The utility of compound muscle action potential and creatinine in childhood spinal muscle atrophy

The utility of compound muscle action potential and creatinine in childhood spinal muscle atrophy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The utility of compound muscle action potential and creatinine in childhood spinal muscle atrophy Ruidi Sun, feng Zhang, Peipei Wei, Xiaoqing Luo, jun Jiang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6686700/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder precipitated by mutations in the survival motor neuron 1 gene (SMN1). Given the significant heterogeneity in patients' responses to Nusinersen treatment, there is an urgent need for sensitive biomarkers in SMA to accurately evaluate the beneficial effects of these therapeutic interventions. We explored the association between motor scores and serum creatinine (Crn) levels and compound muscle action potential(CMAP) in SMA patients undergoing treatment with nusinersen. Methods We measured serum Crn levels, CMAP amplitude and Hammersmith Functional Motor Scale-Expanded (HFMSE), including 40 pediatrics patients with SMA. The association between Crn ,CMAP and motor scores was investigated through partial rank correlation analysis and linear mixed models. Results 40 pediatrics patients were included. Among them, 35 patients had Nusinersen treatment. Nine patients did not have their CMAP amplitude and motor scores data recorded during the follow-up therapy period. Four patients only had their motor scores available during the follow-up therapy, while 22 patients had both their CMAP amplitude and motor scores measured during the follow-up therapy. Except for femoral nerve, the amplitudes of the left tibial, peroneal, ulnar, and median nerves demonstrated enhancements following nusinersen treatment(P<0.05), as well as HFMSE. Both at the baseline assessment and during the follow-up period, the left tibial, peroneal, ulnar, and femoral nerves showed correlations with the HFMSE(p<0.05). After accounting for the effects of age and sex, Crn were found to be associated with motor scores and the ulnar CMAP amplitude at baseline and follow-up(p<0.05). The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients(p=0.012). Conclusions In conclusion, for patients with SMA who were treated with nusinersen, notable improvements in motor scores and CMAP were observed. Crn at baseline and follow-up had relationship with HFMSE. The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients. spinal muscle atrophy pediatrics compound muscle atrophy creatinine Background Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder precipitated by mutations in the survival motor neuron 1 gene (SMN1). The underlying pathology of SMA is characterized by the degeneration of α-motor neurons in the spinal cord and brainstem. Based on motor function, SMA has been classified into types 0-IV[ 1 ]. Clinically, SMA is manifested by muscle atrophy and affects multiple organ systems, presenting a complex and challenging disease profile. Since 2016, the US Food and Drug Administration has approved three disease-modifying therapies, namely Nusinersen, risdiplam, and Onasemnogene abeparvovec, for the treatment of SMA. Given the significant heterogeneity in patients' responses to Nusinersen treatment, there is an urgent need for sensitive biomarkers in SMA to accurately evaluate the beneficial effects of these therapeutic interventions. Motor function scores, which have been widely used in therapeutic trials, are subject to evaluator subjectivity. Additionally, issues such as ceiling and floor effects associated with the scoring scales have been reported[ 2 – 4 ]. The compound muscle action potential (CMAP) represents the electrophysiological activity of a muscle or a group of muscles when a peripheral nerve is stimulated at a supramaximal level[ 5 ]. CMAP has emerged as a valuable tool for assessing treatment efficacy in SMA. Changes in CMAP have been observed in symptomatic infants as well as in patients with later-onset forms of the disease following therapeutic intervention[ 6 , 7 ]. For instance, in pediatric SMA patients after two years of Nusinersen treatment, a strong correlation was found between the CMAP amplitude of the ulnar nerve and motor scores[ 8 ]. In adolescent and adult SMA patients, Nusinersen has been shown to effectively improve both motor function and electrophysiological parameters[ 9 ]. In type 2 SMA patients, routine follow-up using CMAP measurements of the median nerve has demonstrated clear improvements with Nusinersen treatment [ 10 ]. Moreover, baseline CMAP amplitudes were associated with motor function outcomes after AVXS-101 (Onasemnogene Abeparvovec) therapy, and both CMAP amplitudes and motor scores were found to be predictive of motor outcomes following this treatment[ 11 ]. Even in SMA patients without gene therapy, the maximum ulnar CMAP amplitude has been shown to correlate well with motor function, suggesting its potential value in monitoring disease status [ 12 ]. However, most existing literature primarily focuses on the correlation between CMAP amplitude and motor scores, while the predictive value of the baseline CMAP amplitude remains largely unexplored. Creatinine (Crn) plays a crucial role in maintaining skeletal muscle function and is closely associated with muscle mass, activity levels, and metabolic rate[ 13 , 14 ]. A study in adult SMA patients investigated the relationship between Crn levels, disease severity, and the amplitude of the ulnar CMAP[ 15 ]. These findings suggest that Crn could potentially serve as a biomarker for assessing disease severity in adolescent and adult SMA patients[ 15 ]. A previous study indicated that reduced Crn levels are indicative of disease severity in SMA types 1–3, encompassing both pediatirics and adult patients [ 14 ]. Nevertheless, the potential role of Crn as a biomarker for muscle denervation and motor function in pediatric SMA patients remains to be elucidated. Therefore, further research is essential to determine whether serum Crn levels are associated with muscle denervation and motor function in childhood SMA. Additionally, it is necessary to explore the potential of CMAP and Crn levels as reliable biomarkers for accurately assessing disease severity and predicting improvements in pediatric SMA patients following Nusinersen treatment. Methods Study population This was a retrospective, observational study. Between January 1, 2021, and January 1, 2025, patients with symptomatic, genetically confirmed SMA (homozygous SMN1 exon 7 deletions as well as c.22dupA mutation) were enrolled at the Wuhan Children’s Hospital. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP-INTEND) (score, 0–64) was available for children with type 1 SMA who were less than 38 months old, Hammersmith Functional Motor Scale Expanded (HFMSE) (score, 0–66) was used for children with type 2 and 3 SMA, and Revised Upper Limb Module (RULM)RULM (score, 0–37) was used for children with SMA who were older than three years of age. The change of motor function scores defined as difference between follow-up and baseline motor function scores. The demographic features and creatinine(Crn) level in serum parameters, were obtained from the clinical laboratory data in the electronic medical records system. Electrophysiological examination Electrophysiological examinations were conducted using a four-channel Keypoint electromyograph, with no sedation administered. The recorded distal skin temperature was between 36.5 and 37°C in all children. Surface electrodes were used. Active recording electrodes were placed at different muscles to measure the potential of corresponding nerves: the muscle bellies of the abductor pollicis brevis for the median nerve, the abductor digiti minimi for the ulnar nerve, the adductor hallucis for the tibial nerve, the extensor digitorum brevis for the peroneal nerve, and the vastus intermedius for the femoral nerve. The left nerves in lower limbs and unilateral nerves in upper limbs (the more severe side if clinical feature was asymmetrical or the left side if clinical feature was symmetrical) were selected in SMA. Patients who had at least two nerves tested were included. Ethical approval The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Wuhan Children’s Hospital (2021R110-E02). Written informed consent was obtained from participants or their parents or guardians. Clinical trial number: not applicable. Statistical analysis Data were analyzed using SPSS version 20.0 software. Continuous data are expressed as the means and standard deviations(SD) if normally distributed or medians and interquartile ranges (IQRs) if non-normally distributed. The Mann–Whitney U test or Kruskal–Wallis test was used for comparing two or more groups for non-normal distribution data, respectively. The spearman was used for correlation Analysis for non- normal distribution data and Pearson was used for normal distribution data. The paired t-test was used to compare between two groups for normal distribution data and Wilcoxon test was used for non-normal distribution data . Partial rank correlation was conducted to correct for age, gender, and analyze the correlation between Crns , CMAP and HFMSE. A linear mixed-effects model was utilized to establish the relationship between CMAP at baseline and changes in motor function by controlling for the duration from onset to therapy. P-values of < 0.05 were considered statistically significant. Results There were 40 patients who had their compound muscle action potential (CMAP) amplitude and motor scores measured at baseline. At the follow-up stage, five patients did not undergo the disease-modifying treatment with nusinersen. Specifically, three of these patients did not receive any disease-modifying treatment, and two patients received risdiplam therapy instead. Additionally, nine patients did not have their CMAP amplitude and motor scores data recorded during the follow-up therapy period. Four patients only had their motor scores available during the follow-up therapy, while 22 patients had both their CMAP amplitude and motor scores measured during the follow-up therapy. The baseline characteristics of the spinal muscular atrophy (SMA) patients are presented in Table 1. Table 1 Baseline characteristics Overall (N=40) Onset age, median (IQR), months(n=40) Nusinersen therapy age (IQR), months(n=35) 8(6-12) 56(13-102) Sex Male 23 (57.5) Female 17(42.5) SMA type 1 11 (27.5) 2 19 (47.5) 3 10 (25) Functional classification at initial therapy Non-sitters 14(35) Sitters 20(50) Walkers 6 (15) HFMSE median (SD), months(n=30) 21.50±17.19 RULM median (SD), months(n=17) 23.29±11.08 CHOP-INTEND median (SD), months(n=10) 14.20±12.99 SMN copy number 2 5 (12.5) 3 14 (35) 4 3 (7.5) Nerve measured for compound muscle action potential Left peroneal nerves (IQR), mv(n=40) 1.74(0.49-2.85) Left tibial nerve (IQR), mv (n=39) 1.41(0.24-4.35) Left femoral nerve (IQR), mv (n=39) 0.00(0.00-0.53) Median nerve (IQR), mv (n=38) 4.25±4.20 Ulnar nerve (IQR), mv (n=38) 2.15±2.88 Data are n (%) unless indicated otherwise Abbreviation IQR interquartile range, SMA spinal muscular atrophy, SMN survival motor neuron, HFMSE Hammersmith Functional Motor Scale Expanded, RULM Revised Upper Limb Module, CHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. Follow-up characteristics There were 26 patients who underwent follow-up. Among these patients, 4 had only motor scores available, while 22 had both motor scores and compound muscle action potential (CMAP) amplitude data recorded (Table 2). The number of intrathecal injections during the follow-up period was 10, with a range of 8 to 11 injections. Table 2 Follow-up characteristics Overall (N=26) Sex Male 18 (69) Female 8(31) SMA type 1 4 (15.4) 2 14 (53.8) 3 8 (30.8) Functional classification at follow-up Non-sitters 1 (3.8) Sitters 18(69.2) Walkers 7 (26.9) The intrathecal injection time 10(8-11) HFMSE (n=23) 30.57±17.66 RULM(n=13) 34(27-37) CHOP-INTEND(n=3) 61±3.61 SMN copy number 2 3 (11.5) 3 11 (42.3) 4 3 (11.5) Nerve measured for compound muscle action potential Left peroneal nerves (IQR), mv(n=22) 2.45(1.09-4.10) Left tibial nerve (IQR), mv (n=22) 3.30(1.16-7.20) Left femoral nerve (IQR), mv (n=22) 0.395(0.10-1.30) Median nerve (IQR), mv (n=22) 6.59±4.16 Ulnar nerve (IQR), mv (n=22) 2.09(0.86-6.10) Data are n (%) unless indicated otherwise Abbreviation IQR interquartile range, SMA spinal muscular atrophy, SMN survival motor neuron, HFMSE Hammersmith Functional Motor Scale Expanded, RULM Revised Upper Limb Module, CHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. The comparison between CMAP and motor function at baseline and follow-up There were significant difference between baseline and follow-up in left peroneal nerve, left tibial nerve, median nerve and ulnar nerve( P <0.05). There was no significant difference in left femoral nerve between baseline and follow-up(Table 3). There were 23 patients had baseline HFMSE and follow-up, 12 patients had baseline RULM and follow-up, three patients had CHOP-INTEND baseline(12±7.21) and follow-up(61±3.61). Baseline HFMSE was 20.04±15.98 and follow-up was 30.57±17.66, baseline RULM was 23.77±10.85 and follow-up was 34(27-37). There were statistical significant difference between baseline and follow-up in HFMSE(p<0.001) and RULM(P=0.008). Table 3 The comparison between CMAP at baseline and follow-up The baseline CMAP Follow-up CMAP P Left peroneal nerves (IQR), mv(n=22) 1.875(0.82-4.10) 2.45(1.09-4.10) 0.027 1 Left tibial nerves (IQR), mv(n=19) 2.2(0.29-5.20) 3.20(1.52-5.23) 0.005 1 Left femoral nerve (IQR), mv (n=18) 0.12(0.00-0.59) 0.37(0.04-1.02) 0.205 1 Median nerve (IQR), mv (n=20) 4.45(1.65-6.50) 6.72±4.22 0.008 1 Ulnar nerve (IQR), mv (n=21) 1.55(0.32-4) 2.09(0.81-5.25) 0.003 1 1 Wilcoxon test Abbreviation IQR, interquartile range; CMAP compound muscle action potentails. The relationship between CMAP and motor scores. We also compare RULM at baseline and CMAP amplitude in median nerve and ulnar nerve, there was 16 patients had RULM and CMAP value. RULM scores was 22.44±10.84, median nerve CMAP amplitude was 6.39±4.07mV, ulnar nerve CMAP amplitude was 3.83±3.54mV, there was statistical difference between RULM and ulnar nerve CMAP amplitude at baseline( P =0.012)，after adjusting for age and sex. There was no statistical difference between RULM and median nerve CMAP amplitude at baseline( P >0.05). Ten patients had CHOP-Intend, the average score was 14.20±12.99. Ten patients had peroneal nerve CMAP amplitude, the average CMAP amplitude was 0.23(0.00-0.49)mV, nine patients had tibial and femoral nerve CMAP amplitude, the average CMAP amplitude were 0.17(0.12-0.26)mV and 0(0-0)mV respectively, there were no statistical difference between CMAP amplitude in lower limbs and CHOP-Intend( P >0.05). Ten patients had ulnar nerve CMAP amplitude and CHOP-Intend , the average CMAP amplitude was 0.06(0.00-0.34)mV, nine patients had median nerve CMAP amplitude and CHOP-Intend, the average CMAP amplitude was 0.067(0.039-0.27)mV, there were no statistical difference between CMAP amplitude in upper limbs and CHOP-Intend( P >0.05). At baseline, there were statistical relationship between CMAP and HFMSE after adjusting for age and sex (Table 4). Table 4 The relationship between CMAP and HFMSE at baseline HFMSE at baseline The baseline CMAP P Left peroneal nerves (IQR), mv(n=30) 18(6-30) 2.145(1.40-3.50) 0.024 1 Left tibial nerves (IQR), mv(n=30) 18(6-30) 2.40(0.97-5.30) 0.000 1 Left femoral nerve (IQR), mv (n=30) 18(6-30) 0.26(0.00-0.64) 0.000 1 Median nerve (IQR), mv (n=29) 18（6-30） 4.20（2.70-6.60） 0.009 1 Ulnar nerve (IQR), mv (n=28) 17.50（6-30） 1.825（0.33-4.10） 0.000 1 1 Spearman, Abbreviation IQR, interquartile range; CMAP, compound muscle action potentials; HFMSE Hammersmith Functional Motor Scale Expanded At follow-up, CMAP amplitude in left peroneal nerves, tibial nerves, femoral nerve and ulnar nerves had relationship with HFMSE(Table 5)，after adjusting for age and sex. CMAP amplitude in median nerve had no relationship with HFMSE( P >0.05)，after adjusting for age and sex. Table 5 The relationship between CMAP and HFMSE at follow-up. HFMSE follow-up The follow-up CMAP P Left peroneal nerves (IQR), mV(n=19) 30.79±18.63 2.90(1.28-4.15) 0.004 1 Left tibial nerves (IQR), mV(n=19) 30.79±18.63 3.70(1.01-6.85) 0.005 1 Left femoral nerve (IQR), mV (n=19) 30.79±18.63 0.16(0.93-1.11) 0.001 1 Median nerve (IQR), mV(n=19) 30.79±18.63 7.05±4.22 0.313 2 Ulnar nerve (IQR), mV (n=19) 30.79±18.63 3.10（0.96-6.55） 0.000 1 1 Spearman, 2 Pearson. Abbreviation CMAP, compound muscle action potentials; HFMSE Hammersmith