Elucidation of Mechanism of tremor brain by the integrated interactive approach

• Project/Area Number: 17K09798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: Hitomi Takefumi 京都大学, 医学研究科, 講師 (50402904)
• Co-Investigator(Kenkyū-buntansha): 松本 理器 神戸大学, 医学研究科, 教授 (00378754) ; 小林 勝哉 京都大学, 医学研究科, 特定病院助教 (70737121) ; 池田 昭夫 京都大学, 医学研究科, 特定教授 (90212761)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 不随意運動 / てんかん / BAFME / 皮質振戦 / 臨床神経生理学 / 振戦脳 / 双方向的解析

Outline of Final Research Achievements

In this research project, we investigated clinical symptom, so called cortical tremor, and electroencephalography and evoked potential in benign adult familial myoclonus epilepsy. Then we performed integrated analysis and disclosed the following findings. 1: Epileptiform discharges, namely cortical irritability, reduced during sleep (Hitomi et al., 2018). 2: The administration of glutamate receptor antagonist caused the change of evoked potential, and the change related to the clinical improvement (Oi et al., 2019). 3: A patient with genetically homozygous BAFME showed progressive clinical course similar to cerebellar degeneration (Kawamura et al., Kinki district meeting of Japan Neurology Society 2019).

Academic Significance and Societal Importance of the Research Achievements

本研究により、良性成人型家族性ミオクローヌスてんかん（BAFME）を標的にした振戦などの不随意運動およびてんかんのメカニズムの解明や治療に関する研究が、成果の通り進みました。研究成果には治療に関する知見も含まれていることから、BAFMEの今後の診療にも役立つものと考えられます。
加えて、上記の解析方法やえられた知見は、皮質ミオクローヌスや本態性振戦など他の不随意運動における病態解明・新規治療法導入時の評価法にも応用できると考えられます。以上より、本研究は不随意運動の診療全体にも大きく役立つと考えられます。

