, including accelerated aging and anoxic insults, may be involved in the increased occurrence of NFT and/or spheroids in non-progressive developmental disorders. A detailed investigation is useful to clarify the neuronal changes secondary to the brain damages early in development.

Adolescent↗
PubMed2001

Oxidative stress and disturbed glutamate transport in hereditary nucleotide repair disorders.

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each of XPA, CS, and control groups. All oxidative products, including nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE) were deposited in large amounts in the globus pallidus of CS patients compared to XPA patients. They were frequently recognized in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of HNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA patients. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They were also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may be involved in pallidal and/or cerebellar degeneration in hereditary nucleotide repair disorders.

ATP-Binding Cassette Transporters↗
PubMed2000

Cerebellar degeneration in hereditary dentatorubral-pallidoluysian atrophy and Machado-Joseph disease.

We examined the mechanism of cerebellar degeneration in brains obtained at autopsy from six cases of hereditary dentatorubral-pallidoluysian atrophy (DRPLA) and six cases of Machado-Joseph disease (MJD), using terminal deoxynucleotidyltransferase-mediated in situ nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins, neurotrophin receptors and glutamate transporters. In three subjects with DRPLA, who developed dementia and cerebellar ataxia at over 50 years of age, the number of Purkinje cells was mildly reduced, TUNEL-positive cells were observed in the molecular layer of the cerebellar cortex, and immunoreactivities for calbindin D28K and excitatory amino acid transporter-1 (EAAT1) were altered in the molecular layer. In addition, all cases of DRPLA showed a reduction of immunoreactivity for EAAT1 in the dentate nucleus. In MJD, augmentation of Bcl-x expression by the Purkinje cells, and increases in Trk B- and GFAP-immunopositive glial cells in the granular layer were observed in half of the cases, whereas immunoreactivity for EAAT-1 was preserved both in the cerebellar cortex and dentate nucleus. One case of MJD showed TUNEL-positive granular cells in the cerebellar cortex. Age-matched control subjects did not show TUNEL-positive cells or immunohistochemical changes in the cerebellum. There were neither TUNEL-positive cells nor alteration of the in situ expression of apoptosis-related proteins in the dentate nucleus in either variant of hereditary spinocerebellar degeneration, although both exhibited grumose degeneration in the dentate nucleus. These findings indicate that latent degeneration in the cerebellar cortex may occur in DRPLA and MJD, in addition to the dentate change, which is the cardinal feature in the neuropathology of these two diseases. The lesion of Purkinje cells and their processes in the molecular layer associated with altered glutamate transport may be important in DRPLA, while the significance of the abnormalities observed in some MJD cases, which might be related to apoptotic mechanism, remains unclear.

ATP-Binding Cassette Transporters↗
PubMed2000

The cerebellar and thalamic degeneration in Fukuyama-type congenital muscular dystrophy.

We report a male autopsy case of Fukuyama-type congenital muscular dystrophy (FCMD), with unusual neuropathological findings. The patient was a Japanese man aged 26 years at the time of death. He had shown severe psychomotor retardation and muscular dystrophy since early infancy, and was diagnosed as having FCMD at the age of 5 years. He died of respiratory failure. The main neuropathological finding was extensive cerebral and cerebellar cortical dysplasia, characteristic of this disorder. In addition, degeneration of the cerebellar efferent pathway, including the dentate nucleus, superior cerebellar peduncle, and red nucleus, and that of the lateral thalamic nucleus were observed. These findings suggest the possibility that the long survival can clarify the latent neurodegeneration in the cerebellum and thalamus in FCMD, in addition to congenital malformations. The system degeneration should be carefully evaluated in the pathological examination of this disorder.

Adult↗
PubMed2000

Reversible frontal lobe syndrome associated with influenza virus infection in children.

Two patients, a 3-year-old female and a 1-year-old female, both with a focal encephalopathic process associated with influenza A virus infection, are reported. Both children had neuropsychologic signs suggesting frontal and limbic dysfunction, without disturbances of consciousness or motor function, and had good recoveries. The results of single-photon emission computed tomography and electroencephalography support the finding of reversible impairment of the frontal and limbic areas. Focal reversible encephalopathy has rarely been reported in association with influenza virus infection, although it often provokes diffuse encephalopathies, with a poor prognosis.

Child, Preschool↗
PubMed2000

Immunohistochemical analysis of brainstem lesions in infantile spasms.

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.

Adolescent↗
PubMed2000

Nocturnal enuresis and the pontine reticular formation.

OBJECTIVES: To assess the previously proposed hypothesis that enuretic patients have a dysfunction in the pontine reticular formation. METHODS: In 18 patients with intractable nocturnal enuresis, rapid eye movement (REM)-related phasic chin muscle activity loss in REM sleep was examined by means of a single-night polysomnography. RESULTS: In 5 of 18 patients, this physiologically seen phenomenon was found to be disturbed. CONCLUSIONS: Since REM-related phasic chin muscle activity loss is disturbed by the functional impairment in the pontine reticular formation, some enuretic patients could be considered as presenting a dysfunction in this structure.

Adolescent↗
PubMed2000

[Clinical symptoms and characteristic MR spectroscopic findings in Pelizaeus-Merzbacher disease].