Functional Motor Scale Expanded. Prediction of change of motor function using CMAP amplitude in nerves We used the baseline CMAP amplitude to predict the change of motor function in HFMSE. The duration from onset to therapy defined CMAP amplitude in ulnar nerve can predict the change of motor function(p=0.012) , while other nerve CMAP amplitude at baseline can not predict the change of motor function(P>0.05). Table 6 Simple linear regression between nerve and motor improvement in SMA patients（n=21）. B Standard error t p -value 95%CI The duration from onset to therapy -0.164 0.028 -5.800 0.000 -0.223-0.104 Ulnar CMAP at baseline 1.356 0.484 2.802 0.012 0.339-2.372 Abbreviation CMAP, compound muscle action potentials; HFMSE Hammersmith Functional The correlation between the baseline Crn and disease severity and CMAP amplitude At baseline, there were 32 patients had Crn , among these, 16 patients had low level of Crn according to the standard reference range in our hospital. At follow-up, there were 26 patients had Crn, among these, 15 patients had low level of Crn. At baseline, there were 29 patients had ulnar CMAP and Crn , a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.000, r=0.704) after adjusting for age and sex, there were 27 patients had HFMSE and Crn at baseline, a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.001, r=0.683) after adjusting for age and sex. However, Crn at baseline can not predict the change of motor function in follow-up (Table 6). 21 patients had Crn at baseline and motor functional at baseline(13.50(12.30-16.50)) and follow-up(19.30(14.10-23.60)), and there were statistical difference between the baseline and follow-up Crn(P=0.000). In the follow-up, there were 21 patients had HFMSE and Crn, a positive correlation was found between Crn and HFMSE at follow-up (p=0.001, r=0.679) after adjusting for age and sex, there were 22 patients had ulnar CMAP and Crn at follow-up, a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.015, r=0.533) after adjusting for age and sex. Discussion At the follow-up stage, CMAP amplitudes of the ulnar, median, tibial, and peroneal nerves demonstrated improvement. In the context of SMA, following Nusinersen therapy, the CMAP amplitude of the femoral nerve did not show any statistically significant improvement. This finding aligns well with the underlying pathology of SMA. It is known that in SMA patients, the lower limbs are generally more severely affected compared to the upper limbs, as previously reported [10]. Moreover, in SMA, the involvement of proximal nerves is more pronounced than that of the distal parts. Given these characteristics, in order to attain more favorable therapeutic outcomes after Nusinersen treatment, rehabilitation therapy should prioritize the proximal nerves of the lower limbs. By focusing rehabilitation efforts on these more severely affected areas, it may be possible to better support nerve function recovery and enhance overall motor function in SMA patients undergoing Nusinersen therapy. The correlation between CMAP amplitude and motor scores has been previously documented in the literature[10]. In our investigation, the CMAP amplitudes of all the nerves examined were found to be related to the HFMSE at baseline. However, at the follow-up stage, except for the median nerve, the CMAP amplitudes of most of the nerves maintained a relationship with the HFMSE. The differences between our study and the previous manuscript can likely be attributed to several factors. Firstly, our study cohort encompassed patients with SMA types 1-3, whereas the previous research only included patients with SMA type 2. Secondly, in our study, we utilized the HFMSE to evaluate motor function, while the previous study employed the Motor Function Measure[10]. Regarding the lack of a relationship between the CMAP amplitude of the median nerve and the HFMSE at follow-up, potential explanations may involve phenomena such as "reverse split hand" and muscle contracture in the upper limbs. These factors could disrupt the expected association between the CMAP amplitude of the median nerve and the HFMSE scores, highlighting the complexity of the neuromuscular manifestations in SMA and the need for further in-depth exploration. As several other manuscripts reported[2, 6, 16-18], there is an improvement in motor function during gene therapy in SMA. The motor scores, such as HFMSE and RULM, showed enhancements from the baseline to the follow-up. This indicates the effectiveness of the therapy, and it is paralleled by the improvement in amplitude of CMAP between the baseline and follow-up. The RULM is used to evaluate motor scores related to the function of the upper limbs. Both the median and ulnar nerves are nerves of the upper limbs. Interestingly, among them, only the ulnar nerve was found to have a relationship with the RULM. Moreover, the ulnar nerve not only demonstrated an association with the RULM but also with the HFMSE. This finding is consistent with previous studies[8, 12], which further validates the significance of the ulnar nerve as a potential indicator in assessing motor function in SMA patients undergoing therapy. Prognostic factors are crucial parameters in SMA as they can help monitor and predict better outcomes for patients. In previous research, the distal amplitude of the CMAP, motor functional scales, and the timely implementation of diagnosis and treatment have all been recognized as key factors contributing to a better prognosis[8]. In another investigation, it was found that early initiation of treatment, the presence of mild bone and joint complications, and consistent engagement in regular rehabilitation training were associated with improved outcomes for SMA patients[19]. In the context of Onasemnogene Abeparvovec therapy for SMA, a novel scoring system that combines CMAP amplitudes and motor scores has been developed. This system suggests that a median CMAP amplitude exceeding 0.5 mV at baseline may serve as a predictor of better motor recovery[11]. Furthermore, the distal amplitude of the CMAP in the ulnar nerve has shown statistical significance in indicating motor improvement in SMA patients in our investigation. This finding is in line with previous studies[8, 11], reinforcing the importance of the ulnar nerve's CMAP amplitude as a valuable prognostic indicator in the assessment and management of SMA. Crn plays a vital and indispensable role in maintaining the proper function of skeletal muscle, as previously reported [14]. At baseline, half of patients had low level of Crn, most of patients had low level of Crn at follow-up. Low level of Crn most likely caused by the reduced muscle mass due to the remarkable muscle atrophy and/or impaired muscle energy metabolism due to the leakage of different cytosolic components[20, 21]. In our study, Crn levels were associated with motor performance and ulnar CMAP amplitude after adjusting for age and sex effects. Considering the positive correlation between Crn levels and disease severity at baseline and follow-up, Crn concentrations could serve as a valuable tool for evaluating the therapeutic effectiveness of disease-modifying treatments. The limitations of this manuscript are as follows. One is the absence of data regarding the proximal function of the upper limbs, specifically concerning the accessory and musculocutaneous nerves. Additionally, only three cases of SMA type 1 had available follow-up data. The scarcity of data for SMA type I represents a major limitation of this manuscript. Moreover, the inconsistent timing of the follow-up evaluations also constitutes a limitation within the scope of this manuscript. In conclusion, for patients with SMA who were treated with nusinersen, notable improvements in motor scores were observed. The amplitudes of the left tibial, peroneal, ulnar, and median nerves demonstrated enhancements following nusinersen treatment. Both at the baseline assessment and during the follow-up period, the left tibial, peroneal, ulnar, and femoral nerves showed correlations with the HFMSE. After accounting for the effects of age and sex, Crn were found to be associated with motor performance and the ulnar CMAP amplitude. The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients. Abbreviations IQR interquartile range SMA spinal muscular atrophy SMN survival