ABSTRACT
BACKGROUND: Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China. METHODS: In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen. RESULTS: Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed. CONCLUSIONS: Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Muscular Atrophy, Spinal , Spinal Muscular Atrophies of Childhood , Infant , Child , Humans , Retrospective Studies , Oligonucleotides/pharmacology , Oligonucleotides/therapeutic use , ChinaABSTRACT
Background and purpose: A growing body of research suggests that inflammation and maternal infections may lead to an increased risk of neurodevelopmental problems such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), cerebral palsy (CP), and epilepsy in offspring. The aim of this study was to observe the connection between prenatal antibiotic exposure and the risk of these neurodevelopmental disorders in offspring. Patients and methods: A comprehensive search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Google Scholar, and Scopus databases for observational studies that looked into the link between prenatal exposure to antibiotics and the risk of neurodevelopmental problems in offspring, published from 1 January 1950 to 31 January 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Data were analyzed using the STATA version 12 software, and an odds ratio (OR) with a 95% confidence interval (CI) was reported. Results: A total of 15 studies were included in the meta-analysis. Prenatal antibiotic exposure was associated with the increased risk of ADHD (OR = 1.14; 95% CI = 1.13 to 1.15; I 2 = 0%) and epilepsy (OR = 1.34; 95% CI = 1.02 to 1.66; I 2 = 96.8%). The link between prenatal antibiotic exposure and the risk of ASD [OR = 1.09; 95 % CI = 0.88 to 1.31; I 2 = 78.9%] and CP [OR = 0.99; 95% CI = 0.56 to 1.43; I 2 = 91%] was found to be non-significant. In all of the included prospective cohort studies, subgroup analysis suggested a significant association between prenatal antibiotic exposure and the incidence of ASD [OR = 1.17; 95% CI = 1.03 to 1.31; I 2 = 48.1%] and CP [OR = 1.18; 95% CI = 1.02 to 1.34; I 2 = 0%]. Conclusion: Prenatal antibiotic exposure during pregnancy is linked to a higher incidence of ADHD and epilepsy in the offspring. Further prospective studies that compare prenatal antibiotic use and are adjusted for various confounders are needed to further assess the association of prenatal antibiotic exposure and neurological disorders in offspring. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022306248.
ABSTRACT
BACKGROUND: Typical patients with KCNQ2 (OMIM# 602235) epileptic encephalopathy present early neonatal-onset intractable seizures with a burst suppression EEG pattern and severe developmental delay or regression, and those patients always fail first-line treatment with sodium channel blockers. Vitamin B6, either pyridoxine or pyridoxal 50-phosphate, has been demonstrated to improve seizure control in intractable epilepsy. METHODS: Here, we collected and summarized the clinical data for four independent cases diagnosed with pyridoxine-responsive epileptic encephalopathy, and their exome sequencing data. Moreover, we reviewed all published cases and summarized the clinical features, genetic variants, and treatment of pyridoxine-responsive KCNQ2 epileptic encephalopathy. RESULTS: All four cases showed refractory seizures during the neonatal period or infancy, accompanied by global development delay. Four pathogenetic variants of KCNQ2 were uncovered and confirmed by Sanger sequencing: KCNQ2 [NM_172107.4: c.2312C > T (p.Thr771Ile), c.873G > C (p.Arg291Ser), c.652 T > A (p.Trp218Arg) and c.913-915del (p. Phe305del)]. Sodium channel blockers and other anti-seizure medications failed to control their seizures. The frequency of seizures gradually decreased after treatment with high-dose pyridoxine. In case 1, case 2, and case 4, clinical seizures relapsed when pyridoxine was withdrawn, and seizures were controlled again when pyridoxine treatment was resumed. CONCLUSION: Our study suggests that pyridoxine may be a promising adjunctive treatment option for patients with KCNQ2 epileptic encephalopathy.