Updated on 2021/10/22

写真a

 
TSUBOI Takashi
 
Organization
Nagoya University Hospital Center for Postgraduate Clinical Training and Career Development Assistant professor of hospital
Title
Assistant professor of hospital

Degree 1

  1. 医学博士 ( 2015.1   名古屋大学 ) 

Research Interests 4

  1. 脳深部刺激療法

  2. ジストニア

  3. 振戦

  4. パーキンソン病

Research Areas 1

  1. Life Science / Neurology  / Parkinson's disease, tremor, movement disorders, DBS, FUS

Research History 4

  1. Nagoya University   Neurology department & Center for Medical Education   Assistant Professor   MD., PhD.

    2020.12

  2. 名古屋大学医学部附属病院 医員

    2020.4

  3. フロリダ大学神経内科 研究員

    2018.4 - 2020.3

  4. 名古屋大学医学部附属病院 医員

    2015.4 - 2018.3

Education 2

  1. Nagoya University

    2010.4 - 2014.3

  2. Nagoya University

    1999.4 - 2005.3

Professional Memberships 4

  1. Movement Disorders Society Japan

  2. Movement Disorders Society

  3. 日本神経学会

  4. 日本内科学会

Awards 4

  1. パーキンソン病・運動障害疾患コングレス最優秀賞

    2021.3   Movement Disorders Society Japan  

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    Award type:Award from Japanese society, conference, symposium, etc. 

  2. パーキンソン病・運動障害疾患コングレス最優秀賞

    2017.10  

  3. 2017 international PD symposium Best Video Presentation Award

    2017.2  

  4. The Best Presentation Award

    2015.8   Movement Disorders Society  

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    Award type:Award from international society, conference, symposium, etc. 

    the Basic Scientist Summer School

 

Papers 40

  1. Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway.

    Middlebrooks EH, Okromelidze L, Wong JK, Eisinger RS, Burns MR, Jain A, Lin HP, Yu J, Opri E, Horn A, Goede LL, Foote KD, Okun MS, Quiñones-Hinojosa A, Uitti RJ, Grewal SS, Tsuboi T

    NeuroImage. Clinical   Vol. 32   page: 102846   2021.10

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    Background and purpose: Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation “sweet spots,” as well as assess the value of structural connectivity in predicting treatment outcomes. Materials and methods: Ninety-seven ET individuals with unilateral thalamic DBS were retrospectively included. Using normative brain connectomes, structural connectivity measures were correlated with the percentage improvement in contralateral tremor, based on the Fahn-Tolosa-Marin tremor rating scale (TRS), after parameter optimization (range 3.1–12.9 months) using a leave-one-out cross-validation in 83 individuals. The predictive feature map was used for cross-validation in a separate cohort of 14 ET individuals treated at another center. Lastly, estimated volumes of tissue activated (VTA) were used to assess a treatment “sweet spot,” which was compared to seven previously reported stimulation sweet spots and their relationship to the tract identified by the predictive feature map. Results: In the training cohort, structural connectivity between the VTA and dentato-rubro-thalamic tract (DRTT) correlated with contralateral tremor improvement (R = 0.41; p < 0.0001). The same connectivity profile predicted outcomes in a separate validation cohort (R = 0.59; p = 0.028). The predictive feature map represented the anatomical course of the DRTT, and all seven analyzed sweet spots overlapped the predictive tract (DRTT). Conclusions: Our results strongly support the possibility that structural connectivity is a predictor of contralateral tremor improvement in ET DBS. The results suggest the future potential for a patient-specific functionally based surgical target. Finally, the results showed convergence in “sweet spots” suggesting the importance of the DRTT to the outcome.

    DOI: 10.1016/j.nicl.2021.102846

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  2. Corrigendum to: Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation.

    Tsuboi T, Wong JK, Eisinger RS, Okromelidze L, Burns MR, Ramirez-Zamora A, Almeida L, Shukla AW, Foote KD, Okun MS, Grewal SS, Middlebrooks EH

    Brain : a journal of neurology   Vol. 144 ( 8 ) page: e71   2021.9

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    DOI: 10.1093/brain/awab192

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  3. Evolution of Globus Pallidus Targeting for Parkinson's and Dystonia Deep Brain Stimulation: A 15-Year Experience

    Holanda Vanessa M., Eisinger Robert Stephen, Almeida Leonardo, Tsuboi Takashi, Wang Huimin, Okun Michael S., Deeb Wissam, Patterson Addie, Shukla Aparna Wagle, Lopes Janine Lobo, Foote Kelly Douglas

    FRONTIERS IN NEUROLOGY   Vol. 12   page: 679918   2021.8

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    Language:Japanese   Publisher:Frontiers in Neurology  

    Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting. Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies. Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (β = 0.09, p < 0.0001), posteriorly [slope (β) = 0.04, p < 0.05], and dorsally (β = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (β = 0.06, p = 0.053). Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.

    DOI: 10.3389/fneur.2021.679918

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  4. Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation.

    Tsuboi T, Wong JK, Eisinger RS, Okromelidze L, Burns MR, Ramirez-Zamora A, Almeida L, Wagle Shukla A, Foote KD, Okun MS, Grewal SS, Middlebrooks EH

    Brain : a journal of neurology   Vol. 144 ( 6 ) page: 1774 - 1786   2021.7

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    The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

    DOI: 10.1093/brain/awab074

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  5. Safety and Tolerability of Burst-Cycling Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease

    Wong Joshua K., Hu Wei, Barmore Ryan, Lopes Janine, Moore Kathryn, Legacy Joseph, Tahafchi Parisa, Jackson Zachary, Judy Jack W., Raike Robert S., Wang Anson, Tsuboi Takashi, Okun Michael S., Almeida Leonardo

    FRONTIERS IN HUMAN NEUROSCIENCE   Vol. 15   page: 651168   2021.4

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    Language:Japanese   Publisher:Frontiers in Human Neuroscience  

    Background: Freezing of gait (FOG) is a common symptom in Parkinson’s disease (PD) and can be difficult to treat with dopaminergic medications or with deep brain stimulation (DBS). Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation (BCDBS) delivers current in various frequencies of bursts (e.g., 4, 10, or 15 Hz), while maintaining an intra-burst frequency identical to conventional DBS. Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG. Methods: Ten PD subjects with STN or GPi DBS and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state. Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS. Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy.

    DOI: 10.3389/fnhum.2021.651168

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  6. Pallidal Connectivity Profiling of Stimulation-Induced Dyskinesia in Parkinson's Disease. Reviewed International journal

    Takashi Tsuboi, Marc Charbel, David T Peterside, Mohit Rana, Ahmad Elkouzi, Wissam Deeb, Adolfo Ramirez-Zamora, Janine Lemos Melo Lobo Jofili Lopes, Leonardo Almeida, Pamela R Zeilman, Robert S Eisinger, Kelly D Foote, Lela Okromelidze, Sanjeet S Grewal, Michael S Okun, Erik H Middlebrooks

    Movement disorders : official journal of the Movement Disorder Society   Vol. 36 ( 2 ) page: 380 - 388   2021.2

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    OBJECTIVES: The aim of this study is to identify anatomical regions related to stimulation-induced dyskinesia (SID) after pallidal deep brain stimulation (DBS) in Parkinson's disease (PD) patients and to analyze connectivity associated with SID. METHODS: This retrospective study analyzed the clinical and imaging data of PD patients who experienced SID during the monopolar review after pallidal DBS. We analyzed structural and functional connectivity using normative connectivity data with the volume of tissue activated (VTA) modeling. Each contact was assigned to either that producing SID (SID VTA) or that without SID (non-SID VTA). Structural and functional connectivity was compared between SID and non-SID VTAs. "Optimized VTAs" were also estimated using the DBS settings at 6 months after implantation. RESULTS: Of the 68 consecutive PD patients who underwent pallidal implantation, 20 patients (29%) experienced SID. SID VTAs were located more dorsally and anteriorly compared with non-SID and optimized VTAs and were primarily in the dorsal globus pallidus internus (GPi) and dorsal globus pallidus externus (GPe). SID VTAs showed significantly higher structural connectivity than non-SID VTAs to the associative cortex and supplementary motor area/premotor cortex (P < 0.0001). Simultaneously, non-SID VTAs showed greater connectivity to the primary sensory cortex, cerebellum, subthalamic nucleus, and motor thalamus (all P < 0.0004). Functional connectivity analysis showed significant differences between SID and non-SID VTAs in multiple regions, including the primary motor, premotor, and prefrontal cortices and cerebellum. CONCLUSION: SID VTAs were primarily in the dorsal GPi/GPe. The connectivity difference between the motor-related cortices and subcortical regions may explain the presence and absence of SID. © 2020 International Parkinson and Movement Disorder Society.