motor neuron HFMSE Hammersmith Functional Motor Scale Expanded RULM Revised Upper Limb Module CHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders Crn Creatinine Declarations Acknowledgements We are grateful to the doctor in neurology department for their contributions to the study. Author contributions Concept, design and analysis: rui di SUN, F.Z and PP.W. Interpretation of data: rui di SUN, J.J and XQ.L. Drafting of the manuscript: rui di SUN, F.Z and PP.W. Statistical analysis: rui di SUN, J.J and XQ.L. Supervision: J.J and XQ.L. All authors read and approved the final manuscript. CONFLICT OF INTEREST The authors have no conflicts of interest to declare. Funding This work was supported by Hubei Provincial Science and Technology Plan Project for Clinical Research Center of Neurodevelopment Disorders in Children (No.2022DCC020) Ethics approval and consent to participate The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Wuhan Children’s Hospital (2021R110-E02). Written informed consent was obtained from participants or their parents or guardians. Clinical trial number : not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article [and its supplementary information files]. References Kolb SJ, Kissel JT. Spinal Muscular Atrophy. 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Osredkar D, Jílková M, Butenko T, Loboda T, Golli T, Fuchsová P, et al. Children and young adults with spinal muscular atrophy treated with nusinersen. Eur J Pediatr neurology: EJPN : official J Eur Pediatr Neurol Soc. 2021;30:1–8. PubMed PMID: 33307321. Hagenacker T, Wurster CD, Günther R, Schreiber-Katz O, Osmanovic A, Petri S, et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol. 2020;19(4):317–25. 10.1016/s1474-4422(20)30037-5 . PubMed PMID: 32199097. Coratti G, Cutrona C, Pera MC, Bovis F, Ponzano M, Chieppa F et al. Motor function in type 2 and 3 SMA patients treated with Nusinersen: a critical review and meta-analysis. Orphanet journal of rare diseases. 2021;16(1):430. 10.1186/s13023-021-02065-z . PubMed PMID: 34645478. Peng Y, Feng L, Wu J, Zhou Q, Liu H, Chen J, et al. Motor function and compound muscle action potential amplitude in children with spinal muscular atrophy treated with nusinersen. Brain Dev. 2025;47(1):104316. 10.1016/j.braindev.2024.104316 . PubMed PMID: 39787994. Chiò A, Calvo A, Bovio G, Canosa A, Bertuzzo D, Galmozzi F, et al. Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study. JAMA Neurol. 2014;71(9):1134–42. 10.1001/jamaneurol.2014.1129 . Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107–213. 10.1152/physrev.2000.80.3.1107 . Additional Declarations No competing interests reported. Supplementary Files SMAdatas.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6686700","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471761651,"identity":"67a37baa-e51c-4403-8873-3f28f97ae36b","order_by":0,"name":"Ruidi Sun","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Ruidi","middleName":"","lastName":"Sun","suffix":""},{"id":471761652,"identity":"31741478-edcb-4954-a80a-75aa3f544f75","order_by":1,"name":"feng Zhang","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"feng","middleName":"","lastName":"Zhang","suffix":""},{"id":471761654,"identity":"c653803a-dbc5-47c4-a2b7-9faf50233525","order_by":2,"name":"Peipei Wei","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Peipei","middleName":"","lastName":"Wei","suffix":""},{"id":471761657,"identity":"075197cb-7e49-41b5-9e84-939d0a50a3fe","order_by":3,"name":"Xiaoqing Luo","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqing","middleName":"","lastName":"Luo","suffix":""},{"id":471761658,"identity":"94ec9b68-345c-4d2c-87e2-b5164281e692","order_by":4,"name":"jun Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACxmYQyQMimA8c+PCDNC1siQdn9pBmIY/xYQ42ItQxtzM/e/hF5nCe/LQzHw4DrZPnFztAyGFs5sYyPIeLGWfnbjhcYMFgOHN2AiEtDGbSEjyHE5ulgVpm8DAkGNwmqIX9G1hLm3TOg8M8bERp4TGT/ADU0iOdw0C0ljJpBp70xBnSaQbAQJYg7BfD/uPbJH/2WCfOn538+MOHHzby/NKEtDQAA5oXEYMS+JWDgDzIcT+ISSejYBSMglEwcgEA5AZCVAsbi0MAAAAASUVORK5CYII=","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"jun","middleName":"","lastName":"Jiang","suffix":""}],"badges":[],"createdAt":"2025-05-17 11:38:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6686700/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6686700/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101294042,"identity":"5691943e-8d8b-47d3-816f-b6f626c00f5f","added_by":"auto","created_at":"2026-01-28 08:44:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":626877,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6686700/v1/8d8f0c74-d471-4673-b524-044c476d07ef.pdf"},{"id":84824288,"identity":"b13adeac-00f4-414a-85f5-0d51f9b46cbd","added_by":"auto","created_at":"2025-06-17 16:46:32","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":31936,"visible":true,"origin":"","legend":"","description":"","filename":"SMAdatas.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6686700/v1/fa7d468ad6c85ac6da359cb2.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The utility of compound muscle action potential and creatinine in childhood spinal muscle atrophy","fulltext":[{"header":"Background","content":"\u003cp\u003eSpinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder precipitated by mutations in the survival motor neuron 1 gene (SMN1). The underlying pathology of SMA is characterized by the degeneration of α-motor neurons in the spinal cord and brainstem. Based on motor function, SMA has been classified into types 0-IV[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Clinically, SMA is manifested by muscle atrophy and affects multiple organ systems, presenting a complex and challenging disease profile.\u003c/p\u003e \u003cp\u003eSince 2016, the US Food and Drug Administration has approved three disease-modifying therapies, namely Nusinersen, risdiplam, and Onasemnogene abeparvovec, for the treatment of SMA. Given the significant heterogeneity in patients' responses to Nusinersen treatment, there is an urgent need for sensitive biomarkers in SMA to accurately evaluate the beneficial effects of these therapeutic interventions. Motor function scores, which have been widely used in therapeutic trials, are subject to evaluator subjectivity. Additionally, issues such as ceiling and floor effects associated with the scoring scales have been reported[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe compound muscle action potential (CMAP) represents the electrophysiological activity of a muscle or a group of muscles when a peripheral nerve is stimulated at a supramaximal level[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. CMAP has emerged as a valuable tool for assessing treatment efficacy in SMA. Changes in CMAP have been observed in symptomatic infants as well as in patients with later-onset forms of the disease following therapeutic intervention[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. For instance, in pediatric SMA patients after two years of Nusinersen treatment, a strong correlation was found between the CMAP amplitude of the ulnar nerve and motor scores[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In adolescent and adult SMA patients, Nusinersen has been shown to effectively improve both motor function and electrophysiological parameters[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In type 2 SMA patients, routine follow-up using CMAP measurements of the median nerve has demonstrated clear improvements with Nusinersen treatment [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, baseline CMAP amplitudes were associated with motor function outcomes after AVXS-101 (Onasemnogene Abeparvovec) therapy, and both CMAP amplitudes and motor scores were found to be predictive of motor outcomes following this treatment[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Even in SMA patients without gene therapy, the maximum ulnar CMAP amplitude has been shown to correlate well with motor function, suggesting its potential value in monitoring disease status [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, most existing literature primarily focuses on the correlation between CMAP amplitude and motor scores, while the predictive value of the baseline CMAP amplitude remains largely unexplored.