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Background : Infectious disease outbreaks affect physical and mental health of humans worldwide. Studies showed that the prevalence of post-traumatic stress disorder (PTSD) symptoms increased in these conditions. This systematic-review and meta-analysis aimed to assess the prevalence of PTSD related symptoms in coronavirus outbreaks. Methods : Systematic search of literature was conducted in Scopus, Embase, PubMed, and Web of Science. Google Scholar and Grey literature including conference proceedings were also checked. Published articles from November 1, 2012 until May 18, 2020 were searched. Subgroup analysis, meta-regression and sensitivity analysis were also conducted to assess heterogeneity. Results : We found 38 articles with 19,428 individuals met the eligibility criteria. Of these papers, 35 studies were included in meta-analysis. The prevalence of PTSD symptoms was estimated to be about 18% (95%CI: 15% to 20%). These symptoms were more frequent in cohort studies (29%) compared to cross-sectional (15%) and case-control (11%) studies. Prevalence rates of PTSD symptoms in MERS (36%) outbreaks were higher than SARS (18%) and COVID-19 (9%) outbreaks. Meta-regression showed that the geographical location of study was the source of heterogeneity (R2: 19.8%, P-value: 0.003). Meta-analysis reported that about three in every ten survivors of coronavirus infection, about two in every ten healthcare workers, and about one in every ten individuals of general population experienced PTSD symptoms in outbreaks. Limitations : PTSD cannot be objectively assessed and this can lead to information bias of included studies. Conclusion : PTSD symptoms are shown to be common in coronavirus outbreaks. Mental care should be, therefore, considered in the present COVID-19 pandemic.

Background Obsessive-compulsive disorder (OCD) is an anxiety disorder that causes impairment in daily activities. This study aimed to assess the safety and efficacy of transcranial direct current stimulation (tDCS) as adjunctive therapy with fluoxetine in individuals diagnosed with moderate to severe OCD. Methods This is a randomized, double-blind sham-controlled trial. Individuals with OCD who had baseline Yale-Brown obsessive-compulsive scale (Y-BOCS) of > 15 were enrolled. Eligible cases were randomly assigned in 1:1 ratio to receive either 20-min-period of stimulation with tDCS and fluoxetine (experimental arm) or fluoxetine only (sham control arm). The anodal electrode of tDCS was placed over the left dorsolateral prefrontal cortex (Fp3) and the cathodal electrode was placed over the right orbitofrontal cortex (F8). Two mA electrical stimulation with the tDCS was used for 20 min in individuals of experimental group. In the control group, electrodes were placed and stimulation was administered for 30 s to induce the same skin sensation as in experimental group. This procedure was performed three times per week for 8 weeks. Y-BOCS test was assessed at baseline, week 4 (after 12th stimulation), week 8 (after 24th stimulation), and 1 month after the last stimulation. The primary endpoints were the mean changes in Y-BOCS total score from baseline to the last visit. The secondary endpoints were the mean changes in obsession and compulsion sub-scores from baseline to the last visit. Adverse events were also assessed. Mixed design repeated measures analysis of variance assessed the endpoints. Results Sixty individuals (30 in each group) were participated. All individuals in control group and 28 cases in experimental arm completed the trial. The mean Y-BOCS (F(1.85) = 30.83; P (2.23) = 25.01; P (2.06) = 10.81; P P > 0.05). The tDCS was well tolerated and no major adverse events were reported. Conclusion This study showed that among individuals with moderate to severe OCD, there was no significant difference regarding OC symptoms between cases used tDCS as adjunctive therapy with fluoxetine and individuals used fluoxetine only. Trial registration IRCT2017030632904N1. Registered 14 July 2017, http://irct.ir/user/trial/44193/view

Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.

Background Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. Methods We carried out a randomized double-blind placebo-controlled trial in the Children’s Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. Results A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: −8.0; 95% confidence interval (CI): −9.3 to −6.6), sodium valproate (difference: −8.3; 95% confidence interval: −9.3 to −7.2), and placebo (difference: −4.4; 95% confidence interval: −5.4 to −3.4) arms. The decrease was statistically greater in cinnarizine (difference: −3.6; 95% confidence interval: −5.5 to −1.6) and sodium valproate (difference: −3.9; 95% confidence interval: −5.8 to −1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: −4.6; 95% confidence interval: −5.2 to −4.0; sodium valproate: −4.0; 95% confidence interval: −4.8 to −3.3; placebo: −2.6; 95% confidence interval: −3.4 to −1.8). The decrease was statistically greater in cinnarizine (difference: −2.0; 95% confidence interval: −3.2 to −0.8) and sodium valproate (difference: −1.5; 95% confidence interval: −2.7 to −0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. Conclusion Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.

