Satoko Kumada

Tokyo Metropolitan Hiroo Hospital, Edo, Tōkyō, Japan

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Publications (50)205.71 Total impact

  • No preview · Article · Mar 2015
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    ABSTRACT: We measured anti-N-methyl-d-aspartate receptor (NMDAR) autoantibody levels and assessed B cell subsets using multicolor flow cytometry of peripheral blood mononuclear cells (PBMCs) from a recurrent anti-NMDAR encephalitis case to evaluate the effectiveness of rituximab treatment. Rituximab depleted CD20(+) fractions of naïve and memory B cell subsets and reduced the number of CD20(-) plasmablasts. This study suggests that short-lived plasmablasts are removed by rituximab-induced depletion of the CD20(+) B cell population. Increased numbers of plasmablasts in PBMCs may be a candidate predictive factor for unfavorable prognosis of anti-NMDAR encephalitis and an indication of when to commence second-line immunotherapy.
    No preview · Article · Sep 2013 · Journal of neuroimmunology

  • No preview · Article · Mar 2013 · Movement Disorders
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    ABSTRACT: Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA) is a recently established subtype of neurodegeneration with brain iron accumulation (NBIA). By exome sequencing, we found de novo heterozygous mutations in WDR45 at Xp11.23 in two individuals with SENDA, and three additional WDR45 mutations were identified in three other subjects by Sanger sequencing. Using lymphoblastoid cell lines (LCLs) derived from the subjects, aberrant splicing was confirmed in two, and protein expression was observed to be severely impaired in all five. WDR45 encodes WD-repeat domain 45 (WDR45). WDR45 (also known as WIPI4) is one of the four mammalian homologs of yeast Atg18, which has an important role in autophagy. Lower autophagic activity and accumulation of aberrant early autophagic structures were demonstrated in the LCLs of the affected subjects. These findings provide direct evidence that an autophagy defect is indeed associated with a neurodegenerative disorder in humans.
    No preview · Article · Feb 2013 · Nature Genetics
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    ABSTRACT: Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham's chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection.
    No preview · Article · Nov 2012 · Brain & development
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    ABSTRACT: To elucidate a relationship between CAG repeat expansion length and disease progression history in patients with childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA). We retrospectively evaluated information from nine Japanese patients with disease onset reported as between 6 months and 12 years of age. CAG repeat length in these patients ranged from 62 to 93. A strong correlation was confirmed for the age of disease onset, with the onset of epilepsy and involuntary movements, emergence of regression, and autonomic symptoms. The age at becoming wheelchair-bound and initiation of tube feeding also showed a significant correlation with CAG repeat length. This is the first report detailing this aspect of DRPLA focusing on the childhood-onset population. Earlier disease milestones were revealed compared to the expected age based upon a previous report that contained data from the entire patient population, including adult-onset cases (Hasegawa et al. in Mov Disord 25:1694-1700, 2010). These results provide a basis for predicting the outcome of patients in this particular age group, as well as for assessing the results of future clinical therapeutic trials.
    No preview · Article · Apr 2012 · Journal of Neurology
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    ABSTRACT: We examined oxidative stress markers, tau protein and cytokines in the cerebrospinal fluid (CSF) in six patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). In the CSF, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct levels increased over the cutoff index in four and one out of six MERS patients, respectively. The CSF IL-6 and IL-10 levels were increased in three out of six patients, two of which had extended lesion of the cerebral white matter. The CSF value of tau protein, marker of the axonal damage, was not increased, and neuron specific enolase (NSE) in the CSF was not increased. The increased 8-OHdG levels in the CSF, DNA oxidative stress marker, in four MERS patients, suggesting involvement of oxidative stress in MERS. MERS is occasionally accompanied with hyponatremia, although our patients lacked hyponatremia. It is possible that the disequilibrium of systemic metabolism including electrolytes may lead to facilitation of oxidative stress and reversible white matter lesion in MERS. The increase of cytokine production seems to be involved in the distribution of lesions in MERS.
    No preview · Article · May 2011 · Brain & development

