Cerebral Necrotizing Encephalopathy in a 7-year-old Child after being Infected with COVID-19, A Case Report.

New daily data on the COVID-19 pandemic are circulating globally. This disease usually appears with respiratory symptoms such as cough, shortness of breath, and fever. The neurological complications of the disease are somewhat known in adults but rarely reported in children. Acute necrotizing encephalopathy of childhood (ANEC) is one of the brain complications associated| with Coronavirus disease that usually has a poor prognosis in children. In this case, we report a rare case of a 7-year-old boy who was referred to the hospital with symptoms of convulsions after contracting COVID-19 and developed cerebral necrotizing encephalopathy caused by COVID-19 infection. Although ANEC is a rare disease, clinical examination and MRI and CT scan findings play an essentialrole in diagnosing and treating the disease.|.

Oral Levetiracetam as Add-On Therapy in Refractory Neonatal Seizures.

OBJECTIVE: Seizure is the most common signs of nervous system disease in neonates. The first line of treatments in neonatal seizures (after ruling out and emergency treatment of electrolyte imbalance and hypoglycemia) are phenobarbital and phenytoin. We aimed to evaluate drugs that are more effective on neonatal seizure. MATERIALS & METHODS: Patients admitted to neonatal wards & NICUs (level   IIa&  IIb) in Qom hospitals (2015-2017), central Iran with presentation of seizure, were enrolled in this clinical trial study. After ruling out electrolyte imbalance and hypoglycemia these neonates were managed by intravenous phenobarbital, then if no response was seen we added intravenous phenytoin and for remaining neonates with refractory seizure we applied oral levetiracetam as add on therapy. The study was registered as code number of IRCT2016051527896N1. RESULTS: Initially, 245 neonates were enrolled. According to exclusion criteria, 12 cases were excluded, and phenobarbital was prescribed to the remaining patients. Out of these, 86 patients did not respond, and phenytoin was prescribed for them. Forty two patients who were not responding to phenytoin were finally treated with oral levetiracetam. Finally, 95.3% of seizures were controlled with oral levetiracetam but 4.7% were not cured. CONCLUSION: When the intravenous form of levetiracetam is not available and neonatal seizure does not respond to first line classic drugs, oral levetiracetam as add on therapy maybe effective.

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.

Glutaric AciduriaType 1: Clinical and Molecular Study in Iranian Patients, 3 Novel Mutations.

OBJECTIVE: Glutaricaciduria type 1 (GA1), is a rare, treatable neuro metabolic disease, due to glutaryl- CoA dehydrogenase (GCDH) gene mutation.In regions without neonatal blood screening (NBS), patients are diagnosed in symptomatic period. This study was carried out to assess patients with GA1 for clinical, biochemical, neuroimaging findings and GCDH gene mutations analysis. MATERIALS & METHODS: In this cross-sectional study, clinical manifestation, neuroimaging and metabolic findings of eleven Iranian GA1 patients of MofidChildren's Hospital, Tehran, Iranbetween 2001 and 2011,were evaluated.Mutational analysis of the GCDH gene was performed on genomic DNA. Genomic DNA was extracted from peripheral lymphocytes using QIAamp DNA Micro Kit (Qiagen). All 11 exons and flanking intronic regions of the GCDH gene were amplified by polymerase chain reaction (PCR). RESULTS: All patients were diagnosed before 32 months old. Clinical presentations of GA1 include acute encephalopathic crisis and/or developmental delay and macrocephaly. Seven GCDH gene mutations were detected in our patients. The most frequent GCDH mutations occurred in exon7 then exon8, 10 and11. G244 C in exon7, R294 Q in exon8 and N373 S in exon 10 were three novel mutations. There was no correlation between of genotype and phenotype in our patients. CONCLUSION: Physician must remember GA1 in differential diagnosis of acute encephalopathic crisis, macrocephaly, developmental delay, movement disorders such as dystonia and dyskinesia. Early detection, proper treatment and selective screening of patients' siblings can prevent neurologic disabilities.

Ataxia in Childhood: Epidemiological, Clinical and Neuroradiologic Features, and the Risk of Recurrence.

