Pub Date : 2024-02-07DOI: 10.1016/j.braindev.2024.01.001
Constanze Weber , Anne Müller , Maren Freigang , Maja von der Hagen , René Günther
Background
Innovative RNA modifying and gene replacement therapies are currently revolutionizing the therapeutic landscape in 5q-associated spinal muscular atrophy (SMA). In order to provide individual recommendations for choice of treatment and therapy (dis-) continuation, objective outcome measures are needed. The purpose of this study was to determine whether maximum isometric voluntary grip and finger flexion strength is a useful sensitive outcome measure in children and adult patients with SMA.
Methods
In this non-interventional, longitudinal pilot study, we assessed grip and finger flexion strength on 39 patients with SMA II and III (n = 16 children, mean age = 10.0; n = 23 adults, mean age = 38.4) using the Weber hand and finger dynamometer HFD 200. Grip and finger flexion strength, clinical examinations and motor function scores (Revised Upper Limb Module, Hammersmith Functional Motor Scale Expanded) were assessed over a 12-month treatment period concurrent with the nusinersen treatment.
Results
Grip and finger flexion strength was highly associated with motor function and disease severity, SMA type and SMN2 copy number. During nusinersen treatment, grip and finger flexion strength significantly increased in children and adults with SMA.
Conclusion
Grip and finger flexion strength measured with the HFD 200 is a promising sensitive outcome measure for SMA.
背景：目前，创新的 RNA 修饰和基因替代疗法正在彻底改变 5q 相关性脊髓性肌萎缩症（SMA）的治疗格局。为了提供有关治疗选择和治疗（中断）持续性的个人建议，需要客观的结果测量。本研究的目的是确定最大等距自主握力和手指屈曲力是否是衡量儿童和成年 SMA 患者疗效的有用敏感指标：在这项非干预性纵向试验研究中，我们使用韦伯手部和手指测力计 HFD 200 评估了 39 名 II 期和 III 期 SMA 患者（n = 16 名儿童，平均年龄 = 10.0 岁；n = 23 名成人，平均年龄 = 38.4 岁）的握力和手指屈曲力。在12个月的治疗期内，在使用奴西那森治疗的同时，还对握力和手指屈伸力、临床检查和运动功能评分（修订的上肢模块、哈默史密斯功能性运动量表扩展版）进行了评估：结果：握力和手指屈曲力与运动功能、疾病严重程度、SMA类型和SMN2拷贝数高度相关。在努西能森治疗期间，SMA 儿童和成人的握力和手指屈曲力显著增加：结论：使用 HFD 200 测量握力和手指屈曲力是一种很有前景的 SMA 敏感结果测量方法。
{"title":"‘Reading the palm’ – A pilot study of grip and finger flexion strength as an outcome measure in 5q spinal muscular atrophy","authors":"Constanze Weber , Anne Müller , Maren Freigang , Maja von der Hagen , René Günther","doi":"10.1016/j.braindev.2024.01.001","DOIUrl":"10.1016/j.braindev.2024.01.001","url":null,"abstract":"<div><h3>Background</h3><p><span>Innovative RNA modifying and gene replacement therapies are currently revolutionizing the therapeutic landscape in 5q-associated </span>spinal muscular atrophy<span> (SMA). In order to provide individual recommendations for choice of treatment and therapy (dis-) continuation, objective outcome measures are needed. The purpose of this study was to determine whether maximum isometric voluntary grip and finger flexion strength is a useful sensitive outcome measure in children and adult patients with SMA.</span></p></div><div><h3>Methods</h3><p>In this non-interventional, longitudinal pilot study, we assessed grip and finger flexion strength on 39 patients with SMA II and III (n = 16 children, mean age = 10.0; n = 23 adults, mean age = 38.4) using the Weber hand and finger dynamometer HFD 200. Grip and finger flexion strength, clinical examinations and motor function scores (Revised Upper Limb Module, Hammersmith Functional Motor Scale Expanded) were assessed over a 12-month treatment period concurrent with the nusinersen treatment.</p></div><div><h3>Results</h3><p>Grip and finger flexion strength was highly associated with motor function and disease severity, SMA type and <em>SMN2</em><span> copy number. During nusinersen treatment, grip and finger flexion strength significantly increased in children and adults with SMA.</span></p></div><div><h3>Conclusion</h3><p>Grip and finger flexion strength measured with the HFD 200 is a promising sensitive outcome measure for SMA.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 5","pages":"Pages 189-198"},"PeriodicalIF":1.7,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.braindev.2024.01.002
Tejas C. Sekhar
{"title":"Key considerations for the diagnosis of Guillain-Barré syndrome in pediatric populations","authors":"Tejas C. Sekhar","doi":"10.1016/j.braindev.2024.01.002","DOIUrl":"10.1016/j.braindev.2024.01.002","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 4","pages":"Page 187"},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics.
