Kotaro Asanuma

The University of Tokushima, Tokusima, Tokushima, Japan

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Publications (27)101.77 Total impact

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    ABSTRACT: Botulinum neurotoxin type A1 (BoNTs/A1) and type B (BoNT/B) have been used for treating hyperactive muscle contractions. In the present study, we compared the effect of botulinum neurotoxin subtype A2 (6.5 mouse LD50 units A2 neurotoxin, A2NTX) and onabotulinumtoxinA (10 mouse LD50 units BoNT/A1 product) by measuring the compound muscle action potentials (CMAPs) before and after administration. In total, 8 healthy subjects were examined in the present study. A2NTX was injected into the extensor digitorum brevis (EDB) muscle, followed by onabotulinumtoxinA injection into the contralateral EDB muscle after 16 weeks. The CMAP amplitudes from the EDB, abductor hallucis (AH), and abductor digiti minimi pedis (ADM) muscles were measured after each BoNT injection on days 1, 3, 7, 14, 28, 56, 84, and 112 to assess the effect of the toxin. On day 14, both A2NTX and onabotulinumtoxinA produced an approximately 70% decline in EDB CMAP amplitude compared to the baseline values; significant reduction of the CMAP continued through day 112. The CMAP amplitudes from neighboring muscles (AH and ADM) remained intact throughout the study period, except for a slight but significant drop at day 28 after onabotulinumtoxinA injection compared to A2NTX. The current findings indicate that small doses (6.5 units and 10 units) of A2NTX and onabotulinumtoxinA have at least comparable onset and duration of action, although similar clinical effects were obtained with lower dose using A2NTX.
    Toxicon 04/2014; 81. DOI:10.1016/j.toxicon.2013.12.012 · 2.49 Impact Factor

  • Movement Disorders 08/2012; 27(9):1198-9. DOI:10.1002/mds.25081 · 5.68 Impact Factor
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    ABSTRACT: Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5-20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician's. Drowsiness was the dose-limiting factor.
    Frontiers in Neurology 04/2012; 3:58. DOI:10.3389/fneur.2012.00058
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterized by increased excitability of motor neurons and early involvement of large motor fibers that have low electrical thresholds. Despite the advent of new techniques of threshold tracking, exploration of this abnormal excitability has not been straightforward, by tracking at the single target level as previous reported, because of the heterogeneous nature of the disease process among fibers that have variable thresholds. We have assessed different populations of motor axons by tracking at four different target response levels (10, 20, 40 and 60% of maximum compound muscle action potentials), and conducted multiple nerve excitability tests in 27 ALS patients and 23 control subjects. In normal controls, axons with low thresholds have the following characteristics compared to those with high thresholds: greater threshold reduction during depolarizing currents and smaller threshold increase to hyperpolarizing currents, reflecting the order of the fiber size. In contrast, ALS patients lacked these relationships, suggesting increased variability of axonal membrane potentials. Three ALS patients demonstrated changes in threshold electrotonus, consistent with overt membrane depolarization, as seen in ischemic nerves. The variability of motor nerve excitability accounts for fasciculations, confirms previously reported dysfunction of potassium channels, and suggests failure of Na(+)/K(+)pumps, possibly caused by mitochondrial dysfunctions at the early stage.
    11/2011; 51(11):1114-7. DOI:10.5692/clinicalneurol.51.1114
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    ABSTRACT: Rehabilitation, a treatment strategy that involves group effort with multiple specialists, roles, and facilities, is widely offered to patients in need. The current rehabilitation strategy is mainly disability oriented, and, in principle, starts from the evaluation of motor function and aims to strengthen the deteriorated function/s. Therefore, this method is very effective for patients with acute diseases. However, the effect of such a rehabilitation strategy on gradually progressive neurodegenerative diseases is not well clarified. In particular, Disability-oriented Rehabilitation has not shown an adequate effect in Parkinson disease, which is associated with psychological stress. In this report, we provide an outline of a new rehabilitation strategy and introduce Mentality-oriented Rehabilitation for patients with Parkinson disease.
    Brain and nerve = Shinkei kenkyū no shinpo 08/2011; 63(8):878-83.