  • No preview · Article · Oct 2010 · Movement Disorders
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    ABSTRACT: We report a 17-year-old female patient with Lance-Adams syndrome caused by anoxic encephalopathy during a severe attack of bronchial asthma. She had difficulty in writing because of action myoclonus in her arms. She also exhibited freezing gait and was unable to walk without cane. Although her gait disturbance resembled those seen in patients with parkinsonism secondary to anoxic encephalopathy, surface electromyography revealed that it was caused by action myoclonus in her legs. The presence of giant somatosensory evoked potentials and enhanced cortical reflexes in response to the electrical stimulation to her posterior tibial nerves supported our diagnosis. A combined therapy with valproate sodium, clonazepam and piracetam (15 g/day) was not effective. However, her freezing gait remarkably improved and she was able to walk without help, after the treatment with sufficient dose of piracetam (21 g/day). Cortical hyperexcitability as revealed by electrophysiological examination also improved. We concluded that the combined therapy with antiepileptic drugs and piracetam was effective in the treatment for action myoclonus. However, because the effects seemed dose-related, the dosage of piracetam needed to be increased until the optimum effects were obtained.
    No preview · Article · Sep 2009 · No to hattatsu. Brain and development
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    ABSTRACT: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a recently clinicoradiologically-established encephalopathy syndrome. In the present study, we examined the levels of cerebrospinal fluid (CSF) tau protein, a marker of axonal damage, in 11 patients with AESD. CSF tau levels were normal on day 1 and increased from day 3 of the disease between the initial and the secondary seizures. Magnetic resonance imaging (MRI) reveals reduced diffusion in the subcortical white matter during days 3-7. Two patients showed elevated tau protein prior to the diffusion abnormality of subcortical white matter on MRI. Levels of CSF neuron specific enolase (NSE), a neuronal marker, were elevated in only two out of seven patients with AESD, and CSF tau levels were also increased in these patients. Our results indicated that tau protein is a more sensitive marker than NSE and axonal damage causes the conspicuous MRI findings in AESD patients. A therapeutic strategy for axonal protection should be developed to prevent severe neurological impairment of AESD patients.
    No preview · Article · Sep 2009 · Brain & development
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    ABSTRACT: A 64-year-old woman with Parkinson is disease had a severe resting tremor that was not completely relieved by right-sided gamma knife thalamotomy (GKT). We performed bilateral staged thalamic deep brain stimulation (DBS) and compared the right and left ventral intermediate nucleus (Vim) of the thalamus including the frequency of single units recorded with microelectrodes, and also the somatotopical distribution of kinaesthetic cells (Ki). The average frequency of units for the presumed left Vim exceeded that of the right (22.6 +/- 19.2 Hz vs. 14.3 +/- 8.8 Hz). Regarding the somatotopic distribution of Ki, the receptive field for the leg, which is usually situated in the dorsolateral Vim, was more widely scattered in the right Vim than the non-lesioned left side. Our findings raise the possibility that the specific properties of the neurons changed due to partial coagulation by GKT within both the coagulated and the surrounding thalamic lesions.
    No preview · Article · Aug 2008 · Acta Neurochirurgica
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    ABSTRACT: Early infantile epileptic encephalopathy with suppression-burst (EIEE), also known as Ohtahara syndrome, is one of the most severe and earliest forms of epilepsy. Using array-based comparative genomic hybridization, we found a de novo 2.0-Mb microdeletion at 9q33.3-q34.11 in a girl with EIEE. Mutation analysis of candidate genes mapped to the deletion revealed that four unrelated individuals with EIEE had heterozygous missense mutations in the gene encoding syntaxin binding protein 1 (STXBP1). STXBP1 (also known as MUNC18-1) is an evolutionally conserved neuronal Sec1/Munc-18 (SM) protein that is essential in synaptic vesicle release in several species. Circular dichroism melting experiments revealed that a mutant form of the protein was significantly thermolabile compared to wild type. Furthermore, binding of the mutant protein to syntaxin was impaired. These findings suggest that haploinsufficiency of STXBP1 causes EIEE.
    Full-text · Article · Jul 2008 · Nature Genetics