\u003c/p\u003e \u003cp\u003eCreatinine (Crn) plays a crucial role in maintaining skeletal muscle function and is closely associated with muscle mass, activity levels, and metabolic rate[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A study in adult SMA patients investigated the relationship between Crn levels, disease severity, and the amplitude of the ulnar CMAP[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These findings suggest that Crn could potentially serve as a biomarker for assessing disease severity in adolescent and adult SMA patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A previous study indicated that reduced Crn levels are indicative of disease severity in SMA types 1\u0026ndash;3, encompassing both pediatirics and adult patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Nevertheless, the potential role of Crn as a biomarker for muscle denervation and motor function in pediatric SMA patients remains to be elucidated.\u003c/p\u003e \u003cp\u003eTherefore, further research is essential to determine whether serum Crn levels are associated with muscle denervation and motor function in childhood SMA. Additionally, it is necessary to explore the potential of CMAP and Crn levels as reliable biomarkers for accurately assessing disease severity and predicting improvements in pediatric SMA patients following Nusinersen treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective, observational study. Between January 1, 2021, and January 1, 2025, patients with symptomatic, genetically confirmed SMA (homozygous SMN1 exon 7 deletions as well as c.22dupA\u0026nbsp;mutation) were enrolled at the Wuhan Children’s Hospital. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP-INTEND) (score, 0–64) was available for children with type 1 SMA who were less than 38 months old,\u0026nbsp;Hammersmith Functional Motor Scale Expanded (HFMSE)\u0026nbsp;(score, 0–66) was used for children with type 2 and 3 SMA, and\u0026nbsp;Revised Upper Limb Module (RULM)RULM (score, 0–37) was used for children with SMA who were older than three years of age.\u0026nbsp;The change of motor function scores defined as difference between follow-up and baseline motor function scores. The demographic features and creatinine(Crn) level in serum parameters, were obtained from the clinical laboratory data in the electronic medical records system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectrophysiological examination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElectrophysiological examinations were conducted using a four-channel Keypoint electromyograph, with no sedation administered. The recorded distal skin temperature was between 36.5 and 37°C in all children. Surface electrodes were used. Active recording electrodes were placed at different muscles to measure the potential of corresponding nerves: the muscle bellies of the abductor pollicis brevis for the median nerve, the abductor digiti minimi for the ulnar nerve, the adductor hallucis for the tibial nerve, the extensor digitorum brevis for the peroneal nerve, and the vastus intermedius for the femoral nerve. The left nerves in lower limbs and unilateral nerves in upper limbs (the more severe side if clinical feature was asymmetrical or the left side if clinical feature was symmetrical) were selected in SMA. Patients who had at least two nerves tested were included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Wuhan Children’s Hospital (2021R110-E02). Written informed consent was obtained from participants or their parents or guardians. Clinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS version 20.0 software. Continuous data are expressed as the means and standard deviations(SD) if\u0026nbsp;normally\u0026nbsp;distributed or\u0026nbsp;medians\u0026nbsp;and interquartile ranges (IQRs) if non-normally distributed.\u0026nbsp;The Mann–Whitney U test or Kruskal–Wallis test was used for comparing two or more groups for non-normal distribution data, respectively. The spearman was used for correlation Analysis for non- normal distribution data and Pearson was used for normal distribution data. The paired t-test was used to compare between two groups for normal distribution data and Wilcoxon test was used for non-normal distribution data\u003cem\u003e.\u003c/em\u003e Partial rank correlation was conducted to correct for age, gender, and analyze the correlation between Crns , CMAP and HFMSE. A linear mixed-effects model was utilized to establish the relationship between CMAP at baseline and changes in motor function by controlling for the duration from onset to therapy. P-values of \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 40 patients who had their compound muscle action potential (CMAP) amplitude and motor scores measured at baseline. At the follow-up stage, five patients did not undergo the disease-modifying treatment with nusinersen. Specifically, three of these patients did not receive any disease-modifying treatment, and two patients received risdiplam therapy instead. Additionally, nine patients did not have their CMAP amplitude and motor scores data recorded during the follow-up therapy period. Four patients only had their motor scores available during the follow-up therapy, while 22 patients had both their CMAP amplitude and motor scores measured during the follow-up therapy. The baseline characteristics of the spinal muscular atrophy (SMA) patients are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Baseline characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (N=40)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOnset age, median (IQR), months(n=40)\u003c/p\u003e\n \u003cp\u003eNusinersen therapy age (IQR), months(n=35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8(6-12)\u003c/p\u003e\n \u003cp\u003e56(13-102)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17(42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSMA type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFunctional classification at initial therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNon-sitters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14(35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSitters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWalkers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHFMSE median\u0026nbsp;(SD), months(n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.50±17.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRULM median\u0026nbsp;(SD), months(n=17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23.29±11.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCHOP-INTEND\u0026nbsp;median (SD), months(n=10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.20±12.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSMN copy number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNerve measured for compound muscle action potential\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft peroneal nerves (IQR), mv(n=40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.74(0.49-2.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft tibial nerve (IQR), mv (n=39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.41(0.24-4.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft femoral nerve (IQR), mv (n=39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.00(0.00-0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian nerve (IQR), mv (n=38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.25±4.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar nerve (IQR), mv (n=38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.15±2.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are n (%) unless indicated otherwise\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eIQR interquartile range, SMA spinal muscular atrophy, SMN survival motor neuron, HFMSE Hammersmith Functional Motor Scale Expanded,\u0026nbsp;RULM\u0026nbsp;Revised Upper Limb Module,\u0026nbsp;CHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were 26 patients who underwent follow-up. Among these patients, 4 had only motor scores available, while 22 had both motor scores and compound muscle action potential (CMAP) amplitude data recorded (Table 2). The number of intrathecal injections during the follow-up period was 10, with a range of 8 to 11 injections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Follow-up characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (N=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8(31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSMA type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14 (53.