    DOI: 10.1002/mds.28324

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  7. Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary. Reviewed International journal

    Ka Loong Kelvin Au, Joshua K Wong, Takashi Tsuboi, Robert S Eisinger, Kathryn Moore, Janine Lemos Melo Lobo Jofili Lopes, Marshall T Holland, Vanessa M Holanda, Zhongxing Peng-Chen, Addie Patterson, Kelly D Foote, Adolfo Ramirez-Zamora, Michael S Okun, Leonardo Almeida

    Neurology and therapy     2020.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media {LLC}  

    INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

    DOI: 10.1007/s40120-020-00220-5

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  8. Cerebello-basal ganglia connectivity fingerprints related to motor/cognitive performance in Parkinson's disease. Reviewed International journal

    Kazuya Kawabata, Hirohisa Watanabe, Epifanio Bagarinao, Reiko Ohdake, Kazuhiro Hara, Aya Ogura, Michihito Masuda, Toshiyasu Kato, Takashi Tsuboi, Satoshi Maesawa, Masahisa Katsuno, Gen Sobue

    Parkinsonism & related disorders   Vol. 80   page: 21 - 27   2020.11

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    INTRODUCTION: The role of the cerebellum in Parkinson's disease (PD) has attracted increasing attention; however, the role of functional connectivity (FC) between the basal ganglia and particular cerebellar subregions remains to be elucidated. We aimed to clarify the FC and its contribution to motor and cognitive performances in patients with PD. METHODS: We included 99 patients with PD and 99 age- and sex-matched healthy controls in this study. We created a cerebellar functional parcellation by performing cerebellum-only independent component analysis. Using the functional parcellation map, we performed seed-based connectivity analysis using each region as a seed and extracted the mean correlation coefficients within the thalamus and basal ganglia, including the caudate, pallidum, putamen and subthalamic nucleus. We examined the group differences and correlations with the motor and general cognitive scores. In addition, we conducted a mediation analysis to clarify the relationship among FC, motor severity, and cognition. RESULTS: The PD group showed decreased FC between a wide range of cerebellar subregions and the basal ganglia. Motor severity was correlated with FC between the subthalamic nucleus and posterior Crus I/II, and general cognitive performance scores correlated with FC between the caudate nucleus and medial-posterior part of the Crus I/II (p < 0.05, corrected for multiple comparisons). The cerebello-caudate network had a direct effect on cognitive performance (p = 9.0 × 10-3), although partially mediated by motor performance (p = 8.2 × 10-3). CONCLUSION: FC between cerebellar Crus I/II and divergent basal ganglia related to motor and cognitive performance in PD.

    DOI: 10.1016/j.parkreldis.2020.09.005

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  9. Long-term clinical outcomes of bilateral GPi deep brain stimulation in advanced Parkinson's disease: 5 years and beyond. Reviewed International journal

    Takashi Tsuboi, Janine Lemos Melo Lobo Jofili Lopes, Kathryn Moore, Bhavana Patel, Joseph Legacy, Adrianna M Ratajska, Dawn Bowers, Robert S Eisinger, Leonardo Almeida, Kelly D Foote, Michael S Okun, Adolfo Ramirez-Zamora

    Journal of neurosurgery     page: 1 - 10   2020.10

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    OBJECTIVE: Few studies have reported long-term outcomes of globus pallidus internus (GPi) deep brain stimulation (DBS) in Parkinson's disease (PD). The authors aimed to investigate long-term outcomes of bilateral GPi DBS for 5 years and beyond for PD patients. METHODS: The authors retrospectively analyzed the clinical outcomes in 65 PD patients treated with bilateral GPi DBS at a single center. The outcome measures of motor symptoms and health-related quality of life (HRQoL) included the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39). Scores at baseline were compared with those at 1, 3, 5, and 6-8 years after implantation using Wilcoxon signed-rank tests with α correction. RESULTS: GPi DBS significantly improved the off-medication UPDRS III total scores, UPDRS IV, and dyskinesia score at 1 year when compared with baseline (all p < 0.001). The off- and on-medication tremor scores, UPDRS IV, and dyskinesia scores showed moderate and sustained improvement (the ranges of the mean percentage improvement at each time point were 61%-75%, 30%-80%, 29%-40%, and 40%-65%, respectively) despite lacking statistical significance at long-term follow-up with diminishing sample sizes. The off-medication UPDRS III total scores did not show significant improvement at 5 years or later, primarily because of worsening in rigidity, akinesia, speech, gait, and postural stability scores. The on-medication UPDRS III total scores also worsened over time, with a significant worsening at 6-8 years when compared with baseline (p = 0.008). The HRQoL analyses based on the PDQ-39 revealed significant improvement in the activities of daily living and discomfort domains at 1 year (p = 0.003 and 0.006, respectively); however, all the domains showed gradual worsening at the later time points without reaching statistical significance. At 3 years, the communication domain showed significant worsening compared with baseline scores (p = 0.002). CONCLUSIONS: GPi DBS in PD patients in this single-center cohort was associated with sustained long-term benefits in the off- and on-medication tremor score and motor complications. HRQoL and the cardinal motor symptoms other than tremor may worsen gradually in the long term. When counseling patients, it is important to recognize that benefits in tremor and dyskinesia are expected to be most persistent following bilateral GPi DBS implantation.

    DOI: 10.3171/2020.6.JNS20617

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  10. Quality of life outcomes after globus pallidus internus deep brain stimulation in idiopathic or inherited isolated dystonia: a meta-analysis. Reviewed International journal

    Takashi Tsuboi, James H Cauraugh, Joshua K Wong, Michael S Okun, Adolfo Ramirez-Zamora

    Journal of neurology, neurosurgery, and psychiatry   Vol. 91 ( 9 ) page: 938 - 944   2020.9

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    BACKGROUND: Several studies reported the beneficial effects of globus pallidus internus deep brain stimulation (GPi DBS) on health-related quality of life (HRQoL) in patients with inherited or idiopathic isolated dystonia. However, the impact of this intervention on physical and mental/psychological domains and the effects over time remain unclear. METHODS: We conducted a systematic literature review from January 2000 to May 2019 and performed a meta-analysis of HRQoL outcomes based on the Short Form Health Survey-36 (SF-36) after GPi DBS in patients with inherited or idiopathic isolated dystonia to evaluate the effects of DBS on physical and mental QoL. RESULTS: Seven studies comprising 144 patients with dystonia (78, generalised; 34, segmental; and 32, focal cervical) were included in this comprehensive analysis. The mean (SD) age at DBS implantation was 41.0 (11.4) years, and the follow-up period after implantation was 3.2 (3.8) years. The random effects model meta-analysis revealed that both physical and mental domains of SF-36 improved following DBS with a significantly larger effect size for the physical domains (effect size=0.781; p<0.0001) compared with the mental domains (effect size=0.533; p<0.0001). A moderator variable analysis demonstrated that effect sizes for HRQoL improvement were maintained over time. CONCLUSIONS: This is the first meta-analysis that demonstrates significant benefits in HRQoL following DBS in patients with inherited or idiopathic isolated dystonia. The benefits are greater for physical QoL domains compared with mental/psychological QoL. These findings highlight the importance of a comprehensive multidisciplinary approach to improve mental/psychological QoL.