Interpersonal violence (IPV) is a major public health concern with a significant impact on physical and mental health. This study was designed to evaluate age–sex-specific IPV mortality trends and the assault mechanisms (firearm, sharp objects, and other means), at national and provincial levels, in Iran. We used the Iranian Death Registration System (DRS) and the population and housing censuses in this analysis. Spatio-temporal and Gaussian Process Regression methods were used to adjust for inconsistencies at the provincial level and to integrate data from various sources. After assessing their validity, all records were reclassified according to the International Classification of Diseases, 10th Revision (ICD-10). All ICD-10 codes were then mapped to Global Burden of Disease (GBD) 2013 coding. More than 700 individuals died due to IPV in 1990 and more than twice this number in 2015. The IPV mortality age-standardized rate, per 100,000, increased from 1.62 (95% Uncertainty Interval [UI] = [0.96, 2.75]) in 1990 to 1.81 [1.15, 2.89] in 2015. Among females, the age-standardized mortality rate at national level per 100,000 due to IPV was 1.27 [0.66, 2.43] in 1990 and decreased to 1.08 [0.60, 1.96] in 2015. Among males, the age-standardized mortality rate was 1.96 [1.25, 3.09] in 1990 rising to 2.54 [1.70, 3.82] in 2015. Data from provinces revealed that during the period of our study, Hormozgan province had the largest increase of IPV among females, and Fars province had the largest increase of IPV among males. Conversely, the largest decrease was detected in West Azarbaijan and Qom provinces in females and males, respectively. This study showed a wide variation in the incidence and trends of IPV in Iran by age, sex, and location. The study has provided valuable information to reduce the burden of IPV in Iran and a means to monitor future progress through repeated analyses of the trends.

Backgrounds The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. Methods Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. Results We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. Conclusion Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

Background This study assessed the safety and efficacy of intrathecal injection of umbilical cord tissue mesenchymal stem cells (UCT-MSC) in individuals with cerebral palsy (CP). The diffusion tensor imaging (DTI) was performed to evaluate the alterations in white-matter integrity. Methods Participants (4–14 years old) with spastic CP were assigned in 1:1 ratio to receive either UCT-MSC or sham procedure. Single-dose (2 × 107) cells were administered in the experimental group. Small needle pricks to the lower back were performed in the sham-control arm. All individuals were sedated to prevent awareness. The primary endpoints were the mean changes in gross motor function measure (GMFM)-66 from baseline to 12 months after procedures. The mean changes in the modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also assessed. Secondary endpoints were the mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR). Results There were 36 participants in each group. The mean GMFM-66 scores after 12 months of intervention were significantly higher in the UCT-MSC group compared to baseline (10.65; 95%CI 5.39, 15.91) and control (β 8.07; 95%CI 1.62, 14.52; Cohen’s d 0.92). The increase was also seen in total PEDI scores (vs baseline 8.53; 95%CI 4.98, 12.08; vs control: β 6.87; 95%CI 1.52, 12.21; Cohen’s d 0.70). The mean change in MAS scores after 12 months of cell injection reduced compared to baseline (−1.0; 95%CI −1.31, −0.69) and control (β −0.72; 95%CI −1.18, −0.26; Cohen’s d 0.76). Regarding CP-QoL, mean changes in domains including friends and family, participation in activities, and communication were higher than the control group with a large effect size. The DTI analysis in the experimental group showed that mean FA increased (CST 0.032; 95%CI 0.02, 0.03. PTR 0.024; 95%CI 0.020, 0.028) and MD decreased (CST −0.035 × 10-3; 95%CI −0.04 × 10-3, −0.02 × 10-3. PTR −0.045 × 10-3; 95%CI −0.05 × 10-3, −0.03 × 10-3); compared to baseline. The mean changes were significantly higher than the control group. Conclusions The UCT-MSC transplantation was safe and may improve the clinical and imaging outcomes. Trial registration The study was registered with ClinicalTrials.gov (NCT03795974).