Methods
This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS).
Results
We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups.
Conclusions
Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.
{"title":"Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study","authors":"Tomoyuki Akiyama , Daisuke Saigusa , Takushi Inoue , Chiho Tokorodani , Mari Akiyama , Rie Michiue , Atsushi Mori , Eiji Hishinuma , Naomi Matsukawa , Takashi Shibata , Hiroki Tsuchiya , Katsuhiro Kobayashi","doi":"10.1016/j.braindev.2023.12.004","DOIUrl":"10.1016/j.braindev.2023.12.004","url":null,"abstract":"<div><h3>Objective</h3><p><span>The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under </span>treatment<span><span> and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine </span>metabolomics.</span></p></div><div><h3>Methods</h3><p>This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome<span> analysis of spot urine samples was conducted using gas chromatography<span> (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS).</span></span></p></div><div><h3>Results</h3><p>We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups.</p></div><div><h3>Conclusions</h3><p>Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 4","pages":"Pages 180-186"},"PeriodicalIF":1.7,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-21DOI: 10.1016/j.braindev.2023.12.003
Sareh Hosseinpour , Ehsan Razmara , Morteza Heidari , Zahra Rezaei , Mahmoud Reza Ashrafi , Ali Zare Dehnavi , Reyhaneh Kameli , Ali Hosseini Bereshneh , Hassan Vahidnezhad , Reza Azizimalamiri , Zahra Zamani , Neda Pak , Maryam Rasulinezhad , Bahram Mohammadi , Homa Ghabeli , Mohammad Ghafouri , Mahmoud Mohammadi , Gholam Reza Zamani , Reza Shervin Badv , Sasan Saket , Ali Reza Tavasoli
Objective
Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies.
Methods
This study summarizes the clinical, imaging, and molecular data of these patients for five years.
Results
The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis.
Conclusions
The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).
{"title":"A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies","authors":"Sareh Hosseinpour , Ehsan Razmara , Morteza Heidari , Zahra Rezaei , Mahmoud Reza Ashrafi , Ali Zare Dehnavi , Reyhaneh Kameli , Ali Hosseini Bereshneh , Hassan Vahidnezhad , Reza Azizimalamiri , Zahra Zamani , Neda Pak , Maryam Rasulinezhad , Bahram Mohammadi , Homa Ghabeli , Mohammad Ghafouri , Mahmoud Mohammadi , Gholam Reza Zamani , Reza Shervin Badv , Sasan Saket , Ali Reza Tavasoli","doi":"10.1016/j.braindev.2023.12.003","DOIUrl":"10.1016/j.braindev.2023.12.003","url":null,"abstract":"<div><h3>Objective</h3><p><span>Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial </span>respiratory chains<span>. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric<span> patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis<span> of leukodystrophies.</span></span></span></p></div><div><h3>Methods</h3><p>This study summarizes the clinical, imaging, and molecular data of these patients for five years.</p></div><div><h3>Results</h3><p><span>The three most common symptoms<span><span><span><span> were neurologic regression (58.5%), pyramidal signs (58.5%), and </span>extrapyramidal signs (43.9%). Because nuclear </span>DNA mutations<span> are responsible for a high percentage of pediatric MLs, whole exome sequencing<span> was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. </span></span></span>Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in </span></span><em>PDSS1, NDUFB9, FXBL4, SURF1</em>, and <em>NDUSF1</em><span> were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis.</span></p></div><div><h3>Conclusions</h3><p><span><span>The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and </span>periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of </span>corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 4","pages":"Pages 167-179"},"PeriodicalIF":1.7,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.
Methods
We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (“the PEE group”, n = 6; “the non-PEE group”, n = 14) according to inclusion criteria.
Results
The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1–32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01).
Conclusions
This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.