    DOI: 10.1136/jnnp-2019-322575

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  11. Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics Reviewed International journal

    E.H. Middlebrooks, R.A. Domingo, T. Vivas-Buitrago, L. Okromelidze, T. Tsuboi, J.K. Wong, R.S. Eisinger, L. Almeida, M.R. Burns, A. Horn, R.J. Uitti, R.E. Wharen, Jr, V.M. Holanda, S.S. Grewal

    American Journal of Neuroradiology   Vol. 41 ( 9 ) page: 1558 - 1568   2020.9

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    DOI: 10.3174/ajnr.A6693

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  12. Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review. Reviewed International journal

    Takashi Tsuboi, Ka Loong Kelvin Au, Wissam Deeb, Leonardo Almeida, Kelly D Foote, Michael S Okun, Adolfo Ramirez-Zamora

    Parkinsonism & related disorders   Vol. 76   page: 32 - 41   2020.7

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    Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40-50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy.

    DOI: 10.1016/j.parkreldis.2020.06.008

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  13. Secondary Worsening Following DYT1 Dystonia Deep Brain Stimulation: A Multi-country Cohort. Reviewed International journal

    Takashi Tsuboi, Laura Cif, Philippe Coubes, Jill L Ostrem, Danilo A Romero, Yasushi Miyagi, Andres M Lozano, Philippe De Vloo, Ihtsham Haq, Fangang Meng, Nutan Sharma, Laurie J Ozelius, Aparna Wagle Shukla, James H Cauraugh, Kelly D Foote, Michael S Okun

    Frontiers in human neuroscience   Vol. 14   page: 242 - 242   2020.6

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    Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.

    DOI: 10.3389/fnhum.2020.00242

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  14. Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes. Reviewed International journal

    Takashi Tsuboi, Janine Lemos Melo Lobo Jofili Lopes, Bhavana Patel, Joseph Legacy, Kathryn Moore, Robert S Eisinger, Leonardo Almeida, Kelly D Foote, Michael S Okun, Adolfo Ramirez-Zamora

    Parkinsonism & related disorders   Vol. 75   page: 7 - 13   2020.6

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    OBJECTIVE: We aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making. METHODS: This single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes. RESULTS: For the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes. CONCLUSION: Bilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.

    DOI: 10.1016/j.parkreldis.2020.05.004

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  15. Steroid-responsive recurrent tumefactive demyelination with multiple petechial hemorrhages along non-displaced medullary veins. Reviewed International journal

    Takashi Tsuboi, Yumiko Harada, Masashi Suzuki, Takashi Ando, Naoki Atsuta, Fumiharu Ohka, Kazuhito Takeuchi, Toshiaki Taoka, Shigeo Ohba, Masato Nakaguro, Masato Abe, Ichiro Nakashima, Mari Yoshida, Masahisa Katsuno

    Clinical neurology and neurosurgery   Vol. 193   page: 105764 - 105764   2020.6

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  16. A pooled meta-analysis of GPi and STN deep brain stimulation outcomes for cervical dystonia. Reviewed International journal

    Takashi Tsuboi, Joshua K Wong, Leonardo Almeida, Christopher W Hess, Aparna Wagle Shukla, Kelly D Foote, Michael S Okun, Adolfo Ramirez-Zamora

    Journal of neurology   Vol. 267 ( 5 ) page: 1278 - 1290   2020.5

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    OBJECTIVE: To analyze deep brain stimulation (DBS) outcomes in patients with cervical dystonia (CD), the relationships between motor and disability/pain outcomes, and the differences in outcomes between globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS, and to identify potential outcome predictors. METHODS: A systematic literature search identified individual patient data of CD patients who underwent DBS and whose outcomes were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Then, we performed a pooled meta-analysis on this cohort. RESULTS: A review of 39 papers yielded 208 patients with individual TWSTRS scores and demographic information. At a mean follow-up period of 23.3 months after either GPi or STN DBS, the TWSTRS total (58.8%), severity (53.9%), disability (61.3%), and pain (46.6%) scores significantly improved compared to baseline status (all p < 0.001). There were no significant outcome differences between short-term (< 23.3 months) and long-term (≥ 23.3 months). The TWSTRS outcomes after GPi and STN DBS were comparable, whereas these two targets showed different adverse effect profiles. The rates of responders to DBS according to the TWSTRS total and severity (defined as ≥ 25% improvement) were both 89%. Regression analyses demonstrated motor benefits associated with disability improvement more than pain relief (R2 = 0.345 and 0.195, respectively). No clinically meaningful predictors for DBS outcomes were identified. CONCLUSION: DBS improves motor symptoms, disability, and pain in CD patients and may provide sustained benefits over 2 years. GPi and STN appear to be equally effective targets with different adverse effect profiles.

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  17. Subjects at risk of Parkinson's disease in health checkup examinees: cross-sectional analysis of baseline data of the NaT-PROBE study. Reviewed International journal

    Makoto Hattori, Takashi Tsuboi, Katsunori Yokoi, Yasuhiro Tanaka, Maki Sato, Keisuke Suzuki, Yutaka Arahata, Akihiro Hori, Motoshi Kawashima, Akihiro Hirakawa, Yukihiko Washimi, Hirohisa Watanabe, Masahisa Katsuno

    Journal of neurology   Vol. 267 ( 5 ) page: 1516 - 1526   2020.5

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    INTRODUCTION: The present study aimed to survey the prevalence of prodromal symptoms of Parkinson's disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. METHODS: We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. RESULTS: Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p < 0.001) and ESS (9.6 ± 5.0 vs. 6.3 ± 3.2, p < 0.001), in addition to SCOPA-AUT, SAOQ, and RBDSQ. Male at-risk subjects showed lower values of hemoglobin (14.8 ± 1.3 vs. 15.0 ± 1.1, p = 0.032) and low density lipoprotein cholesterol (114.5 ± 30.3 vs. 123.0 ± 28.9, p = 0.004) than the examinees reporting no prodromal symptoms. CONCLUSION: Approximately 6% of the population aged 50 years or older was at risk for PD. Male at-risk subjects had mild hematological and metabolic changes relevant to PD.

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  18. Functional and Structural Connectivity Patterns Associated with Clinical Outcomes in Deep Brain Stimulation of the Globus Pallidus Internus for Generalized Dystonia Reviewed International journal

    L. Okromelidze, T. Tsuboi, R.S. Eisinger, M.R. Burns, M. Charbel, M. Rana, S.S. Grewal, C.-Q. Lu, L. Almeida, K.D. Foote, M.S. Okun, E.H. Middlebrooks

    American Journal of Neuroradiology   Vol. 41 ( 3 ) page: 508 - 514   2020.3

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  19. Longitudinal follow-up with VIM thalamic deep brain stimulation for dystonic or essential tremor. Reviewed International journal

    Takashi Tsuboi, Zakia Jabarkheel, Pamela R Zeilman, Matthew J Barabas, Kelly D Foote, Michael S Okun, Aparna Wagle Shukla

    Neurology   Vol. 94 ( 10 ) page: e1073-e1084   2020.3

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    OBJECTIVE: To assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET). METHODS: We retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2-3 years, 4-5 years, and ≥6 years after surgery. RESULTS: Twenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4-5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2-3 years follow-up. CONCLUSION: Overall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

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  20. Hospital Management of Parkinson Disease Patients. Reviewed International journal

    Adolfo Ramirez-Zamora, Takashi Tsuboi

    Clinics in geriatric medicine   Vol. 36 ( 1 ) page: 173 - 181   2020.2

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    Management of patients with Parkinson disease (PD) during inpatient hospital stays is complex and poses unique challenges for physicians and ancillary staff. Patients with PD have a high risk of complications, encephalopathy, and prolonged hospital stay. Early recognition of complications and implementation of rehabilitation strategies along with appropriate management of medications are critical to improve outcomes. Patients with PD can exhibit worsening mobility and balance, insomnia, orthostatic hypotension, multiple neuropsychiatric symptoms, and gastrointestinal dysfunction while hospitalized. This review summarizes the specific in-hospital concerns observed in patients with PD and discusses potential treatment approaches.

