Griscelli syndrome type 1: a novel pathogenic variant, and review of literature.

Griscelli syndrome type 1 (GS1) is a rare inherited autosomal recessive disease caused by a deleterious variant in the MYO5A gene and characterized by general hypopigmentation, neurological symptoms, motor disability, hypotonia, and vision abnormality. Only nine pathogenic variants in the MYO5A gene have been confirmed in association with the GS1. All of the reported pathogenic variants are truncating. Herein, two siblings from a consanguineous Iranian family with abnormal pigmentation and neurological symptoms were referred for genetic counseling. Whole-exome sequencing (WES) revealed a novel homozygous truncating variant c.1633_1634delAA (p.Asn545Glnfs*10) in the MYO5A gene, which was completely co-segregated with the phenotype in all affected and unaffected family members. Computational analysis and protein modeling demonstrated the deleterious effects of this variant on the structure and function of the protein. The variant, according to ACMG guidelines, was classified as pathogenic. Besides the novelty of the identified variant, our patients manifested more severe clinical symptoms and presented distal hyperlaxity in all four limbs, which was a new finding. In conclusion, we expanded the mutational and phenotypic spectrum of the GS1. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype-phenotype correlation.

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy. Exome sequencing of the probands revealed an ultra-rare homozygous pathogenic missense DPM3 variant NM_018973.4:c.221A>G, p.(Tyr74Cys) which segregated with the phenotype in all families. Haplotype analysis indicated that the variant arose independently in three families. Functional analysis did not reveal any alteration in the N-glycosylation pathway caused by the variant; however, this does not exclude its pathogenicity in the function of the DPM complex and related cellular pathways. This report provides supporting evidence that, besides DPM1 and DPM2, defects in DPM3 can also lead to a muscle and brain phenotype.

Effect of parenting intervention through "Care for Child Development Guideline" on early child development and behaviors: a randomized controlled trial.

BACKGROUND: Several studies showed that parenting intervention programs play a core component in early child development. Considering the limited healthcare resources in developing countries, group-session intervention based on care for child development (CCD) guideline might be cost-effective. METHODS: This randomized controlled trial was conducted at an outpatient public Pediatrics clinic in Isfahan, Iran. We included 210 pregnant women aged 18-45 years in their third trimester and followed their children for 18 months. The intervention group underwent 5 educational group sessions, each lasting for almost 45 minutes. The main outcomes were the children's development and socio-emotional behavior problems based on Bayley Scales of Infant and Toddler Development-III (BSID-III) at 12 months and the Children Behavior Checklist (CBCL) at 18 months. RESULTS: Overall, data of 181 children were included in the current study, including 80 in the intervention group and 101 controls. The adjusted median/mean differences between intervention and control groups using median/linear regression were not significant for all BSID-III domains except for median differences for cognitive score based on BSID-III (ß (SE): - 4.98(2.31), p:0.032) and mean differences for anxiety/depression score based on CBCL (ß (SE): - 2.54(1.27), p:0.046). CONCLUSION: In this study, parenting interventions through CCD group sessions were significantly effective on just one subscale of children's socio-emotional behavior domains based on CBCL and one domain of children's development based on BSID-III. There might be a ceiling or floor effects for the BSID-III and CBCL assessment, respectively, leaving little room for improvement as almost all children have achieved their full developmental potential in our study. TRIAL REGISTRATION: IRCT20190128042533N2, Date of registration: 16/01/2020, www.irct.ir.

Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.

In recent years, the tropomyosin-receptor kinase fused gene (TFG) has been linked to diverse hereditary neurodegenerative disorders, including a very rare complex hereditary spastic paraplegia, named spastic paraplegia type 57 (SPG57). Until now, four pathogenic homozygous variants of the TFG gene have been reported associated with SPG57. Two consanguineous Iranian families (1 and 2), the first one with two affected members and the second one with one, all with an early-onset progressive muscle weakness, spasticity, and several neurological symptoms were examined via the whole-exome sequencing. Two homozygous missense variants including c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) have been found in the related families. The candidate variants were confirmed by Sanger sequencing and found to co-segregate with the disease in families. The bioinformatics analysis showed the deleterious effects of these nucleotide changes and the variants were classified as pathogenic according to ACMG guidelines. A comparison of the clinical presentation of the patients harboring c.41A>G (p.Lys14Arg) with previously reported SPG57 revealed variability in the severity state and unreported clinical presentation, including, facial atrophy, nystagmus, hyperelastic skin, cryptorchidism, hirsutism, kyphoscoliosis, and pectus excavatum. The affected member of the second family carried a previously reported homozygous c.316C>T (p.Arg106Cys) variant and displayed a complex HSP including optic atrophy. Remarkable clinical differences were observed between the family 1 and 2 harboring the c.41A>G (p.Lys14Arg) and c.316C>T (p.Arg106Cys) variants, which could be attributed to the distinct affected domains (PB1 domains and coiled-coil domains), and therefore, SPG57 might have been representing phenotype vs. variant position correlation.