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFunctional classification at follow-up\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNon-sitters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSitters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18(69.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWalkers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe intrathecal injection time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10(8-11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHFMSE (n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.57±17.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRULM(n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34(27-37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCHOP-INTEND(n=3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61±3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSMN copy number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11 (42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNerve measured for compound muscle action potential\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft peroneal nerves (IQR), mv(n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.45(1.09-4.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft tibial nerve (IQR), mv (n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.30(1.16-7.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft femoral nerve (IQR), mv (n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.395(0.10-1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian nerve (IQR), mv (n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.59±4.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar nerve (IQR), mv (n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.09(0.86-6.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are n (%) unless indicated otherwise\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eIQR interquartile range, SMA spinal muscular atrophy, SMN survival motor neuron, HFMSE Hammersmith Functional Motor Scale Expanded,\u0026nbsp;RULM\u0026nbsp;Revised Upper Limb Module,\u0026nbsp;CHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe comparison between CMAP and motor function at baseline and follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were significant difference between baseline and follow-up in left peroneal nerve, left tibial nerve, median nerve and ulnar nerve(\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). There was no significant difference in left femoral nerve between baseline and follow-up(Table 3).\u003c/p\u003e\n\u003cp\u003eThere were 23 patients had baseline HFMSE and follow-up, 12 patients had baseline RULM and follow-up, three patients had CHOP-INTEND baseline(12±7.21) and follow-up(61±3.61). Baseline HFMSE was 20.04±15.98 and follow-up was 30.57±17.66, baseline RULM was 23.77±10.85 and follow-up was 34(27-37). There were statistical significant difference between baseline and follow-up in HFMSE(p\u0026lt;0.001) and RULM(P=0.008).\u003c/p\u003e\n\u003cp\u003eTable 3 \u0026nbsp;The comparison between CMAP at baseline and follow-up\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe baseline CMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFollow-up CMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft peroneal nerves (IQR), mv(n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.875(0.82-4.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.45(1.09-4.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.027\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft tibial nerves (IQR), mv(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.2(0.29-5.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.20(1.52-5.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.005\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft femoral nerve (IQR), mv (n=18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.12(0.00-0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.37(0.04-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.205\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian nerve (IQR), mv (n=20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.45(1.65-6.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.72±4.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.008\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar nerve (IQR), mv (n=21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.55(0.32-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.09(0.81-5.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.003\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eWilcoxon test\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eIQR, interquartile range; CMAP compound muscle action potentails.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe relationship between CMAP and motor scores.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe also compare RULM at baseline and CMAP amplitude in median nerve and ulnar nerve, there was 16 patients had RULM and CMAP value. RULM scores was 22.44±10.84, median nerve CMAP amplitude was 6.39±4.07mV, ulnar nerve CMAP amplitude was 3.83±3.54mV, there was statistical difference between RULM and ulnar nerve CMAP amplitude at baseline(\u003cem\u003eP\u003c/em\u003e=0.012)，after adjusting for age and sex. There was no statistical difference between RULM and median nerve CMAP amplitude at baseline(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eTen patients had CHOP-Intend, the average score was 14.20±12.99. Ten patients had peroneal nerve CMAP amplitude, the average CMAP amplitude was 0.23(0.00-0.49)mV, nine patients had tibial and femoral nerve CMAP amplitude, the average CMAP amplitude were 0.17(0.12-0.26)mV and 0(0-0)mV respectively, there were no statistical difference between CMAP amplitude in lower limbs and CHOP-Intend(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eTen patients had ulnar nerve CMAP amplitude and CHOP-Intend , the average CMAP amplitude was 0.06(0.00-0.34)mV, nine patients had median nerve CMAP amplitude and CHOP-Intend, the average CMAP amplitude was 0.067(0.039-0.27)mV, there were no statistical difference between CMAP amplitude in upper limbs and CHOP-Intend(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eAt baseline, there were statistical relationship between CMAP and HFMSE after adjusting for age and sex (Table 4).\u003c/p\u003e\n\u003cp\u003eTable 4 \u0026nbsp;The relationship between CMAP and HFMSE at baseline\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHFMSE at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe baseline CMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft peroneal nerves (IQR), mv(n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18(6-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.145(1.40-3.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.024\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft tibial nerves (IQR), mv(n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18(6-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.40(0.97-5.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.000\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft femoral nerve (IQR), mv (n=30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18(6-30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.26(0.00-0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.000\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian nerve (IQR), mv (n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18（6-30）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.20（2.70-6.60）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.009\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar nerve (IQR), mv (n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17.50（6-30）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.825（0.33-4.10）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.000\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1 \u0026nbsp;\u003c/sup\u003eSpearman,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eIQR, interquartile range;\u0026nbsp;CMAP, compound muscle action potentials; HFMSE Hammersmith Functional Motor Scale Expanded\u003c/p\u003e\n\u003cp\u003eAt follow-up, CMAP amplitude in left peroneal nerves, tibial nerves, femoral nerve and ulnar nerves had relationship with HFMSE(Table 5)，after adjusting for age and sex. CMAP amplitude in median nerve had no relationship with HFMSE(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05)，after adjusting for age and sex.