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  21. Quality of life outcomes after deep brain stimulation in dystonia: A systematic review. Reviewed International journal

    Takashi Tsuboi, Joshua K Wong, Michael S Okun, Adolfo Ramirez-Zamora

    Parkinsonism & related disorders   Vol. 70   page: 82 - 93   2020.1

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    Dystonia is an incurable movement disorder which can cause not only physical but also mental problems, leading to impaired health-related quality of life (HRQoL). For patients with dystonia refractory to medical treatment, deep brain stimulation (DBS) is a well-established surgical treatment. The objective of this systematic review is to provide a better understanding of HRQoL outcomes after DBS for dystonia. A search of the literature was conducted using Medline (PubMed), Embase, and Cochrane Library databases in May 2019. HRQoL outcomes after DBS along with motor outcomes were reported in a total of 36 articles involving 610 patients: 21 articles on inherited or idiopathic isolated dystonia, 5 on tardive dystonia, 3 on cerebral palsy, 2 on myoclonus-dystonia, 1 on X-linked dystonia-parkinsonism, and 3 on mixed cohorts of different dystonia subtypes. DBS improved motor symptoms in various subtypes of dystonia. Most studies on patients with inherited or idiopathic isolated dystonia showed significant improvement in physical QoL, whereas gains in mental QoL were less robust and likely related to the complexity of associated neuropsychiatric problems. HRQoL outcomes beyond 5 years remain scarce. Although the studies on patients with other subtypes of dystonia also demonstrated improvement in HRQoL after DBS, the interpretation is difficult because of a limited number of articles with small cohorts. Most articles employed generic measures (e.g. Short Form Health Survey-36) and this highlights the critical need to develop and to utilize sensitive and disease-specific HRQoL measures. Finally, long-term HRQoL outcomes and predictors of HRQoL should also be clarified.

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  22. Dysarthria and Speech Intelligibility Following Parkinson's Disease Globus Pallidus Internus Deep Brain Stimulation. Reviewed International journal

    Shannon Y Chiu, Takashi Tsuboi, Karen W Hegland, Nicole E Herndon, Aparna Wagle Shukla, Addie Patterson, Leonardo Almeida, Kelly D Foote, Michael S Okun, Adolfo Ramirez-Zamora

    Journal of Parkinson's disease   Vol. 10 ( 4 ) page: 1493 - 1502   2020

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    BACKGROUND: Although earlier studies reported variable speech changes following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients, the effects of globus pallidus internus (GPi) DBS on speech performance in PD remain largely unknown. OBJECTIVE: We aimed to characterize speech changes following PD GPi-DBS. METHODS: We retrospectively analyzed clinical and speech outcomes of 25 PD patients treated with bilateral GPi-DBS at a single center. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), speech subsystem domains (respiratory, laryngeal, resonance, orofacial, rate, prosody, rhythm, and naturalness), and overall speech intelligibility. Scores at baseline were compared with those at 6 months, 1 year, and the longest clinical follow-up available. RESULTS: In the off-medication state, activities of daily living and motor function based on UPDRS II and III significantly improved postoperatively. We observed unique patterns of speech changes in patients with PD following GPi-DBS in the short- (n = 25) and longer-term (n = 8) follow-up periods. Velopharyngeal (resonance), laryngeal components, and prosody worsened after bilateral GPi-DBS (p < 0.015). Speech intelligibility did not worsen after GPi-DBS in the short-term, but there was a trend to deteriorate at long-term follow-up (e.g., one year and beyond). We observed worsening of hypokinetic dysarthria in individual patients. Also, a minority of patients developed stuttering, spastic dysarthria, or ataxic dysarthria. CONCLUSION: Bilateral GPi-DBS worsened several modalities of parkinsonian speech without compromising overall speech intelligibility. GPi-DBS can potentially worsen or induce hypokinetic dysarthria, stuttering, spastic dysarthria, or ataxic dysarthria. GPi-DBS may have different and variable effects on speech function when compared to STN-DBS.

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  23. Three-Year Gait and Axial Outcomes of Bilateral STN and GPi Parkinson's Disease Deep Brain Stimulation. Reviewed International journal

    Shanshan Mei, Robert S Eisinger, Wei Hu, Takashi Tsuboi, Kelly D Foote, Christopher J Hass, Michael S Okun, Piu Chan, Adolfo Ramirez-Zamora

    Frontiers in human neuroscience   Vol. 14   page: 1 - 1   2020

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    Objective: To examine the short- and long-term clinical outcomes of the bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on gait and axial symptoms in Parkinson's disease (PD) patients. Available data have been inconsistent and mostly short-term regarding the effect of both brain targets on gait and axial symptoms. We aimed to identify potential target specific differences at 3-year follow-up from a large single-center experience. Methods: We retrospectively reviewed short-term (6-month follow-up) and long-term (36-month follow-up) changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II and III total scores of 72 PD patients (53 with bilateral STN-DBS and 19 with bilateral GPi-DBS). An interdisciplinary team made target-specific decisions for each DBS patient. We analyzed changes in gait and axial subscores derived from UPDRS II and III. Results: In both the STN- and GPi-DBS cohorts, we observed no significant differences in gait and axial UPDRS derived subscores in the off-med/on stimulation state at long-term follow-up when compared to baseline. On-med axial scores remained similar in the short-term but worsened in both groups (STN, 2.23 ± 3.43, p < 0.001; GPi, 2.53 ± 2.37, p < 0.01) in the long-term possibly due to disease progression. At long-term follow-up, the UPDRS III off-med/on stimulation scores worsened but were persistently improved from baseline in both groups (-9.07 ± 13.9, p < 0.001). Conclusions: The study showed that long-term both STN- and GPi-DBS had a similar effect on gait and axial symptoms in UPDRS derived subscores at 36-month follow-up despite potential baseline differences in criteria for selection of each target. More sophisticated measures of gait and balance beyond the categorical UPDRS score will be needed for future studies.

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  24. Longitudinal Speech Change After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease Patients: A 2-Year Prospective Study. Reviewed International journal

    Yasuhiro Tanaka, Takashi Tsuboi, Hirohisa Watanabe, Daisuke Nakatsubo, Satoshi Maesawa, Sachiko Kato, Yasukazu Kajita, Maki Sato, Reiko Oodake, Makoto Hattori, Masahiko Yamamoto, Toshihiko Wakabayashi, Masahisa Katsuno, Gen Sobue

    Journal of Parkinson's disease   Vol. 10 ( 1 ) page: 131 - 140   2020

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    BACKGROUND: Speech disorders are among the most common adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. However, longitudinal speech changes after STN-DBS are not fully understood. OBJECTIVE: We performed a two-year prospective study on PD patients who underwent STN-DBS and analyzed changes in speech function to clarify factors predicting for speech deterioration. METHODS: Twenty-five PD patients were assessed before and up to two years after STN implantation. Speech function was evaluated in the on-stimulation condition and 30 min after stimulation cessation using auditory-perceptual assessment. Patients who experienced overall worsening in speech intelligibility or naturalness ≥1 point during follow-up were classified into a deteriorated group (n = 16), with the remaining subjects being classified into a stable group (n = 9). Cognitive and motor functions were also assessed. RESULTS: The stable group had significantly better values of low volume, monoloudness, and asthenic voice subscores of the auditory-perceptual assessment in the on-stimulation condition compared with the off-stimulation condition. Imprecise consonants, excess loudness variation, and strained voice subscores were improved via cessation of stimulation in both groups. Before surgery, the deteriorated group had significantly lower scores in the Stroop Color-Word Test and Digit Span compared to the stable group. CONCLUSIONS: During follow-up, some subscores showed significant worsening in the on-stimulation condition in both groups. However, beneficial effects of STN-DBS on speech appeared to counterbalance negative effects of STN-DBS on speech function only in the stable group. Worse cognitive function may be a potential predictor for speech deterioration after STN-DBS in PD patients.