OBJECTIVE: This study was conducted on the demographic data, clinical characteristics, electroencephalography, neuroradiological findings, and their impact on the recurrence of ataxia. MATERIALS & METHODS: A 3-yr retrospective review of 49 children with ataxia in Mofid Children Hospital, Tehran, Iran was conducted from Apr 2013 to Apr 2016. The demographic, clinical and paraclinical data were recorded in pre-prepared questionnaires. The patients were also classified in two groups of with or without recurrence and the results were compared. The diagnostic etiologies in our patients were classified as brain tumor, drug ingestion, encephalitis, post infectious immune-mediated disorders, pseudoataxia, trauma, congenital malformations of the central nervous system and hereditary ataxias. RESULTS: Forty-nine children with ataxia were enrolled. The mean age of the patients with a recurrence of ataxia was more than those without a recurrence. Neurodevelopmental delay in patients with recurrence was more frequent than those without a recurrence. Abnormal findings in the neuroimaging were seen more in the patients with recurrence than those without recurrence. The most common cause of ataxia in patients with recurrence was hereditary ataxia and in patients without recurrence was a viral post infectious disorder. CONCLUSION: After a mean follow-up period of 16.36 months (range: 2-37 months), 9 cases (18.4%) showed recurrence. Older age, abnormal neuroimaging, and neurodevelopmental delay should be considered as the risk factors of recurrence of ataxia in children.

Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy.

OBJECTIVE: Intractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy. MATERIALS & METHODS: This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients' clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography. RESULTS: Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430). CONCLUSION: Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended.

Neurodegeneration with brain iron accumulation: an overview.

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.

Pregabalin in childhood epilepsy: a clinical trial study.

OBJECTIVE: The prevalence of active epilepsy is about 0.5-1%, and approximately 70% of patients are cured with first anti-epileptic drugs and the remaining patients need multiple drugs. Pregabalin as an add-on therapy has a postive effect on refractory seizures in adults. To the best of our knowledge, there is no research with this drug in childhood epilepsy. We use pregabalin in children with refractory seizures as an add-on therapy. The objective of this study is to evaluate the effects of pregabalin in the reduction of seizures for refractory epilepsy. MATERIAL & METHODS: Forty patients with refractory seizures who were referred to Mofid Children's Hospital and Hazrat Masoumeh Hospital were selected. A questionnaire based on patient record forms, demographic data (age, gender,…), type of seizure, clinical signs, EEG record, imaging report, drugs that had been used, drugs currently being used, and the number of seizures before and after Pregabalin treatment was completed. We checked the number of seizures after one and four months. RESULTS: After one month, 26.8% of patients had more than a 50% reduction in seizures and 14.6% of these patients were seizure-free; 12.2% had a 25-50% reduction; and approximately 61% had less than a 25% reduction or no change in seizures. After the fourth month, 34.1% of patients had more than a 50% reduction in seizures and 24.4% of these patients were seizure-free. Additionally, 65.9% of patients had less than 50% reduction in seizures (9.8% between 25-50% and 56.1% less than 25% or without improvement). CONCLUSION: We recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures) for children.

The Clinical Features and Diagnosis of Canavan's Disease: A Case Series of Iranian Patients.

OBJECTIVE: Canavan's disease is a lethal illness caused by a single gene mutation that is inherited as an autosomal recessive pattern. It has many different clinical features especially in the non-Ashkenazi Jewish population. MATERIAL & METHODS: 45 patients were referred to the Pediatric Neurology Department of Mofid Children's Hospital in Tehran-Iran from 2010-2014 with a chief complaint of neuro developmental delays, seizures, and neuroimaging findings of leukodystrophy were included in this study. Magnetic Resonance Spectrometry (MRS) and neuro metabolic assessment from a referral laboratory in Germany confirmed that 17 patients had Canavan's disease. RESULTS: Visual impairment, seizure, hypotonia, neuro developmental arrest, and macrocephaly were the most consistent findings in the patients in this study. Assessments of neuro developmental status revealed that 13 (76%) patients had neuro developmental delays and 4 (24%) patients had normal neuro development until 18 months of age and then their neuro developmental milestones regressed. In this study, 100% of cases had macrocephalia and 76% of these patients had visual impairment. A history of seizures was positive in 8 (47%) patients and began around 3 months of age with the most common type of seizure was tonic spasm. EEGs were abnormal in all epileptic patients. In ten of the infantile group, we did not detect elevated level of N-acetylaspartic acid (NAA) in serum and urine. However, the MRS showed typical findings for Canavan's disease (peaks of N-acetylaspartic acid). CONCLUSION: We suggest using MRS to detect N-acetylaspartic acid as an acceptable method for the diagnosis of Canavan's disease in infants even with normal serum and urine N-acetylaspartic acid levels.