Research Products

• [Journal Article] Scalp-EEG could record both ictal DC shift and HFO together even with time constant 2 sec (2020)
  • Author(s): Tomohiko Murai, Takefumi Hitomi, Masao Matsuhashi, Riki Matsumoto, Yuki Kawamura, Masutaro Kanda, Ryosuke Takahashi, Akio Ikeda
  • Journal Title: Journal of Clinical Neurophysiology Volume: 37 Issue: 2 Pages: 191-194
  • DOI: 10.1097/wnp.0000000000000670
  • Peer Reviewed
• [Journal Article] A rational, multispectral mapping algorithm for primary motor cortex: A primary step before cortical stimulation (2019)
  • Author(s): Shuichiro Neshige, Katsuya Kobayashi, Masao Matsuhashi, Takefumi Hitomi, Akihiro Shimotake, Takayuki Kikuchi, Kazumichi Yoshida, Takeharu Kunieda, Riki Matsumoto, Susumu Miyamoto, Ryosuke Takahashi, Hirofumi Maruyama, Akio Ikeda
  • Journal Title: Epilepsia Volume: 60 Issue: 3 Pages: 547-559
  • DOI: 10.1111/epi.14669
  • Peer Reviewed / Open Access
• [Journal Article] Low-dose perampanel improves refractory cortical myoclonus by the dispersed and suppressed paroxysmal depolarization shifts in the sensorimotor cortex (2019)
  • Author(s): Kazuki Oi, Shuichiro Neshige, Takefumi Hitomi, Katsuya Kobayashi, Masao Matsuhashi, Akihiro Shimotake, Daiki Fujii, Riki Matsumoto, Shuhei Kasama, Masutaro Kanda, Yoshiaki Wada, Hirofumi Maruyama, Ryosuke Takahashi, Akio Ikeda
  • Journal Title: Clinical Neurophysiology Volume: 130 Issue: 10 Pages: 1804-1812
  • DOI: 10.1016/j.clinph.2019.07.006
  • Peer Reviewed / Open Access
• [Journal Article] A score to map the lateral non-primary motor area: multi-spectrum intrinsic brain activity vs. cortical stimulation (2019)
  • Author(s): Shuichiro Neshige, Katsuya Kobayashi, Masao Matsuhashi, Masaya Togo, Mitsuhiro Sakamoto, Akihiro Shimotake, Takefumi Hitomi, Takayuki Kikuchi, Kazumichi Yoshida, Takeharu Kunieda, Riki Matsumoto, Hirofumi Maruyama, Ryosuke Takahashi, Susumu Miyamoto, Akio Ikeda
  • Journal Title: Epilepsia Volume: 60 Issue: 11 Pages: 2294-2305
  • DOI: 10.1111/epi.16367
  • Peer Reviewed
• [Journal Article] The neural tides of sleep and consciousness revealed by single-pulse electrical brain stimulation. (2019)
  • Author(s): Usami K, Korzeniewska A, Matsumoto R, Kobayashi K, Hitomi T, Matsuhashi M, Kunieda T, Mikuni N, Kikuchi T, Yoshida K, Miyamoto S, Takahashi R, Ikeda A, Crone NE.
  • Journal Title: Sleep. Volume: in press Issue: 6 Pages: 1-9
  • DOI: 10.1093/sleep/zsz050
  • NAID: 120006647295
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Progressive Restrictive Ventilatory Impairment in Idiopathic Diffuse Pulmonary Ossification (2018)
  • Author(s): Matsuo H, Handa T, Tsuchiya M, Kubo T, Yoshizawa A, Nakayama Y, Shiga S, Hitomi T, Adachi S, Date H, Hirai T, Ichiyama S.
  • Journal Title: Internal Medicine Volume: 57 Issue: 11 Pages: 1631-1636
  • DOI: 10.2169/internalmedicine.9433-17
  • NAID: 130007382812
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-06-01
  • Peer Reviewed / Open Access
• [Journal Article] Interictal Slow and High-Frequency Oscillations: Is it an Epileptic Slow or Red Slow? (2018)
  • Author(s): Inoue T, Inouchi M, Matsuhashi M, Matsumoto R, Hitomi T, Daifu-Kobayashi M, Kobayashi K, Nakatani M, Kanazawa K, Shimotake A, Kikuchi T, Yoshida K, Kunieda T, Miyamoto S, Takahashi R, Ikeda A.
  • Journal Title: J Clin Neurophysiol. Volume: 36 Issue: 2 Pages: 166-170
  • DOI: 10.1097/wnp.0000000000000527
  • Peer Reviewed
• [Journal Article] Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy (2018)
  • Author(s): Ishiura Hiroyuki、Doi Koichiro、Mitsui Jun、Yoshimura Jun、Matsukawa Miho Kawabe、Takahashi Yuji、Date Hidetoshi、Matsukawa Takashi、Shimizu Jun、Koh Kishin、Takiyama Yoshihisa、Goto Jun、Morishita Shinichi、Tsuji Shoji
  • Journal Title: Nature Genetics Volume: 50 Issue: 4 Pages: 581-590
  • DOI: 10.1038/s41588-018-0067-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multi-component intrinsic brain activities as a safe alternative to cortical stimulation for sensori-motor mapping in neurosurgery. (2018)
  • Author(s): Neshige S, Matsuhashi M, Kobayashi K, Sakurai T, Shimotake A, Hitomi T, Kikuchi T, Yoshida K, Kunieda T, Matsumoto R, Takahashi R, Miyamoto S, Maruyama H, Matsumoto M, Ikeda A.
  • Journal Title: Clin Neurophysiol. Volume: 129 Issue: 9 Pages: 2038-2048
  • DOI: 10.1016/j.clinph.2018.06.007
  • Peer Reviewed
