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The evidence for the hemispheric specialization of motor planning reveals several inconsistencies between the left-lateralized hypothesis and a distributed system across the hemispheres. We compared participants with left hemiplegic cerebral palsy (HCP) to right-handed control subjects in this study's first experiment by inviting them to perform a motor planning task. Participants were required to release the start button, grasp a hexagon, and rotate it according to the instructions. In the second experiment, we compared left-HCP subjects with right-HCP subjects inviting them to perform the same task (we used the data for left-HCP subjects from the first experiment). P2 amplitude, as well as planning time, grasping time, releasing time, and initial grip selection planning patterns, were used as outcome measures in both experiments. The first experiment revealed that controls acted more quickly and chose more effective planning patterns. Also, the P2 amplitude was smaller in left-HCP subjects than in control subjects. No significant group effect was observed in the second experiment for any movement-related measure or P2. At the neural level, however, there was an interaction between 'region' and 'group,' indicating the distinction between the two groups in the right region. The results are discussed in terms of motor planning's hemispheric distribution and individual differences in the HCP group.

Background Autosomal recessive genetic disorders are leading health concerns in countries with consanguineous marriage. However, previously there was no strong association of consanguinity with autosomal dominant or X-linked inheritance patterns. Whether this would be the case in singlet consanguineous families remained unexplored. Methods The current study aimed to identify the disease genes and their inheritance patterns in 12 independent Iranian consanguineous singlet families with syndromic autism. Results Exome sequencing revealed two missense and two nonsense variants (one in each gene: IQSEC2, FOXG1, DMD, and CHKB) in four out of 12 families, thereby offering an aetiologic diagnosis. Autism, intellectual disability, learning disability, developmental delay, and behavioral problems were common features in these four families, and three individuals presented with impaired motor skills such as abnormal gait. Muscular dystrophy coupled with hypotonia were noted in two individuals, whereas in the remaining two families ADHD combined with language/speech delay were present. Along with the two X-linked (IQSEC2 and DMD), one autosomal dominant (FOXG1) and one autosomal recessive genes (CHKB) were found in these four consanguineous families. Two genes-DMD and CHKB- are known to be mainly involved in muscular dystrophy. Limitation: our study significance is limited by the small sample size, 12 individuals, and lack of functional experiment on a VUS on the DMD variant. Conclusion Our findings illustrate the mixed inheritance pattern in consanguineous singlet families and highlight the association of autism spectrum disorder with muscular dystrophy, both of which are seemingly not related.

Introduction & Background. Central nervous system (CNS) tumors are common types of malignancies in children and the recognition of these tumors and related factors can help to improve the prognosis. The purpose of the present study was to evaluate demographic, neuroradiological, and neuropathological characteristics in 1-14-year-old children with central nervous system tumors in the Department of Pediatrics of Shohada-e Tajrish Hospital. Methods. In this descriptive study, 96 children aged 1-14 years with central nervous system tumors in the Department of Pediatrics of Shohada-e Tajrish Hospital from 2014 to 2016 were selected by convenience sampling, and the demographic, neuroradiological, and neuropathological characteristics were determined and compared according to other variables. Results. 60.4% of the patients were aged 1-10 years and 55.2% of them were male. The most common types of tumors were astrocytoma (33.3%), glioma (16.7%) and medulloblastoma (10.4%). 46.9% of the tumors were supratentorial and 53.1% were infratentorial. Enhancement was observed in 53.1% of the patients in imaging. Conclusion. Overall, based on the obtained results, it may be concluded that the most common types of CNS tumor in children are astrocytomas and these tumors are usually infratentorial with enhancement in imaging.

