A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: a randomized double-blind clinical trial.

BACKGROUND: Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis. METHODS: In a randomized, double-blind trial, patients aged 4-17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with p < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed. RESULTS: Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 (p = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods (p < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups (p > 0.005). No serious adverse events were observed. CONCLUSIONS: Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects.Trial Registration: The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1.

A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies.

OBJECTIVE: Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. METHODS: This study summarizes the clinical, imaging, and molecular data of these patients for five years. RESULTS: The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. CONCLUSIONS: The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).

High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial.

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Genetic Analysis of Forty MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing.

This manuscript aimed to determine the underlying point mutations causing Duchenne muscular dystrophy (DMD) in a heterogeneous group of Iranian patients, who are clinically suspected. Whole-exome sequencing was utilized to detect disease-causing variants in 40 MLPA-negative DMD patients. Disease-causing variants were detected in the DMD gene in 36/40 of the patients (90%), and 4/40 of them (10%) remained undiagnosed. WES analysis revealed that nonsense variant was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift variant, and one of the patients had a likely pathogenic splice variant in the DMD gene. Carrier testing revealed that 21/40 of the mothers had the identified variant. Therefore, most variants were inherited (58.3%), while 19/40 were de novo (41. 7%). The present study has demonstrated the importance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patients and to identify carrier females. Due to regulatory challenges, the clinical development of therapeutic approaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that the techniques used to accurately detect disease-causing variants in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD.

Clinical Characteristics and Electrodiagnostic Features of Guillain-Barré Syndrome Among the Pediatric Population.

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.

Clonidine Versus Chloral Hydrate for Recording Sleep EEG in Children.

OBJECTIVE: One of the difficulties to conduct electroencephalography (EEG) in pediatric patient population is that they are not always cooperative during the procedure. Different medications are used to induce sedation during EEG recording. In order to find a medication with the least adverse effects and high efficacy, the current study aimed at comparing clonidine and chloral hydrate as a premedication prior to EEG recording in pediatric population. MATERIALS & METHODS: A prospective, randomized, single-blinded, controlled trial was conducted on 198 children (9 to 156 months old) to investigate the sedative and adverse effects of clonidine and chloral hydrate. Patients, partially sleep-deprived the night before, were randomly divided into two groups of clonidine (n=100) and chloral hydrate (n=98) on an alternative day basis. RESULTS: The average sleep onset latency was significantly longer in the clonidine group than chloral hydrate group (the Mann-Whitney test, p <0.0001). Sleep duration ranged 15 to 150 minutes and it was not significantly different between the two groups (the Mann-Whitney test, p = 0.2). Drowsiness terminated faster with chloral hydrate than clonidine.Drowsiness after arousal was observed in 58% and 26.1% of patients in the clonidine and chloral hydrate groups, respectively; the difference between the groups was significant (the Mann-Whitney test, p = 0.058). EEG results were reported normal in 77 subjects in the chloral hydrate group (77%) and 69 subjects (69%) in the clonidine group (p = 0.161). Generalized epileptiform discharges were significant in the clonidine group (the Mann-Whitney test, p = 0.006). CONCLUSION: The results of the current study showed that both 5% chloral hydrate (1 mL/kg) and clonidine (4 µg/kg) could be administered as a premedication prior to EEG recording in children, although drowsiness after arousal was higher with clonidine than chloral hydrate. However, the yield of generalized epileptiform discharges in the clonidine group was greater than that of the chloral hydrate group.

Levetiracetam for prophylactic treatment of pediatric migraine: A randomized double-blind placebo-controlled trial.

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.

The First Report of Relative Incidence of Inherited White Matter Disorders in an Asian Country Based on an Iranian Bioregistry System.

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.

The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder.

To evaluate the efficacy, safety, and tolerability of a classic 4:1 ketogenic diet using a formula-based powder in infants and children with refractory seizures who are reluctant to eat homemade foods. We conducted an open label trial and administered a ketogenic diet using formula-based power (Ketocal®). Twenty-seven infants and children aged between 12 months and 5 years were enrolled who had refractory seizures and were reluctant to eat homemade foods. Of 27 children, 5 were lost to follow-up and 22 were remained at the end of the study. After 4 months, the median frequency of seizures per week was reduced >50% in 68.2% of patients, while 9/22 children (40.9%) showed a 50-90% reduction in seizure frequency per week, and 6/22 children (27.3%) showed more than 90% reduction in seizure frequency per week. Over the study course, 6/22 (27%) children who continued to receive the diet developed constipation, one child developed gastroesophageal reflux, and one child developed hypercholesterolemia. None of these children discontinued the diet because of the complications. Thirteen children and their parents (59%) reported that the diet was palatable and tolerable enough. The ketogenic diet using a formula-based powder (Ketocal®) is effective, safe, and tolerable in infants and children with refractory seizures who are reluctant to eat homemade foods according to the rules of the ketogenic diet.