Comparison of the Efficacy of Buspirone and Placebo in Childhood Functional Abdominal Pain: A Randomized Clinical Trial.

INTRODUCTION: Pharmacological interventions have not been successful in the treatment of childhood functional abdominal pain (FAP) hitherto. Buspirone is suggested to be efficacious in some of the abdominal pain-related functional gastrointestinal disorders based on evidences from the studies on adults. We aim to investigate the efficacy of buspirone on childhood FAP. METHODS: This randomized clinical trial was conducted on 117 patients with childhood FAP aged 6-18 years. We randomly assigned patients to receive buspirone or placebo for 4 weeks, with the adjusted dosage for age. Participants completed the questionnaires assessing pain, depression, anxiety, somatization, and sleep disturbances at baseline, at the end of the 4-week therapy (first follow-up), and at 8 weeks after medication discontinuation (second follow-up). The primary outcome was treatment response rate, defined as reduced pain score of ≥2 or reporting no pain at the follow-up assessments. RESULTS: Ninety-five patients completed the 4-week therapy (48 and 47 in buspirone and placebo groups, respectively). Both buspirone and placebo reduced pain after 4 weeks of treatment, and these effects were persistent 8 weeks after medication discontinuation (P < 0.001 for both groups at weeks 4 and 12). Treatment response rates for buspirone and placebo were 58.3% and 59.6% at week 4 (P = 0.902) and 68.1% and 71.1% at week 12 (P = 0.753), respectively. DISCUSSION: Buspirone effectively improves pain and associated psychological symptoms including depressive symptoms, anxiety, somatization, and sleep disturbances in childhood FAP but has no superiority over placebo. Further studies, with the higher doses of buspirone and longer follow-ups are recommended.

Prophylactic Therapy of Cyclic Vomiting Syndrome in Children: Comparison of Amitriptyline and Cyproheptadine: A Randomized Clinical Trial.

OBJECTIVES: Cyclic vomiting syndrome (CVS) is a common functional gastrointestinal disorder characterized by recurrent episodes of nausea and vomiting. There is no definite treatment for the condition, although some medications are recommended. We aimed to compare the efficacy of amitriptyline and cyproheptadine in prophylactic therapy of CVS. METHODS: This is a single-blinded randomized clinical trial conducted during 2015-2016 in Isfahan, Iran. Sixty-four children who were 3-15 years old, with a diagnosis of CVS (based on Rome III criteria), were included in the study and were randomly divided into two groups of amitriptyline and cyproheptadine. They were followed for 6 months, looking for frequency and duration of attacks as the primary outcome. RESULTS: The mean monthly frequency of attacks in the last 2 months of the study in the amitriptyline and cyproheptadine group were 0.38±0.55 and 0.59±0.71, respectively (P-value=0.197), after intervention. The mean duration of attacks between amitriptyline and cyproheptadine group were 1.41±2.86 and 1.81±2.22 h, respectively (P-value=0.212). In the amitriptyline group 65.6% of patients reported 100% remission, whereas in the cyproheptadine group 50% reported full remission (P-value=0.206). CONCLUSIONS: There was no superiority of one of the medications over the other. We did not find any age-related effect on the efficacy of these medications as well.

The association of socioeconomic status of family and living region with self-rated health and life satisfaction in children and adolescents: The CASPIAN-IV study.