Falls are one of the major causes of unintentional injuries. Understanding the epidemiology of fall-related mortality helps to identify the root causes of this event and planning preventive strategies to inhibit falls. The aim of this study was to assess the trend of fall-related mortality rate and its epidemiological patterns based on sex and age-groups at national and subnational levels in Iran during the years 1990 to 2015. All data were gathered from Death Registration Systems, cemetery databases of Tehran and Isfahan, the Demographic and Health Survey of 2000 and three rounds of national population and housing censuses. The age-standardized death rate (ASDR) due to falls per 100,000 people decreased from 2.61 (95% Uncertainty Interval (UI): 1.94-3.51) in 1990 to 2.13 (1.62-2.80) in 2015 at national level. Males were at higher risk of death due to falls than females. Our data showed that the elderly population was at higher risk of death due to falls and individuals less than 4-year old had the highest fall-related mortality rate among children and adolescents. Our data should be used to accelerate interventions to reduce fall-related mortality.

Introduction: Guillain-Barré syndrome is an immune-mediated peripheral neuropathy characterized by different clinical manifestations. We aimed to describe the clinical features, seasonal distribution, subtypes, and electrodiagnostic characteristics of Iranian children with Guillain-Barré syndrome. Methods: In this prospective study, a total of 30 children with Guillain-Barré syndrome were evaluated. All demographic features were collected and electrodiagnostic study was assessed. Results: Twelve participants were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy and 18 patients were identified with acute motor axonal neuropathy. The initial findings showed that a significant number of patients (23 cases, P = .003) resided in rural areas. Our results showed a higher incidence of Guillain-Barré syndrome in summer and autumn months. No significant difference was observed between the seasonal distribution of acute inflammatory demyelinating polyradiculoneuropathy and acute motor axonal neuropathy subtypes. Antecedent history of pulmonary infections was recorded in 14 children with Guillain-Barré syndrome. Electrophysiological findings revealed a pattern of prolonged F wave latency with reduced persistency, absence of sensory nerve action potential, reduced compound muscle action potential amplitude, prolonged distal motor latency, reduced nerve conduction velocity, and abnormal temporal dispersion or conduction block in most patients with acute inflammatory demyelinating polyradiculoneuropathy. However, reduced compound muscle action potential amplitude, F wave with normal latency and reduced persistency, normal sensory nerve action potential amplitude, normal distal latency, normal sensory nerve conduction velocity, and conduction block or temporal dispersion were observed in most acute motor axonal neuropathy patients. Conclusion: The data support a correlation between Guillain-Barré syndrome incidence with seasonal variation and living area. Further studies should assess the Guillain-Barré syndrome features in pediatric population.

Background Specific phobia (SP) is one of the most common mental disorders among general population. In this national survey in Iran, we aimed to identify the lifetime prevalence, predictors, and co-morbidities of SP among children and adolescents. Methods A face-to-face household interview was applied by 250 skilled clinical psychologists using the Persian version of the kiddie schedule for affective disorders and schizophrenia for school-age children/present and lifetime version (K-SADS-PL) to determine the prevalence of SP and its co-morbid conditions. Results About 30 000 individuals participated in this study. We identified 923 individuals (378 boys and 545 girls) with SP. The lifetime prevalence rate of SP was 4.8%. This condition was related to gender, age, and type of settlement. Female gender and living in urban areas were the main positive predictors of developing SP. We showed that parental educations and their history of psychiatric hospitalization were not predictors of SP occurrence. Anxiety and behavioral disorders were the most common reported co-morbidities in our included children and adolescents. Conclusions The findings of this study indicate that SP is a prevalent disorder among pediatric population with different co-morbidities and should not be underestimated.

Childhood leukodystrophies are a fast-growing field of pediatric neurology practice. Epidemiologic studies on the incidence of these disorders in children show different results. This is the first report of childhood leukodystrophies incidence from Iran. The enrolled patients were recruited from the neurometabolic bioregistry system that was organized in 2010 in the Children’s Medical Center, Tehran, Iran. Herein is reported the incidence rate of leukodystrophies in those patients who were residents of 2 big popular provinces near Iran’s capital city Tehran, with an average child population of 2 988 800 children. Ninety cases of leukodystrophies from Tehran and Alborz provinces who were registered between 2010 and 2016 in the bioregistry system were enrolled in this study. The annual incidence of inherited white matter disorders was 3.01/100 000, the highest number compared with those found in other studies using similar methods throughout the world. One of the main cause of this higher incidence could be the higher number of consanguineous marriages in Iran.

Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases. Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used MEDLINE, EMBASE, and GOOGLE SCHOLAR to provide an extensive update about epidemiology, classifications, pathology, clinical findings, diagnostic tools, and treatments of leukodystrophies. Comprehensive evaluation of clinical findings, brain magnetic resonance imaging, and genetic studies play the key roles in the early diagnosis of individuals with leukodystrophies. No cure is available for most heritable white matter disorders but symptomatic treatments can significantly decrease the burden of events. New genetic methods and stem cell transplantation are also under investigation to further increase the quality and duration of life in affected population. Expert opinion: The improvements in molecular diagnostic tools allow us to identify the meticulous underlying etiology of leukodystrophies and result in higher diagnostic rates, new classifications of leukodystrophies based on genetic information, and replacement of symptomatic managements with more specific targeted therapies. Abbreviations: 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A–related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus‐Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive

Background Social anxiety disorder is a frequent psychiatric disorder. We aimed to estimate the life-time prevalence, socio-demographic characteristics, risk factors and co-morbidities of this condition among children and adolescents. Methods This was a cross sectional national survey conducted in Iranian individuals aged 6 to 18 years. Face-to-face household interviews were performed by trained clinical psychologists. The Farsi version of the kiddie schedule for affective disorders and schizophrenia for school-age children/present and lifetime version (K-SADS-PL) was administered to estimate the SAD prevalence. Parental personality traits and their psychopathologies were also obtained using Millon clinical multiaxial inventory, third edition (MCMI-III) to find the possible risk factors. Results From 29,878 participants, 585 individuals were diagnosed with SAD and weighted lifetime prevalence of 1.8% was observed. The odds of this condition was significantly higher among older adolescents (odds ratio (OR):1.47; 95% confidence interval(CI): 1.11-1.95) and individuals with paternal history of psychiatric hospitalization (OR: 2.96; 95%CI: 1.29-6.79). Higher means of persistent depression disorder (OR: 1.009; 95%CI: 1.000-1.018) and melancholic personality trait (OR: 1.007; 95%CI: 1.001-1.014) in mothers as well as schizophrenia spectrum (OR: 1.014; 95%CI: 1.001-1.027) and anxiety (OR: 1.010; 95%CI: 1.010-1.021) in fathers were statistically associated with higher odds of SAD in their children. Other anxiety disorders and behavioral disorders were the most prevalent co-morbidities. Limitations The cross-sectional analysis does not enable analyses of possible causal associations. Lacking control group and follow-up periods were other major limitations that should be resolved in future studies. Conclusion Clinicians and researchers need to continue studying this condition at all levels and in all developmental periods.

Background Ribonucleases (RNases) are crucial for degradation of ribosomal RNA (rRNA). RNASET2 as a subtype of RNASEs is a 256 amino acid protein, encoded by RNASET2 gene located on chromosome six. Defective RNASET2 leads to RNASET2-deficient leukoencephalopathy, a rare autosomal recessive neurogenetic disorder with psychomotor delay as its main clinical symptom. The clinical findings can be similar to congenital cytomegalovirus (CMV) infection and Aicardi-Goutieres syndrome (AGS). Methods Herein, we presented a patient with motor delay, neurological regression, infrequent seizures and microcephaly at 5 months of age. Brain imaging showed white matter involvement, calcification and anterior temporal cysts. Basic metabolic tests, serum and urine CMV polymerase chain reaction (PCR) were requested. According to clinical and imaging findings, screening of RNASET2 and RMND1 genes were performed. The clinical data and magnetic resonance imaging (MRI) findings of previous reported individuals with RNASET2-deficient leukodystrophy were also reviewed and compared to the findings of our patient. Results Brain MRI findings were suggestive of RNASET2-deficient leukoencephalopathy, AGS and CMV infection. Basic metabolic tests were normal and CMV PCR was negative. Molecular study revealed a novel homozygous variant of c.233C > A; p.Ser78Ter in exon 4 of RNASET2 gene compatible with the diagnosis of RNASET2-deficient leukoencephalopathy. Conclusions RNASET2-deficiency is a possible diagnosis in an infant presented with a static leukoencephalopathy and white matter involvement without megalencephaly. Due to overlapping clinical and radiologic features of RNASET2-deficient leukoencephalopathy, AGS and congenital CMV infections, molecular study as an important and helpful diagnostic tool should be considered to avoid misdiagnosis.