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5 \u0026nbsp;The relationship between CMAP and HFMSE at follow-up.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHFMSE follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe follow-up CMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft peroneal nerves (IQR), mV(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.79±18.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.90(1.28-4.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.004\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft tibial nerves (IQR), mV(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.79±18.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.70(1.01-6.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.005\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft femoral nerve (IQR), mV (n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.79±18.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.16(0.93-1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian nerve (IQR), mV(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.79±18.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.05±4.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.313\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar nerve (IQR), mV (n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30.79±18.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.10（0.96-6.55）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.000\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1 \u0026nbsp;\u003c/sup\u003eSpearman,\u0026nbsp;\u003csup\u003e2\u0026nbsp;\u003c/sup\u003ePearson.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eCMAP, compound muscle action potentials; HFMSE Hammersmith Functional Motor Scale Expanded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrediction of change of motor function using CMAP amplitude in nerves\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used the baseline CMAP amplitude to predict the change of motor function in HFMSE. The duration from onset to therapy defined CMAP amplitude in ulnar nerve can predict the change of motor function(p=0.012) , while other nerve CMAP amplitude at baseline can not predict the change of motor function(P\u0026gt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 6 Simple linear regression between nerve and motor improvement in SMA patients（n=21）.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"617\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStandard\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eerror\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e95%CI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThe duration from onset to therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-5.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.223-0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUlnar CMAP at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.339-2.372\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eAbbreviation\u0026nbsp;\u003c/em\u003eCMAP, compound muscle action potentials; HFMSE Hammersmith Functional\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe correlation between the baseline Crn and disease severity and CMAP amplitude\u003c/p\u003e\n\u003cp\u003eAt baseline, there were 32 patients had Crn , among these, 16 patients had low level of Crn according to the standard reference range in our hospital. At follow-up, there were 26 patients had Crn, among these, 15 patients had low level of Crn. At baseline, there were 29 patients had ulnar CMAP and Crn , a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.000, r=0.704) after adjusting for age and sex, there were 27 patients had HFMSE and Crn at baseline, a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.001, r=0.683) after adjusting for age and sex. However, Crn at baseline can not predict the change of motor function in follow-up (Table 6).\u003c/p\u003e\n\u003cp\u003e21 patients had Crn at baseline and motor functional at baseline(13.50(12.30-16.50)) and follow-up(19.30(14.10-23.60)), and there were statistical difference between the baseline and follow-up Crn(P=0.000). In the follow-up, there were 21 patients had HFMSE and Crn, a positive correlation was found between Crn and HFMSE at follow-up (p=0.001, r=0.679) after adjusting for age and sex, there were 22 patients had ulnar CMAP and Crn at follow-up, a positive correlation was found between Crn and ulnar nerve CMAP at baseline(p=0.015, r=0.533) after adjusting for age and sex.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAt the follow-up stage, CMAP amplitudes of the ulnar, median, tibial, and peroneal nerves demonstrated improvement. In the context of SMA, following Nusinersen therapy, the CMAP amplitude of the femoral nerve did not show any statistically significant improvement. This finding aligns well with the underlying pathology of SMA. It is known that in SMA patients, the lower limbs are generally more severely affected compared to the upper limbs, as previously reported [10]. Moreover, in SMA, the involvement of proximal nerves is more pronounced than that of the distal parts.\u003c/p\u003e\n\u003cp\u003eGiven these characteristics, in order to attain more favorable therapeutic outcomes after Nusinersen treatment, rehabilitation therapy should prioritize the proximal nerves of the lower limbs. By focusing rehabilitation efforts on these more severely affected areas, it may be possible to better support nerve function recovery and enhance overall motor function in SMA patients undergoing Nusinersen therapy.\u003c/p\u003e\n\u003cp\u003eThe correlation between CMAP amplitude and motor scores has been previously documented in the literature[10]. In our investigation, the CMAP amplitudes of all the nerves examined were found to be related to the HFMSE at baseline. However, at the follow-up stage, except for the median nerve, the CMAP amplitudes of most of the nerves maintained a relationship with the HFMSE.\u003c/p\u003e\n\u003cp\u003eThe differences between our study and the previous manuscript can likely be attributed to several factors. Firstly, our study cohort encompassed patients with SMA types 1-3, whereas the previous research only included patients with SMA type 2. Secondly, in our study, we utilized the HFMSE to evaluate motor function, while the previous study employed the Motor Function Measure[10].\u003c/p\u003e\n\u003cp\u003eRegarding the lack of a relationship between the CMAP amplitude of the median nerve and the HFMSE at follow-up, potential explanations may involve phenomena such as \"reverse split hand\" and muscle contracture in the upper limbs. These factors could disrupt the expected association between the CMAP amplitude of the median nerve and the HFMSE scores, highlighting the complexity of the neuromuscular manifestations in SMA and the need for further in-depth exploration.\u003c/p\u003e\n\u003cp\u003eAs several other manuscripts reported[2, 6, 16-18], there is an improvement in motor function during gene therapy in SMA. The motor scores, such as HFMSE and RULM, showed enhancements from the baseline to the follow-up. This indicates the effectiveness of the therapy, and it is paralleled by the improvement in amplitude of CMAP between the baseline and follow-up.\u003c/p\u003e\n\u003cp\u003eThe RULM is used to evaluate motor scores related to the function of the upper limbs. Both the median and ulnar nerves are nerves of the upper limbs. Interestingly, among them, only the ulnar nerve was found to have a relationship with the RULM. Moreover, the ulnar nerve not only demonstrated an association with the RULM but also with the HFMSE. This finding is consistent with previous studies[8, 12], which further validates the significance of the ulnar nerve as a potential indicator in assessing motor function in SMA patients undergoing therapy.