Yoshiko Nomura

The University of Tokyo, Tōkyō, Japan

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Publications (110)508.88 Total impact

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    ABSTRACT: Objective: To study saccade abnormalities associated with focal cerebral lesions, including the cerebral cortex and basal ganglia (BG). Methods: We studied the latency and amplitude of reflexive and voluntary saccades in 37 patients with focal lesions of the frontal and parietal cortices and BG (caudate and putamen), and 51 age-matched controls, along with the ability to inhibit unwanted reflexive saccades. Results: Latencies of reflexive saccades were prolonged in patients with parietal lesions involving the parietal eye field (PEF), whereas their amplitude was decreased with parietal or putaminal lesions. In contrast, latency of voluntary saccades was prolonged and their success rate reduced with frontal lesions including the frontal eye field (FEF) or its outflow tract as well as the dorsolateral/medial prefrontal cortex, and caudate lesions, whereas their amplitude was decreased with parietal lesions. Inhibitory control of reflexive saccades was impaired with frontal, caudate and, less prominently, parietal lesions. Conclusions: PEF is important in triggering reflexive saccades, also determining their amplitude. Whereas FEF and the caudate emit commands for initiating voluntary saccades, their amplitude is mainly determined by PEF. Commands not only from FEF and dorsolateral/medial prefrontal cortex but also from the caudate and PEF serve to inhibit unnecessary reflexive saccades. Significance: The findings suggested how cortical and BG commands shape reflexive and voluntary saccades in humans.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 09/2015; DOI:10.1016/j.clinph.2015.07.041 · 3.10 Impact Factor
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    ABSTRACT: Segawa disease (SD), an autosomal dominant dopa-responsive dystonia with marked diurnal fluctuation, can be clinically classified into the postural dystonia type (SD-P) and action dystonia type (SD-A). Compared to SD-A, SD-P has an earlier onset and is characterized by postural dystonia. In SD-A, along with postural dystonia, dystonic movements appear in late childhood. To evaluate the differences between these two types of SD, we studied the gating of SEPs, which is useful to investigate sensory-motor integration and might be one of the methods to detect the thalamo-cortical involvement. Fourteen patients with SD (11-63years) and 18 age-matched normal subjects (11-51years) were studied. Among the 14 patients with SD, 8 patients had SD-P and 6 had SD-A. Using median nerve stimulation at the wrist, the amplitude of the frontal N30 (FrN30) was compared between pre-movement and rest conditions. We found that the amplitude of the contralateral FrN30 was attenuated before movement in normal controls and in the majority of both SD types. On the other hand, the pre-movement-rest amplitude ratio in patients with SD-A was significantly larger than in patients with SD-P (P=0.0025). No significant differences were observed in the pre-movement-rest ratio between SD-P and normal subjects. The preservation or impairment of pre-movement gating shown here suggests a physiological difference between the two types of SD. More specifically, sensorimotor integration of the basal ganglia-thalamo-cortical circuits may be intact in SD-P, but are affected in SD-A. We discuss the different pathophysiology seen in the different phenotype of SD based on the different developmental involvement in the basal ganglia. Copyright © 2015. Published by Elsevier B.V.
    Brain & development 06/2015; DOI:10.1016/j.braindev.2015.05.007 · 1.88 Impact Factor

  • Clinical Neurophysiology 06/2015; 126(6):e59. DOI:10.1016/j.clinph.2015.02.039 · 3.10 Impact Factor
  • Masaya Segawa · Yoshiko Nomura ·
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    ABSTRACT: DYT1 and DYT5 are early-onset dominant inherited dystonias. DYT1 is caused by mutations of the TOR1A gene, located on 9q34, which causes dysfunction of the D1 direct pathway or the indirect pathway. Dysfunction of the former causes postural-type and segmental dystonia; the latter causes action-type dystonia. In families with action-type dystonia, there are cases with focal and segmental dystonia. Ages of onset of postural-type dystonia are around 6 years, and 8 to 10 years in cases of action-type dystonia. Focal and segmental dystonia develops in the teens. Mental and psychological functions are preserved. DYT5 is caused by heterozygous mutations of the GCH1 gene, located on 14q22.1-q22.2. Again, mental and psychological functions are preserved. Clinically, there are two types: postural and action. Postural-type dystonia occurs around 6 years of age, with postural dystonia of one leg, and all extremities and trunk muscles are involved by the late teens. Action-type dystonia shows dystonic movements from around 8 to 10 years of age. In both types, all symptoms show diurnal fluctuations that diminish with age and are no longer apparent in the late teens. L-dopa produces dramatic effects, which continue throughout the course of the illness. In both postural and action types, each family or sporadic case has a particular mutation. It remains unclear why specific mutations cause certain age- and gender-specific symptoms.
    Seminars in Neurology 07/2014; 34(3):306-11. DOI:10.1055/s-0034-1386768 · 1.79 Impact Factor