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    ABSTRACT: Tracheoarterial fistula (TAF) is an unusual but highly lethal complication of tracheostomy, and successful surgical intervention for TAF has been reported. Few investigations are available for TAF in severe motor and intellectual disability (SMID). The aim of the present paper was to analyzed TAF in SMID to clarify which clinical variables might predict the occurrence of TAF, and adequate management for lifesaving. Medical records at Metropolitan Fuchu Medical Center were retrospectively investigated for SMID between 1970 and 2000, and 10 TAF patients verified on operation or autopsy were identified. Details were reviewed including clinical status, emergency treatment at the occurrence of TAF, and operation and/or autopsy recordings. Four of 10 patients underwent successful operation and survived, while the other six died from hemorrhagic shock. Eight patients had tracheoinnominate artery fistula, the others had tracheocarotid artery fistula. Characteristic features as SMID such as etiology of brain disease, muscle tonus and convulsion were no apparent relevance to occurrence of TAF. All patients suffered from endotracheal granuloma extending to the arterial walls. Seven of 10 patients had re-bleeding after stabilization of the first massive hemorrhage, especially fiber bronchoscopy to confirm the diagnosis of TAF precipitated to fatal re-bleeding. One patient underwent interruption of the artery at relapse of TAF, the other three underwent suturing and had good outcome. There were no apparent predictors of TAF in SMID. Tracheal granuloma was recognized and consequent on formation of TAF, so control of granuloma may prevent TAF. Fiber bronchoscopy for suspected TAF is not recommended because it precipitates fatal bleeding.
    No preview · Article · Jul 2008 · Pediatrics International
  • Masaharu Hayashi · Satoko Kumada · Kei Shioda · Ryo Fukatsu
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    ABSTRACT: In order to investigate epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy (DRPLA), we immunohistochemically examined the expression of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex in autopsy cases. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 cases of juvenile and 2 cases of early adult types with progressive myoclonus epilepsy (PME), 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to tyrosine hydroxylase, tryptophan hydroxylase, substance P, methionine-enkephalin, parvalbumin, calbindin-D28K, calretinin, and excitatory amino acid transporters. Although the size of the tegmentum was small, we failed to find any PME-specific brainstem changes in the expression of neurotransmitters, neuropeptides and calcium-binding proteins. The number of interneurons immunoreactive for calbindin-D28K and parvalbumin, markers of GABAergic inhibitory interneurons, were reduced throughout the cerebral cortex, but there was no significant difference in the density of immunoreactive neurons between DRPLA patients of each type. The expression of glutamate transporters was comparatively spared. The current study revealed an absence of PME-specific brainstem lesions and indicated a possible involvement of the reduced GABAergic interneurons in the cerebral cortex in formation of PME in DRPLA.
    No preview · Article · Oct 2007 · Brain and Development
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    ABSTRACT: We describe an autopsy female case of multiple anomalies with lobulation of caudate nucleus tail, diaphragmatic eventration, skeletal anomalies, pyramidal tract anomaly, and meningothelial meningioma. Her psychomotor development was delayed, and she developed bilateral eventration of the diaphragms on X-ray film in her third decades. Right hemi-colonectomy was performed for volvulus at the age of 44 years, and meningioma was incidentally identified. She died at the age of 47 years. Autopsy demonstrated the partial deficiency of the muscular tissue in the circular thinned membranous area predominantly on left side including the central tendon of the diaphragm. The tails of the bilateral caudate nucleus demonstrated excessive lobulations, and the brainstem pyramidal tract showed hypoplasia. Immunoreactivity for tyrosine hydroxylase was deficient in the lobulated tail of caudate. We believe that this case is characterized by a rare combination of eventration, skeletal and nervous anomalies.
    No preview · Article · Aug 2006 · Brain and Development
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    ABSTRACT: 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.
    No preview · Article · Jun 2006 · Neurology