\u003c/p\u003e\n\u003cp\u003ePrognostic factors are crucial parameters in SMA as they can help monitor and predict better outcomes for patients. In previous research, the distal amplitude of the CMAP, motor functional scales, and the timely implementation of diagnosis and treatment have all been recognized as key factors contributing to a better prognosis[8].\u003c/p\u003e\n\u003cp\u003eIn another investigation, it was found that early initiation of treatment, the presence of mild bone and joint complications, and consistent engagement in regular rehabilitation training were associated with improved outcomes for SMA patients[19]. In the context of Onasemnogene Abeparvovec therapy for SMA, a novel scoring system that combines CMAP amplitudes and motor scores has been developed. This system suggests that a median CMAP amplitude exceeding 0.5 mV at baseline may serve as a predictor of better motor recovery[11].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, the distal amplitude of the CMAP in the ulnar nerve has shown statistical significance in indicating motor improvement in SMA patients in our investigation. This finding is in line with previous studies[8, 11], reinforcing the importance of the ulnar nerve's CMAP amplitude as a valuable prognostic indicator in the assessment and management of SMA.\u003c/p\u003e\n\u003cp\u003eCrn plays a vital and indispensable role in maintaining the proper function of skeletal muscle, as previously reported\u0026nbsp;[14]. At baseline, half of patients had low level of Crn, most of patients had low level of Crn at follow-up. Low level of Crn most likely caused by the reduced muscle mass due to the remarkable muscle atrophy and/or impaired muscle energy metabolism due to the leakage of different cytosolic components[20, 21]. In our study, Crn levels were associated with motor performance and ulnar CMAP amplitude after adjusting for age and sex effects. Considering the positive correlation between Crn levels and disease severity at baseline and follow-up, Crn concentrations could serve as a valuable tool for evaluating the therapeutic effectiveness of disease-modifying treatments.\u003c/p\u003e\n\u003cp\u003eThe limitations of this manuscript are as follows. One is the absence of data regarding the proximal function of the upper limbs, specifically concerning the accessory and musculocutaneous nerves. Additionally, only three cases of SMA type 1 had available follow-up data. The scarcity of data for SMA type I represents a major limitation of this manuscript. Moreover, the inconsistent timing of the follow-up evaluations also constitutes a limitation within the scope of this manuscript.\u003c/p\u003e\n\u003cp\u003eIn conclusion, for patients with SMA who were treated with nusinersen, notable improvements in motor scores were observed. The amplitudes of the left tibial, peroneal, ulnar, and median nerves demonstrated enhancements following nusinersen treatment. Both at the baseline assessment and during the follow-up period, the left tibial, peroneal, ulnar, and femoral nerves showed correlations with the HFMSE. After accounting for the effects of age and sex, Crn were found to be associated with motor performance and the ulnar CMAP amplitude. The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIQR interquartile range\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSMA spinal muscular atrophy\u003c/p\u003e\n\u003cp\u003eSMN survival motor neuron\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHFMSE Hammersmith Functional Motor Scale Expanded\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRULM\u0026nbsp;Revised Upper Limb Module\u003c/p\u003e\n\u003cp\u003eCHOP-INTEND The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders\u003c/p\u003e\n\u003cp\u003eCrn \u0026nbsp;Creatinine\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe are grateful to the doctor in neurology department for their contributions to the study.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eConcept, design and analysis: rui di SUN, F.Z and PP.W. Interpretation of data: rui di SUN, J.J and XQ.L. Drafting of the manuscript: rui di SUN, F.Z and PP.W. Statistical analysis: rui di SUN, J.J and XQ.L. Supervision: J.J and XQ.L. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch3\u003eCONFLICT OF INTEREST\u0026nbsp;\u003c/h3\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis work was supported by Hubei Provincial Science and Technology Plan Project for Clinical Research Center of Neurodevelopment Disorders in Children (No.2022DCC020)\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Wuhan Children\u0026rsquo;s Hospital (2021R110-E02). Written informed consent was obtained from participants or their parents or guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurol Clin. 2015;33(4):831\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ncl.2015.07.004\u003c/span\u003e\u003cspan address=\"10.1016/j.ncl.2015.07.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 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Physiol Rev. 2000;80(3):1107\u0026ndash;213. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1152/physrev.2000.80.3.1107\u003c/span\u003e\u003cspan address=\"10.1152/physrev.2000.80.3.1107\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"spinal muscle atrophy, pediatrics, compound muscle atrophy, creatinine","lastPublishedDoi":"10.21203/rs.3.rs-6686700/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6686700/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder precipitated by mutations in the survival motor neuron 1 gene (SMN1). Given the significant heterogeneity in patients' responses to Nusinersen treatment, there is an urgent need for sensitive biomarkers in SMA to accurately evaluate the beneficial effects of these therapeutic interventions. We explored the association between motor scores and serum creatinine (Crn) levels and compound muscle action potential(CMAP) in SMA patients undergoing treatment with nusinersen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eWe measured serum Crn levels, CMAP amplitude and Hammersmith Functional Motor Scale-Expanded (HFMSE), including 40 pediatrics patients with SMA. The association between Crn ,CMAP and motor scores was investigated through partial rank correlation analysis and linear mixed models.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e 40 pediatrics patients were included. Among them, 35 patients had Nusinersen treatment. Nine patients did not have their CMAP amplitude and motor scores data recorded during the follow-up therapy period. Four patients only had their motor scores available during the follow-up therapy, while 22 patients had both their CMAP amplitude and motor scores measured during the follow-up therapy. Except for femoral nerve, the amplitudes of the left tibial, peroneal, ulnar, and median nerves demonstrated enhancements following nusinersen treatment(P\u0026lt;0.05), as well as HFMSE. Both at the baseline assessment and during the follow-up period, the left tibial, peroneal, ulnar, and femoral nerves showed correlations with the HFMSE(p\u0026lt;0.05). After accounting for the effects of age and sex, Crn were found to be associated with motor scores and the ulnar CMAP amplitude at baseline and follow-up(p\u0026lt;0.05). The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients(p=0.012).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e In conclusion, for patients with SMA who were treated with nusinersen, notable improvements in motor scores and CMAP were observed. Crn at baseline and follow-up had relationship with HFMSE. The CMAP amplitude of the ulnar nerve at baseline exhibited predictive value in indicating motor function improvement in SMA patients.\u003c/p\u003e","manuscriptTitle":"The utility of compound muscle action potential and creatinine in childhood spinal muscle atrophy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 16:46:27","doi":"10.21203/rs.3.rs-6686700/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e430c4ae-0e6d-4aab-9234-564f3e3fb4e4","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-28T08:43:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 16:46:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6686700","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6686700","identity":"rs-6686700","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}