Abstract: Background Nusinersen has been officially used for the treatment of 5q spinal muscular atrophy (SMA) in China recently. By now there are few domestic case reports on the treatment of SMA with nusinersen. Objective To investigate the efficacy, safety and levels of neurofilament light chain protein (NFL) in cerebrospinal fluid with treatment of nusinersen in children with 5q spinal muscular atrophy. Design Case series report. Methods Patients with 5q SMA who were initially treated with nusinersen as monotherapy for not less than 14 months in the Department of Neurology, Children's Hospital of Shandong University from January 2020 to June 30, 2023 were enrolled. Multiple ligation dependent probe amplification (MLPA) or fluorescence quantitative PCR (qPCR) methods were used to detect exon 7 of SMN1 gene. Clinical classification is based on the age of symptom onset and the maximum motor function achieved. Cerebrospinal fluid samples for the detection of neurofilament light chain protein (NFL) level were collected by routine lumbar punctures or ultrasound-guided lumbar punctures, and nusinersen was administrated via intrathecal injection. The Children′s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP INTEND), the Revised Upper Limb Module Test (RULM), the Hammersmith functional motor scale expanded (HFMSE), and the 6-minute walk test (6MWT) were performed by a professionally trained and qualified rehabilitation physician before and after treatment. General information such as gender, date of birth, date of symptom onset, and adverse events during treatment were collected. Main outcome measures The scores of motor function scale after 14 months treatment with nusinersen. Results In total, 68 SMA pediatric patients with treatment duration not less than 14 months were included in this study, including 32 girls (47.0%). There were 9 cases of type I (13.2%), 40 cases of typeⅡ (58.8%), and 19 cases of type Ⅲ (27.9%). The median age of disease onset is 10 (7,13.8) months, and the median age of diagnosis is 17.5 (12,37) months. Homozygous deletion of exon 7 in SMN1 gene occurred in 64 cases (94.1%), and intragenic mutation of SMN1 gene occurred in 4 cases. The improvement of motor function in 60 children (88.2%) had clinical significance, including 7 cases of type I, 37 cases of typeⅡ, and 16 cases of type Ⅲ. In total, 90.0% (18/20) cases showed a score improvement by ≥4 points on the CHOP INTEND scale, while 97.8% (44/45) cases showed a score improvement by ≥3 points on the HFMSE scale. In total, 92.3% (12/13) cases showed a distance extension by ≥30 meters on the 6MWT; 66.7% (12/18) cases showed a score improvement by ≥2 points on the RULM scale. Two cases achieved new motor function milestones after treatment. The NFL level in the cerebrospinal fluid of 15 children with SMA typeⅡ declined to 69.2 (40.5, 89.3) pg·mL-1 after the loading dose therapy (184th day after first drug administration) comparing with 176.6 (104.5,199.6) pg·mL-1 before treatment, the difference is statistically significant. Adverse events during treatment included fever in 3 cases with 1 case of type Ⅲ, 2 cases of type Ⅱ, all of which were relieved spontaneously; respiratory tract infection in 2 cases with 1 case of type I and 1 case of type Ⅱ, which were relieved after treatment; constipation, myalgia, vertigo and cough occurred in 1 type Ⅱ case each, all of which were relieved spontaneously and 1 case of typeⅡ with abnormal liver function, which normalized after 7 days treatment. No serious adverse event occurred. Conclusions Nusinersen can improve the motor function of children with 5q SMA after 14 months of treatment with good safety. The NFL level in cerebrospinal fluid of children with SMA typeⅡ can be significantly decreased after the nusinersen loading dose therapy.

Key words: Spinal muscular atrophy, Nusinersen, Neurofilament light chain, Children, Treatment