PMID- 36460551 OWN - NLM STAT- MEDLINE DCOM- 20230213 LR - 20230213 IS - 1872-7131 (Electronic) IS - 0387-7604 (Linking) VI - 45 IP - 3 DP - 2023 Mar TI - Muscle impairment in MRI affect variability in treatment response to nusinersen in patients with spinal muscular atrophy type 2 and 3: A retrospective cohort study. PG - 161-170 LID - S0387-7604(22)00191-7 [pii] LID - 10.1016/j.braindev.2022.11.002 [doi] AB - BACKGROUND: Real-world data have shown variability in treatment responses to nusinersen in spinal muscular atrophy (SMA). We investigated whether the magnitude of muscle impairment assessed by magnetic resonance imaging (MRI) at baseline can predict the treatment response. METHODS: We retrospectively assessed the clinical data in relevance to the thigh and pelvic MRI taken before the nusinersen treatment. A total of 16 patients with SMA types 2 and 3 (age = mean [SD]; 9.2 [4.6] year) receiving nusinersen treatment were enrolled. The T1-weighted MRI images of the pelvis and thigh were scored for muscle fatty infiltration and atrophy. The minimally clinically important difference (MCID) was considered as gaining at least 3 points of Hammersmith Functional Motor Scale-Expanded (HFMSE) from baseline. RESULTS: Of these 16 individuals, 14 had been treated for at least 15 months with baseline data. At 15 months, seven individuals obtained MCID in HFMSE. Baseline muscle MRI score could not differentiate the two groups; however, individuals who obtained MCID had significantly less severe scoliosis. In addition, there was a significant and negative relationship between baseline MRI score and the change of score in HFMSE after 15 months of treatment. Further, baseline Cobb angle along with MRI score also indicated the correlation to the degree of change in motor function. CONCLUSION: The degree of muscle damage may confer the variability in response to nusinersen in SMA types 2 and 3. Muscle MRI score along with the severity of scoliosis assessed at baseline may help to predict the motor function change. CI - Copyright (c) 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. FAU - Shimizu-Motohashi, Yuko AU - Shimizu-Motohashi Y AD - Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Chiba, Emiko AU - Chiba E AD - Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Mizuno, Katsuhiro AU - Mizuno K AD - Department of Rehabilitation Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan; Department of Physical Rehabilitation, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Yajima, Hiroyuki AU - Yajima H AD - Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Ishiyama, Akihiko AU - Ishiyama A AD - Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183-0042, Japan. FAU - Takeshita, Eri AU - Takeshita E AD - Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Sato, Noriko AU - Sato N AD - Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Oba, Mari AU - Oba M AD - Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan; Clinical Research & Education Promotion Division, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Sasaki, Masayuki AU - Sasaki M AD - Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. FAU - Ito, Shuichi AU - Ito S AD - Department of Pediatrics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. FAU - Komaki, Hirofumi AU - Komaki H AD - Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan; Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan; Clinical Research & Education Promotion Division, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. Electronic address: komakih@ncnp.go.jp. LA - eng PT - Journal Article DEP - 20221129 PL - Netherlands TA - Brain Dev JT - Brain & development JID - 7909235 RN - 5Z9SP3X666 (nusinersen) SB - IM MH - Humans MH - *Spinal Muscular Atrophies of Childhood MH - Retrospective Studies MH - *Scoliosis MH - *Muscular Atrophy, Spinal/diagnostic imaging/drug therapy MH - Muscles MH - Magnetic Resonance Imaging OTO - NOTNLM OT - 5q spinal muscular atrophy OT - Antisense oligonucleotide OT - Hammersmith Functional Motor Scale-Expanded OT - Magnetic resonance imaging OT - Skeletal muscle COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/12/03 06:00 MHDA- 2023/02/14 06:00 CRDT- 2022/12/02 22:04 PHST- 2022/09/02 00:00 [received] PHST- 2022/11/08 00:00 [revised] PHST- 2022/11/09 00:00 [accepted] PHST- 2022/12/03 06:00 [pubmed] PHST- 2023/02/14 06:00 [medline] PHST- 2022/12/02 22:04 [entrez] AID - S0387-7604(22)00191-7 [pii] AID - 10.1016/j.braindev.2022.11.002 [doi] PST - ppublish SO - Brain Dev. 2023 Mar;45(3):161-170. doi: 10.1016/j.braindev.2022.11.002. Epub 2022 Nov 29.