Background Niemann-Pick disease type C (NPC) is a rare lysosomal neurovisceral storage disease caused by mutations in the NPC 1 (95%) or NPC2 (5%) genes. The products of NPC1 and NPC2 genes play considerable roles in glycolipid and cholesterol trafficking, which could consequently lead to NPC disease with variable phenotypes displaying a broad spectrum of symptoms. Materials In the present study 35 Iranian NPC unrelated patients were enrolled. These patients were first analysed by the Filipin Staining test of cholesterol deposits in cells for NPC diagnostics. Genomic DNA was extracted from the samples of peripheral blood leukocytes in EDTA following the manufacturer's protocol. All exon–intron boundaries and coding exons of the NPC1gene were amplified by polymerase chain reaction (PCR) using appropriate sets of primers. Thereafter, the products of PCR were sequenced and analysed using the NCBI database (https://blast.ncbi.nlm.nih.gov/Blast.cgi). The variants were reviewed by some databases including the Human Gene Mutation Database (HGMD) (http://www.hgmd.cf.ac.uk/ac/index.php) and ClinVar (https://www.ncbi.nlm.nih.gov/clinvar (. Moreover, all the variants were manually classified in terms of the American College of Medical Genetics and Genomics (ACMG) guideline. Results The sequence analysis revealed 20 different variations, 10 of which are new, including one nonsense mutation (c.406C > T); three small deletions, (c.3126delC, c.2920_2923delCCTG, and c.2037delG); and six likely pathogenic missense mutations, (c.542C > A, c.1970G > A, c.1993C > G, c.2821 T > C, c.2872C > G, and c.3632 T > A). Finally, the pathogenicity of these new variants was determined using the ACMG guidelines. Conclusion The present study aimed to facilitate the prenatal diagnosis of NPC patients in the future. In this regard, we identified 10 novel mutations, and verified that the majority of them occurred in six NPC1 exons (5, 8, 9, 13, 19, and 21), that should be considered with a high priority for Iranian patients' cost-effective evaluation.

Lysosomal storage diseases (LSDs) are known as genetic disorders with an overall prevalence of 1 per 7700 live births. Sphingolipidosis, which is a subgroup of LSDs, is resulted from mutations in the coding genes of specific enzymes of sphingolipid hydrolases. The current study aimed to provide additional knowledge on the genotype of sphingolipidoses disease among Iranian patients affected by the disease. In this research, we studied 68 unrelated Iranian patients diagnosed with one kind of sphingolipidoses from 2014 to 2019. Thereafter, genomic DNA was isolated from their peripheral blood leukocytes samples in EDTA in terms of the manufacturer’s protocol. All the coding exons and exon–intron boundaries of the related genes were sequenced and then analyzed using the NCBI database. Finally, they were reviewed using some databases such as the Human Gene Mutation Database (HGMD) and ClinVar ( https://www.ncbi.nlm.nih.gov/clinva ). By studying 22 MLD patients, 18 different variations of the ARSA gene were found, one of which was new including, named as c.472 T > G p. (Cys158Gly). Out of 15 Sandhoff disease (SD) patients, 11 different variations of the HEXB gene were found. Correspondingly, the c.1083-2delA was not reported earlier. By investigating 21 Iranian patients with Tay-Sachs disease (TSD), one new variant was found as c.622delG. The study of 10 Niemann–Pick disease A/B (NPDA/B (patients has led to the identification of 9 different SMPD1 gene variations, among which 3 variations were novel mutations. The results of the present study can be expanded to the genotypic spectrum of Iranian patients with MLD, SD, TSD, and NPD diseases and also used to innovate more effective methods for the detection of genetic carriers as well as diagnosing and counseling of Iranian patients affected with these disorders.

Background CD59 deficiency is a congenital mutation disorder in complement pathway which can present with various manifestations. Case presentation Herein, we presented an adolescent 16-years-old girl with recurrent attacks of Guillain-Barre in early childhood and then recurrent attacks of angioedema, paresthesia, and myelitis. Finally, she presented with quadriplegia, malar rash, proteinuria, lymphopenia, and high titer of antinuclear antibody. So, the patient developed systemic lupus erythematosus. Furthermore, we performed whole exome sequencing which revealed homozygote mutations in CD59 for the patient and heterozygote one for her parents. CD flow cytometry showed less than 1 percent expression of CD59 on the surface of the patient’s peripheral blood cells confirming the disorder. So, she had CD59 deficiency. The patient’s episodes were managed with plasma exchanges, corticosteroids, Cyclophosphamide, and Mycophenolate Mofetil which induced and maintained remission. Conclusion CD59 deficiency can be presented with various clinical features such as neurologic, hematologic, dermatologic, and rheumatologic problems including systemic lupus erythematosus.

