Long-Lasting COVID-Associated Brain Fog: A Follow-Up Study.

INTRODUCTION: We investigated the longevity of COVID-associated brain fog in patients who have survived the COVID-19. METHODS: This was a follow-up study of 2,696 adult patients with COVID-19 from our previous study. We selected every other patient in our database. The follow-up data were collected during a phone call to the participants in January-February 2022 (11 months after the initial study): concentration difficulty and the patient's self-declared status in their ability to concentrate. RESULTS: In total, 1,164 people were included; 35 people (3.0%) had concentration difficulty and 65 individuals (5.6%) had a worsened status in their ability to concentrate and think; 26 people (2.2%) responded yes to both questions and were considered as having long-lasting brain fog. People with long-lasting brain fog were more often admitted to ICUs during the initial hospitalization (23.1% vs. 9.3%; p = 0.032) compared with those without long-lasting brain fog. CONCLUSION: We may conclude that a minority of the hospitalized patients with COVID-19 may suffer from long-lasting post-COVID brain fog, at least for more than 1 year after their initial illness. Long-lasting post-COVID brain fog has a significant association with the severity of the initial illness.

Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology.

Long COVID syndrome-associated brain fog.

We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients. In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).

Parents' opinions about epilepsy surgery in children with epilepsy.

OBJECTIVE: This survey aimed to investigate the opinions of the parents of children with epilepsy with regard to the application of epilepsy surgery for their children. METHODS: We surveyed all the parents of children with epilepsy referred to our neurology clinic (Shiraz University of Medical Sciences) in April-July 2022. We collected their opinions about epilepsy surgery based on a predesigned questionnaire. The inclusion criteria included parents of all children with epilepsy (1 to 16 years of age, with at least one-year history of epilepsy, and with at least one drug used in the past 12 months). RESULTS: In total, 472 people participated in the study; 277 participants (58.7%) were willing to have epilepsy surgery for their child; the most common reason was to be able to discontinue the drugs. Sex (male), age (younger), and education (college) of the parents had significant associations with the parental willingness to have surgery for their children. The patient's drug regimen (polytherapy) and history of ictal injury (in the child) also had significant associations with the parental willingness to have surgery for the children. CONCLUSION: Most parents of children with epilepsy are willing to have epilepsy surgery for their children if their physician presents epilepsy surgery to them as an established, safe, and effective treatment option. Patient and parental-related factors should be considered when designing educational materials and programs for preoperative counseling for the parents of children with drug-resistant seizures.

COVID-19 vaccine-related frequently asked questions (FAQs) by people with epilepsy and carers in Iran; educational video is included.

OBJECTIVE: The aim of the current study was to inquire the questions and concerns of people with epilepsy (PWE) about COVID-19 vaccines in order to provide a more realistic list of their frequently asked questions (FAQs). METHODS: We surveyed all the consecutive PWE or their care-givers who were referred to our neurology clinics (Shiraz University of Medical Sciences) during January-February 2022. We collected their questions and concerns in relation to COVID vaccines based on a predesigned brief questionnaire. Informed consent to participate in the study was obtained from the participants. RESULTS: In total, 452 people participated in the study; 291 people (64.4%) did not have any questions or concerns with regard to the COVID-19 vaccination. Having any questions or concerns about COVID-19 vaccination was significantly associated with not being vaccinated. Questions and concerns about the adverse effects of COVID-19 vaccines [seizure worsening, general adverse effects, long-term effects (e.g., infertility, cognitive dysfunction)] were by far the most common questions by people with epilepsy and their carers. CONCLUSION: Our findings may be used by policy-makers to prepare appropriate educational materials to provide the best targeted and tailored information to people with epilepsy and their carers to convince them of the necessity and safety of COVID-19 vaccination. Such an educational material must include enough information on the associated adverse effects of COVID-19 vaccines and should also discuss some other important issues such as indications of these vaccines in special populations and drug-vaccine interactions.

