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Abstract Background Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in the pediatric population. The manifestations of this disease include progressive muscle weakness, gait dysfunction, and motor impairment, leading to a loss of ambulation by the age of 13 years. Molecular diagnosis is the standard diagnostic tool for DMD. This study aimed to investigate disease progression and genetic patterns in Iranian ambulant boys and to find the correlation between genotypes and motor function phenotypes. Methods This study was performed on 152 DMD patients. Clinical history, including the disease phenotype, steroid therapy, and the North Star Ambulatory Assessment (NSAA) score, was taken for all the patients. Molecular diagnoses were confirmed by multiplex ligation-dependent probe amplification and next-generation sequencing tests. Results A total of 152 Iranian DMD patients were examined in this study. The mean age at the time of disease onset was 4.04 ± 2.00 years, and the mean age at diagnosis was 5.05 ± 2.08 years. The mean age of ambulation loss was 10.9 years. Contracture was reported in 38.9% of cases. In terms of age, the mean total NSAA score showed a peak at 4 years of age, with a mean NSAA score of 24. Annual changes in the NSAA score were determined for all cases, based on the mutation type and exon site. Deletion mutation was found in 79.1% of cases, duplication in 6.8%, nonsense in 12.8%, and splice site in 1.4%. The most common single exon deletion was exon 44 (5.3%), and the most common multiexon deletions were attributed to exons 45–50 and exons 45–52 (4.6%). The results did not indicate any correlation between the mutation type and age at the time of disease onset, loss of ambulation age, and wheelchair dependence; however, a significant association was found between contracture and mutation type. The results showed a significant difference in the NSAA score between the deletion and nonsense groups at the age of 3 years (P = 0.04). No significant correlation was found between the phenotype and exon site. Overall, 91.1% of the study population had a history of corticosteroid use, and 54.1% showed compliance with rehabilitation therapy. Conclusion This study demonstrated the phenotypes and mutational features of Iranian DMD boys and provided information regarding the natural motor history of the disease, disease progression, diagnosis, and status of DMD management in Iran. The present findings can promote the development of clinical trials and future advanced molecular therapies in Iran.

Abstract Introduction The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. Methods Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. Results There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. Conclusions This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. Trial Registration The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Epilepsies and epileptic syndromes are among the most common chronic neurological disorders in neonates, infants, and children. Remission occurs in 70% of epileptic children, while other cases experience frequent seizures and become refractory to various treatment modalities. Refractory seizures have a significant adverse impact on the quality of life of epileptic children and their families. Prognosis of epilepsies is determined based on the risk of seizure or convulsion recurrence. Some of the most important risk factors for recurrence are the age at seizure presentation, neurodevelopment of the child, etiology of seizures, seizure frequency before anticonvulsant withdrawal, response to antiepileptic medications, type of epileptic syndromes, and electroencephalography of the patient. Recognition of the risk factors for seizure recurrence results in the optimal management of the treatment protocols, thereby reducing the adverse effects of epileptic seizures on patients and their families. The present study aimed to provide a narrative review of the most important risk factors for the recurrence of epilepsies in children by two child neurologists.

Abstract Metachromatic leukodystrophy disorder (MLD) is an autosomal recessive and lysosomal storage disease. The disease is caused by the deficiency of the enzyme arylsulfatase A (ARSA) which is encoded by the ARSA gene. Different mutations have been reported in different populations. The present study was aimed to detect the mutation type of the ARSA gene in three relative Iranian patients. We found a novel homozygous missense mutation c.1070 G > T (p.Gly357Val) in exon 6 of these patients. The mutation was found to be reported for the first time in MLD patients. The data can update the mutation profile and contribute toward improved clinical management and counseling of MLD patients.

Charcot-Marie-Tooth type 4 (CMT4) is an autosomal recessive severe form of neuropathy with genetic heterogeneity. CMT4B1 is caused by mutations in the myotubularin-related 2 (MTMR2) gene and as a member of the myotubularin family, the MTMR2 protein is crucial for the modulation of membrane trafficking. To enable future clinical trials, we performed a detailed review of the published cases with MTMR2 mutations and describe four novel cases identified through whole-exome sequencing (WES). The four unrelated families harbor novel homozygous mutations in MTMR2 (NM_016156, Family 1: c.1490dupC; p.Phe498IlefsTer2; Family 2: c.1479+1G>A; Family 3: c.1090C>T; p.Arg364Ter; Family 4: c.883C>T; p.Arg295Ter) and present with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity. The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. Whereas the few reported missense mutations and also those truncating mutations occurring at the C-terminus after the phosphatase domain cause a rather mild phenotype and patients were still ambulatory above the age 30 years. Charcot-Marie-Tooth neuropathy and Centronuclear Myopathy causing mutations have been shown to occur in proteins involved in membrane remodeling and trafficking pathway mediated by phosphoinositides. Earlier studies have showing the rescue of MTM1 myopathy by MTMR2 overexpression, emphasize the importance of maintaining the phosphoinositides equilibrium and highlight a potential compensatory mechanism amongst members of this pathway. This proved that the regulation of expression of these proteins involved in the membrane remodeling pathway may compensate each other's loss- or gain-of-function mutations by restoring the phosphoinositides equilibrium. This provides a potential therapeutic strategy for neuromuscular diseases resulting from mutations in the membrane remodeling pathway.