Introduction Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine. Methods A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4–17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported. Results Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group ( p-value: 0.007). Irritability, day-time sedation, and mild tic were reported. Conclusion Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity. Trial Registration The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.

Leukodystrophies are heterogeneous group of genetic white matter disorders with a wide range of neurologic and systemic manifestations. Defects in genes encoding aminoacyl tRNA (transfer ribonucleic acid) synthetase enzymes (aaRSs) are recently identified as the etiology of some leukodystrophies. Herein, we described two unrelated children referred to Children's Medical Center, Tehran, Iran, with developmental delay, nystagmus, seizures, psuedo-bulbar palsy and dystonia. Whole exome sequencing (WES) in both patients identified a homozygous (c.2T > C) variant in exon one of RARS gene, encoding cytoplasmic arginyl-tRNA synthetase. Our finding was confirmed by segregation analysis. In silico analyses of the c.2T > C variant showed its possible pathogenic role due to the absence of the start codon. Severe hypomyelination was the common neuroimaging finding of both cases. Spinal cord involvement was found in one of our patients which was not previously reported in studies. We, therefore, showed that RARS-related hypomyelination might affect spinal cord.

The risk of epileptic seizures seems increased in several systemic autoimmune disorders including systemic lupus erythematosus, type 1 diabetes mellitus, myasthenia gravis, celiac disease, rheumatoid arthritis, Hashimoto’s encephalopathy, psoriasis, multiple sclerosis, neuromyelitis optica, and bullous pemphigoid. Immune dysfunction may be partly responsible for this association. Elevated levels of pro-inflammatory cytokines, autoantibodies seen in these autoimmune disorders and antibodies against neuronal antigens may contribute to the etiopathogenesis of seizures and epilepsy associated to immune conditions. Other unknown factors, the effect of different co-morbid conditions of epilepsy as well as shared risk factors such as common etiological factors, environmental triggers, or a common genetic predisposition may also explain the association. We review different autoimmune disorders which may present with co-morbid seizures and discuss possible underlying mechanisms of this co-occurrence focusing on a potential role of immune system dysfunction.

To date, various conditions with immunodeficiency accompanied by different systemic features have been classified as other well-defined primary immunodeficiencies (PIDs). Many aspects of these diseases remain unknown due to their rarity. Furthermore, in clinical care, it was pointed out that morbidities of disorders continued to be under-recognized and sometimes under-managed. Respiratory manifestations are common in PIDs including other well-defined ones. However, they remained underappreciated in literature, while they are one of the commonest causes of death among this population. Recurrent upper and lower respiratory tract infections as the result of immunodeficiency are the most frequent respiratory features in these diseases. By underestimating these infections, different complications such as bronchiectasis may occur which can lead to poorer prognosis and even early death of patients. Intravenous immunoglobulin (IVIg) therapy is now a good option in treatment and prevention of these infections. Also, stem cell transplant is a choice for long-term prevention due to repairing immune system. Other reported pathologic respiratory tract features in individuals with other well-defined PIDs include asthma and malignancies. Overall, in this chapter, we review different conditions in other well-defined PIDs which their respiratory manifestations were reported in literature.

Introduction: Vanishing white matter disease (VWM) is considered as one of the most frequent types of inherited childhood leukoencephalopathies. Various neurological and non-neurological manifestations have been reported in this type of leukodystrophy; however, seizures are rarely described in infantile type of VWM. Case Presentation: To patient is a 12 months old boy who experienced frequent seizures at 4th month of age. The seizures were resistant to anti-epileptic drugs and caused 3 periods of hospitalization. Magnetic resonance imaging (MRI) demonstrated demyelinating pattern and whole exome sequencing (WES) reported homozygous mutation (c.922G > A) in EIF2B2 gene in exon 8 leading to an amino-acid substitution (p.Val308Met). Conclusions: Infantile onset of vanishing white matter disease can be considered as one of few childhood leukodystrophies that are associated with early onset seizures.

