Comparing Pregabalin and Sodium Valproate in Pediatric Migraine Prophylaxis: A Randomized Clinical Trial.

Objectives: Migraine is a common disorder in children, and its prophylaxis with minimal side effects is momentous. This study aimed to compare the efficacy of Pregabalin and Sodium Valproate in preventing migraine attacks. Material & methods: Sixty-four children (aged 6-18) with migraines were recruited, as defined by Internation Headache Criteria (ICHD-III). They were randomly assigned to two groups: Sodium Valproate (n=32) and Pregabalin (n=32). The minimum dosage of drugs was prescribed in both groups. The patients were followed for four months. The parameters such as frequency, intensity, duration of migraine attacks, and the number of painkillers that the patients used monthly were recorded. The Spence Children's anxiety scale was also used to evaluate medications' effect on patients' anxiety levels. Results: Two medications were equally effective in reducing the intensity and duration of attacks. Additionally, their effect on reducing the anxiety level of patients was equal. There was a significant difference between the effect of drugs on the frequency of migraine attacks at the end of the first and fourth months and the number of painkillers used at the end of the fourth month. The frequency of attacks was decreased by more than 50% in twenty-eight patients (90%) of Pregabalin recipients and twenty-one patients (84%) of Sodium Valproate recipients. Conclusion: Considering the better effect of Pregabalin in the reduction of frequency of migraine attacks and pain-reducing medications consumption, Pregabalin could be a proper substitute for Sodium Valproate for prophylactic migraine treatment in children.

Epidemiology of Guillain-Barré Syndrome in Iranian Children Aged 0-15 Years (2008-2013).

OBJECTIVE: Guillain-Barré Syndrome (GBS) is an acute inflammatory polyneuropathy characterized by a rapid progressive symmetric weakness. The GBS is the most common cause of acute flaccid paralysis (AFP) in most parts of the world. This study was carried out to investigate the epidemiological features of GBS in Iranian children. MATERIALS & METHODS: The data were extracted using the AFP surveillance system that is a national screening program to detect all cases of AFP aged 0-15 years around the country. National Population Statistics data and AFP demographic data during 2008-2013 intervals were obtained from the relevant authorities in the Ministry of Health in Iran. The GBS cases were then extracted from the aforementioned database. The Chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: A total of 1884 cases of GBS were identified in the study period, and the average annual incidence rate was 1.72 per 100,000 individuals. The highest incidence rate was within the range of 0-5 years. There was no statistically significant relationship between the incidence of GBS and the season in the whole country. CONCLUSION: High costs of GBS treatment, morbidity and occasional mortality, and number of new cases, which is estimated to be approximately 300 individuals per year, need the particular attention of the health system.

Epidemiological, Clinical, and Laboratory Characteristics of Acute Disseminated Encephalomyelitis in Children: A Retrospective Study.

OBJECTIVES: We aimed to study the precipitating factors, demographic data, clinical and radiological manifestations, electroencephalography and laboratory findings, as well as association with infections, immunization and incidence of relapse of acute disseminated encephalomyelitis (ADEM) in children admitted to Mofid Children Hospital, Tehran, Iran from Mar 2013 to Mar 2016. MATERIALS & METHODS: A 3-yr retrospective review of 29 children with definite final diagnosis of ADEM in Mofid Hospital in Tehran, Iran was performed. The diagnosis was based on specified criteria, including a presumed acute demyelinating process with no history of unexplained neurological symptoms and at least one demyelinating lesion shown on magnetic resonance imaging without evidence of previous destructive white matter lesions. RESULTS: Overall, 29 children diagnosed as ADEM were studied in terms of demographic characteristics, clinical manifestations and laboratory findings in two groups according to their recurrence. The mean age of the patients with recurrence was less than those without it were. It was more common in females but the difference was not statistically meaningful. There was no relationship between the season of the first episode of the disease and the recurrence incidence. Moreover, the relationship between viral infections and recurrence was statistically non-meaningful. No relationship between the recurrence of ADEM and clinical manifestations, radiological and laboratory findings was found. CONCLUSION: The reason for high rate of recurrence in our patients may be related to the younger age of children in our study.

Hyperkinetic Movement Disorders in Children: A Brief Review.

Movement disorders are common neurologic disturbances in childhood. There are two major types of movement disorders. Hypokinetic disorders are with paucity of voluntary movements and are very uncommon in pediatric age group. Hyperkinetic movement abnormalities are very common in children and defined as abnormal repetitive involuntary movements. Movement disorders in childhood and even in adolescents are different in etiology, timing, treatment and prognosis versus adulthood movement abnormalities. In this brief article, we reviewed common types of hyperkinetic abnormal movements in children and adolescents with emphasis on etiologies, new classifications and recent treatment strategies.