  • Clinical Neurophysiology 08/2011; 122(8). DOI:10.1016/j.clinph.2011.01.020 · 3.10 Impact Factor
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    ABSTRACT: Recently, new electrophysiological ALS criteria incorporating fasciculation potentials (FPs) as evidence for lower motor neuron signs (Awaji Criteria (AC)) was proposed to provide earlier detection of early-stage ALS than revised El Escorial electrophysiological criteria (REEC). However, serial electrophysiological analysis is lacking to ascertain the original intention. The objective for this study was to elucidate whether electrophysiological criteria set for AC detects ALS earlier than REEC's counterpart in patients with ALS. Of the 51 patients who were clinically suspected of ALS, 35 patients prospectively received serial electrophysiological studies every 3 months until (1) both electrophysiological AC and REEC criteria were met in more than two muscles representing both of the cervical and lumbosacral segments or (2) either clinically definite or clinically probable REEC criteria was met. The intervals were determined between the initial disease onset and when the respective electrophysiological criteria were met. Electrophysiological diagnostic criteria were met in 94.3% by AC and 40% by REEC at the initial visits. The intervals between the disease onset and the time of meeting the electrophysiological criteria were shorter in AC (mean: 9.0 months) than in REEC (mean: 15.2 months) (P<0.01). Eleven patients who met only AC electrophysiological criteria on the initial study subsequently met REEC electrophysiological criteria with the mean interval of 3.8 months. A higher percentage of bulbar-type ALS (83.3%) met AC than limb-onset ALS (43.4%) (P<0.05). FPs tended to be more frequently observed than fib/psw in the muscles outside the region of initial clinical onset. Electrophysiological criteria of AC were met earlier than that of REEC in ALS patients, especially in patients with bulbar onset. Early recognition of ALS by AC may allow effective therapeutic intervention in the early disease stage.
    Journal of the neurological sciences 03/2011; 302(1-2):29-32. DOI:10.1016/j.jns.2010.12.007 · 2.47 Impact Factor
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    ABSTRACT: Slow potassium current (I(Ks)) is important in controlling nerve excitability and its impairment is known in various neurological diseases, including amyotrophic lateral sclerosis (ALS). I(Ks) gives rise to the late subexcitability phase of the recovery cycle, which can be amplified by the use of multiple conditioning pulses. The clinical utility of this technique has not previously been explored. Nerve excitability tests, including recovery cycles with single and double conditioning pulses 4ms apart (RC and RC2, respectively) were performed in patients with ALS and control subjects. Late subexcitability values obtained by RC and RC2 were compared in both groups. RC2 was well tolerated in all the subjects. The threshold changes in late subexcitability by RC2 were greater than those by RC in both groups (mean (%): RC, 16.0/13.3; RC2, 34.9/29.4 (Control/ALS)). The ALS group showed lower threshold changes than controls by both methods. Statistical analysis between the ALS and control groups provided smaller P value by RC2 (P=0.018) than by RC (P=0.046). Also, RC2 provided non-significant, but slightly more distinguishing non-parametric rank analysis and greater Area Under the Curve (AUC) by Receiver Operating Characteristic (ROC). RC2 produced more identifiable single peak for late subexcitability than RC in an ALS patient whose late subexcitability was decreased. Two conditioning stimuli provide greater threshold change for late subexcitability and possibly clearer identification of a peak threshold change than conventional recovery cycle. The findings obtained by this new protocol reinforce the previously reported impairment of I(Ks) in ALS. Amplification of I(Ks) by double conditioning pulses is applicable in humans and may help elucidating its clinical significance in pathophysiology in neurological diseases.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 12/2010; 121(12):2117-20. DOI:10.1016/j.clinph.2010.05.015 · 3.10 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.
    Cerebrovascular Diseases 04/2010; 29(6):571-5. DOI:10.1159/000306644 · 3.75 Impact Factor
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    ABSTRACT: In order to investigate the transcallosal effects of repetitive transcranial magnetic stimulation (rTMS), we studied median somatosensory evoked potentials (SEPs) before and after applying monophasic very low-frequency (0.2 Hz) subthreshold rTMS over the right motor cortex. For SEPs, median nerve was stimulated on each side. Sham rTMS served as the control. Twelve healthy subjects participated in this study. After rTMS over the right hemisphere, the amplitude of N34 component in right median SEPs recorded from the left parietal scalp (C3') increased significantly. Other components of right or left median SEPs or those after sham stimulation showed no changes. Monophasic 0.2 Hz subthreshold rTMS over the motor cortex predominantly affected the contralateral SEPs, probably through the transcallosal pathway.
    The Journal of Medical Investigation 02/2010; 57(1-2):109-13. DOI:10.2152/jmi.57.109