Background: Cerebral Palsy (CP) constitutes a heterogeneous group of developmental disorders resulting from damage to the brain which affects motor system. Cerebrolysin, as a neurotrophic peptide has been used for improving symptoms of patients suffering from neurodegenerative disorders. Objectives: Due to the presence of limited information about the usefulness of Cerebrolysin in CP, this study was performed for the evaluation of Cerebrolysin in the management of spasticity in children with CP. Methods: 26 Spastic CP patients aged between 2 and 6 years entered this study. At the first visit, Modified Ashworth scale for assessment of spasticity was used. Then Cerebrolysin was administered at a dose of 0.1 cc/kg intramuscularly (IM) for 3 months. In the first month, the medication was injected 5 times per week. In the second month of therapy, injections were performed as follows: 4 injections in the first week, 3 injections in the second week, 2 injections in the third week and a single one in the fourth week. In the third month of therapy, Cerebrolysin was continued as weekly injections. The spasticity of the patients was evaluated at the end of the first and third month of therapy. Results: Modified Ashworth score at baseline was 20.62 ± 9.65 which reached 15.19 ± 7.30 after 1 month of treatment. This figure was 14.81 ± 3.77 at month 3. Total decline in Modified Ashworth Scale was 5.42 ± 5.33 at the first month and 5.81 ± 2.74 at the third month in comparison to baseline. The difference between Modified Ashworth Scale at baseline and 1 month after therapy was significant (P = 0.000) but there was no significant difference between first month and third month of therapy. (P = 0.755). Also analysis indicates that there was an association between absolute reduction of Modified Ashworth score and the age at beginning of treatment (P = 0.037). Conclusions: Using Cerebrolysin as a neurotrophic peptide may improve spasticity of children with CP and should be considered as a possible useful treatment in CP cases. © 2018, Iranian Journal of Pediatrics.

Background Whether antidiabetic glitazone drugs protect against Parkinson's disease remains controversial. Although a single clinical trial showed no evidence of disease modulation, retrospective studies suggest that a disease‐preventing effect may be plausible. The objective of this study was to examine if the use of glitazone drugs is associated with a lower incidence of PD among diabetic patients. Methods We compared the incidence of PD between individuals with diabetes who used glitazones, with or without metformin, and individuals using only metformin in the Norwegian Prescription Database. This database contains all prescription drugs dispensed for the entire Norwegian population. We identified 94,349 metformin users and 8396 glitazone users during a 10‐year period and compared the incidence of PD in the 2 groups using Cox regression survival analysis, with glitazone exposure as a time‐dependent covariate. Results Glitazone use was associated with a significantly lower incidence of PD compared with metformin‐only use (hazard ratio, 0.72; 95% confidence interval, 0.55‐0.94; P = 0.01). Conclusions The use of glitazones is associated with a decreased risk of incident PD in populations with diabetes. Further studies are warranted to confirm and understand the role of glitazones in neurodegeneration. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Psoriasis used to be known as a skin disorder; however, it can now be considered as a systemic disease with the involvement of multiple organs. Neurological and psychiatric disorders are some of the associated problems that can be observed in patients with psoriasis. Stroke, multiple sclerosis, seizure, migraine, restless leg syndrome, Parkinson’s disease, Guillain-Barré syndrome, and myasthenia gravis are the reported neurological diseases, while depression, bipolar mood disorder, anxiety, psychosis, cognitive impairment, personality disorders, sexual disorders, sleep disturbance, and eating disorders are the recognized psychiatric presentations in patients with psoriasis. Herein, the neurological and psychiatric disorders of psoriasis are described.

Background Comorbid neurological conditions associated with spinal cord injury (SCI) significantly affect an individual's quality of life, yet they are often underrated. Recent reports suggest that SCI may predispose patients to develop other neurological disorders. We aim at providing an overview of the evidence of neurological conditions which are or seem resultant of SCI. Methods We conducted a literature review using PUBMED and GOOGLE SCHOLAR to evaluate the occurrence of different neurological disorders in people with SCI. Results Individuals with SCI seem at an increased risk of stroke, cognitive impairment, dementia, multiple sclerosis, Parkinson's disease, restless leg syndrome, and seizures. The co-occurrence of Guillain-Barre syndrome, and myasthenia gravis, were also reported. Conclusion Neurological comorbidities in individuals with SCI may lead to poor long-term outcomes, which could be minimized by early diagnosis and treatment of these conditions.

This article is an Editorial and does not include an Abstract.