• [Journal Article] Nationwide survey in Japan endorsed diagnostic criteria of benign adult familial myoclonus epilepsy. (2018)
  • Author(s): Kobayashi K, Hitomi T, Matsumoto R, Watanabe M, Takahashi R, Ikeda A.
  • Journal Title: Seizure. Volume: 61 Pages: 14-22
  • DOI: 10.1016/j.seizure.2018.07.014
  • Peer Reviewed
• [Journal Article] Short "Infraslow" Activity (SISA) With Burst Suppression in Acute Anoxic Encephalopathy: A Rare, Specific Ominous Sign With Acute Posthypoxic Myoclonus or Acute Symptomatic Seizures. (2018)
  • Author(s): Togo M, Hitomi T, Murai T, Yoshimura H, Matsuhashi M, Matsumoto R, Kawamoto M, Kohara N, Takahashi R, Ikeda A.
  • Journal Title: J Clin Neurophysiol. Volume: 35 Issue: 6 Pages: 496-503
  • DOI: 10.1097/wnp.0000000000000507
  • Peer Reviewed
• [Journal Article] Sleep is associated with reduction of epileptiform discharges in benign adult familial myoclonus epilepsy. (2018)
  • Author(s): Hitomi T, Inouchi M, Takeyama H, Kobayashi K, Sultana S, Inoue T, Nakayama Y, Shimotake A, Matsuhashi M, Matsumoto R, Chin K, Takahashi R, Ikeda A.
  • Journal Title: Epilepsy Behav Case Rep. Volume: 11 Pages: 18-21
  • DOI: 10.1016/j.ebcr.2018.09.010
  • Peer Reviewed / Open Access
• [Journal Article] Phasic REM transiently approaches wakefulness in the human cortex - a single-pulse electrical stimulation study. (2017)
  • Author(s): Usami K, Matsumoto R, Kobayashi K, Hitomi T, Matsuhashi M, Shimotake A, Kikuchi T, Yoshida K, Kunieda T, Mikuni N, Miyamoto S, Takahashi R, Ikeda A.
  • Journal Title: Sleep Volume: 40 Issue: 8 Pages: 1-7
  • DOI: 10.1093/sleep/zsx077
  • Peer Reviewed
• [Journal Article] Effects of Voice Therapy on Laryngeal Motor Units During Phonation in Chronic Superior Laryngeal Nerve Paresis Dysphonia. (2017)
  • Author(s): Kaneko M, Hitomi T, Takekawa T, Tsuji T, Kishimoto Y, Hirano S.
  • Journal Title: J Voice. Volume: in press Issue: 6 Pages: 729-733
  • DOI: 10.1016/j.jvoice.2017.08.026
  • Peer Reviewed
• [Presentation] No or little progression of EEG abnormality in genetically proven in benign adult familial myoclonus epilepsy (BAFME). (2019)
  • Author(s): Hitomi T, Neshige S, Tojima M, Kobayashi K, Oi K, Murai M, Shamima S, Shimotake A, Matsumoto R, Takahashi R, Ikeda A
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] A homozygotic mutation with severe benign adult familial myoclonus epilepsy (BAFME). (2018)
  • Author(s): Hitomi T, Kobayashi K, Sakurai T, Murai T, Sultana S, Kinoshita M, Shimotake A, Matsumoto R, Takahashi R, Ikeda A.
  • Organizer: 12th Asian & Oceanian Epilepsy Congress
  • Int'l Joint Research
• [Presentation] Temporal change of electroencephalogram in benign adult familial myoclonus epilepsy (BAFME). (2018)
  • Author(s): Hitomi T, Kobayashi K, Neshige S, Sultana S, Sato K, Shimotake A, Matsumoto R, Takahashi R, Ikeda A.
  • Organizer: 12th Asian & Oceanian Epilepsy Congress
  • Int'l Joint Research
• [Presentation] 良性成人型家族性ミオクローヌスてんかんにおける脳波所見の経時的変化。 (2018)
  • Author(s): 人見健文、小林勝哉、音成秀一郎、Shamima Sultana、佐藤啓、谷岡洸介、下竹昭寛、松本理器、高橋良輔、池田昭夫
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 良性成人型家族性ミオクローヌスてんかん(BAFME)における原因遺伝子のリピート数と神経生理学的所見の関係。 (2018)
  • Author(s): 人見健文、音成秀一郎、小林勝哉、戸島麻耶、大井和起、下竹昭寛，松橋眞生，松本理器、神田益太郎、石浦浩之、辻省次、高橋良輔、池田昭夫
  • Organizer: 第52回日本てんかん学会学術集会
• [Presentation] 遺伝子検査陽性の良性成人型家族性ミオクローヌスてんかん(BAFME)における巨大体性感覚誘発電位(巨大SEP)とC反射の陽性率。 (2018)
  • Author(s): 人見健文、音成秀一郎、小林勝哉、松本理器、高橋良輔、池田昭夫
  • Organizer: 第48回日本臨床神経生理学会学術大会
• [Presentation] 良性成人型家族性ミオクローヌスてんかん(BAFME)。 シンポジウム 高齢者てんかんと脳波 (2018)
  • Author(s): 人見健文、小林勝哉、音成秀一郎、高橋良輔、池田昭夫
  • Organizer: 第48回日本臨床神経生理学会学術大会
  • Invited
• [Presentation] Positive rate of giant somatosensory evoked potential (giant SEP) and C reflex in benign adult familial myoclonus epilepsy (BAFME). (2017)
  • Author(s): Hitomi T, Kobayashi K, Murai T, Sakurai T, Matsumoto R, Takahashi R, Ikeda A.
  • Organizer: 17th World Congress of Neurology
  • Int'l Joint Research
• [Presentation] 遠隔脳波判読。シンポジウム6遠隔医療（脳波とテレメディスン） (2017)
  • Author(s): 人見健文、谷岡洸介、高橋良輔、池田昭夫
  • Organizer: 第51回日本てんかん学会学術集会
  • Invited
• [Presentation] 日本の地域レベルでの遠隔脳波判読の取り組みの現状と問題点。シンポ (2017)
  • Author(s): 人見健文、谷岡洸介、高橋良輔、池田昭夫
  • Organizer: 第47回日本臨床神経生理学会学術大会
  • Invited
• [Book] 所見の解釈と脳波レポートの作成 1基礎篇。モノグラフ 臨床脳波を基礎から学ぶ人のために 第2版：64-71 (2019)
  • Author(s): 人見健文、池田昭夫
  • Total Pages: 253
  • Publisher: 診断と治療社
  • ISBN: 9784787824455