  • Clinical Neurophysiology 05/2009; 120(5). DOI:10.1016/j.clinph.2009.02.098 · 3.10 Impact Factor

  • Clinical Neurophysiology 05/2009; 120(5). DOI:10.1016/j.clinph.2009.02.142 · 3.10 Impact Factor
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    ABSTRACT: To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.
    Clinical Neurophysiology 11/2008; 119(11):2538-45. DOI:10.1016/j.clinph.2008.07.279 · 3.10 Impact Factor
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    ABSTRACT: We compared the metabolic and neurovascular effects of levodopa (LD) therapy for Parkinson's disease (PD). Eleven PD patients were scanned with both [15O]-H2O and [18F]-fluorodeoxyglucose positron emission tomography in the unmedicated state and during intravenous LD infusion. Images were used to quantify LD-mediated changes in the expression of motor- and cognition-related PD covariance patterns in scans of cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMR). These changes in network activity were compared with those occurring during subthalamic nucleus (STN) deep brain stimulation (DBS), and those observed in a test-retest PD control group. Separate voxel-based searches were conducted to identify individual regions with dissociated treatment-mediated changes in local cerebral blood flow and metabolism. We found a significant dissociation between CBF and CMR in the modulation of the PD motor-related network by LD treatment (p < 0.001). This dissociation was characterized by reductions in network activity in the CMR scans (p < 0.003) occurring concurrently with increases in the CBF scans (p < 0.01). Flow-metabolism dissociation was also evident at the regional level, with LD-mediated reductions in CMR and increases in CBF in the putamen/globus pallidus, dorsal midbrain/pons, STN, and ventral thalamus. CBF responses to LD in the putamen and pons were relatively greater in patients exhibiting drug-induced dyskinesia. In contrast, flow-metabolism dissociation was not present in the STN DBS treatment group or in the PD control group. These findings suggest that flow-metabolism dissociation is a distinctive feature of LD treatment. This phenomenon may be especially pronounced in patients with LD-induced dyskinesia.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2008; 28(16):4201-9. DOI:10.1523/JNEUROSCI.0582-08.2008 · 6.34 Impact Factor
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    ABSTRACT: It has been proposed that deep brain stimulation (DBS) of the subthalamic nucleus (STN DBS) and dopaminergic therapy ameliorate the symptoms of Parkinson's disease through similar functional mechanisms. We examined this notion using PET to compare the metabolic effects of these treatment approaches. Nine Parkinson's disease patients (age 61.7 +/- 11.1 years) were scanned ON and OFF STN stimulation and nine others (age 60.0 +/- 9.3 years) were scanned ON and OFF an individual titrated intravenous levodopa infusion. The two treatment groups were matched for baseline disease severity as well as clinical response to therapy. Similarities and differences in the effects of treatment on regional metabolism were assessed using statistical parametric mapping (SPM). In addition, we used network analysis to assess the effect of therapy on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). We found that both STN DBS and levodopa therapy were associated with significant (P < 0.001) metabolic reductions in the putamen/globus pallidus, sensorimotor cortex and cerebellar vermis, as well as increases in the precuneus (BA 7). The metabolic effects of the two interventions differed in the STN and medial prefrontal cortex, with relative increases with stimulation in the former structure and decreases in the latter. Network quantification disclosed reductions in PDRP activity with both interventions, which correlated with clinical improvement (P < 0.05). The degree of network modulation by therapy did not differ significantly for the two treatment approaches (P > 0.6). These findings support the results of previous imaging studies indicating that effective symptomatic therapies for Parkinson's disease involve a common mechanism. The modulation of pathological brain networks is a critical feature of the treatment response in parkinsonism.
    Brain 10/2006; 129(Pt 10):2667-78. DOI:10.1093/brain/awl162 · 9.20 Impact Factor
