Pulse Methylprednisolone with Oral Prednisolone versus Adrenocorticotropic Hormone in Children with West Syndrome: a Randomized Controlled Trial

Background and Purpose: West syndrome is an epileptic encephalopathy of infancy. According to guidelines, adrenocorticotrophic hormone (ACTH) is probably effective for the short-term management of infantile spasm, but there is little uniformity in treatment due to variable response. This study has been done to evaluate the efficacy of pulse methylprednisolone as compared to ACTH in children with West syndrome.Methods: Children between 3 months to 24 months with the diagnosis of West syndrome were included and ACTH and pulse methyl prednisolone followed by oral prednisolone were given after randomization. Total duration of treatment was 6 weeks in both groups.Results: Total 87 children were enrolled; 12 patients lost in follow up. Finally, 43 received ACTH and 32 received pulse methylprednisolone. In pulse methylprednisolone group, 28.13% showed 50-80% response, 28.13% showed 80-99% response and 21.87% patients showed 100% response. In ACTH group, 41.86% showed 50-80% response, 25.58% showed 80-99% response and only 3 (6.97%) patients showed 100% response. Methylprednisolone treatment regimen did not cause significant or persistent adverse effects.Conclusions: Pulse methylprednisolone followed by oral prednisolone for 6 weeks is as effective as ACTH. Thus, methylprednisolone therapy can be an important alternative to ACTH.

Early Infantile Thiamine Transporter-2 Deficiency with Epileptic Spasms—A Phenotypic Spectrum with a Novel Mutation

Epileptic seizures are a frequent feature of thiamine transporter deficiency that may present as a clinical continuum between severe epileptic encephalopathy and mixed focal or generalized seizures. Thiamine metabolism dysfunction syndrome 2 (MIM: 607483) or biotin-thiamine-responsive basal ganglia disease (BTBGD) due to biallelic pathogenic mutation in the SLC19A3 gene is a well-recognized cause of early infantile encephalopathy with a Leigh syndrome-like presentation and a lesser-known phenotype of atypical infantile spasms. We report a 4-month-old infant who presented with progressive epileptic spasms since 1 month of age, psychomotor retardation, and lactic acidosis. Magnetic resonance imaging (MRI) revealed altered signal intensities in bilateral thalamic and basal ganglia, cerebellum, brainstem, cortical and subcortical white matter. Whole exome sequencing identified a homozygous ENST00000258403.3: c.871G > C (p.Gly291Arg) variant in the SLC19A3 gene. We elucidate the features in the proband, which were an amalgamation of both the above subtypes of the SLC19A3 associated with early infantile encephalopathy. We also highlight the features which were atypical for either “Leigh syndrome-like” or “atypical infantile spasm” phenotypes and suggest that the two separate entities can be merged as a clinical continuum. Treatment outcome with high-dose biotin and thiamine is promising. In addition, we report a novel pathogenic variant in the SLC19A3 gene.

Phenotypic variability and genetic characteristics of PRRT2-associated paroxysmal movement disorders in 13 Chinese families

PRRT2-associated paroxysmal movement disorders (PRRT2-PxMDs) include paroxysmal kinesigenic dyskinesias (PKD), benign familial infantile epilepsy (BFIE), infantile convulsions and choreoathetosis (ICCA), episodic ataxia (EA), paroxysmal nonkinesiasgenic dyskinesias (PNKD), and, in addition, other childhood-onset movement disorders and different types of seizures may be caused by PRRT2 mutations, suggesting that the understanding of the spectrum of PRRT2-PxMDs is still evolving. We collected and analyzed retrospectively the clinical of children diagnosed with paroxysmal movement disorders by the Department of Neurology of Anhui Provincial Children's Hospital from January 2015 to June 2020. The genetic tests were performed in the probands and their family members. Thirteen children and their family members, 30 in total, were tested. Twenty six patients and 4 (13.34%) carriers from 13 families were identified, 14 (46.67%) were diagnosed with BIE, 7 (23.33%) with PKD, 2 (6.67%) with ICCA, 1 (3.33%) with epilepsy (focal), 1 (3.33%) with infantile spasm (IS), and 1 (3.33%)was diagnosed with PKD and PNKD, Eight different variants were identified in 13 families, and NM_145239.2:c.640-641insC was found in 4 families while recurrent mutation c.649dupC was not found. Three novel mutation, c.884G > C, c.865G > C, and c.-65-1G > C were identified in this study. This study confirmed that there is no clear genotype-phenotype correlation in patients with PRRT2-PxMDs, in addition, the clinical findings show variable phenotype within families, including the families affected due to the newly identified pathogenic variants in this study.

