Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center.

Infantile spasms are a devastating infantile epileptic syndrome with multiple etiologies. Hereditary neurometabolic disorders are rarely recognized causes of infantile spasms. The aim of this study was to identify hereditary neurometabolic disorders when they were the cause of infantile spasms in patients presenting to a tertiary care center in Saudi Arabia. We conducted a retrospective review of children presenting to the Pediatric Department of King Abdulaziz Medical City in Riyadh, Saudi Arabia over a 15-year interval. Eighty patients with infantile spasms were identified. A hereditary neurometabolic disorder was diagnosed in 10 patients (12.5%). Of these patients, two had a Leigh-like disorder and one patient had each of the following diagnoses: ethylmalonic aciduria, nonketotic hyperglycinemia, hyperinsulinemic hypoglycemia, leukodystrophy, short-chain acyl-coenzyme A dehydrogenase deficiency, molybdenum cofactor deficiency, primary carnitine deficiency, and neonatal hypoglycemia due to panhypopituitarism. This article is the first to report the association of the last three conditions with infantile spasms. Compared with the other etiologies, the hereditary neurometabolic disorder group had a strong history of similar disease in the same family (P = 0.002), and most of the patients were born of consanguineous parents (P = 0.021). In addition, a typical hypsarrhythmia pattern was more common in the hereditary neurometabolic disorder group (P = 0.003). Furthermore, this group had a poor response to therapy (P = 0.04). Otherwise, there were no significant differences regarding the type of spasms, neuroimaging or outcome; however, there was a trend toward poorer outcomes and death in the hereditary neurometabolic disorder group. Hereditary neurometabolic disorders are relatively common causes of infantile spasms in this subpopulation of Saudi patients. An early diagnosis via proper metabolic and genetic testing has significant implications for applying specific treatments and for facilitating proper family counseling.

Alrifai MT ，AlShaya MA ，Abulaban A ，Alfadhel M ... -  《-》

Brain malformation and infantile spasms in a SCAD deficiency patient.

Mikati MA ，Chaaban HR ，Karam PE ，Krishnamoorthy KS ... -  《PEDIATRIC NEUROLOGY》

Metabolic etiologies in children with infantile epileptic spasm syndrome: Experience at a tertiary pediatric neurology center.

Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies. This study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years. Most patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication. This study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity.

Yüksel MF ，Doğulu N ，Yıldırım M ，Köse E ，Bektaş Ö ，Eminoğlu FT ，Teber S ... -  《-》

Neurometabolic Disorders-Related Early Childhood Epilepsy: A Single-Center Experience in Saudi Arabia.

Data on the pattern of epilepsy caused by metabolic disorders in the first 2 years of life are limited in developing countries. We aimed to identify the metabolic causes of epilepsy presented in the first 2 years of life and to describe their clinical, radiological, molecular, and electroencephalographic characteristics. This retrospective study was conducted between January 2010 and December 2011 at Saad Specialist Hospital (Al Khobar, Saudi Arabia). All patients younger than 2 years at the onset of epilepsy caused by metabolic disorders were reviewed. The International League Against Epilepsy definition was used, and febrile convulsion was excluded. Of 221 children diagnosed with epilepsy in the first 2 years of life at our hospital, 24 had metabolic diseases. The characteristics of these 24 children included the following: consanguinity in 18 patients (75%), developmental delay in 13 (54%), generalized tonic-clonic seizures in 10 (42%), infantile spasms in four (17%), myoclonic in seven (29%), and focal seizures in three. The diagnosis was confirmed by DNA studies in 17 patients (71%) and enzyme assay in seven (29%). The main diagnoses were peroxisomal disorders (n = 3), nonketotic hyperglycinemia (n = 3), Menkes disease (n = 2), neuronal ceroid lipofuscinosis (n = 2), biotinidase deficiency (n = 2), and mitochondrial disorder (n = 2). The remaining patients had lysosomal storage disease, aminoacidopathy, fatty acid oxidation defects, and organic aciduria. Seizure freedom was achieved in one third of patients in this cohort. Different metabolic disorders were identified in this cohort, which caused different types of epilepsy, especially myoclonic seizures and infantile spasms.

Mohamed S ，El Melegy EM ，Talaat I ，Hosny A ，Abu-Amero KK ... -  《-》

Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics.

Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.

Wilmshurst JM ，Gaillard WD ，Vinayan KP ，Tsuchida TN ，Plouin P ，Van Bogaert P ，Carrizosa J ，Elia M ，Craiu D ，Jovic NJ ，Nordli D ，Hirtz D ，Wong V ，Glauser T ，Mizrahi EM ，Cross JH ... -  《-》