'Long COVID': Symptom persistence in children hospitalised for COVID-19.

AIM: We aimed to describe the long-term outcome with respect to symptom persistence amongst children hospitalised for COVID-19. METHODS: This was a follow-up study of 58 children and adolescents hospitalised with COVID-19. For all patients, the data were collected in a phone call to the family in December 2021 (9 months after the initial study and more than 13 months after their admission to hospital). We inquired about their current health status and obtained information, if the responding parent consented orally to participate and answer the questions. RESULTS: Fifty-one children and adolescents were studied. Only five patients (10%) had persistent symptoms compatible with long-COVID; the reported symptoms include fatigue in four (8%), weakness in three (6%), exercise intolerance in two (4%) and shortness of breath in two (4%) patients. Four patients (7.8%), who did not have any symptoms of long-COVID in phase 1 of the study, reported new-onset symptoms or complaints that are potentially compatible with the diagnosis of long-COVID (weakness, myalgia, excess sputum, cough, fatigue) in the current phase. CONCLUSIONS: Symptom persistence of long-COVID is infrequent amongst children hospitalised for COVID-19. Most of the symptoms of long-COVID will resolve with the passage of time and the residual symptoms are often mild and tolerable. The scientific community should carefully and clearly define long-COVID and its natural course in order to facilitate and harmonise future studies.

Application of cinnarizine in migraine prevention: A systematic review and meta-analysis.

OBJECTIVE: To investigate and analyze the available data on the prophylactic effectiveness of cinnarizine in migraine disorder. BACKGROUND: Cinnarizine has demonstrated encouraging potential in preventing the attacks of migraine. Therefore, we opted to evaluate whether its sole administration leads to positive outcomes. METHODS: The PubMed, Scopus, Web of Science, and Embase databases were searched for English-only original interventional studies published until April 2022, then screened for relevancy and eligibility. The resulting data from the included studies, including the primary (ie, headache episode frequency, intensity, duration, monthly timing, and analgesic intake frequency) and secondary (ie, reported adverse events, quality of life, and activities of daily living) outcome changes compared to placebo and active controls (e.g., sodium valproate and propranolol) were then recorded by two independent assessors. Ultimately, these data were synthesized qualitatively and quantitatively (achieved by determining the mean difference via the random-effects model). RESULTS: A total of 10 studies comprising seven randomized controlled trials and three quasi-experimental studies were included. Compared to placebo, cinnarizine demonstrated significant improvements in migraine episode frequency (Mean difference = -3.10; Confidence interval = [-3.33, -2.88]; p-value < 0.001; I2  < 0.001%), and intensity (Mean difference = -1.54; Confidence interval = [-2.08, -0.99]; p-value < 0.001; I2  < 37.97%). Moreover, cinnarizine led to similar or better results when compared to active controls, including sodium valproate, topiramate, and propranolol. CONCLUSIONS: Cinnarizine can be considered a safe and effective medication for migraine prophylaxis. However, the relatively small sample size made reaching a definite conclusion impossible. Therefore, a higher number of randomized controlled trials are recommended to be taken place to clarify the situation further.

Educational needs of physicians (in training) for management of patients with epilepsy.

OBJECTIVES: To investigate the opinions of medical students, residents in different disciplines, and clinical attendings in various disciplines on the educational needs and learning objectives about epilepsy at the basic and intermediate levels of medical education. METHODS: On July 15th, 2021, we posted an online invitation including a questionnaire to all the medical students, residents, and attendings of Shiraz University of Medical Sciences, Iran. The survey anonymously collected data about the participants [sex, age, educational level, and their disciplines (attendings)], and answers to the questions about their opinions about the educational needs and learning objectives of the medical students and residents about epilepsy. RESULTS: Five hundred and seventy-eight trainees and 53 attendings participated in the study. Trainees at different educational levels and in various disciplines had significantly different opinions on their educational needs and learning objectives about epilepsy. At the undergraduate level, the opinions of the trainees and their attendings were similar and the most reported needs by both groups included: Terminology and definitions, Physiopathology and etiology, Semiology and clinical characteristics, Medical treatment, Comorbidities. For the residents in neurology, psychiatry, and neurosurgery, the most reported needs included: all aspects of epilepsy. SIGNIFICANCE: Trainees at various educational levels/disciplines in medicine have different educational needs and learning objectives with regard to epilepsy and management of PWE. Policy makers in medical education should consider the observations of this study in order to design tailored and targeted educational curricula about epilepsy for various educational levels/disciplines in medicine.

