A novel analysis of the disease progression patterns in ALS using electrophysiological data

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09710
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kanouchi Tadashi 東京医科歯科大学, 医学部附属病院, 講師 (50345287)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 筋委縮性側索硬化症 / プリオン様伝播仮説 / 病変進展 / 定量的疾患進行パターン / Local progression / Regional spread / 電気生理学的検査

Outline of Final Research Achievements

The speed of symptom spreading from the onset site to the next body region tended to be positively correlated with the speed of CMAP amplitude reduction in the onset limb in 8 of 21 ALS patients, in whom the involved spinal segments with acute denervation in needle EMG are contiguously distributed from the onset segment. In 7 ALS patients with the upper limb onset, the smaller the response of onset limb to transcranial magnetic stimulation using the triple stimulation tecnique is, the faster the inter-regional symptom spreading relative to the CMAP amplitude reduction speed in the onset limb is. The first finding seems to be consistent with the hypothesis in which the ALS lesion would spread out with domino-like cell-to-cell propagation of the pathogenic proteins. The second finding suggests that impairment of the upper motor neurons may affect the regional spreading of ALS lesion. But both findings are not sufficiently certain and further research will be necessary in the future.

Free Research Field

脳神経内科学、臨床神経生理学

Academic Significance and Societal Importance of the Research Achievements

プリオン様伝播仮説などの病態機序を視野に入れたALSの疾患進行パターンを新しく考案した。電気生理学的検査により得られる上位および下位運動ニューロンの情報を入れ込むことで疾患進行パターンを立体的かつ定量的に扱うことができるようになった。これにより、病変の進展が病因因子のドミノ倒し的な神経細胞間伝播によるという仮説と合うような進行パターンを示している可能性のある一群を見出すことができた。