Background: Nemaline myopathy has been associated with mutations in twelve genes to date. However, for some patients diagnosed with nemaline myopathy, definitive mutations are not identified in the known genes, suggesting there are other genes involved. This study describes compound heterozygosity for rare variants in RYR3 in one such patient. Results: Clinical examination of the patient at 22 years of age revealed a long-narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear areas, subsarcolemmal and within the cytoplasm. No likely pathogenic mutations in known nemaline myopathy genes were identified. Copy number variation in known nemaline myopathy genes was excluded by nemaline myopathy targeted array-CGH. Next generation sequencing revealed compound heterozygous missense variants in the ryanodine receptor type 3 gene (RYR3). RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain or cauda equina samples. Immunofluorescence of human skeletal muscle revealed a "single-row" appearance of RYR3, interspaced between the "double-rows" of RYR1 at each A-I junction. Conclusion: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain and the subcellular localization of RYR1 and RYR3 in human skeletal muscle. CC BY 4.0

Objective Knowledge about epilepsy and attitudes towards patients with epilepsy can affect measures taken to manage epilepsy and seizures. Support and understanding of mothers is invaluable in enabling children with epilepsy to develop normal life skills in living with epilepsy. In order to identify the educational needs of mothers of children with epilepsy, their knowledge, attitudes, and practices should be assessed. Therefore, we interviewed a group of mothers of children with epilepsy who were referred to a pediatric neurology clinic in a teaching hospital. The objective of this study was to assess knowledge, attitudes, and practices among mothers of children with epilepsy in order to identify their educational needs. Methods In the period of August 2014 to January 2015, mothers whose children were diagnosed with epilepsy for at least six months participated in this cross sectional study, while returning to the neurology clinic of a pediatric hospital for usual follow-up. Data were collected through face-to-face interviews, held by trained female general practitioners. The interviewer used questions from a questionnaire. The knowledge section of the questionnaire included questions regarding prevalence and general knowledge about epilepsy, its etiology, symptoms, and seizure provoking factors. The attitudes section included statements regarding the mother's attitudes towards epilepsy and patients with the disease. The practice section included questions about first-aid measures taken by mothers who had witnessed generalized seizures by the time of interview. Results Responses of 206 participants were analyzed. At least 83% of mothers knew that epilepsy is a noncontagious neurological disorder which can be treated by regular drug therapy. In spite of demonstrating good knowledge scores, the majority of mothers felt the need for further training in epilepsy. More than 98% of mothers were against the idea that patients with epilepsy should hide their disease. Though having been referred to physicians, 84% of mothers had provided their children with at least one ineffective treatment, mostly based on superstitions. Conclusion Mothers' level of knowledge of epilepsy was good, and their attitudes towards epilepsy were mainly positive. Regarding the right first-aid measures at time of the last seizure, mothers' practices were acceptable. However, there is still room for improvement regarding avoiding the wrong measures. It is suggested that both practice-related issues and other aspects of epilepsy be taken into account in epilepsy-related education programs.

THOC6 is a part of the THO complex, which is involved in coordinating mRNA processing with export. The THO complex interacts with additional components to form the larger TREX complex (transcription export complex). Previously, a homozygous missense mutation in THOC6 in the Hutterite population was reported in association with syndromic intellectual disability. Using exome sequencing, we identified three unrelated patients with bi-allelic mutations in THOC6 associated with intellectual disability and additional clinical features. Two of the patients were compound heterozygous for a stop and a missense mutation, and the third was homozygous for a missense mutation; the missense mutations were predicted to be pathogenic by in silico analysis and modeling. Clinical features of the three newly identified patients and those previously reported are reviewed; intellectual disability is moderate to severe, and malformations are variable including renal and heart defects, cleft palate, microcephaly, and corpus callosum dysgenesis. Facial features are variable and include tall forehead, short upslanting palpebral fissures +/- deep set eyes, and a long nose with overhanging columella. These subtle facial features render the diagnosis difficult to make in isolation with certainty. Our results expand the mutational and clinical spectrum of this rare disease, confirm that THOC6 is an intellectual disability causing gene, while providing insight into the importance of the THO complex in neurodevelopment.