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  25. Importance of the initial response to GPi deep brain stimulation in dystonia: A nine year quality of life study. Reviewed International journal

    Takashi Tsuboi, Zakia Jabarkheel, Kelly D Foote, Michael S Okun, Aparna Wagle Shukla

    Parkinsonism & related disorders   Vol. 64   page: 249 - 255   2019.7

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    BACKGROUND: Long-term efficacy of deep brain stimulation (DBS) on health-related quality-of-life (HRQoL) for isolated dystonia is not well established. This study aims to determine the long-term impact of DBS on HRQoL outcomes and identify clinical predictors. METHODS: We retrospectively investigated 16 inherited or idiopathic isolated dystonia patients treated with bilateral globus pallidus internus DBS who were followed beyond 9 years at our center. The cohort consisted of 9 males, 7 females; 10 generalized, 6 segmental; mean (range) age at implantation, 37.0 (8-67) years; mean follow-up duration after implantation, 10.9 (9-13) years. We employed the Unified Dystonia Rating Scale for motor and Short Form Health Survey for HRQoL assessments to monitor the change longitudinally. We analyzed the changes in motor and HRQoL at 1-2 years (short-term) and ≥9 years (long-term) follow-up as compared to baseline with a Wilcoxon signed-rank test. We assessed the factors that predicted motor and HRQoL improvement with univariate regression analyses. RESULTS: Motor (41.6%; p = 0.004) and HRQoL (total score, p = 0.039) improvements remained significant at long-term follow-up and, in the regression analysis, change in HRQoL outcomes correlated significantly with change in motor outcomes (R2 = 0.384, p = 0.010). Additionally, short-term motor and HRQoL improvements predicted the long-term motor (R2 = 0.384, p = 0.010) and HRQoL (total score, R2 = 0.594, p < 0.001) outcomes, respectively. CONCLUSION: Motor and HRQoL improvements with DBS in isolated dystonia remain sustained for nearly a decade and may largely be predictable by the short-term response to DBS.

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  26. Clinical correlates of repetitive speech disorders in Parkinson's disease. Reviewed International journal

    Takashi Tsuboi, Hirohisa Watanabe, Yasuhiro Tanaka, Reiko Ohdake, Maki Sato, Makoto Hattori, Kazuya Kawabata, Kazuhiro Hara, Daisuke Nakatsubo, Satoshi Maesawa, Yasukazu Kajita, Masahisa Katsuno, Gen Sobue

    Journal of the neurological sciences   Vol. 401   page: 67 - 71   2019.6

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    OBJECTIVES: This study aimed to explore clinical correlates of repetitive speech disorders in patients with Parkinson's disease (PD). METHODS: This study investigated speech function (Assessment of Motor Speech for Dysarthria and Stuttering Severity Instrument-3), motor function (Unified Parkinson's Disease Rating Scale III [UPDRS-III] and UPDRS-IV), cognitive function (Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], Stroop color-word test, verbal fluency, digit span tests, and line orientation), and activities of daily living of 113 PD patients. Comparison between groups (independent t-tests, Mann-Whitney U tests, or χ2 test) and linear regression analyses were performed to determine clinical correlates of repetitive speech disorders. RESULTS: Totally, 65 patients (57.5%) had repetitive speech disorders. Patients with repetitive speech disorders had significantly worse UPDRS-III (P = .049), MoCA (P = .030), and speech function and higher levodopa equivalent daily dose (LEDD; P = .031) than those without repetitive speech disorders. Males were significantly predominant in patients with repetitive speech disorders (64.6%) compared to those without repetitive speech disorders (18.7%; P < .001). The univariate and subsequent multiple linear regression analyses revealed that the severity of repetitive speech disorders significantly correlated with gender (P < .001), MoCA (P = .006), and speech variables (abnormal rate, P = .007; imprecise consonants, P = .043), independent from disease duration, UPDRS III, and LEDD. CONCLUSIONS: PD patients with repetitive speech disorders had worse motor, cognitive, and speech functions than those without repetitive speech disorders. The most influential factor for repetitive speech disorders might be male gender.

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  27. Dorsal GPi/GPe Stimulation Induced Dyskinesia in a Patient with Parkinson's Disease.

    Elkouzi A, Tsuboi T, Burns MR, Eisinger RS, Patel A, Deeb W

    Tremor and other hyperkinetic movements (New York, N.Y.)   Vol. 9   2019

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  28. Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy. International journal

    Kazuhiro Hara, Hirohisa Watanabe, Epifanio Bagarinao, Kazuya Kawabata, Noritaka Yoneyama, Reiko Ohdake, Kazunori Imai, Michihito Masuda, Takamasa Yokoi, Aya Ogura, Takashi Tsuboi, Mizuki Ito, Naoki Atsuta, Hisayoshi Niwa, Toshiaki Taoka, Satoshi Maesawa, Shinji Naganawa, Masahisa Katsuno, Gen Sobue

    Journal of neurology   Vol. 265 ( 9 ) page: 2079 - 2087   2018.9

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    OBJECTIVE: We examined the anatomical involvement related to cognitive impairment in patients with multiple system atrophy (MSA). METHODS: We examined 30 patients with probable MSA and 15 healthy controls. All MSA patients were assessed by the Unified MSA-Rating scale and Addenbrooke's Cognitive Examination-Revised (ACE-R). We classified 15 MSA patients with ACE-R scores > 88 as having normal cognition (MSA-NC) and 15 with scores ≤ 88 as having cognitive impairment (MSA-CI). All subjects underwent 3 T MRI scanning and were investigated using voxel-based morphometry and diffusion tensor imaging. RESULTS: Both the MSA-NC and MSA-CI patients exhibited cerebellar but not cerebral atrophy in voxel-based morphometry compared to controls. In contrast, tract-based spatial statistics revealed widespread and significantly decreased fractional anisotropy (FA) values, as well as increased mean diffusivity, radial diffusivity, and axial diffusivity in both the cerebrum and cerebellum in MSA-CI patients compared to controls. MSA-NC patients also exhibited similar involvement of the cerebellum but less extensive involvement of the cerebrum compared with the MSA-CI patients. In particular, FA values in MSA-CI patients were significantly decreased in the anterior part of the left corpus callosum compared with those in MSA-NC patients. The mean FA values in the left anterior part of the corpus callosum were significantly correlated with total ACE-R scores and subscores (memory, fluency, and language) in MSA patients. CONCLUSIONS: Decreased FA values in the anterior corpus callosum showed a significant correlation with cognitive impairment in MSA.

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  29. Biomarker-based analysis of preclinical progression in spinal and bulbar muscular atrophy. Reviewed International journal

    Yasuhiro Hijikata, Atsushi Hashizume, Shinichiro Yamada, Tomonori Inagaki, Daisuke Ito, Akihiro Hirakawa, Keisuke Suzuki, Naoki Atsuta, Takashi Tsuboi, Makoto Hattori, Akihiro Hori, Haruhiko Banno, Gen Sobue, Masahisa Katsuno

    Neurology   Vol. 90 ( 17 ) page: E1501 - E1509   2018.4

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    OBJECTIVE: To identify a candidate biomarker reflecting biological changes during the preclinical progression of spinal and bulbar muscular atrophy (SBMA). METHODS: We analyzed longitudinal changes in biochemical parameters obtained during health examinations before and after the diagnosis of SBMA. We estimated trajectories of clinical markers across years from the onset of weakness using linear mixed models and compared these trajectories with those estimated for male healthy controls and patients with amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). Moreover, we examined the relationship between serum creatinine level and the onset of symptoms using Kaplan-Meier curves. RESULTS: Between October 2014 and October 2017, we enrolled 40 patients with genetically confirmed SBMA, 48 healthy controls, 25 patients with ALS, and 20 patients with PD. In patients with SBMA, we evaluated the patients' data for a period of 17.3 ± 7.5 years, including 11.4 ± 7.1 years of preclinical phase. Decreases in serum creatinine occurred >10 years before the onset. The mean serum creatinine concentration was 0.56 mg/dL at the onset of weakness in patients with SBMA compared to 0.88 ± 0.10 mg/dL on final evaluation in healthy controls. Serum levels of alanine transaminase and aspartate transaminase showed tendencies to increase in preclinical SBMA. These preclinical changes of biomarkers were not observed in either ALS or PD. CONCLUSIONS: Our findings suggest that serum creatinine begins to decrease before the onset of clinical symptoms and is a biomarker for disease progression and the efficacy of therapeutics in preclinical SBMA.