The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

Association of Interleukin-1 Gene Cluster and Interleukin-1 Receptor Polymorphisms With Febrile Seizures.

Interleukin-1 (IL-1) plays a key role in inflammation, has an effect on a wide variety of cells, and often leads to tissue destruction. While the ratio between IL-1 and IL-1Ra could influence the development of different diseases of the central nervous system, its gene polymorphisms were investigated in a group of patients with febrile seizures. Ninety patients with febrile seizures were enrolled and compared with 140 controls. The allele and genotype frequency of single nucleotide polymorphisms within the IL-1α, ß, IL-1 R and IL-1Ra gene were determined. The frequency of the IL-1Ra/C allele at position Mspa-I 11100 was decreased significantly (P= .002) and the IL-1Ra/T frequency was significantly increased in patients (P= .002). In addition, the CT genotype frequency at the same position was significantly overrepresented in controls compared to patients (P= .001). Certain alleles and genotypes in the IL-1 gene were overrepresented in patients with febrile seizures, which possibly could predispose individuals to this disease.

Analysis of dystrophin gene in Iranian Duchenne and Becker muscular dystrophies patients and identification of a novel mutation.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45-50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3-5 and 41-43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C>T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.

Association of IL4 single-nucleotide polymorphisms with febrile seizures.

As of importance of interleukin-4 (IL-4) in inhibiting the production of proinflammatory cytokines, the IL4 gene polymorphisms were investigated in patients with febrile seizure. This association has not been investigated yet, except 1 study which has been done in Japanese population. Eighty-two patients with febrile seizure were enrolled in this study, compared with 139 controls. The allele and genotype frequency of 3 single-nucleotide polymorphisms of IL4 gene were determined. Frequency of the IL4-590/C allele in the patient group was significantly higher than in the control group (P < .0001). Frequency of the following genotypes was significantly lower in patients compared to controls: IL-4 (-590) TC (P = .0001) and IL-4 (-33) TC (P = .001). The most frequent IL-4 haplotype in the patient group was TCC (P = .00) haplotype. In contrast, frequencies of GCC (P = .01), TTT (P = .009), and TTC (P = .0007) haplotypes were significantly lower in febrile seizure patients. Certain alleles, genotypes, and haplotypes in the IL4 gene were overrepresented in Iranian patients with febrile seizure, which could predispose individuals to this disease, and further investigations in other ethnicities are required.

Sleep Inducing for EEG Recording in Children: A Comparison between Oral Midazolam and Chloral Hydrate.

OBJECTIVE: Electroencephalography (EEG) recording is a long duration procedure that needs patient's cooperation for device setup and performing the procedure. Many children lose their cooperation during this procedure. Therefore, sedation and sleep are frequently induced using a few agents as pre procedure medication in children before EEG recording. We aimed to compare the sedative effects of oral midazolam versus chloral hydrate before the procedure along with their impacts on EEG recording in children. MATERIALS & METHODS: A randomized trial was carried out to compare the sedative effects of oral midazolam versus chloral hydrate and their impacts on EEG recording in children. A total of 198 children (100 in the midazolam group and 98 in the chloral hydrate group) were enrolled in the study and randomly allocated to receive either oral moidazolam or chloral hydrate. RESULTS: Oral midazolam had superiority neither in sleep onset latency nor in sleep duration when compared to chloral hydrate. Moreover, the yield of epileptiform discharges in the chloral hydrate group was more than the midazolam group. CONCLUSION: The results of this study showed that both chloral hydrate 5% (one ml/kg) and oral midazolam (0.5 mg/kg) could be administered as a pre medication agent for EEG recording in children. However, oral midazolam at this dose had no advantage compared with chloral hydrate.

CNS structural anomalies in Iranian children with global developmental delay.