Background: Socioeconomic status (SES) is a major determinant of health inequality in children and adolescents. The aim of this study was to evaluate the association of SES of family and living region with self-rated health (SRH) and life satisfaction (LS) among children and adolescents. Methods: This study was a part of the fourth survey of a national surveillance program, which was conducted in 30 provinces of Iran in 2011-2012. LS and SRH were assessed by a questionnaire based on the World Health Organization-Global School-based student Health Survey (WHO-GSHS). Family SES was estimated using principal component analysis (PCA) and based on family assets, parental education and occupation, and type of school. Region SES was calculated using PCA and some variables including literacy rate, family assets and employment rate. Results: Out of 14,880 invited students, 13,486 (participation rate: 90.6%) completed the survey; of whom, 49.2% were girls, and 75.6% were from urban areas with the mean ± SD age of 12.47±3.36 years. In the multivariate model, SES of family and living region was associated with LS and good SRH. In the full models, in addition to all potential confounders, family and living region SES were included simultaneously. However, only the association of family SES with LS, and good SRH remained statistically significant. Conclusion: The effect of families' SES on SRH and LS is more important than regional SES. The presented patterns of SRH and LS may be useful in developing better health policies and conducting complementary studies in this field.

Endothelial dysfunction state in migraine headache and neutrally mediated syncope in children and young adults.

BACKGROUND: Recent evidences have supported migraine headache and neurally mediated syncope as the especial types of endotheliopathies. To determine endothelial function in patients with migraine headache or those with neurally mediated syncope, the present study was conducted. MATERIALS AND METHODS: This cross-sectional study was performed on 93 consecutive patients aged 5-20 years in four groups; neurally mediated syncope, migraine, both neurally mediated syncope and migraine, and control groups. All subjects were tested for basic biophysical and biochemical features including age, gender, body mass index, systolic, and diastolic blood pressures, intima-media thickness (IMT) and flow-mediated dilation (FMD), blood hemoglobin, fasting blood glucose, lipid profile, intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and E-selectin. RESULTS: The mean levels of VCAM and ICAM were significantly higher in all groups when compared to control group (P < 0.05). FMD was significantly higher in syncope, migraine, and syncope and migraine groups than in the control group (P < 0.05). Furthermore, mean IMT was significantly lower in migraine and also in syncope and migraine groups than in syncope group and control group (P < 0.05). Examining the association between IMT and other baseline parameters showed positive association of IMT with systolic and diastolic blood pressures. CONCLUSION: Endothelial dysfunction is seen in both migraine headache and neurally mediated syncope. Changes in endothelial functional indices are also dependent on the blood pressure.

The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy.

BACKGROUND: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. OBJECTIVE: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). METHODS: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. RESULTS: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. CONCLUSIONS: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Efficacy of Lacosamide Add-on Therapy on Refractory Focal Epilepsies in Children and Adolescents: An Open-Label Clinical Trial.

Objective: Epilepsy is a chronic neurological disorder that affects 0.5%-1% of children. 30%-40% of patients are resistant to current anti-epileptic drugs. Lacosamide (LCM) appeared to be effective, safe, and well tolerated in children and adolescents. This study was aimed to evaluate whether LCM could be an effective add-on therapy in children with refractory focal epilepsies. Methods: This study was conducted from April 2020 to April 2021 in Imam Hossein Children Hospital, Isfahan, Iran. We included 44 children aged 6 months to 16 years with refractory focal epilepsy (based on International League Against Epilepsy criteria). LCM was given in divided doses of 2 mg/kg/day, increasing by 2 mg/kg every week. The first follow-up visit was 6 weeks later, when all patients had reached the therapeutic dose. Findings: The average age of the patients was 89.9 months. 72.5% of children had focal motor seizures. Evaluation of percent change in seizure frequency and duration before and after treatment showed a 53.22% reduction in seizure frequency and 43.72% reduction in seizure duration after treatment. Our study group tolerated LCM well, with few side effects. Headache, dizziness, and nausea were common side effects. In line with other studies, none of the suspected risk factors could predict response to LCM treatment. Conclusion: LCM appears to be an effective, safe, and well-tolerated medication in children with uncontrolled drug-resistant focal epilepsy.

The Effect of Low-Grade Intraventricular Hemorrhage on the Neurodevelopment of Very Low Birth Weight Infants.