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  30. Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson's disease. Reviewed International journal

    Kazuya Kawabata, Hirohisa Watanabe, Kazuhiro Hara, Epifanio Bagarinao, Noritaka Yoneyama, Aya Ogura, Kazunori Imai, Michihito Masuda, Takamasa Yokoi, Reiko Ohdake, Yasuhiro Tanaka, Takashi Tsuboi, Tomohiko Nakamura, Masaaki Hirayama, Mizuki Ito, Naoki Atsuta, Satoshi Maesawa, Shinji Naganawa, Masahisa Katsuno, Gen Sobue

    Journal of neurology   Vol. 265 ( 3 ) page: 688 - 700   2018.3

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    Cognitive deficits in Parkinson's disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke's Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum-brainstem network. Significant differences in the FC within the vDMN and cerebellum-brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

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  31. Long-standing overt ventriculomegaly without aqueductal stenosis: A case report Reviewed International journal

    Kazuhiro Ikumi, Takashi Tsuboi, Naoki Atsuta, Kazuhito Takeuchi, Haruki Koike, Masahisa Katsuno

    Neurology and Clinical Neuroscience   Vol. 6 ( 2 ) page: 42 - 44   2018.3

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    DOI: 10.1111/ncn3.12176

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  32. Peritonitis after percutaneous endoscopic gastrojejunostomy for levodopa-carbidopa intestinal gel treatment despite concomitant use of gastropexy Reviewed International journal

    Takashi Tsuboi, Hirohisa Watanabe, Kouhei Funasaka, Mikiko Takebayashi, Kazushi Miyata, Masahisa Katsuno

    Neurology and Clinical Neuroscience   Vol. 6 ( 2 ) page: 64 - 66   2018.3

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley-Blackwell  

    DOI: 10.1111/ncn3.12183

    Web of Science

  33. Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease. Reviewed International journal

    Noritaka Yoneyama, Hirohisa Watanabe, Kazuya Kawabata, Epifanio Bagarinao, Kazuhiro Hara, Takashi Tsuboi, Yasuhiro Tanaka, Reiko Ohdake, Kazunori Imai, Michihito Masuda, Tatsuya Hattori, Mizuki Ito, Naoki Atsuta, Tomohiko Nakamura, Masaaki Hirayama, Satoshi Maesawa, Masahisa Katsuno, Gen Sobue

    PloS one   Vol. 13 ( 1 ) page: e0190072   2018.1

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    Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear. METHODS: We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs). RESULTS: Decreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH. CONCLUSION: PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

    DOI: 10.1371/journal.pone.0190072

    Web of Science

    Scopus

    PubMed

  34. Early detection of speech and voice disorders in Parkinson's disease patients treated with subthalamic nucleus deep brain stimulation: a 1-year follow-up study. Reviewed International journal

    Takashi Tsuboi, Hirohisa Watanabe, Yasuhiro Tanaka, Reiko Ohdake, Makoto Hattori, Kazuya Kawabata, Kazuhiro Hara, Mizuki Ito, Yasushi Fujimoto, Daisuke Nakatsubo, Satoshi Maesawa, Yasukazu Kajita, Masahisa Katsuno, Gen Sobue

    Journal of neural transmission (Vienna, Austria : 1996)   Vol. 124 ( 12 ) page: 1547 - 1556   2017.12

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Nature  

    We previously reported that Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) had distinct phenotypes of speech and voice disorders: hypokinetic dysarthria, stuttering, breathy voice, strained voice, and spastic dysarthria. However, changes over time remain unclear. In the present study, 32 consecutive PD patients were assessed before and up to 1 year after surgery (PD-DBS). Eleven medically treated PD patients were also assessed (PD-Med). Speech, voice, motor, and cognitive functions were evaluated. At baseline, the incidence of hypokinetic dysarthria (63% of PD-DBS vs. 82% of PD-Med), stuttering (50% vs. 45%), breathy voice (66% vs. 73%), and strained voice (3% vs. 9%) was similar between groups. At 1 year, a slight but significant deterioration in speech intelligibility (p < 0.001) and grade of dysphonia (p = 0.001) were observed only in PD-DBS group compared with baseline. During the follow-up, stuttering (9% vs. 18%) and breathy voice (13% vs. 9%) emerged in PD-DBS and PD-Med, but strained voice (28%) and spastic dysarthria (44%) emerged only in PD-DBS. After the stimulation was stopped, strained voice and spastic dysarthria improved in most patients, while stuttering and breathy voice improved in a minority of patients. These findings indicate that the most common DBS-induced speech and voice disorders are strained voice and spastic dysarthria and that STN-DBS potentially aggravates stuttering and breathy voice. An improved understanding of these types of disorders may help detect speech and voice deteriorations during the early phase and lead to appropriate treatments.

    DOI: 10.1007/s00702-017-1804-x

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    Scopus

    PubMed

  35. Corpus callosum involvement by diffusion tensor imaging is early marker of cognitive decline in multiple system atrophy Reviewed International journal

    Hara K., Watanabe H., Bagarinao E., Kawabata K., Yoneyama N., Ohdake R., Imai K., Masuda M., Yokoi T., Tsuboi T., Ito M., Atsuta N., Katsuno M., Sobue G.

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 256 - 256   2017.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.730

    Web of Science

  36. Early cognitive decline pattern is associated with distinct resting-state networks disruption in non-demented Parkinson's disease patients Reviewed International journal

    Kawabata K., Watanabe H., Hara K., Bagarinao E., Yoneyama N., Ogura A., Imai K., Masuda M., Yokoi T., Ohdake R., Tsuboi T., Ito M., Atsuta N., Katsuno M., Sobue G.

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 128 - 128   2017.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.389

    Web of Science

  37. Highly asymmetric and subacutely progressive motor weakness with unilateral T2-weighted high intensities along the pyramidal tract in the brainstem in adrenomyeloneuropathy. Reviewed International journal

    Takashi Tsuboi, Yasuhiro Tanaka, Yusuke Yoshida, Tomohiko Nakamura, Nobuyuki Shimozawa, Masahisa Katsuno

    Journal of the neurological sciences   Vol. 381   page: 107 - 109   2017.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.018

    Web of Science

    Scopus

    PubMed

  38. Instability of syllable repetition in Parkinson's disease after subthalamic nucleus deep brain stimulation Reviewed International journal

    Tanaka Y., Tsuboi T., Watanabe H., Nakatsubo D., Maesawa S., Kajita Y., Hattori M., Ohdake R., Yamamoto M., Wakabatkabayashi T., Katsuno M., Sobue G.

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 1036 - 1036   2017.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.2924

    Web of Science

  39. Longitudinal changes in speech and voice functions after subthalamic nucleus deep brain stimulation in Parkinson's disease patients Reviewed International journal

    Tsuboi T., Watanabe H., Tanaka Y., Ohdake R., Hattori M., Kawabata K., Hara K., Ito M., Nakatsubo D., Maesawa S., Kajita Y., Katsuno M., Sobue G.

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 1042 - 1042   2017.10

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jns.2017.08.2943

    Web of Science

  40. Voice and speech treatment of Parkinson's disease:Treatment approach toward generalization

    Tanaka Yasuhiro, Tsuboi Takashi, Levitt June S., Tanaka Mayu, Tanaka Noriyoshi, Watanabe Hirohisa, Katsuno Masahisa

    Journal of allied health sciences   Vol. 8 ( 1 ) page: 80 - 88   2017

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    Publisher:Society of Allied Health Sciences  

    <p><b>ABSTRACT: </b>Following the Lee Silverman Voice Treatment® program, multiple treatment options became available to address dysphonia, secondary to Parkinson's disease (PD). One of the treatment methods, developed by Elandary and colleagues of the Parkinson Voice Project (a speech clinic solely specialized for PD) in the U.S., takes a unique, two-layer approach. The program starts with a series of one-on-one therapy sessions (SPEAK OUT!®) followed by a group therapy program designed to maintain speech improvements (LOUD Crowd®). With its catchphrase, "Speak with Intent," the SPEAK OUT!®/LOUD Crowd® program's aim is to activate the pyramidal system that is relatively intact with PD. Two of the authors (YT and NT) recently participated in the SPEAK OUT!®/LOUD Crowd® workshop for clinicians to learn about this new treatment approach. The present report provides the overview of the program as well as a brief summary of other methods that address speech issues for individuals with PD.</p>

    DOI: 10.15563/jalliedhealthsci.8.80

    CiNii Article

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Books 3

  1. パーキンソン病 200年 Reviewed

    坪井崇,渡辺宏久,勝野雅央( Role: Joint author ,  パーキンソン病における不安・パニック障害)