Neurodegeneration with brain iron accumulation-2A (NBIA2A, also called infantile neuroaxonal dystrophy) is an autosomal recessive disorder of the central nervous system (CNS) caused by mutations in PLA2G6 gene. The characteristic features of NBIA2A are progressive course of mental and motor regression, cerebellar ataxia, hypotonia, spastic tetraplegia, hyperreflexia and visual defects. In the present study we report four independent cases of NBIA2A whose genetic defects have been identified through whole exome sequencing. Three novel mutations and a previously reported mutation have been detected in PLA2G6 gene in these patients. Identification of these mutations facilitated effective genetic counseling and prenatal diagnosis in the families.

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.

Dravet syndrome is a severe form of epilepsy and also is called severe myoclonic epilepsy of infancy (SMEI). It appears during the first year of life with frequent febrile se izures, fever related seizures, which is rare beyond the age of 5 years. Children with SMEI typically experience poor development of language, motor skills, hyperactivity, and difficulty in m aking relationship. Thirty to eighty percent of patients with Dra vet syndrome, which is known as classical form of SMEI, suffer from defects in a gene involved in proper function of brain cells. The patient is a 3-years-old girl presenting with a sudden epileptic seizure. She had 2-year history of severe myoclonic epilepsy and developmental delay that was diagnosed as Dravet syndrome. A novel missense substitution in sodium channel alpha subunit type 1 was detected and the novelty of substitution confirm ed by molecular analysis in healthy family members as well as control group. As an early diagnosis, the clinical screening pro cedure used by pediatricians as well as a sodium channel alpha subunit type 1 mutation analysis could help to predict Dravet syndrome before 1 year of age, so the pediatricians could be able to manage clinical work-up properly.

Genetic variability in drug metabolism affects its treatment with anti epilepsy drugs (AEDs). Allelic variations in genes include SCN1A and ABCB1. Encoding the AEDs’ target and drug transport proteins may affect the efficacy and tolerability of antiepileptic drugs. A study was designed to evaluate the frequency of the ABCB1- and the SCN1A-selected SNPs in the genotype and haplotype combination within the Iranian population who were affected by idiopathic refractory epilepsy (IRE). About 81 healthy normal samples and 34 probands, clinically diagnosed as one type of IRE, were selected. The genotype of the two SNPs in the SCN1A gene (rs2298771, rs7601520) and one SNP in ABCB1 (rs1045642) were determined in two groups by ARMS-PCR and PCR-RFLP, and confirmed by direct sequencing. The data analysis shows no statistically significant differences, and thus, the predicted haplotype frequencies (including the three SNPs) did not show any significant differences between the patients and the control groups.

Objective: This study was conducted to predict the response to treatment in patients treated with anti-epilepsy drugs. Material and Methods: This analytical questionnaire-based study was conducted in 2014 among 128 patients with epilepsy admitted to Mofid Children's Hospital, Tehran, Iran. The inclusion criteria were children 2 months to 12 yr of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. Patients were followed up for 6 months and the response to their treatment was recorded. The good response to treatment was defined as the absence of seizure with two drugs during follow up. Results: Seventy-two patients (56.3%) were boys. The age of the first seizure was under 2 yr old in 90 patients (70.3%). History of febrile convulsion, family history of epilepsy and history of asphyxia was found in 16 (12.5%), 41 (32%), and 27 (21.1%) patients, respectively. Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1-2 in 36 patients (28.1%). Overall, 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. History of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment. Conclusion: Abnormal EEG is an effective factor in treatment response in the children studied.

Objective The aim of this study was to translate and validate the psychometric properties of the Quality of Life Kindl questionnaire. Materials & Methods Parents of 4-7 yr-old healthy and ill children referred to Mofid Children Hospital in Tehran in 2013, Iran were sampled randomly in two groups each of which 130 people. After translation, the questionnaie’s validity and reliability was evaluated and was confirmed for face and content validity. Questionnaire was also completed by two (one healthy and one ill) groups for which inclusion criteria included consent of the parents, age of the children being beween 4 and 7 yr, and presence of the child in a nursery school, kindergarten, school or any class at least for one month. Exclusion criteria were inability of the parents in answering the questions accurately. Inclusion criterion for the ill group was having chronic cardiac, neurologic, hematologic, or respiratory diseases, lasting longer than 3 months for which they were followed up in outpatient clinic in the hospital. The reliability of questionnaire was measured by the Cronbach’s alpha. Data were analyzed using factor analysis, Spearman’s correlation coefficient, Mann-Whitney and Chi-square test. Results The reliability was 0.85 and 0.81 in healthy and ill groups, respectively. The results of factor analysis showed that each of eight subscales of questionnaire had acceptable construct validity. Only two of 52 questions of the questionnaire did not have proper correlation coefficient. Conclusion Quality of Life Kindl Questionnaire is a valid and reliable test for assessing healthy and ill children in Iran.