A follow-up study of patients with COVID-19 presenting with seizures.

OBJECTIVE: We performed a follow-up study of patients with COVID-19 presenting with seizures. METHODS: All consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. RESULTS: In total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had pre-existing epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. CONCLUSION: Seizures in patients with COVID-19 are either acute symptomatic (in about two-thirds) or an exacerbation of a pre-existing epilepsy/functional seizures (in about one-third). A thorough investigation of the underlying etiology of seizures in patients with COVID-19 is necessary. Seizure outcome in patients, who are hospitalized with COVID-19 and seizures, is generally good.

A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: a Case report.

BACKGROUND: Muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by variable degrees of progressive muscle degeneration and weakness. There is a wide variability in the age of onset, symptoms and rate of progression in subtypes of these disorders. Herein, we present the results of our study conducted to identify the pathogenic genetic variation involved in our patient affected by rigid spine muscular dystrophy. CASE PRESENTATION: A 14-year-old boy, product of a first-cousin marriage, was enrolled in our study with failure to thrive, fatigue, muscular dystrophy, generalized muscular atrophy, kyphoscoliosis, and flexion contracture of the knees and elbows. Whole-exome sequencing (WES) was carried out on the DNA of the patient to investigate all coding regions and uncovered a novel, homozygous missense mutation in SEPN1 gene (c. 1379 C > T, p.Ser460Phe). This mutation has not been reported before in different public variant databases and also our database (BayanGene), so it is classified as a variation of unknown significance (VUS). Subsequently, it was confirmed that the novel variation was homozygous in our patient and heterozygous in his parents. Different bioinformatics tools showed the damaging effects of the variant on protein. Multiple sequence alignment using BLASTP on ExPASy and WebLogo, revealed the conservation of the mutated residue. CONCLUSION: We reported a novel homozygous mutation in SEPN1 gene that expands our understanding of rigid spine muscular dystrophy. Although bioinformatics analyses of results were in favor of the pathogenicity of the mutation, functional studies are needed to establish the pathogenicity of the variant.

Bone mineral density loss in ambulatory children with epilepsy in spite of using supplemental vitamin D in Southern Iran: a case-control study.

Epilepsy might have adverse effect on bone density due to underlying disease, drugs, vitamin D deficiency, immobilization and malnutrition. We investigated the bone mineral density in ambulatory vitamin-D supplemented children with epilepsy. This case-control study was conducted on 90 epileptic children aged 11.4 ± 3.3 years, and age and gender matched controls in pediatric neurology clinics of Shiraz, in Southern Iran, 2016. Anthropometric measurements, puberty, sun exposure, physical activity and biochemical variables were assessed. Bone mineral density was evaluated by dual-energy X-ray absorptiometry method. Data were analyzed by SPSS.v21. Prevalence of low bone mass in femur was more in patients (27%) than the controls (9%) (P value = 0.002). Age, weight Z score and height Z score were the most significant associated factors on lumbar BMD, BMAD, and femur BMD. Seizure duration and how it responded to anticonvulsants were the most associated factors with both lumbar and femur bone density. Sodium valproate and carbomazepin usage had negative association with lumbar Z score (beta = - 0.216, P = 0.017 and beta = - 0.336, P = 0.027, respectively). We hypothesized that epilepsy per se could affect bone density by an unknown pathophysiology, which was independent from vitamin D deficiency, effects of anticonvulsant and physical activity.

Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17. The purpose of this study was to investigate disease-causing mutations in two patients with distinct NBIA disorders. CASE PRESENTATION: Whole Exome sequencing using Next Generation Illumina Sequencing was used to enrich all exons of protein-coding genes as well as some other important genomic regions in these two affected patients. A deleterious homozygous four-nucleotide deletion causing frameshift deletion in PANK2 gene (c.1426_1429delATGA, p.M476 fs) was identified in an 8 years old girl with dystonia, bone fracture, muscle rigidity, abnormal movement, lack of coordination and chorea. In addition, our study revealed a novel missense mutation in PLA2G6 gene (c.3G > T:p.M1I) in one and half-year-old boy with muscle weakness and neurodevelopmental regression (speech, motor and cognition). The novel mutations were also confirmed by Sanger sequencing in the proband and their parents. CONCLUSIONS: Current study uncovered two rare novel mutations in PANK2 and PLA2G6 genes in patients with NBIA disorder and such studies may help to conduct genetic counseling and prenatal diagnosis more accurately for individuals at the high risk of these types of disorders.

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene.

BACKGROUND: Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. CASE PRESENTATION: Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. CONCLUSIONS: Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

How does COVID-19 vaccination affect long-COVID symptoms?

OBJECTIVE: The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition. METHODS: This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate. RESULTS: In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032). CONCLUSIONS: In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

Pediatric Stroke in the Southern Region of Iran: A Retrospective Prognostic Cohort Study.

Objective: Childhood stroke is linked to high personal costs for affected children and their families since more than half of the survivors are impaired for a long time, hampering their normal development and lifestyle. Thus, the present study aimed to evaluate the neurological developmental outcomes of children admitted to Namazi hospital, Shiraz, Iran, for ischemic and hemorrhagic stroke with a five-year follow-up. Ma a retrospective cohort study on children admitted to Namazi Hospital due to ischemic and hemorrhagic stroke during the past three years (2012-2015). The information was collected by reviewing the medical records and clinically visiting the patients on follow-up. The SPSS 21.0 software was used for statistical analysis. Materials & Method: This is a retrospective cohort study on children admitted to Namazi hospital due to ischemic and hemorrhagic stroke during past three years (2012-2015). The information was collected by reviewing the medical records and clinically visiting the patients at the time of follow up. The SPSS 21.0 software was used for statistical analysis Settings. Results: The patients' mean age at the time of stroke was 6.87 ± 4.60 years. The mean follow-up period was 3.5 ± 1.64 years. 53.1% of the children (N=17) were diagnosed with hemorrhagic stroke, and 46.9% (N=15) with ischemic stroke. The most frequent symptoms first presented by the study population were a decrease in the level of consciousness (LOC) (40.6%), headaches (37.5 %), and hand/arm/leg weakness (34.4%), respectively. The number of patients in the poor.and severe outcome group was 73.3% in the ischemic and 52.9% in the hemorrhagic group. Conclusion: Hemorrhagic stroke was slightly more frequent than ischemic stroke, and stroke was more frequent in boys. A decrease in LOC and headaches were the most common symptoms upon admission. The left sensorimotor area was the most involved in both ischemic and hemorrhagic groups. In addition, trauma was the most common cause of stroke in this study population.

Inborn Errors of Metabolism Associated With Autism Among Children: A Multicenter Study from Iran.