    中外医学社  2020.1  ( ISBN:978-4-498-32846-4

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    Total pages:440   Responsible for pages:292-300   Language:Japanese Book type:Scholarly book

  2. 言語聴覚士のためのパーキンソン病のリハビリテーションガイド Reviewed

    坪井崇(パーキンソン病の概論)

    共同医書出版社  2019.7  ( ISBN:978-4-7639-3056-9

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    Total pages:154   Responsible for pages:3-5   Language:Japanese Book type:Textbook, survey, introduction

  3. 神経疾患治療ストラテジー

    坪井崇(言語療法)

    中山書店  2017.9  ( ISBN:978-4-521-74543-5

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    Total pages:465   Responsible for pages:175-181  

MISC 22

  1. 音節の繰り返しにてリズム異常を認める視床下核脳深部刺激術後のパーキンソン病患者の特徴 小脳疾患との比較 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 佐藤 茉紀, 服部 誠, 横井 克典, 山本 正彦, 勝野 雅央, 祖父江 元

    言語聴覚研究   Vol. 16 ( 3 ) page: 189 - 190   2019.9

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    Language:Japanese   Publisher:(一社)日本言語聴覚士協会  

  2. 視床下核脳深部刺激術後のパーキンソン病患者に生じる発話のリズム異常 小脳疾患との比較 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 佐藤 茉紀, 服部 誠, 横井 克典, 山本 正彦, 祖父江 元, 勝野 雅央

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 13回   page: 120 - 120   2019.7

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  3. SNCA点変異を有する家族性パーキンソン病の1例 International journal

    蛭薙 智紀, 坪井 崇, 辻河 高陽, 中村 亮一, 熱田 直樹, 岩井 克成, 勝野 雅央

    臨床神経学   Vol. 59 ( 1 ) page: 46 - 46   2019.1

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    Language:Japanese   Publisher:(一社)日本神経学会  

  4. 封入体ミオパチーに骨Paget病を合併しmultisystem proteinopathyを疑われた一例 International journal

    原田 祐三子, 村上 あゆ香, 野田 成哉, 木村 正剛, 坪井 崇, 熱田 直樹, 勝野 雅央

    臨床神経学   Vol. 59 ( 1 ) page: 46 - 46   2019.1

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    Language:Japanese   Publisher:(一社)日本神経学会  

  5. 【首下がり症候群】錐体外路疾患による首下がり症候群 その病態と分類,治療 International journal

    渡辺 宏久, 坪井 崇, 勝野 雅央, 祖父江 元

    脊椎脊髄ジャーナル   Vol. 31 ( 12 ) page: 1042 - 1048   2018.12

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    Language:Japanese   Publisher:(株)三輪書店  

    <文献概要>はじめに 首下がり症候群は,体幹に比して頸部が異常に前屈した状態を呈する疾患群を指す(図1).高橋は,「いくつかの基礎疾患に伴ってみられる症候としての首下がり」を首下がり症候群とした.首下がり症候群は,神経筋疾患が原因となる場合,神経変性疾患が原因となる場合,さらには脊椎・脊髄病変が原因となる場合に大別される(図1).一方,"首下がり"は,神経学用語集改訂第3版において,「三浦謹之助が詳述した項部筋不全麻痺による首下がりを主徴とする病態.当初地方病[Gerlier病]とされたが諸原因による」との記載がある.三浦の報告した「Kubisagari」で認めた頸部の前屈は,発作性,麻痺性,再発性で,しばしば家族性であるなど,現在,われわれが診療している首下がり症候群とは臨床像が大きく異なる.このため,目崎は,その総説の中で,dropped headを首下がりと訳すことに対して異を唱えている.この過度の頸部の前屈が,錐体外路疾患において注目されるようになったのは比較的最近であり,用語についてもその成因をジストニアと考えたことに由来するdisproportionate anterocollisや,筋力低下と考えたことに由来するdropped head syndrome(首下がり症候群)が用いられてきた.本レビューでは,錐体外路疾患におけるdisproportionate anterocollis(antecollis)・首下がり症候群の病態,分類,治療について整理したい.

  6. Tumefactive demyelinatiing lesionsにステロイドパルス療法は有用か? International journal

    深見 祐樹, 岡田 弘明, 山口 啓二, 原田 祐三子, 坪井 崇, 熱田 直樹, 勝野 雅央

    神経治療学   Vol. 35 ( 6 ) page: S222 - S222   2018.11

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    Language:Japanese   Publisher:(一社)日本神経治療学会  

  7. めまいを契機に診断された神経核内封入体病の1例 International journal

    岸本 祥之, 坪井 崇, 曽根 淳, 勝野 雅央

    臨床神経学   Vol. 58 ( 11 ) page: 710 - 710   2018.11

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    Language:Japanese   Publisher:(一社)日本神経学会  

  8. 高度な壊死所見と髄液細胞数増多を伴ったTumefactive demyelinating lesionの一例 International journal

    原田 祐三子, 坪井 崇, 熱田 直樹, 勝野 雅央, 大岡 史治, 竹内 和人

    臨床神経学   Vol. 58 ( 11 ) page: 709 - 709   2018.11

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    Language:Japanese   Publisher:(一社)日本神経学会  

  9. パーキンソン病患者の発話機能に対して視床下核脳深部刺激術が与える影響 2年の縦断研究 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 服部 誠, 佐藤 茉紀, 原 一洋, 川畑 和也, 山本 正彦, 勝野 雅央, 祖父江 元

    言語聴覚研究   Vol. 15 ( 3 ) page: 214 - 214   2018.9

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    Language:Japanese   Publisher:(一社)日本言語聴覚士協会  

  10. 健診受診者におけるパーキンソン病(PD)の非運動症状のスコア分布とPD at risk群抽出の試み International journal

    服部 誠, 坪井 崇, 渡辺 宏久, 田中 康博, 川島 基, 堀 明洋, 勝野 雅央

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 12回   page: 88 - 88   2018.7

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  11. 視床下核脳深部刺激術後に発話障害を呈すパーキンソン病患者の臨床背景 2年の縦断研究 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 服部 誠, 佐藤 茉紀, 原 一洋, 川畑 和也, 大嶽 れい子, 山本 正彦, 勝野 雅央, 祖父江 元

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 12回   page: 83 - 83   2018.7

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  12. 各種疾患 変性疾患 パーキンソン病における発声・発話障害 International journal

    坪井 崇, 渡辺 宏久, 祖父江 元, 勝野 雅央

    Annual Review神経   Vol. 2018   page: 201 - 209   2018.1

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    Language:Japanese   Publisher:(株)中外医学社  

  13. 健診受診者におけるパーキンソン病(PD)の非運動症状のスコア分布とPD at risk群抽出の試み International journal

    服部 誠, 坪井 崇, 渡辺 宏久, 田中 康博, 川島 基, 堀 明洋, 勝野 雅央

    総合健診   Vol. 45 ( 1 ) page: 237 - 237   2018.1

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    Language:Japanese   Publisher:(一社)日本総合健診医学会  

  14. パーキンソン病患者の発話機能に対する視床下核脳深部刺激術の影響 縦断的観察研究 International journal

    坪井 崇, 渡辺 宏久, 田中 康博, 大嶽 れい子, 服部 誠, 川畑 和也, 原 一洋, 中坪 大輔, 前澤 聡, 梶田 泰一, 若林 俊彦, 勝野 雅央, 祖父江 元

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 11回   page: 69 - 69   2017.10

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  15. 認知機能低下を示す多系統萎縮症の脳内神経回路解析 International journal

    原 一洋, 渡辺 宏久, 川畑 和也, 大嶽 れい子, 小倉 礼, 横井 孝政, 桝田 道人, 坪井 崇, 伊藤 瑞規, 熱田 直樹, バガリナオ・エピファニオ, 勝野 雅央, 祖父江 元

    Dementia Japan   Vol. 31 ( 4 ) page: 597 - 597   2017.10

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    Language:Japanese   Publisher:(一社)日本認知症学会  

  16. 視床下核脳深部刺激術を施行したパーキンソン病患者における発話の不安定性 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 服部 誠, 加藤 祥子, 大嶽 れい子, 原 一洋, 川畑 和也, 山本 正彦, 勝野 雅央, 祖父江 元