Clinical symptoms and MR spectroscopic findings were studied on 4 cases of Pelizaeus-Merzbacher disease including 1 autopsy case. Common symptoms were severe mental retardation and spastic tetraplegia. These cases had nystagmus, and one had involuntary athetotic movement. Genetical diagnosis revealed in 2 cases, duplication of proteolipid protein (PLP) and deletion in 1, whereas one case had no abnormality of PLP gene. MRI indicated the reversal of signal intensities on T1- and T2-weighed images, a characteristic finding of PMD MR spectroscopy demonstrated a pattern of NAA in 3 cases. This was specific to PMD because other white matter diseases show a decrease in NAA. In conclusion, MRS was useful to differentiate PMD from other white matter diseases.

Adult↗
PubMed1997

Recovery of portal blood flow after percutaneous transhepatic biliary drainage in patients with obstructive jaundice.

Using an ultrasonic Doppler system, we prospectively studied the changes in portal venous flow (PVF) following percutaneous transhepatic biliary drainage (PTBD) and evaluated the correlation between PVF and liver function in 10 patients with obstructive jaundice. The patients were divided into two groups according to their rate of decrease in serum bilirubin ("b"). Group A comprised 5 patients with a "b" of less than -0.1, while group B consisted of 5 patients who did not meet this criterion. The mean PVF increased following PTBD (P < 0.01). The increase in PVF was due to an increase in the maximum velocity of the portal vein (Vmax). The rate of increase in the Vmax in group A was significantly higher than that in group B on both the 7th and 14th postdrainage days (P < 0.05). The rate of increase in the Vmax correlated significantly with the rate of decrease in the serum bilirubin concentration (P < 0.01). Based on the above findings, we conclude that measuring the Vmax by Doppler ultrasonography is useful in evaluating the liver function in patients with obstructive jaundice.

Aged↗
PubMed1997

Neuropathology of the dentate nucleus in developmental disorders.

The dentate nucleus was examined histologically and immunohistochemically in 47 cases of nonprogressive developmental disorders. Neuronal loss and/or atrophy was observed in 13 cases, while mild neuronal lesions, characterized by dendritic swelling and/or the appearance of eosinophilic materials around the neurons, were exhibited in 20 cases. The former change was accompanied by diffuse central nervous system involvement, and the etiology was perinatal hypoxic ischemic encephalopathy, acute encephalopathy, and meningoencephalitis in most cases. On the other hand, most of the patients with kernicterus showed the latter change. Immunohistochemically, the mild neuronal lesions mimicking grumose, degeneration, described in some neurodegenerative diseases, seemed to reflect the changes of Purkinje cell terminals. It is suggested that secondary structural alteration of the dentate neurons in the absence of severe atrophy can occur in nonprogressive developmental disorders.

Adolescent↗
PubMed1997

Encephalomyelitis subsequent to mycoplasma infection with elevated serum anti-Gal C antibody.

We report a 7-year-old girl with acute disseminated encephalomyelitis subsequent to a mycoplasma infection. She manifested a prolonged state of akinetic mutism, during which EEG revealed well-synchronized spindles. Four months later, she regained consciousness, with no mental deficit, but complete flaccid quadriplegia persisted and magnetic resonance imaging disclosed extensive destruction of the spinal cord. Antibody against galactocerebroside was detected in her serum during the acute phase. The anti-Gal C antibody is suggested to be involved in the pathogenesis of immune-mediated demyelinating diseases in the central nervous system subsequent to mycoplasma infections.

Akinetic Mutism↗
PubMed1994

[Sleep disordered breathing in group A xeroderma pigmentosum].

We studied sleep disordered breathing (SDB) in 12 patients with group A xeroderma pigmentosum (XP) by means of respiratory inductive plethysmography (Respisomnograph:Nims) during polysomnographical examination. The subjects were 6 male and 6 female patients aged from 10 months to 25 years. Four out of the subjects had SDB:3 showed sleep apnea (apnea index ranged from 5.2 to 44.2/h) and 1 presented desaturation during sleep (desaturation time per total sleep time was 4.3%). All these patients were over 12 years. The patients below 14 years had mainly the central type of SDB, and the others aged over 16 years had both the central and obstructive types of SDB. Three of the 4 patients had daytime sleepiness or restless sleep, which seemed to be due to SDB. We discussed the pathophysiology of SDB with XP in relation with brain stem function and peripheral neuropathy. We must pay attention to SDB in patients with XP aged over 12 years.

Adolescent↗
PubMed1994

[Polygraphical sleep study on typical absence: relationship between the effect of sodium valproate and nigrostriatal function].

In order to clarify the mechanism of the effect of sodium valproate (VPA) on absence seizures, we performed sleep polygraph recordings in 10 patients with typical absence. VPA was effective in six cases (group A), partially effective in two (group B), and ineffective in two (group C). In 5 of 9 cases, the tonic sleep components were abnormal. In 4 cases, the percentage of slow wave sleep increased before administration of VPA, and did not change remarkably by its administration. In group A and B, twitch movements (TM), one of the phasic sleep components detected in the mentalis muscle on surface EMG, decreased or were unchanged after administration of VPA, especially during the REM period. In contrast, TM increased in group C. We speculate that the changes of TM (especially in the REM periods) after administration of VPA are well related to its effectiveness. Since TMs are thought to be controlled by the nigrostriatal dopaminergic pathway, the different response of basal ganglia to VPA among cases with absence epilepsy would have some relation to the different effectiveness of VPA in controlling seizures.

Child↗