Prediction of Response to Treatment in Children with Epilepsy.

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.

Metabolic Screening in Children with Neurodevelopmental Delay, Seizure and/or Regression.

OBJECTIVE: Neurometabolic disorder is one of the important groups of diseases that prominently has presentation early infantile period. In this study, we evaluated the result of metabolic screening of the patient with seizure, developmental delay and/or regression in development, demographic disease clinical and radiological findings on admitted and outpatient visited children. MATERIALS & METHODS: Two-year retrospective review of 187 children with seizure, developmental delay and/or regression in the Mofid Children Hospital, Tehran, Iran was performed. The diagnosis was based on observation, findings of EEG and history of the patient, besides evaluation of patient milestones. The result of metabolic screening with Tandem mass spectrometry was evaluated using SPSS (ver.18.0) Statistical software. RESULTS: Totally, 187 children with seizure, regression and/or developmental delay were evaluated by metabolic screening with tandem mass spectrometry method. The results of laboratory examination had no relationship between positive results of metabolic screening and the mentioned disease. The relations between positive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful. CONCLUSION: Positive results of metabolic screening and seizure, regression and/or developmental delay were not statistically meaningful.

Clinical and Epidemiological Aspects of Multiple Sclerosis in Children.

OBJECTIVE: Overall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children. MATERIALS & METHODS: In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software. RESULTS: Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively. CONCLUSION: MS is significantly more common among women. The most common age of onset is during the second decades. Sensory and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results.

Comparative efficacy of zonisamide and pregabalin as an adjunctive therapy in children with refractory epilepsy.

OBJECTIVE: Approximately one third of epileptic children are resistant to anticonvulsant drugs. This study evaluates the effectiveness, safety, and tolerability of pregabalin as adjunctive therapy in epileptic children relative to Zonisamide. MATERIALS & METHODS: From April 2012 to November 2012,121 children were referred to Mofid Children's Hospital with intractable epilepsy and enrolled in the study. The patients were divided into two groups (A and B) randomly. Group A was treated with Zonisamide and group B was treated with Pregabalin in addition to prior medication. We assessed seizure frequency and severity during a 4-week interval from the beginning of the drug treatment and compared the efficacy of each in these two groups. RESULTS: Group A consists of 61 patients, 26 (42.6%) girls, and35 (57.4%) boys with an age range from 1.5 months-14 years (mean, 73.9± 44.04 months). Group B consists of 60 patients, 31(51.7%) girls, 29 (48.3%) boys with an age range from 6 months-16 years (mean, 71±42.9 months). Age, gender, seizure onset, seizure frequency, seizure type, and previous antiepileptic medications showed that there was no significant difference between the groups (P>0.05). Zonisamide and pregabalin reduced more than 50% of seizure intensity in 40.2%; 45.8% of patients also had a seizure frequency decline between35.8-44.4%, respectively and there was no significant superiority between these two novel anticonvulsants (P>0.05). CONCLUSION: In this survey both pregabalin and Zonisamide were impressive for seizure control in children with intractable epilepsy and well sustained with mild complications that were completely reversible.

Infantile spasm: a review article.

OBJECTIVE: Infantile spasm (IS) is a convulsive disease characterized by brief, symmetric axial muscle contraction (neck, trunk, and/or extremities). IS is a type of seizure that was first described by West in 1841, who witnessed the seizure in his own son. West's syndrome refers to the classic triad of spasms, characteristic EEG, and neurodevelopmental regression. Most cases involve flexors and extensors, but either of the types may be involved independently. IS, as its name implies, most often occurs during the first year of life with an incidence of approximately 1 per 2000-4000 live births. Most, but not all, patients with this disorder have severe EEG abnormalities; this pattern was originally referred to as hypsarrhythmia by Gibbs and Gibbs. Cases with known etiology or signs of brain damage are considered as symptomatic. The Overall prognosis of the disease is poor. Peak onset age of the epileptic syndrome is 3 to 7 months, which mainly occurs before 2 years of age in 93% of patients. Hypsarrhythmia is the EEG hallmark of IS, which comprised a chaotic, bilaterally asynchronous high-voltage polyspike, and slow wave discharges interspersed with multifocal spikes and slow waves. ETIOLOGICAL CLASSIFICATION IS AS FOLLOWS: 1) Symptomatic: with identifiable prenatal, perinatal, and postnatal causes with developmental delay at the presentation time; 2) Cryptogenic: unknown underlying cause, normal development at the onset of spasms, normal neurological exam and neuroimaging, and no abnormality in the metabolic evaluation; 3) Idiopathic: pure functional cerebral dysfunction with complete recovery, no residual dysfunction, normal neuroimaging and normal etiologic evaluation, and normal neurodevelopment.

GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series).

OBJECTIVE: GM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay-Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creating hexosaminidases A, B, and AB. MATERIALS & METHODS: Patients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children's Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and AB in reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease. RESULTS: 83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint. 38%of patients had a history of developmental delay or regression and 22% had seizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowing disorders. Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). CONCLUSION: According to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease.

Propionic acidemia: diagnosis and neuroimaging findings of this neurometabolic disorder.

OBJECTIVE: Propionic acidemia is one of the rare congenital neurometabolic disorders with autosomal recessive inheritance. This disorder is caused by a defect in the propionyl-CoA carboxylase enzyme and can be presented with life-threatening ketoacidosis, lethargy, failure to thrive, and developmental delay. MATERIALS & METHODS: The patients diagnosed as having propionic acidemia in Neurology Department of Mofid Children's Hospital in Tehran, Iran, between 2002 and 2012 were include in our study. This disorder was confirmed by clinical manifestations, neuroimaging findings, and neurometabolic assessment in the reference laboratory in Germany. Our study was conducted to define the sex, age, gender, past medical history, developmental status, clinical findings, and neuroimaging manifestations in 10 patients with propionic acidemia. RESULTS: Seventy percent of patients were offspring of consanguineous marriages. In this study, only one patient had microcephaly at birth, but at detection time, 30% of patients had head circumference and weight below the 3rd percentile. The patients were followed for approximately 5 years and this follow-up showed that the patients with early diagnosis had a more favorable clinical response. Neuroimaging findings included brain atrophy, white matter and globus pallidus involvement. CONCLUSION: Finally we suggest that early diagnosis and treatment have an important role in the prevention of disease progression.

Electroretinographic responses in epileptic children treated with vigabatrin.

Vigabatrin is an antiepileptic drug that results in higher gamma-aminobutyrate levels in the brain and retina. Vigabatrin-induced visual field defects are usually asymptomatic and only detectable by perimetry. Further, perimetry requires good cooperation, and children aged under 10 years cannot do it. Electroretinogram response amplitude to full-field 30-Hz flicker shine has been offered to be more specific in predicting visual field defects. This study is scheduled to investigate the vigabatrin-associated visual complications in 67 epileptic children taking vigabatrin using full-field electroretinogram. Electroretinographic surveys showed normal range parameters despite 3 months of vigabatrin treatment, and just 3 (4.47%) children had been visually impaired at the end of 6-month treatment. Among these 3 cases, 1 patient had persistent electroretinogram abnormality despite vigabatrin discontinuation. Our study suggests that vigabatrin is secure for short-term pediatric antiepileptic treatment, with few cases of visual impairments and that are often reversible.

Prophylaxis of childhood migraine: topiramate versus propranolol.

OBJECTIVE: Headache is a common disabling neurological disorder and migraine comprises more than half the causes of recurrent headaches in children. Despite extended prevalence of this type of headache there is lack of evidence about best drug treatment for migraine. So we aimed to compare the therapeutic effects of these drugs on childhood migraine. MATERIALS & METHODS: In the current study, a randomized clinical trial consisting of 78 patients according to 2004 International Headache Association criteria were randomly assigned to two groups that matched by age and sex. One of these two groups was treated with Topiramate, while the other was given Propranolol. After one and four months, the efficiency of these treatments was measured in terms of frequency, severity and duration of migraine attacks. RESULTS: Results obtained from the data collected showed that of these 78 studied patients, 38 patients received Topiramate treatment (group A) and the rest (40 patients; group B) was treated with Propranolol. The average age of group A was 8.5± 2.9 years and that of group B was 8.3 ± 2.8 years. No significant difference was observed between these two groups in terms of reduction in frequency, severity and duration of migraine attacks. CONCLUSION: Results showed that both treatments had the same efficiency in healing migraine headaches and there was no significant difference between their treating results. However, further studies are needed to examine medical effects of these two medicines.

Zonisamide efficacy as adjunctive therapy in children with refractory epilepsy.