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 11回   page: 77 - 77   2017.10

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  17. 健診受診者におけるパーキンソン病の非運動症状のスコア分布とPD at risk群抽出の試み International journal

    服部 誠, 坪井 崇, 渡辺 宏久, 田中 康博, 川島 基, 堀 明洋, 勝野 雅央

    パーキンソン病・運動障害疾患コングレスプログラム・抄録集   Vol. 11回   page: 71 - 71   2017.10

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    Language:Japanese   Publisher:Movement Disorder Society of Japan (MDSJ)  

  18. 中脳水道狭窄を伴わなかったlong-standing overt ventriculomegaly in adults(LOVA)様水頭症の1例 International journal

    井汲 一尋, 坪井 崇, 田中 康博, 川端 哲平, 秋 禎樹, 永田 雄一, 竹内 和人, 若林 俊彦, 伊藤 瑞規, 勝野 雅央

    臨床神経学   Vol. 57 ( 10 ) page: 613 - 613   2017.10

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    Language:Japanese   Publisher:(一社)日本神経学会  

  19. 両側声帯麻痺を合併した球脊髄性筋萎縮症1症例の治療経験 International journal

    辻河 高陽, 山田 晋一郎, 橋詰 淳, 坪井 崇, 熱田 直樹, 伊藤 瑞規, 勝野 雅央

    臨床神経学   Vol. 57 ( 10 ) page: 608 - 608   2017.10

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  20. 脳深部刺激調整においてSTが関われること DBSチームの発足 International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 伊藤 瑞規, 原 一洋, 川畑 和也, 服部 誠, 山本 正彦, 勝野 雅央, 祖父江 元

    言語聴覚研究   Vol. 14 ( 3 ) page: 196 - 196   2017.9

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  21. 視床下核脳深部刺激術後のパーキンソン病で認める発話のリズム障害 なぜDBS後のPD患者発話はしばしば小脳失調様に聴こえるか? International journal

    田中 康博, 坪井 崇, 渡辺 宏久, 中坪 大輔, 前澤 聡, 加藤 祥子, 大嶽 れい子, 伊藤 瑞規, 原 一洋, 川畑 和也, 服部 誠, 山本 正彦, 勝野 雅央, 祖父江 元

    言語聴覚研究   Vol. 14 ( 3 ) page: 196 - 196   2017.9

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    Language:Japanese   Publisher:(一社)日本言語聴覚士協会  

  22. パーキンソン病における発声・発話治療 般化に向けて International journal

    田中 康博, 坪井 崇, レビット 順子, 田中 まゆ, 田中 教義, 渡辺 宏久, 勝野 雅央

    保健医療学雑誌   Vol. 8 ( 1 ) page: 80 - 88   2017.4

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    Language:Japanese   Publisher:保健医療学学会  

    パーキンソン病(PD)に対する言語療法はLee Silverman Voice Treatmentが嚆矢となり,その後に病態解明や治療法の開発が進んできた.本稿では,米国のParkinson Voice Project(PD専門の言語治療クリニック)で行われている治療法を中心に紹介する.本施設ではPDにより低下した発声・発話機能の回復を目的とした個別療法と,改善した発声・発話機能の維持を目的とした集団療法の2つの治療プログラムが提供されている.いずれの治療法においてもPD患者が日常生活で良好な発話が保てるよう緻密に構想化されたアプローチのみならず,患者のモチベーションを高めるための創意工夫が随所に施されていた.(著者抄録)

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J06406&link_issn=&doc_id=20170411330011&doc_link_id=%2Fem9allhe%2F2017%2F000801%2F011%2F0080-0088%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fem9allhe%2F2017%2F000801%2F011%2F0080-0088%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. 遺伝性ジストニアに対する脳深部刺激療法(Deep Brain Stimulation)の治療効果に関わる臨床的および遺伝的因子の解明

    2019.4 - 2020.3

    上原記念生命科学財団 

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    Authorship:Coinvestigator(s) 

  2. リリー・サイエンティフィック・フェローシップ・プログラム

    2018.4 - 2019.3

    日本イーライリリー株式会社 

  3. Pathological elucidation of tremor by various modality and modification by Focal Ultrasounds and Deep Brain Stimulation

    Grant number:17K10891  2017.4 - 2020.3

    Nakatsubo Daisuke

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    Authorship:Coinvestigator(s) 

    MRgFUS (MR-guided focused ultrasound) has become possible in Japan as a non-invasive coagulation therapy for the treatment of involuntary movements such as essential tremor. In this study, the improvement rate of the upper limbs was about 65% one year after treatment, and no serious complications were observed. In addition, network analysis by resting fMRI revealed that the more severe the tremor, the lower the connectivity of the network, and the higher brain function mainly in the frontal lobe is also impaired.

  4. 認知症を伴うパーキンソン病の大脳皮質における前初期遺伝子発現異常の解析

    2016.12 - 2018.3

    グラクソスミスクラインジャパン 

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    Authorship:Principal investigator 

  5. Pathophysiology of speech and voice disorders in Parkinson's disease patients treated with deep brain stimulation

    Grant number:16K19507  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Takashi Tsuboi

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    Authorship:Principal investigator 

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    We aimed to reveal the pathophysiology of speech and voice disorders in Parkinson’s disease (PD) patients treated with deep brain stimulation (DBS) and establish the treatment strategies for them. We found that Approximately 90% of PD patients had one or more types of speech and voice disorders (hypokinetic dysarthria, breathy voice, and stuttering) before surgery, which stemmed from PD itself, that Strained voice and spastic dysarthria were the most common DBS-induced speech and voice disorders, and that stuttering and breathy voice can be worsened by STN-DBS in a minority of patients. Additionally, male gender, worse cognitive function especially visuospatial/executive function and memory, worse motor function, and higher dose of anti-parkinsonian drugs are the possible risk factors for stuttering. Further studies are warranted to establish objective evaluation methods of speech and voice disorders and effective treatment strategies.

  6. 多系統萎縮症の正確な病期診断法の開発

    Grant number:16K09714  2016.4 - 2017.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    伊藤 瑞規, 勝野 雅央, 坪井 崇, 小池 春樹, 原 一洋, 熱田 直樹

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    Authorship:Principal investigator 

    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    多系統萎縮症(MSA)は、50~60代の働き盛りの年代に好発する神経難病であり、現在のところ早期診断や正確な病期診断が難しい疾患の一つである。50~60代は初老期にあたり、認知症を発症したり、また健常者であっても脳の様々な変化を起こし得ると思われる。多系統萎縮症の早期診断や正確な病期診断を行うためには、これら健常者に起こり得ると思われる脳の萎縮や解剖学的・機能的神経回路の変化を確認することは極めて重要であると考えられる。
    そこで、本年度は名古屋大学 脳とこころの研究センターで構築中の正常健常者の大規模な認知機能と頭部MRIのコホートを用いて、年齢とともに小脳の萎縮、小脳の解剖学的、機能的神経回路がどのように変化しているかを検討した。
    研究に同意の得られた連続445例のうち、うつ症状がなく、各種認知機能検査で異常を認めず、頭部MRI画像で脳梗塞・脳出血や脳腫瘍などを認めない295例の解析を行った。
    Voxel-based morphometry(VBM)、Tract-based spatial statistics(TBSS)および安静時脳機能MRIを大脳と小脳で評価した。VBMでは、大脳において頭頂葉、側頭葉、一部の前頭葉に萎縮を認め、小脳では小脳歯状核、虫部頭側に萎縮を認めた。TBSSでは、大脳で側脳室周囲の異常を認めたが、小脳では異常を認めなかった。安静時機能MRIでは、大脳でExecutive control networkやDefault mode networkなどの様々な機能的回路の異常を認めたが、小脳では異常を認めなかった。
    健常者において、大脳は様々な変化を認めていたが、小脳においては萎縮を認めるものの、解剖学的・機能的神経回路の異常を認めず、小脳の異常をきたしやすいMSAと比較するのに適していると考えられた。

  7. 脳深部刺激療法後のパーキンソン病患者における発話障害の病態解明と治療法の開発

    2016.4 - 2017.3

    ノバルティスファーマ 

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    Authorship:Principal investigator 

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