Summary Background Epilepsy is a common disease of childhood, in which almost 25% of cases are resistant to common antiepileptic drugs. Uncontrolled epilepsy increases morbidity and mortality rates, adversely affects growth and development in these children and imposes heavy psychological stress and financial burdens on parents, health care and society, making it mandatory to find effective therapies for the condition. Our aim was to study the efficacy of levetiracetam, as an add-on therapy, in children suffering from refractory epilepsy. Materials and methods In this prospective add-on study, 45 children aged 0.6–15 years (median 5.9 years) with epilepsy not responding to most conventional or new antiepileptic drugs were treated by adding levetiracetam to their present antiepileptic regimen and followed for a minimum period of 12 weeks. The starting dose of 20 mg/kg/day was increased at intervals of 1 week by 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Results Four children (8.7%) became seizure free, in 4 (8.7%), seizure frequency increased, and in 8 (17.4%) and 13 (28.3%) patients, seizure frequency decreased by 75–99% and 50–74% respectively. Overall levetiracetam was effective in 54.3% of patients, decreasing seizure frequency to at least 50% of baseline seizure frequency. Variables such as sex, age, duration of disease, type and cause of seizure, EEG and imaging data, also type of epileptic syndrome showed no statistically significant correlations with these results. Conclusion Levetiracetam can be used as an effective add-on treatment in children with refractory epilepsy.

Background and Aims Epilepsy as a common chronic neurological disorder is characterized by recurrent unprovoked seizures. Febrile seizures are the most common type of epilepsy in infants and children. Our aim was the molecular analysis of SCN1A gene in affected Iranian patients with GEFS+ and Dravet syndrome diagnosed clinically to explain genotype−phenotype correlation and exact classification. Methods The 34 unrelated Iranian families with epilepsy were selected and screened for SCN1A mutations by MLPA, ARMS, and PCR-RFLP confirmed by direct sequencing. Results MLPA analysis showed normal patterns, but direct sequencing revealed that generally 20/34 (0.588) probands have common reported single nucleotide polymorphisms (SNPs) (p.A1067G; rs2298771) with allelic frequency as 0.706/0.294 in patients and 0.515/0.485 in control group, respectively, for A/G. No significant differences between groups were observed. Moreover, four novel allelic variants as missense substitutions included two new sequence variation (p.F412 I, p.Y1274N) and two previously reported mutations (p.R101G, p.S103G) that were detected in 4/34 probands but not in control groups and other healthy normal family members. Conclusions Clinical diagnosis could nearly establish the classification, but mutation screening helps clinicians to confirm their data. We found mutation in four probands and confirmed the net diagnosis. Our data suggest that the clinical symptom variations could be also explained, considering the role of modifier genes such as mitochondrial mutations or other genes responsible for drug metabolism pathways including multiple drug resistance family genes (ABCB1) or MTHFR.

Calpainopathy is an autosomal recessive form of limb girdle muscular dystrophies which is caused by mutation in CAPN3 gene. In the present study, co-segregation of this disorder was analyzed with four short tandem repeat markers linked to the CAPN3 gene. Three apparently unrelated Iranian families with same ethnicity were investigated. Haplotype analysis and sequencing of the CAPN3 gene were performed. DNA sample from one of the patients was simultaneously sent for next-generation sequencing. DNA sequencing identified two mutations. It was seen as a homozygous c.2105C>T in exon 19 in one family, a homozygous novel mutation c.380G>A in exon 3 in another family, and a compound heterozygote form of these two mutations in the third family. Next-generation sequencing also confirmed our results. It was expected that, due to the rare nature of limb girdle muscular dystrophies, affected individuals from the same ethnic group share similar mutations. Haplotype analysis showed two different homozygote patterns in two families, yet a compound heterozygote pattern in the third family as seen in the mutation analysis. This study shows that haplotype analysis would help in determining presence of different founders.