{"title":"Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion","authors":"Makoto Nishioka , Mitsuo Motobayashi , Tetsuhiro Fukuyama , Yuji Inaba","doi":"10.1016/j.braindev.2023.12.002","DOIUrl":"10.1016/j.braindev.2023.12.002","url":null,"abstract":"<div><h3>Background</h3><p><span>Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent </span>in patients<span> with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.</span></p></div><div><h3>Methods</h3><p>We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (“the PEE group”, n = 6; “the non-PEE group”, n = 14) according to inclusion criteria.</p></div><div><h3>Results</h3><p><span><span><span><span>The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1–32). The most common types of seizures were focal seizures, </span>epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had </span>intractable epilepsy. The median values of </span>alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (</span><em>p</em> < 0.01).</p></div><div><h3>Conclusions</h3><p>This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 4","pages":"Pages 161-166"},"PeriodicalIF":1.7,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138818740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.
Methods: We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 ("the PEE group", n = 6; "the non-PEE group", n = 14) according to inclusion criteria.
Results: The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1-32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01).
Conclusions: This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.
{"title":"Risk factors for post-encephalopathic epilepsy in patients with acute encephalopathy with biphasic seizures and late reduced diffusion.","authors":"Makoto Nishioka, Mitsuo Motobayashi, Tetsuhiro Fukuyama, Yuji Inaba","doi":"10.1016/j.braindev.2023.12.002","DOIUrl":"https://doi.org/10.1016/j.braindev.2023.12.002","url":null,"abstract":"<p><strong>Background: </strong>Post-encephalopathic epilepsy (PEE) is a serious complication of acute encephalopathy syndromes, and is more frequent in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) than in children with acute encephalopathy. However, a risk factor analysis using laboratory findings in the acute phase of AESD has not yet been performed. Therefore, the present study examined risk factors of AESD-related PEE using laboratory parameters in the acute phase of AESD.</p><p><strong>Methods: </strong>We retrospectively screened 27 pediatric patients with AESD for inclusion, and enrolled 20 (\"the PEE group\", n = 6; \"the non-PEE group\", n = 14) according to inclusion criteria.</p><p><strong>Results: </strong>The incidence of AESD-related PEE was 30 %, and the median duration from the onset of AESD to the development of PEE was 2.5 months (range, 1-32). The most common types of seizures were focal seizures, epileptic spasms, and startle seizures: 4 out of 6 patients (66.7 %) had intractable epilepsy. The median values of alanine aminotransferase (ALT) in the 1st and 2nd seizure phases of AESD and aspartate aminotransferase (AST) in the 2nd seizure phase were significantly higher in the PEE group than in the non-PEE group (p < 0.01).</p><p><strong>Conclusions: </strong>This is the first study to report higher serum levels of ALT and AST at the onset of AESD as risk factors for AESD-related PEE. We also provided a detailed description on the clinical characteristics on AESD-related PEE, which are consistent with previous findings.</p>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established.
Methods
We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers’ evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes.
Results
All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration.
Conclusions
The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.
背景大多数长期受影响的脊髓性肌萎缩症（SMA）1型患者运动功能严重受损，需要依靠气管造口术进行机械通气。方法我们回顾性评估了持续治疗至少 12 个月的 1 型 SMA 患者鞘内注射奴西那生的疗效。有三名患者（分别为 3 岁、4 岁和 16 岁）参加了我们的研究，他们的大运动功能严重受损，没有头部控制能力或翻身能力。这三名患者都需要气管插管机械通气和管饲。运动功能的评估采用费城儿童医院婴儿神经肌肉疾病测试（CHOP-INTEND）和护理人员的评估。同时，我们对神经传导进行了纵向检查，并比较了复合运动动作电位（CMAP）的振幅。虽然CHOP-INTEND评分没有显著增加，但据护理人员称，所有三名患者的手指或面部肌肉运动均有所改善，使他们能够表达自己的意图。结论运动功能的改善可使交流更加顺畅，这可能是继续使用纽西奈森治疗的基础。目前可用的运动功能评分并不能有效评估对医疗护理复杂的 SMA 患者的治疗干预。纵向神经传导研究可作为一项客观指标。
{"title":"Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function","authors":"Yuki Ueda , Kiyoshi Egawa , Kentaro Kawamura , Noriki Ochi , Takeru Goto , Shuhei Kimura , Masashi Narugami , Sachiko Nakakubo , Midori Nakajima , Atsushi Manabe , Hideaki Shiraishi","doi":"10.1016/j.braindev.2023.12.001","DOIUrl":"10.1016/j.braindev.2023.12.001","url":null,"abstract":"<div><h3>Background</h3><p>Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established.</p></div><div><h3>Methods</h3><p>We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers’ evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes.</p></div><div><h3>Results</h3><p>All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration.</p></div><div><h3>Conclusions</h3><p>The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.</p></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"46 3","pages":"Pages 149-153"},"PeriodicalIF":1.7,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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