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Author(s): Mohammad Reza Mohammadi [sup.1] [sup.2] , Zahra Hooshyari [sup.1] [sup.3] , Ali Delavar [sup.3] , Man Amanat [sup.4] , Abolfazl Mohammadi [sup.5] , Imaneh Abasi [sup.6] , Mona Salehi [...], The Millon clinical multiaxial inventory fourth version (MCMI-IV) is a self-report assessment tool intended to provide information on personality disorders. This study aimed to assess the diagnostic validity of this tool. Participants with recent diagnosis of psychiatric disorders were included in the study. They were interviewed using structured clinical interview for diagnostic and statistical manual of mental disorders-5 (SCID-5) and MCMI-IV. The results showed that the Kappa agreement between the MCMI-IV and SCID-5 ranged between 0.23 to 0.39. The discriminant function analysis was conducted to predict personality clusters and other psychiatric disorders. Schizoid and cluster B personality including antisocial, histrionic, and narcissistic personality disorders were predicted by the MCMI-IV scales. Axis I disorders including major depressive disorder, persistent depressive disorder, bipolar mood disorder, and substance use were also predicted by this assessment tool. MCMI-IV scales were, however, not the predictor of other personality and Axis I psychiatric disorders. Sensitivity (23.08% in somatic symptom to 66.7% in drug and alcohol use), specificity (72.52% in generalized anxiety disorder or GAD to 95.61% schizophrenic spectrum), positive predictive probability (PPP) (6.67% in post-traumatic stress disorder or PTSD to 57.35% in cluster B personality) and negative predictor probability (NPP) (80.81% in GAD to 98.15% in PTSD) were estimated. Overall the validity indexes of MCMI-IV improved compared to the previous version of MCMI but these findings suggested that the diagnostic validity of MCMI-IV was not yet acceptable in some clinical scales and further improvements are needed.

Background: The most common manifestation of X‐linked adrenoleukodystrophy (ALD) is a slowly progressive myeloneuropathy, which leads to imbalance and gait disturbances. The variable progression of the disease complicates evaluation of its progression rate. Wearable sensors allow for easy and frequent balance and gait collection. This study reports baseline data from a longitudinal study on the quantitative assessment of balance and gait with wearable sensors and their clinical relevance. Methods: Data were collected from adult patients in two institutions. Postural body sway and gait parameters were measured using accelerometers. Disease severity was measured by the Expanded Disability Severity Scale (EDSS). Falling frequency and quality of life (QOL) were collected in men. The relationship between sway and gait variables and EDSS score, participants' use of a walking aid, and falling frequency was evaluated. Results: One hundred twenty individuals with ALD were included. Sway variables significantly differentiate participants' assistive device use. Sway and gait variables were correlated to the EDSS in both sexes. Both gait speed and sway were correlated with falling frequency in men from one institution. Select QOL subscores were correlated with the EDSS in males from one institution. Accelerometry generated comparable results across sites. Discussion: This study confirms the clinical correlation between spinal cord disease and imbalance and gait in ALD. For the first time, this study shows clinically meaningful relationships for sway and gait with use of an assistive device, falling frequency and QOL. Wearable accelerometers are a valid means to measure sway and gait in ALD. These measures are promising outcomes for clinical trial designs to assess myeloneuropathy in ALD and to monitor disease progression in individuals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many studies have investigated the efficacy and safety of anti-epileptic drugs (AEDs) in adulthood migraine prophylaxis. Topiramate was the only US FDA-approved preventive migraine medication for the pediatric population, but a recent multi-center population-based study showed that its efficacy was similar to placebo ([4]). A few small, sample-sized RCTs investigated the safety and efficacy of divalproex sodium, sodium valproate, and levetiracetam in migraine prophylaxis of children and adolescents ([5][6]-[7]). [Extracted from the article]

Cell-based therapy has shown promising outcomes in the treatment of cerebral palsy (CP). However, there is no consensus on a standard therapeutic protocol regarding the source of cells, optimal cell dose, timing and frequency of cell injections, route of administration, or the use of combination therapy. This lack of consensus necessitates a comprehensive investigation to clarify these crucial yet undefined factors in cell-based therapy for CP patients. In this commentary, we discuss and compare the trends in Gross Motor Function Measure-66 following intrathecal injection of umbilical cord blood mononuclear cells (UCB-MNCs) and umbilical cord tissue mesenchymal stromal cells (UCT-MSCs) in children with CP. Our study revealed that MNC injections led to earlier improvements in gross motor function, whereas MSC applications resulted in more sustainable changes. These findings provide key insights into the efficacy of different cell types, which will be beneficial for future studies and for refining cell-based therapy protocols for CP treatment. [ABSTRACT FROM AUTHOR]

Antisense oligonucleotides (ASOs) are disease-modifying agents affecting protein-coding and noncoding ribonucleic acids. Depending on the chemical modification and the location of hybridization, ASOs are able to reduce the level of toxic proteins, increase the level of functional protein, or modify the structure of impaired protein to improve function. There are multiple challenges in delivering ASOs to their site of action. Chemical modifications in the phosphodiester bond, nucleotide sugar, and nucleobase can increase structural thermodynamic stability and prevent ASO degradation. Furthermore, different particles, including viral vectors, conjugated peptides, conjugated antibodies, and nanocarriers, may improve ASO delivery. To date, six ASOs have been approved by the US Food and Drug Administration (FDA) in three neurological disorders: spinal muscular atrophy, Duchenne muscular dystrophy, and polyneuropathy caused by hereditary transthyretin amyloidosis. Ongoing preclinical and clinical studies are assessing the safety and efficacy of ASOs in multiple genetic and acquired neurological conditions. The current review provides an update on underlying mechanisms, design, chemical modifications, and delivery of ASOs. The administration of FDA-approved ASOs in neurological disorders is described, and current evidence on the safety and efficacy of ASOs in other neurological conditions, including pediatric neurological disorders, is reviewed.