  • Clinical Neurophysiology 08/2013; 124(8):e31. DOI:10.1016/j.clinph.2013.02.079 · 3.10 Impact Factor
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    ABSTRACT: Background: Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome). Patients and methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations. Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations. Conclusions: MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.
    Brain & development 05/2013; 36(3). DOI:10.1016/j.braindev.2013.03.006 · 1.88 Impact Factor
  • Masaya Segawa · Yoshiko Nomura · Masaharu Hayashi ·
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    ABSTRACT: From the characteristics of its clinical features, Segawa disease is considered to be caused by deficiency of the tyrosine hydroxylase (TH) of the nigrostriatal dopamine neurons, which have high TH activities in the terminal but not in the perikaryon. This hypothesis was confirmed by two autopsied cases. However, these cases were younger than 40 years and left a question as to whether these abnormalities turned to those of Parkinson disease in older ages. An autopsy of a 90-year-old woman with Segawa disease confirmed the hypothesis that Segawa disease has a completely different pathophysiology and pathology than Parkinson disease.
    Neuropediatrics 03/2013; 44(2). DOI:10.1055/s-0033-1337337 · 1.24 Impact Factor

  • Clinical Neurophysiology 09/2012; 123(9):e89. DOI:10.1016/j.clinph.2012.02.010 · 3.10 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate horizontal saccade changes according to disease stage in patients with progressive supranuclear palsy (PSP). METHODS: We studied visually and memory guided saccades (VGS and MGS) in 36 PSP patients at various disease stages, and compared results with those in 66 Parkinson's disease (PD) patients and 58 age-matched normal controls. RESULTS: Both vertical and horizontal saccades were affected in PSP patients, usually manifesting as "slow saccades" but sometimes as a sequence of small amplitude saccades with relatively well preserved velocities. Disease progression caused saccade amplitude reduction in PSP but not PD patients. In contrast, VGS and MGS latencies were comparable between PSP and PD patients, as were the frequencies of saccades to cue, suggesting that voluntary initiation and inhibitory control of saccades are similar in both disorders. Hypermetria was rarely observed in PSP patients with cerebellar ataxia (PSPc patients). CONCLUSIONS: The progressively reduced accuracy of horizontal saccades in PSP suggests a brainstem oculomotor pathology that includes the superior colliculus and/or paramedian pontine reticular formation. In contrast, the functioning of the oculomotor system above the brainstem was similar between PSP and PD patients. SIGNIFICANCE: These findings may reflect a brainstem oculomotor pathology.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 08/2012; 124(2). DOI:10.1016/j.clinph.2012.07.008 · 3.10 Impact Factor
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    ABSTRACT: We describe a 33-year-old male patient with mental retardation and cerebellar ataxia whose brain magnetic resonance imaging (MRI) showed diffuse central hypomyelination. The associated hypogonadotropic hypogonadism and hypodontia were consistent with the clinical diagnosis of 4H syndrome. Two compound heterozygous mutations in POLR3A were found: p.Met852Val and p.Asn1249His. MRI of the brain showed cerebellar atrophy, atrophy of the corpus callosum, and diffuse hypomyelination extending as far as the U-fibers, with preservation of the basal ganglia. T2 hyperintensity was observed in the bilateral middle cerebellar peduncles. The patient showed almost normal development until 4-5years of age. After 25years of age, the patient showed a gradual but consistent motor and cognitive deterioration. We demonstrated the involvement of the corticospinal tract electrophysiologically, but peripheral nerve conduction was normal. Although this disease may start very early in life, the clinical course in the present case suggests that brains that initially appear to have developed normally may show dysfunction later in life, although the pathophysiological bases for this dysfunction may not be evident on MRIs.
    Journal of the neurological sciences 07/2012; 320(1-2):102-5. DOI:10.1016/j.jns.2012.07.005 · 2.47 Impact Factor