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    ABSTRACT: Neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative diseases and autosomal recessive lysosomal storage disorders. We examined the involvement of cell death, oxidative stress, and glutamate excitotoxicity using immunohistochemistry against Bcl-2, Bcl-x, oxidative products to proteins, lipids and DNA, calcium-binding proteins (calbindin-D28K, parvalbumin, calretinin), and glial glutamate transporters (excitatory amino acid transporters 1 and 2), in addition to terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) in the brains from three cases of late infantile form of NCL (LINCL) and one case of juvenile form of NCL (JNCL) to investigate the neurodegenerative mechanisms. In the cerebral and cerebellar cortex, all of three LINCL cases demonstrated neurons with TUNEL-immunoreactive nuclei, whereas the JNCL case did not show TUNEL-immunoreactive nuclei. The coexistence of the nuclear TUNEL-immunoreactivity nuclei and cytoplasmic deposition of 4-hydroxy-2-nonenal-modified protein in the frontal cortex and hypoglossal nucleus may suggest a possible interrelationship between DNA fragmentation and lipid oxidation in LINCL. Additionally, glycoxidation of protein and oxidative stress to DNA seemed to be involved in the cerebellar and cerebral degeneration, respectively. Interneurons immunoreactive for calbindin-D28K and parvalbumin were severely reduced in the cerebral cortex, whereas those for calretinin were comparatively well preserved in LINCL, indicating the possibility of altered GABAergic system. The disturbance of expression of glial glutamate transporters seemed to be heterogeneous and mild. These findings suggest the possibility of new treatments for neurodegeneration in LINCL using antioxidative agents and/or GABAergic medications.
    Preview · Article · Mar 2006 · Acta Neuropathologica
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    ABSTRACT: In Japan, quite a few patients with spinal muscular atrophy type 1 (SMA type 1) survive with mechanical ventilation. Since a patient with SMA type 1 and continuous artificial ventilation exhibited excessive perspiration and tachycardia, we examined the autonomic functions in three cases of SMA type 1, undergoing mechanical ventilation. Two cases exhibited the common sympathetic-vagal imbalance on R-R interval analysis involving 24-h Holter ECG recordings in addition to an abnormality in finger cold-induced vasodilatation. Furthermore, one case showed blood pressure and heart rate fluctuation with the paroxysmal elevation, and a high plasma concentration of norepinephrine during tachycardia. These findings suggest that autonomic dysfunction should be examined in SMA type 1 patients with long survival, although the pathogenesis remains to be clarified.
    No preview · Article · Jan 2006 · Brain and Development
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    ABSTRACT: To elucidate autonomic function in spinal muscular atrophy, we evaluated finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation in 10 patients with spinal muscular atrophy: 7 of type 1, 2 of type 2, and 1 of type 3. Results of finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation were compared with those of healthy children. Finger cold-induced vasodilatation was abnormal in 6 of 10 patients with spinal muscular atrophy; it was normal in the healthy children. The mean sympathetic skin response latency and amplitude did not differ significantly from those of the healthy children. Amplitudes of sympathetic skin response to sound stimulation were absent or low in all six patients with spinal muscular atrophy. No significant difference was found in the mean R-R interval variation of patients with spinal muscular atrophy and healthy children. Results show that some patients with spinal muscular atrophy have autonomic dysfunction, especially sympathetic nerve hyperactivity, that resembles dysfunction observed in amyotrophic lateral sclerosis.
    No preview · Article · Dec 2005 · Journal of Child Neurology
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    ABSTRACT: This report concerns two autopsy cases of severe motor and intellectual disabilities (SMID) who died of bronchospasms or tracheomalasia. One case had no anatomical change in the tracheal wall except for an endotracheal granuloma, while the other showed softening of the tracheal wall. Since patients with SMID have risk factors for bronchospasms and tracheomalasia, such as gastro-esophageal reflux, aspiration, and thoracic deformities, it is important that we suspect the possibility of these conditions, when we see the respiratory distress in cases of SMID.
    No preview · Article · Feb 2005 · Brain and Development

Publication Stats

787 Citations
205.71 Total Impact Points


  • 2008-2013
    • Tokyo Metropolitan Hiroo Hospital
      • Department of Pediatrics
      Edo, Tōkyō, Japan
  • 2010
    • Yamagata University
      • Department of Pediatrics
      Ямагата, Yamagata, Japan
  • 2000-2004
    • Tokyo Metropolitan Institute
      Edo, Tōkyō, Japan
  • 2003
    • Tokyo Metropolitan Tama Medical Center
      Edo, Tokyo, Japan
  • 2001
    • Fukuoka University
      Hukuoka, Fukuoka, Japan
  • 1991-2001
    • Musashino Red Cross Hospital
      Edo, Tōkyō, Japan
  • 1990-2001
    • Tokyo Medical and Dental University
      • • Department of Neuropathology
      • • Department of Pediatrics
      Edo, Tōkyō, Japan