Objective: Intraventricular hemorrhage (IVH) is a significant concern for premature very low birth weight (VLBW) neonates worldwide. Recently, the popular theory of the benign nature of low-grade IVH has been argued with uncertain outcomes. This study aimed to assess the effect of low-grade IVH on the neurodevelopment of VLBW neonates. Materials & Methods: This six-month follow-up cohort study was conducted on VLBW neonates with and without grade I-II IVH diagnosed through brain ultrasonography. Participants were neurologically examined at birth and within six months. Neurodevelopment was assessed using the Bayley-III questionnaire, which includes evaluating cognition, receptive language, expressive language, fine motor, and gross motor performance. Results: A total of 100 VLBW neonates were recruited, including 40 cases with grade I-II IVH diagnosed through brain ultrasonography and 60 controls. Cases and controls were similar in terms of gestational age, body birth weight, hospitalization duration, gender distribution, and age at Bayley-III evaluation (P>0.05). The neurological assessments at birth showed no significant difference between the two groups (P=0.20), while controls showed significantly better results at the sixth month of age (P =0.004). Concerning different neurodevelopmental indices, after adjusting for demographic characteristics and respiratory-related variables at the time of Bayley-III evaluation, controls presented a higher performance in cognition and gross motor aspects compared to cases (P= 0.04 and 0.03, respectively). Conclusions: The low-grade IVH affected the sixth-month neurological examination and gross motor performance of the VLBW newborns. Notably, cognition and gross motor were the two affected subscales in the presence of low-grade IVH, independent of demographic factors.

A Comparative Study on the Efficacy of Coenzyme Q10 and Amitriptyline in the Prophylactic Treatment of Migraine Headaches in Children: A Randomized Controlled Trial.

Background: Migraine, one of the most common headaches in children, has a significant impact on children and their family's quality of life (QoL). There are two approaches for controlling migraine headaches preventative and controlling acute attacks. Several drugs have been used for this purpose, and tricyclic antidepressants were at the top. Amitriptyline has shown not only a desirable effect on controlling the headaches but also some adverse side effects. Recently, finding effective drugs with fewer side effects, become more critical. Among them, nutraceuticals were one of the promising ones. Materials and Methods: In this randomized clinical trial on 72 patients aged 5-15 years old with diagnosis of migraine based on the International Headache Society criteria, we compare the effectiveness of coenzyme Qten on frequency, duration, and severity of childhood migraine. For comparing the QoL, we used the International PedMIDAS questionnaire. Results: Coenzyme Qten showed good therapeutic effects in children, especially in long-term use; however, amitriptyline showed more rapid response. After 3 months of treatment, clinical outcomes in the two groups did not significantly differ from each other. Similarly, Children's QoL increased in the same way. There are more reported side effects in children using amitriptyline compared to coenzyme Qten. Conclusions: According to results, Co-enzyme Q10, with fewer side effects and comparable therapeutic effects, especially in the long term, could be a good drug for prophylactic treatment of migraine headaches.

Efficacy and Safety of Topical Timolol for the Treatment of Facial Angiofibroma in Children with Tuberous Sclerosis Complex.

Objective: This study aimed to assess the efficacy and safety of topical timolol in treating facial angiofibromas (FAs) in pediatric patients with tuberous sclerosis complex (TSC). Methods: A prospective clinical trial was conducted involving 15 children diagnosed with TSC and presenting with FAs. The participants were administered topical timolol gel 0.5% twice daily. Prior to the intervention, the severity of FAs in each patient was evaluated using the FA severity index (FASI), which assessed erythema, size, and extent of lesions. Clinical response was assessed at weeks 2 and 4 during the intervention period as well as 1 month after discontinuation of treatment. Findings: Four weeks after discontinuing topical timolol 0.5%, statistically significant reductions were observed in the mean FASI score, erythema, size, and extent of lesions (P < 0.0001, P < 0.0001, P = 0.012, P = 0.008, respectively). FASI scores at 4 and 12 weeks postintervention, as well as 4 weeks after treatment cessation, demonstrated a significant decrease compared to baseline (P < 0.001). Erythema and extension scores also exhibited a significant decrease 1 month after treatment cessation compared to baseline (P < 0.05), while the mean size of lesions before and after the intervention did not show a statistically significant difference (P = 0.004). Conclusion: Topical timolol 0.5% represents a cost-effective and readily available treatment option for pediatric patients with FAs associated with tuberous sclerosis.