  • Parkinsonism & Related Disorders 07/2011; 17(10):769-70. DOI:10.1016/j.parkreldis.2011.06.008 · 3.97 Impact Factor
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    ABSTRACT: The cardinal pathophysiology of Parkinson's disease (PD) is considered to be the increase in the activities of basal ganglia (BG) output nuclei, which excessively inhibits the thalamus and superior colliculus (SC) and causes preferential impairment of internal over external movements. Here we recorded saccade performance in 66 patients with PD and 87 age-matched controls, and studied how the abnormality changed with disease progression. PD patients were impaired not only in memory guided saccades, but also in visually guided saccades, beginning in the relatively early stages of the disease. On the other hand, they were impaired in suppressing reflexive saccades (saccades to cue). All these changes deteriorated with disease progression. The frequency of reflexive saccades showed a negative correlation with the latency of visually guided saccades and Unified Parkinson's Disease Rating Scale motor subscores reflecting dopaminergic function. We suggest that three major drives converging on SC determine the saccade abnormalities in PD. The impairment in visually and memory guided saccades may be caused by the excessive inhibition of the SC due to the increased BG output and the decreased activity of the frontal cortex-BG circuit. The impaired suppression of reflexive saccades may be explained if the excessive inhibition of SC is "leaky." Changes in saccade parameters suggest that frontal cortex-BG circuit activity decreases with disease progression, whereas SC inhibition stays relatively mild in comparison throughout the course of the disease. Finally, SC disinhibition due to leaky suppression may represent functional compensation from neural structures outside BG, leading to hyper-reflexivity of saccades and milder clinical symptoms.
    Neuropsychologia 03/2011; 49(7):1794-806. DOI:10.1016/j.neuropsychologia.2011.03.002 · 3.30 Impact Factor
  • Yoshiko Nomura · Yuri Nagao · Kazue Kimura · Kei Hachimori · Masaya Segawa ·
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    ABSTRACT: Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8months-30years 3months of age, and the current ages are 5years 8months-42years 3months, 60% reaching to over 30years of age. The average follow up duration is 22.2years±9.4years. The ages of onset of epilepsy were from 7months to 30years of age, with the two peaks at 3.2years and 16.7years. EEG central focus appeared earlier than frontal focus. Abnormality of locomotion and atonic NREM were observed more frequently in epileptic group. These suggest the neuronal system related to abnormality of locomotion and atonic NREM, which are the hypofunction of the brainstem monoaminergic system, is the pathomechanism underling the epilepsy in autism. By showing the abnormal sleep-wake rhythm and locomotion being the very initial symptoms in autism, we had shown the hypofunction of the brainstem monoaminergic system is the initial pathomechanism of autism. Thus, epilepsy in autism is not the secondary manifestation, but one of the pathognomonic symptoms of autism. The brainstem monoaminergic system project to the wider cortical area, and the initial monoaminergic hypofunction may lead to the central focus which appears earlier. The failure of the monoaminergic (serotonergic) system causes dysfunction of the pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA) system, and with development of the DA receptor supersensitivity consequently disinhibits the thalamo-frontal pathway, which after maturation of this pathway in teens cause the epileptogenesis in the frontal cortex.
    Brain & development 11/2010; 32(10):799-804. DOI:10.1016/j.braindev.2010.08.001 · 1.88 Impact Factor
  • K. Kimura · Y. Nomura · Y. Nagao · K. Hachimori · H. Fukuda · Y. Terao · M. Segawa ·

    Clinical Neurophysiology 10/2010; 121. DOI:10.1016/S1388-2457(10)60980-7 · 3.10 Impact Factor
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    ABSTRACT: Japanese childhood onset MG, 226 cases, were evaluated. The highest (50%) onset under age 3 years, the highest frequency of latent general type (50%), and negative to low positive anti-AChR Ab were found. Some showed the increase of the titer around age 20 years. Amblyopia may develop with the cases onset younger than age 3 years. The 75% went into remission with steroid (58.1%) or anticholinesterase (16.2%). General type often needed thymectomy. The total duration and amount of prednisolone revealed the linear correlations with the clinical types and final outcomes. This study in the larger subjects confirmed the previous studies.
    Neuro-Ophthalmology 07/2009; 31(5-6):201-205. DOI:10.1080/01658100701648645 · 0.18 Impact Factor

  • Clinical Neurophysiology 05/2009; 120(5). DOI:10.1016/j.clinph.2009.02.081 · 3.10 Impact Factor
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    ABSTRACT: DYTI dystonia (DYT1-D, early-onset torsion dystonia) is caused by a GAG deletion in the DYTI gene. Here we report a girl with child-onset familial DYT1-D showing localized arm involvement. The patient developed postural and action dystonia in the right and left arms at 7 and 9 years, respectively. She was misdiagnosed as hysteria due to lack of abnormalities on laboratory tests. At 11 years of age she was introduced to our clinic. Increased muscle tonus and dystonic discharges seen on surface electromyogram in the right arm and the sternocleidomastoid muscle led to the diagnosis of dystonia. A GAG deletion in the DYTI gene was confirmed in the patient, her healthy father and paternal grandfather with torsion dystonia. Titration of levodopa resulted in the fluctuation of her arm dystonia. Combined therapy by levodopa and trihexyphenidyl relieved postural dystonia in the right arm but not action dystonia in the left. Both types of dystonia in the right and left arms were well ameliorated by the additional increase of levodopa. Somatosensory evoked potentials demonstrated abnormal premovement gating. The latency and accuracy of the amplitude were disturbed in visually guided saccadic eye movement. Now at more than 11 years after onset, the patient has not shown torsion or involvement of the lower extremities. Most DYT1-D patients are refractory to medication and early surgical intervention is recommended. However, the presence of DYT1-D patients showing a milder disease course should also be considered.
    No to hattatsu. Brain and development 12/2008; 40(6):483-6.
  • Y. Terao · H. Fukuda · Y. Ugawa · S. Tsuji · Y. Nomura · M. Segawa ·

    Clinical Neurophysiology 10/2007; 118(10):e205. DOI:10.1016/j.clinph.2007.06.029 · 3.10 Impact Factor

  • Clinical Neurophysiology 09/2007; 118(9). DOI:10.1016/j.clinph.2007.05.028 · 3.10 Impact Factor

  • Clinical Neurophysiology 09/2007; 118(9):e196. DOI:10.1016/j.clinph.2007.05.036 · 3.10 Impact Factor