OBJECTIVE: Approximately one third of epileptic children do not achieve complete seizure improvement. Zonisamide is a new antiepileptic drug which is effective as adjunctive therapy in treatment of intractable partial seizures. The purpose of the current study was to evaluate the effectiveness, safety, and tolerability of Zonisamide in epileptic children. MATERIALS & METHODS: From November 2011 until October 2012, 68 children who referred to Children's Medical Center and Mofid Children Hospital due to refractory epilepsy (failure of seizure control with the use of two or more anticonvulsant drugs) entered the study. The patients were treated with Zonisamide by dose of 2- 12 mg/kg daily in addition to the previous medication. We followed the children every three to four-weeks intervals based on daily frequency, severity and duration of seizures. During the follow-up equal and more than fifty percent reduction in seizure frequency or severity known as response to the drug. RESULTS: In this study 68 patients were examined that 61 children reached the last stage.35 (57.4%) were male and 26 (42.6%) patients were female. After first and six months of Zonisamide administration daily seizure frequency decreased to 2.95±3.54 and 3.73±3.5 respectively. There was significant difference between seizure frequency in first and six month after Zonisamide toward initial attacks. After six months ZNS therapy a little side effects were created in 10 patients (16.4%) including stuttering(4.9%), decreased appetite (4.9%), hallucination (1.6%), dizziness(1.6%), blurred vision(1.6%) and suspiring(1.6%) as all of them eliminated later dosage reduction. CONCLUSION: This study confirms the short term efficacy and safety of Zonisamide in children with refractory epilepsies.

Methylmalonic acidemia: diagnosis and neuroimaging findings of this neurometabolic disorder (an Iranian pediatric case series).

OBJECTIVE: Methylmalonic acidemia is one of the inborn errors of metabolism resulting in the accumulation of acylcarnitine in blood and increased urinary methylmalonic acid excretion. This disorder can have symptoms, such as neurological and gastrointestinal manifestations, lethargy, and anorexia. MATERIALS & METHODS: The patients who were diagnosed as methylmalonic acidemia in the Neurology Department of Mofid Children's Hospital in Tehran, Iran, between 2002 and 2012 were included in our study. The disorder was confirmed by clinical findings, neuroimaging findings, and neurometabolic and genetic assessment in reference laboratory in Germany. We assessed the age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with methylmalonic acidemia. RESULTS: Eighty percent of the patients were offspring of consanguineous marriages. Half of the patients had Failure to thrive (FTT) due to anorexia; 85% had history of developmental delay or regression, and 20% had refractory seizure, which all of them were controlled. The patients with methylmalonic acidemia were followed for approximately 5 years and the follow-up showed that the patients with early diagnosis had a more favorable clinical response in growth index, refractory seizure, anorexia, and neurodevelopmental delay. Neuroimaging findings included brain atrophy, basal ganglia involvement (often in putamen), and periventricular leukomalacia. 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.

Biotinidase deficiency: a reversible neurometabolic disorder (an Iranian pediatric case series).

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.

Clinical trial of vigabatrin as adjunctive therapy in children with refractory epilepsy.

OBJECTIVE: Approximately one-third of all children with epilepsy do not achieve complete seizure improvement. This study evaluated the efficacy of Vigabatrin in children with intractable epilepsy. METHODS: From November 2011 to October 2012, 73 children with refractory epilepsy (failure of seizure control with the use of two or more anticonvulsant drugs) who were referred to the Children's Medical Center and Mofid Children's Hospital were included in the study. The patients were treated with Vigabatrin in addition to their previous medication, and followed-up after three to four weeks to determine the daily frequency, severity, and duration of seizures in addition to any reported side effects. FINDINGS: Of the 67 children, 41 (61.2%) were males and 26 (38.8%) females, their age ranging from three months to 13 years with an average of 3.1 [standard deviation (SD), 2.6] years. The mean daily frequency of seizures at baseline was 6.61 (SD, 5.9) seizures per day. Vigabatrin reduced the seizure frequency ≤2.9 (SD, 5.2) (56% decline) and 3.0 (SD, 5.3) (54.5% decline) per day after three and six months of treatment, respectively. A significant difference was observed between seizure frequencies at three (P<0.001) and six months (P<0.001) after Vigabatrin initiation compared with the baseline. Somnolence [3 (4.5%)], horse laugh [1 (1.5%)], urinary stones [1 (1.5%)], increased appetite [1 (1.5%)], and abnormal electroretinographic pattern [3 (4.5%)] were the most common side effects in our patients. CONCLUSION: This study confirms the short-term efficacy and safety of Vigabatrin in children with refractory epilepsies.