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    ABSTRACT: Somatosensory-evoked potentials (SEPs) are attenuated by movement. This phenomenon of 'gating' reflects sensorimotor integration for motor control. The frontal N30 component after median nerve stimulation was shown to be reduced in amplitude prior to hand movement. To investigate the mechanism of this sensory gating, we recorded median SEPs immediately before and after application of monophasic very low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) of 250 stimuli over motor cortex (MC), premotor cortex (PMC), or supplementary motor area (SMA) in 9 healthy volunteers. The stimulus intensity for MC or PMC was set 85% of the resting motor threshold for the hand muscle, and that for SMA was at the active motor threshold for the leg muscle. SEPs showed significant increases in amplitudes of the frontal N30 component after PMC stimulation, but not after SMA or MC stimulation. Low-frequency (1 Hz) biphasic stimulation over PMC showed no significant N30 changes in 6 out of 9 subjects tested, indicating the effect being specific for 0.2 Hz monophasic stimulation. To examine the functional anatomy of the N30 change, single photon emission computed tomography was performed immediately before and after monophasic 0.2 Hz rTMS over PMC in all the 9 subjects. Regional cerebral blood flow showed significant increases mainly in PMC and prefrontal cortex, indicating the involvement of these cortical areas in sensory input gating for motor control.
    NeuroImage 07/2006; 31(2):699-709. DOI:10.1016/j.neuroimage.2005.12.027 · 6.36 Impact Factor
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    Kotaro Asanuma · Maren Carbon-Correll · David Eidelberg ·
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    ABSTRACT: Functional neuroimaging, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provides a valuable technique for detecting regional changes in brain metabolic activity associated with human disease. These techniques have been applied in different dystonic disorders including primary generalized dystonia and dopa-responsive dystonia (DRD), as well as focal dystonic syndromes such as torticollis, writer's cramp, and blepharospasm. A common finding is abnormality of the basal ganglia and associated outflow pathways to sensorimotor cortex and other regions involved with motor performance. Other recent imaging research has utilized diffusion-based MRI techniques to localize distinct microstructural abnormalities in dystonia patients and gene carriers. This presentation will focus on an integrated approach to understanding the pathophysiology of this genetic and biochemically diverse disorder.
    The Journal of Medical Investigation 12/2005; 52 Suppl(Supplement):272-9. DOI:10.2152/jmi.52.272
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    ABSTRACT: We used [(18)F]-fluorodeoxyglucose and positron emission tomography to determine a discrete cerebral pattern of abnormal glucose utilization in dopa-responsive dystonia. Network analysis demonstrated that dopa-responsive dystonia is associated with a specific pattern of regional metabolic covariation, characterized by increases in the dorsal midbrain, cerebellum, and supplementary motor area, as well as reductions in motor and lateral premotor cortex and in the basal ganglia. This pattern was not expressed in mutation carriers for primary torsion dystonia. Dopa-responsive dystonia has a unique metabolic architecture that differs from other inherited forms of dystonia.
    Annals of Neurology 04/2005; 57(4):596-600. DOI:10.1002/ana.20442 · 9.98 Impact Factor
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    ABSTRACT: We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.
    European Neurology 02/2005; 53(2):64-7. DOI:10.1159/000084301 · 1.36 Impact Factor
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    K Asanuma · Y Ma · J Okulski · V Dhawan · T Chaly · M Carbon · S B Bressman · D Eidelberg ·
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    ABSTRACT: To determine whether reduced striatal D2 receptor binding reported in patients with idiopathic torsion dystonia is associated with the genotype, the authors used PET and [11C]-raclopride to assess non-manifesting carriers of the DYT1 mutation. D2 receptor binding was reduced by approximately 15% in caudate and putamen (p < 0.005). These results suggest that striatal D2 binding reductions are a trait feature of the DYT1 genotype.
    Neurology 02/2005; 64(2):347-9. DOI:10.1212/01.WNL.0000149764.34953.BF · 8.29 Impact Factor

Publication Stats

619 Citations
101.77 Total Impact Points


  • 2003-2014
    • The University of Tokushima
      • • Department of Clinical Neuroscience
      • • Department of Urology
      Tokusima, Tokushima, Japan
  • 2006-2008
    • The Feinstein Institute for Medical Research
      • Center for Neuroscience
      New York, New York, United States
  • 2004-2005
    • North Shore-Long Island Jewish Health System
      • Center for Neurosciences
      New York City, New York, United States