Background Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms. Methods An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities. Results These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring. Conclusions These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

Objective Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative disorder with deposition of iron in the brain (mainly Basal Ganglia) leading to a progressive Parkinsonism, spasticity, dystonia, retinal degeneration, optic atrophy often accompanied by psychiatric manifestations and cognitive decline. 8 of the 10 genetically defined NBIA types are inherited as autosomal recessive and the remaining two by autosomal dominant and X-linked dominant manner. Brain MRI findings are almost specific and show abnormal brain iron deposition in basal ganglia some other related anatomical locations. In some types of NBIA cerebellar atrophy is the major finding in MRI.

Involvement of the central nervous system due to brucellosis is rare and has a broad range of clinical manifestations. Reported here is a case of neurobrucellosis in a 13-year-old boy leading to visual impairment and unilateral hearing loss. Cranial magnetic resonance imaging revealed a suprasellar mass with extension to the optic chiasm. This case represents a novel finding of pediatric neurobrucellosis involving the optic chiasm. The patient's visual acuity, but not hearing, improved after initiation of antibiotic therapy.

Objective Intractable epilepsy is a major difficulty in child neurology, because the numbers of drugs that are available for treatment are limited and new treatments such as diets must be tried. Now there are some diets available for treating patients with intractable epilepsy. The oldest diet is the classic ketogenic diet and one of the newest diets is the modified Atkins diet. Patients have a harder time accepting the classic ketogenic diet than the Atkins diet, which is easier to accept because the food tastes better. This study compares the efficacy of the ketogenic diet and the Atkins diet for intractable epilepsy in children. Materials & Methods This study is a clinical trial survey with sample size of 40 children with refractory epilepsy who were patients at Mofid hospital in Tehran, Iran. Initially, from Jan 2005–Oct 2007, 20 children were treated with the Atkins diet, and then from Oct 2007–March 2010, the other group was treated with the classic ketogenic diet and the results were compared. Results In this study, response to treatment was greater than a 50% reduction in seizures and at the end of first, second, and third months for the ketogenic diet were 55%, 30%, and 70% and for the Atkins diet were 50%, 65%, and 70%, respectively. Conclusion The results of this study show that there is no significant difference between the classic Ketogenic diet and the Atkins diet at the end of first, second, and third months and both had similar responses to the treatments.

Primary microcephaly (MCPH) is a genetic disorder in which affected individuals present with a head circumference 3 standard deviations (SDs) below the age- and sex-related mean and is accompanied by mental retardation without further associated malformations. Here we report a patient with sporadic MCPH from Northwest of Iran who was investigated for MCPH1 locus. Clinical examination and karyotype analyses were performed and microsatellite based mapping was done by using flanking and intragenic short tandem repeat (STR) markers for MCPH1 locus. For these markers the affected individual was homozygote and the parents were heterozygote. According to this pattern of allele sharing and also the cytogenetic findings, mutation screening of Microcephalin gene was performed and subsequent sequencing revealed a novel mutation in Microcephalin gene.

Objective Seizure is an emergency in pediatrics. It really matters to the parents of the involved child to have information about the causes, management and prognosis. First unprovoked seizures (FUS) are seizures that occur in patients without fever, trauma or infection. Due to the rapid improvement in diagnostic techniques in the last few decades, the etiology will be revealed and this term will no longer exist. This Study was designed to evaluate brain imaging findings in FUS patients. Materials & Methods Ninety-six children with FUS, who were admitted in three major children’s hospitals in Tehran, underwent brain imaging and were enrolled into the study. The decision about the type of imaging (CT or MRI) was based on the patient’s medical and financial conditions. An expert radiologist in the field of pediatric neuroimaging interpreted the images. Results Altogether, 27.1% had abnormal findings of which 29.2% were in the brain MRI group and 14.3% were in the brain CT scan group. Abnormal results were gliosis (10.4%), hemorrhage (4.2%), dysgenesis (2.1%), dysmyelination (7.3%), encephalomalacy (1%), atrophy (5.2%) and infarction (2.1%). In some patients, the lesions were in 2 or 3 sites and some had more than one type of lesion. There was no association between the duration, age and type of seizure and imaging abnormlities. However, we found an association between the location of the lesion and the type of seizure. Conclusion We recommend brain imaging in all patients with FUS and apart from some exceptions, brain MRI is superior to CT.