Introduction: Hemiparetic cerebral palsy refers to an impairment caused by non-progressive damages to premature brain which is more sever in one side of the body than the other side. The aim of the present study was to determine the effects of combining constraint-induced movement therapy (CIMT) with virtual reality (VR) on upper limb functioning of children with hemiparetic cerebral palsy. Materials and Methods: In a single blind randomized, controlled trial, 16 children with hemiparetic cerebral palsy, who were selected through a simple random sampling method in Ahvaz city, were divided into 4 groups of CIMT, VR, CIMT+VR, and controls. Subjects in experimental groups participated in one-and-half-hour therapeutic sessions which were held every other day during a four-week period. Measures were conducted pre, post and 3-month after the treatment period using Pediatrics Motor Activity Log and Bruininks-Oseretsky Test of Motor proficiency (BOTMP). Sample randomization and statistical analysis of data through analysis of variance with repeated measures were conducted via SPSS-16 software in which alpha level was set at 0.05. Results: Data analysis for measurement tools was indicative of significant difference of combined group compared to VR, CIMT, and control groups (P < 0.01) (mean amounts of BOTMP, speed and dexterity changed from 0.15 ± 0.08 to 1.89 ± 0.33 in post-test). Data analysis for follow-up session revealed the retention of results for 4 groups (P = 0.32). Conclusion: Incorporating VR and CIMT may improve upper limb functioning of children with hemiparetic cerebral palsy through combining the advantages of both protocols and implementing them in an integrated program. Keywords: Constraint-induced movement therapy, Virtual reality, Upper limb function, Hemiparetic cerebral palsy

مقدمه: فلج مغزی به گروهی از اختلالات دایمی وضعیت بدن و حرکت اطلاق می‌گردد که ناشی از ضایعات غیر مخرب در مغز جنین یا نوزاد می‌باشد و می‌تواند منجر به اختلال در ساختار و عملکرد و محدودیت فعالیت بدن شود. بنابراین، به علت بروز چنین اختلالاتی، انجام درمان به‌موقع ضروری است. تکنیک کینزیوتیپ یک روش غیر تهاجمی، مقرون به صرفه، تا حدودی نوین و قابل دسترس برای درمان برخی از ضایعات و عملکرد این کودکان می‌باشد. هدف از انجام پژوهش حاضر، مرور منابع به منظور بررسی اثرات استفاده طولانی مدت از تکنیک کینزیوتیپ بر بهبود عملکرد و تعادل کودکان مبتلا به فلج مغزی اسپاستیک بود. مواد و روش‌ها: با استفاده از کلمات کلیدی انگلیسی «Balance، Function، Kinesio tape، Kinesio taping، Cerebral Palsy و CP» و کلمات کلیدی فارسی «کینزیوتیپ، فلج مغزی، فلج مغزی اسپاستیک، عملکرد و تعادل» در پایگاه‌های اطلاعاتی Scopus، Ovid، ProQuest، ScienceDirect، Google Scholar، PubMed و Scientific Information Database (SID)، 14 مقاله بر اساس معیارهای ورود و خروج انتخاب شد و پس از مرور بر اساس محل به کار بردن کینزیوتیپ روی بدن، دسته‌بندی گردید. یافته‌ها: تکنیک کینزیوتیپ باعث بهبود فعالیت‌هایی مانند بلند شدن از حالت نشسته، راه رفتن، نشستن، گرفتن و رها کردن و حرکات مجزای انگشتان دست، الگوهای حرکتی اندام‌های فوقانی و تحتانی، فعالیت‌های روزمره زندگی و تعادل تنه در وضعیت نشسته و یا در حین راه رفتن می‌شود. نتیجه‌گیری: به نظر می‌رسد که استفاده طولانی مدت از کینزیوتیپ می‌تواند در کنار سایر درمان‌های توان‌بخشی، برای بهبود عملکرد و تعادل کودکان مبتلا به فلج مغزی اسپاستیک مؤثر باشد.