OBJECTIVE: This study aimed to find the common inborn errors of metabolism in Iranian patients with autism spectrum disorder. METHODS: In this cross-sectional multicenter study, 105 children and adolescents with autism spectrum disorder from six centers in different cities of Iran were enrolled between August, 2019 and October, 2020. Metabolic screening, including measuring plasma levels of amino acids, acylcarnitines, creatine, and guani-dinoacetate, and urinary levels of organic acids, purines, and pyrimidines was performed. Other data, including age, parental consanguinity, history of seizure, developmental mile-stones, and physical examination, were also recorded. RESULTS: An inborn error of metabolism was found in 13 (12.4%) patients. Five patients (4.8%) had cerebral creatine deficiency syndrome, 4 (3.8%) had arginine succinate aciduria, 2- methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria. There was a strong association between positive meta-bolic evaluation and parental consanguinity, history of seizures, microcephaly, and delayed development. CONCLUSIONS: Our results suggest that metabolic screening should be performed in the cases of autism associated with parental consanguinity, developmental delay, and a history of seizures. The assays to be considered as a screening panel include plasma or blood amino acids, acylcarnitines, creatine and guanidinoacetate, and urinary levels of organic acids.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

Treatment of Child Gratification Disorder.

Objectives: Gratification disorder is a group of self-stimulatory behaviors tending to form a habit. These normal behaviors are common and have various differential diagnoses, including epilepsy. Hence, misdiagnosis may lead to performing unnecessary workups and treatments. In this article, we systematically reviewed available treatment options for gratification disorder. Materials & Methods: We systematically searched Scopus, MEDLINE, and Embase for related articles published from the beginning to 12th May 2021. We followed the search strategy in all electronic databases using keywords ["Self-gratification" AND "treatment"], ["child" AND "masturbation" AND "treatment"], ["Pediatric" AND "masturbation" AND "treatment"], ["infantile" AND "masturbation" AND "treatment"], and ["Benign" AND "Infantile" AND "Dyskinesia" AND "treatment"]. Results: The primary search yielded 241 studies. Five studies fulfilled the inclusion criteria and were used in the systematic review. None of the studies provided a good level of evidence. These studies indicated that behavioral therapy, escitalopram, and aripiprazole could be considered treatment options. Conclusion: Although pediatricians are familiar with gratification behaviors, their optimal management is overlooked. In addition to parental education and behavioral therapy, escitalopram and aripiprazole can be used as treatment options for this issue. We need to perform well-designed randomized controlled trials to obtain adequate evidence on the efficacy of these measures.

The Cerebrospinal Fluid Concentration of Methyltetrahydrofolate and Serum Folate in Children with Developmental Delay, Regression, and/or Refractory Epilepsy.

BACKGROUND AND OBJECTIVES: Folate is an important vitamin with a significant role in cell metabolism processes, and its deficiency is associated with several diseases. In addition, cerebral folate deficiency is associated with neurodevelopmental disorders. Studying the association of serum and cerebral folate deficiency with childhood neurodevelopmental disorders such as refractory epilepsy, developmental delay, and regression can be an important step towards the improvement of symptoms of such disorders. MATERIALS AND METHODS: In this cross-sectional study, from February to October 2018, 60 children aged 6 months to 5 years; known cases of idiopathic refractory epilepsy; were selected randomly. After recording demographic, and clinical characteristics, cerebrospinal fluid (CSF) and blood samples were taken from the patients and sent to a laboratory for measurement of 5-methyltetrahydrofolate (5MTHF), folate, and homocysteine levels. RESULTS: Sixty patients completed the study, including 33 boys (55%) and 27 girls (45%). Mean ± SD of the studied population was 26.93 ± 19.97 months. Eighteen children (30%) had refractory epilepsy, 11 (18.3%) had developmental delay, 12 (20%) had refractory epilepsy and developmental delay, and 19 (31.7%) had refractory epilepsy and developmental regression. The results of brain magnetic resonance imaging (MRI) were normal in 47 (78.3%) children and atrophic in 13 (21.7%) children. Mean ± SD of serum level of homocysteine was 9.14 ± 8.58 µmol/L, that of folate was 11.60 ± 6.89 nmol/L, and that of 5MTHF was 69.23 ± 54.16 nmol/L. CONCLUSION: Measurement of serum folate, homocysteine, and CSF level of 5MTHF are of great importance in patients with developmental disabilities.