Reversible Cerebral Vasoconstriction Syndrome and Multisystem Inflammatory Syndrome in Children With COVID-19.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) involves multiple organs and shows increased inflammatory markers. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, several studies have reported the association between severe COVID-19 and MIS-C. Reversible cerebral vasoconstriction syndrome (RCVS) presents with thunderclap headaches and multifocal reversible vasoconstriction on imaging. RCVS is very rare in children. This article reports two cases of pediatric COVID-19 with severe MIS-C and clinical and imaging features indicative of RCVS. METHODS: Clinical, laboratory, and imaging data of the patients were reviewed. The diagnosis of RCVS was confirmed based on clinical symptomatology and brain magnetic resonance imaging findings. RESULTS: Two pediatric patients with clinical findings compatible with severe MIS-C and hemodynamic compromise presented to the hospital. During their hospitalization course, they developed thunderclap headaches and neurological deficits. Both were receiving vasoactive agents, intravenous immunoglobulin, and immunosuppressants. Imaging studies showed marked multifocal cerebral vasoconstriction in both cases and infarcts in one. The course and management of the patients will be presented. After controlling inflammation and elimination of triggers, both patients were ultimately symptom free upon discharge. Cerebral vasoconstriction had completely resolved on follow-up imaging. CONCLUSIONS: Although a variety of symptoms including headaches may be seen in pediatric COVID-19 patients with MIS-C, RCVS should be considered as a differential diagnosis in cases of thunderclap headache accompanied by neurological signs in these patients. Imaging findings and follow-up are also key in establishing the diagnosis.

L-carnitine versus Propranolol for pediatric migraine prophylaxis.

Objective: Carnitine plays a significant role in fatty acid transportation in mitochondria and has been shown to have a prophylactic effect on adult migraine. The aim of this randomized controlled trial was to compare and evaluate the effects of L-carnitine supplementation versus propranolol in the prevention of pediatric migraine. Materials & Methods: A total of 60 pediatric patients with episodic migraine were randomly allocated to 2 independent groups to receive either 50 mg/kg/day L-carnitine or 1 mg/kg/day propranolol as a prophylactic drug. Frequency, severity, and duration of migraine attacks and headache disability based on the Pediatric Migraine Disability Assessment Score (PedMIDAS) were studied at the baseline and after 2, 4, and 12 weeks. Results: A total of 56 patients were evaluated in the study: 23 girls (41%) and 33 boys (59%) with a mean age of 9.7 ± 2.1 years. Frequency of migraine headaches per month reduced from 11.4 ± 7.1 to 5.34 ± 2.4 in the L-carnitine group and from 10.7 ± 6.2 to 4.96 ± 3.9 in the propranolol group by the end of the study. Headache severity score was also reduced from 19.38 ± 14 to 2.88 ± 7.4 and from 12.92 ± 13 to 0.82 ± 1.3 in the L-carnitine and propranolol groups, respectively. We found a significant decrease in frequency, severity, and duration of headache attacks in both groups (P < 0.01). No significant difference was observed between the efficacies of the 2 drugs.This study concluded that L-carnitine supplementation can play a prophylactic role in the management of pediatric migraine.

A meta-analysis on the effect of telemedicine on the management of attention deficit and hyperactivity disorder in children and adolescents.

INTRODUCTION: This study aims to report the effect sizes of telemedicine treatments on the symptom domains of paediatric ADHD. METHODS: In this systematic review and meta-analysis, electronic databases, i.e. PubMed, Scopus, Web of Science and Embase, were searched for articles published up to December 2020. The inclusion criteria were as follows: children or adolescents diagnosed for ADHD or other hyperkinetic disorders; randomized controlled trials (RCTs); efficacy established with parents and teachers or self-rating scales at least for one of the following domains: inattention, cognitive function, hyperactivity, hyperactivity/impulsivity or oppositional behaviours. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. RESULTS: From 310 records reduced to 228 after removing duplicates, overall 12 studies were fulfilled our inclusion criteria. They consisted of 708 participants (358 with telemedicine intervention and 350 controls). The telemedicine interventions varied from computerized training programmes with phone calls to videoconferencing programmes, virtual reality classrooms or games. The most applicable method consisted of computerized training programmes with phone calls. Pooling results of all studies with available data on each subscale showed a significant effect of telemedicine on inattention/cognitive function (standardized mean difference (SMD) = 0.26, 95% CI: 0.16, 0.36), hyperactivity/impulsivity (SMD = 0.29, 95% CI: 0.06, 0.52), and oppositional behaviours (SMD = 0.72, 95% CI: 0.24, 1.20) subscales in ADHD. Almost all studies had an overall unclear risk of bias. The source of outcome assessment (parents, teachers or self-report questionnaire) was addressed as a potential confounding factor. In almost all symptom domains, the satisfaction from the treatment was higher in parents than in teachers. CONCLUSIONS: The clinical effects of telemedicine on the treatment of ADHD showed a small effect size for inattention/cognitive function, hyperactivity/impulsivity and oppositional behaviours.