OBJECTIVE: Central Nervous system (CNS) malformations are one of the most important causes of global developmental delay (GDD) in Children. About one percent of infants with GDD have an inherited metabolic disorder and 3-10 percent have a chromosomal disorder. This study aimed to survey the frequency of brain structural anomalies and their subtypes among the variety of etiologic factors in children with GDD in our patients. MATERIALS & METHODS: This study used the results of neuroimaging studies [unenhanced brain Magnetic Resonance Imaging (MRI)] of all children who had been referred for evaluation of GDD to outpatient Clinic of Pediatric neurology at Children's Medical Center affiliated to Tehran University of Medical Science between September 2009 and September 2010. RESULTS: In this study, unenhanced brain MRI was performed on 405 children, of which 80 cases (20 percent) had brain structural anomalies. In 8.7 percent of the cases, previous history of brain structural disorders existed in other children of the family and 20 percent of mothers had inadequate consumption of folate during pregnancy. CONCLUSION: Based on the results of this study, unenhanced cranial MRI seems to be a fundamental part of evaluation in all children with GDD. Adequate folate consumption as prophylaxis as well as genetic counseling can be worthy for high-risk mothers who have previous history of CNS anomaly or miscarriage to avoid repeated CNS anomalies in their next pregnancies.

Intragenic DNA polymorphism analysis of DMD/BMD dystrophy gene for carrier and prenatal diagnosis in 60 Iranian healthy individuals.

Duchenne and Becker muscular dystrophies (DMD/BMD) are allelic, x-linked neuromuscular disease resulting from mutations in dystrophin gene. DMD is the most severe and frequent inherited but still incurable disease in males. About two-third of such patients have large deletions or duplications that can be identified by multiplex polymerase chain reaction (PCR). In one-third of remaining cases, a linkage analysis that involves DNA markers of intragenic dystrophic gene is considered a rapid and simple method for carrier detection and prenatal diagnosis. In the present study, we investigated frequency and heterozygosity of three polymorphic restriction sites and also four highly polymorphic (CA)(n) repeat microsatellites loci within hot spots region of human dystrophin gene in 60 healthy Iranian populations. Our findings indicated that the allele frequencies of pERT87-8/TaqI, pERT87-15/BamHI, and pERT87-15/XmnI were 0.23/0.77, 0.221/0.779, and 0.239/0.761, respectively. Among these three polymorphic sites, pERT78-15/XmnI locus had the highest heterozygosity with frequency of 47.17%. We also found that STR49 had the highest heterozygosity among four polymorphic microsatellites. These findings are useful in linkage analysis of Iranian DMD families in both carrier detection and prenatal diagnosis.

Detection of Duchenne/Becker muscular dystrophy carriers in a group of Iranian families by linkage analysis.

This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.

Melatonin versus chloral hydrate for recording sleep EEG.

Although behavioral training could be successful in promoting electroencephalogram (EEG) compliance without restraint or sedation, sleep EEG may increase the yield of seizure activity. Furthermore uncooperative children not amenable to behavioral training require sedation for EEG recording. Our aim was to assess the impact of melatonin on the sleep EEG recording in comparison with chloral hydrate. Three hundred and forty eight patients (aged 1 month to 6 years) that were uncooperative with the EEG setup or referred for sleep EEG were enrolled in the study. Patients, partially sleep-deprived the night before, were randomly divided in two groups of melatonin and chloral hydrate on an alternative day basis, 174 patients in each group. Sleep onset latency in the chloral hydrate and melatonin groups was similar (Mann-Whitney test, P=0.113). However, sleep duration and drowsiness time were significantly shorter in the group of melatonin compared to the group of chloral hydrate (Mann-Whitney test, P<0.0001 and P<0.0001 respectively). More patients in the melatonin group (20 versus six patients in the chloral hydrate group) required a second dose of sedative for sleep induction (chi square test, P value=0.004). Seizure activities appeared in the electroencephalograms of 53% and 46% of patients in the melatonin and chloral hydrate groups respectively that were significantly higher in the melatonin group (chi square test, P=0.005). Few adverse effects occurred in both groups (Fisher's exact test, P=0.64). The shorter sleep duration and drowsiness period were the two advantages of melatonin over chloral hydrate. Furthermore higher yield of seizure activity detection in melatonin sedated patients was in favor of its prescription for sleep EEG recording in the pediatric population.