West syndrome - epileptic encephalopathy at early infancy

West syndrome (WS), synonymously infantile spasm or epileptic spasm, is a rare type of epileptic encephalopathy occurring at early infancy that exists with variable life expectancy. It is the most common form of epileptic encephalopathy. WS presents with spasms marked by extensor or mixed movements with distinct electroencephalogram (EEG) pattern of hypsarrhythmia, flexor and psychomotor arrest. Children with west syndrome always depict abnormal EEG, but sometimes the abnormality is seen only during sleep. The incidence of infantile spasms is found closer to 1 in 2,000 children, that typically begins between 2-12 months of age and peaks between 4-8 months of age. It is observed in otherwise healthy infants and also among infants with abnormal cognitive development. If this spasm happens in older subjects, they are preferably called "epileptic spasms" rather than infantile spasms. The goal for treatment of infantile spasms is to have complete control of spasms. Hormonal therapy with ACTH or vigabatrin is the mainstay of treatment. In spite of the development of new antiepileptic drugs (AEDs), about 35-40% of cases are drug-resistant. Children affected with the west syndrome can be cured, but a successful therapy often depends on the timely diagnosis. This case report is one evidence highlighting the treatment strategy for the west syndrome, and this could be useful for any further study regarding this topic.

Clinical Predictors of Poorly-Controlled Childhood Epilepsy: A Case-Control Study

Introduction:The aim of the present study was to determine clinical factors associated with poorly controlled epilepsy. Materials and Methods: This retrospective study was performed from January 2007 to December 2008 at Paediatric Neurology outpatient department in Bangabandhu Sheikh Mujib Medical University, Dhaka, among the children with epilepsy of 7 months to 15 years age who had history of at least 6 months treatment with rational antiepileptic drugs daily with adequate compliance. There were two groups of patients; group 1, consisted of 50 poorly controlled epilepsy patients and group 2, comprised 50 well-controlled epilepsy patients. We retrospectively reviewed EEGs and medical records from these children. Features of clinical findings were compared between the two groups. Results: In this study, age of onset of initial seizure before 1 year, mixed type of seizure, infantile spasm, high initial seizure frequency (daily seizure), symptomatic etiology, mental retardation, neonatal seizure and more than 20 seizures before starting treatment were also found to be significant clinical predictors of poorly controlled epilepsy. Multivariate analysis detected 2 independent clinical predictors of poorly controlled epilepsy: mixed seizures and more than 20 seizures before starting treatment. Conclusions: The study showed several clinical factors that can be identified early in the course of childhood epilepsy which can predict development of poor seizure control. Knowledge of these factors will help us to discriminate our patients and pay more attention to those at risk of developing poorly controlled epilepsy. Medicine Today 2020 Vol.32(2): 85-90

West syndrome: a comprehensive review

Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

Tuberous sclerosis in a child

Tuberous Sclerosis (TS) is the most common single gene disorder in children. It has an incidence of 1 in 5800 live births. It is an autosomal dominant genetic multisystemic disease characterized by hamartic development of many organs most notably the brain, heart, kidney, lungs and skin. It results from mutation of TSC1 and TSC2 gene coding for hamartin and tuberin respectively. Most of the newborns are asymptomatic. In infancy, seizures are the most common symptoms with a high incidence of infantile spasm while children between 2- 10 years neurological symptoms are most frequent with epilepsy, mental retardation and autism. Authors report a 4-year-old male child born of grade 3 consanguineous marriage presented with seizures in form of Infantile Spasm and Skin Lesions.

Novel ARX mutation identified in infantile spasm syndrome patient

We report a 7-year-old boy with infantile spasms caused by a novel mutation in the Aristaless-related homeobox (ARX) gene. He showed infantile spasms and hypsarrhythmia on electroencephalogram from early infancy. Brain MRI did not reveal severe malformation of the brain except mild hypoplasia of the corpus callosum. Two-fold adrenocorticotropic hormone (ACTH) therapy failed to control the seizures, and ketogenic diet therapy and multi-antiepileptic drug therapy were required as he showed intractable daily tonic-clonic seizures. Exome sequencing identified a hemizygous mutation in the ARX gene, NG_008281.1(ARX_v001):c.1448 + 1 G > A, chrX: 25025227 C > T (GRCh37). To our knowledge, this mutation has not been reported previously.