The Comparison of Levetiracetam and Piracetam Effectiveness on Breath-Holding Spells in Children: A Randomized Controlled Clinical Trial.

BACKGROUND: We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood. MATERIALS AND METHODS: This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up. RESULTS: There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS. CONCLUSIONS: Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS.

Identification of a Missense Variant in the EIF2B3 Gene Causing Vanishing White Matter Disease with Antenatal-Onset but Mild Symptoms and Long-Term Survival.

Vanishing white matter disease (VWM) is a rare autosomal recessive leukodystrophy caused by a mutation in any of the five gene encoding subunits of the translation initiation factors eIF2B1 to eIF2B5. Whole-exome sequencing was performed on a 7-year-old boy with prenatal symptoms, including intrauterine-growth retardation, decreased movements, and oligohydramnios as well as mild intellectual disability, optic atrophy, macrocephaly, mild ataxia, and white matter lesions after birth. Analysis of WES data revealed a homozygous missense variant, c.C590T (p.Thr197Met) in the EIF2B3 gene (NM_0203650). The candidate variant was confirmed by Sanger sequencing and found to co-segregate with disease in family members. Pathogenicity analysis, 3D protein modeling, and stability assessment showed the deleterious effects of this nucleotide change. Previous studies suggest a direct relationship between the onset of symptoms and the progression rate and severity of the disease. All described cases of EIF2B deficiency with antenatal-onset led prenatal death; if they were born, they experienced clinical exacerbation, seizure, severe encephalopathy, and consequent infantile death (< 1 year). The patient of this study had never had seizure, which could be a potential explanation for the observed mild clinical picture, chronic state, and long-term survival until the age of seven. This study reported the first VWM due to EIF2B gene deficiency with antenatal-onset but mild symptoms and long-term survival. The result of this study showed that stressor factors, particularly seizure, could have a substantial role in poor prognosis and early neonatal death.

Longitudinally extensive transverse myelitis as a sign of multisystem inflammatory syndrome following COVID-19 infection: A pediatric case report.

COVID-19 infection can cause inflammatory reactions that could involve several organs. In the pediatric population, Multi-System Inflammatory Syndrome in Children (MIS-C) has been reported as one of the consequences of COVID-19. We report a unique pediatric COVID-19 patient with MIS-C, associated with paralysis of the extremities. MRI showed abnormal signal in the cervical spinal cord compatible with transverse myelitis. Methylprednisolone and IVIG were administered, without significant symptom improvement. As a next step, Infliximab was tried for her, and she responded remarkably well to this treatment. Infliximab may be considered as a treatment option in COVID-19 patients with transverse myelitis.

Efficacy of Levetiracetam in Treatment of Childhood Stuttering.

BACKGROUND: Stuttering is a kind of speech disorder that affects about 1% of total population. As the origin of this disorder is not obviously diagnosed yet, various remedies have been practiced and among them different medicines have been studied, but unfortunately no significant effective drugs have been recognized yet. As stuttering imposes a great social and mental costs to the patients and their families, finding an effective medicine will help significantly. In this study we have focused on the effects of levetiracetam (LEV) treatment on children suffering from stuttering. METHODS: In this clinical trial study, 30 children aged > 3 years (median 3.8 years) with stuttering and abnormal sleep electroencephalogram (EEG) were treated by LEV and followed-up for a minimum period of 6 weeks. The starting dose of 20 mg/kg/day was increased at an interval of 1 week by 20 mg/kg/day, if necessary, up to maximum dose of 60 mg/kg/day. RESULTS: Overall LEV was effective in 70% of patients, decreasing stuttering to at least 50%. Three children (10%) became stuttering-free and only in one (3.3%) child an increase in stuttering was observed. There were statistically significant differences for efficacy in the presence of variables such as age groups, seizure, stuttering family history, and EEG data. CONCLUSIONS: LEV is an effective drug for treatment of childhood stuttering in those that have abnormal sleep EEG.