Objective Biotinidase deficiency is one of the rare congenital metabolic disorders with autosomal recessive inheritance. If this disorder is diagnosed in newborn period, could be prevented well from mental and physical developmental delay and most of clinical manifestations. Materials & Methods The patients were diagnosed as biotinidase deficiency in Neurology Department of Mofid Children’s Hospital in Tehran, Iran, between 2009 and 2012 were included in this study. This study was conducted to define the age, gender, past medical history, developmental status, general appearance, clinical manifestations, neuroimaging findings, and response to treatment in 16 patients with biotinidase deficiency in this department. Results In clinical presentation, cutaneous lesions were not found in 37% of the patients and 43% patients had not alopecia. 75% patients had abnormal neuroimaging that in 56% of them, generalized brain atrophy and myelination delay were found. Results of the present study showed the efficacy of biotin in early diagnosed patients with seizure and dermatological manifestations. The seizure and skin manifestations were improved after biotin therapy. Conclusion According to the results of this study, we suggest that early assessment and diagnosis have an important role in the prevention of disease progression and clinical signs.

Niemann–Pick disease type C is a rare neurodegenerative disorder with autosomal recessive inheritance that can be broadly categorized into different forms dependent on age at disease onset: pre-/perinatal, early infantile, late infantile, juvenile, and adolescent/adult. This study was conducted to define the age at onset, clinical manifestations, neuroimaging findings and response to treatment in 21 patients diagnosed with Niemann–Pick disease type C and managed in the neurology departments of hospitals in Tehran, Iran. The effects of miglustat on patient ambulation, fine and gross motor function, swallowing, hearing, speech, seizures, psychomotor development, and ocular movements were evaluated for up to 26 months of treatment. Ambulation, fine and gross motor movements, swallowing, speech, and supranuclear gaze palsy were generally stabilized during therapy, and psychomotor delay appeared to be improved in early- and late-infantile onset patients. However, miglustat had no effect on organomegaly or other systemic manifestations of the disease. Miglustat was well tolerated.

Objective The purpose of the present study is to compare efficacy and safety of buccal midazolam with intravenous diazepam in control of seizures in Iranian children. Methods This is a randomized clinical trial. 92 patients with acute seizures, ranging from 6 months to 14 years were randomly assigned to receive either buccal midazolam (32 cases) or intravenous diazepam (60 cases) at the emergency department of a children's hospital. The primary outcome of this study was cessation of visible seizure activity within 5 minutes from administration of the first dosage. The second dosage was used in case the seizure remained uncontrolled 5 minutes after the first one. Findings In the midazolam group, 22 (68.8%) patients were relieved from seizures in 10 minutes. Meanwhile, diazepam controlled the episodes of 42 (70%) patients within 10 minutes. The difference was, however, not statistically significant (P=0.9). The mean time required to control the convulsive episodes after administration of medications was not statistically significant (P=0.09). No significant side effects were observed in either group. Nevertheless, the risk of respiratory failure in intravenous diazepam is greater than in buccal midazolam. Conclusion Buccal midazolam is as effective as and safer than intravenous diazepam in control of seizures.

The ketogenic diet is an effective medical therapy for intractable childhood epilepsy. However, it has drawbacks in that it restricts calories, fluids and protein. The Atkins diet may also induce ketosis without those restrictions. Our objective was to evaluate the efficacy of a modified Atkins diet in children with intractable childhood epilepsy.This clinical trial was conducted in 51 epileptic children aged 1 - 16 years with refractory seizures from Feb. 2004 to Oct. 2006. Outcome measures included seizure frequency and adverse reactions. Twenty-seven patients left the study for various reasons, leaving 24 who continued the Atkins diet for a minimum of three months. Carbohydrates were initially limited to 10 g/day and fats constituted 60% of the total energy requirement. All participants received vitamin and calcium supplementation.Following three months of treatment with the Atkins diet, 16 patients (67%) had50% decrease in seizure frequency, and 6 (25%) had90% improvement, of whom 5 were seizure-free. Mean seizure frequency after the first, second and third months of treatment were significantly lower than at baseline (P values0.001, 0.001 and 0.002, respectively).The Atkins diet can be considered as a safe and effective alternative therapy for intractable childhood epilepsy. Atkins diet was well tolerated in our patients with rare complications and it appears to demonstrate preliminary efficacy in childhood refractory epilepsy.