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Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored. [ABSTRACT FROM AUTHOR]

Aim: We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.Method: All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.Results: Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, high dose ACTH (with/without vitamin B6 ), high dose prednisolone, and low dose ACTH were 'best'.Interpretation: Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.What This Paper Adds: Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Infantile spasms syndrome (ISS) being a severe epileptic encephalopathy characterized by epileptic spasms, developmental stagnation and/or regression. Topics include treatment of ISS showing the use of anti‑seizure medications and hormonal therapy in the form of prednisolone or adrenocorticotropic hormone; and determining other forms of steroid therapy being used for the treatment of ISS.

Background: West syndrome is a catastrophic epilepsy syndrome characterized by infantile spasms, hypsarrhythmia, and developmental arrest or regression.Aim: The aim of this study was to explore the role of pyridoxine in the management of infantile spasms.Setting and Design: This was a pilot, randomized, open-label trial conducted at a tertiary level hospital from November 2012 to March 2014.Materials and Methods: Children aged 3 months to 3 years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on electroencephalogram (EEG) were enrolled. The study participants were randomized to receive either oral prednisolone (4 mg/kg/day) alone or 30 mg/kg/day of pyridoxine with oral prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48 h on day-14 after treatment initiation, as per parental reports, in both the groups. The adverse effects were also monitored. The study was registered with clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01828437).Results: Sixty-two children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was similar in the two groups (39 vs. 37%, P = 0.98). The adverse effects were comparable in both the groups.Conclusions: The combination of pyridoxine with oral prednisolone was not found to be a beneficial therapy as compared to prednisolone alone in the treatment of infantile spasms in this pilot study. However, high dose pyridoxine may be safe in children with infantile spasms. [ABSTRACT FROM AUTHOR]

This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range = 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P = .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P = .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management. [ABSTRACT FROM AUTHOR]

The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. [ABSTRACT FROM AUTHOR]

Background: Infantile epileptic spasms syndrome is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. Appropriately selected patients with infantile epileptic spasms syndrome may be candidates for epilepsy surgery. Methods: This is a single-center retrospective case series of children 0-18 years with a current or previous diagnosis of infantile epileptic spasms syndrome with a lesion on magnetic resonance imaging (MRI) and/or positron emission tomography scan who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. The records of 223 patients seen in the infantile epileptic spasms syndrome clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of infantile epileptic spasms syndrome was encephalomalacia in 6 patients (32%), malformations of cortical development in 12 patients (63%), and atypical hypoglycemic injury in 1 patient (5%). Nine patients (47%) underwent hemispherectomy, and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE seizure outcome class 1 (completely seizure free; no auras) at their most recent follow-up visit. The percentage of patients who were ILAE class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome after surgery was improved in 14 of 19 (74%) and stable in 5 of 19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of infantile epileptic spasms syndrome with a structural lesion detected on MRI brain. Patients who undergo surgery earlier have improved seizure freedom rates and improved developmental outcomes. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to test the hypothesis that high-dose prednisolone (4 mg/kg/day) may be more efficacious than usual-dose (2 mg/kg/day) prednisolone for spasm resolution at 14-days in children with infantile spasms. Methods This was a randomized, open-label-trial conducted at a tertiary-level-hospital from February-2012 to March-2013. Children aged 3-months to 2-years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on EEG were enrolled. The study participants were randomized to receive either high-dose prednisolone (4 mg/kg/day) or the usual-dose (2 mg/kg/day) prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48-h at day-14 after treatment initiation as per parental reports in both the groups. The adverse effects were also monitored. The study was registered with the clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01575639). Results Sixty-three children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was significantly higher in the high-dose group as compared to the usual-dose group (51.6% vs. 25%, p = 0.03). The absolute risk reduction was 26.6% (95% confidence interval 11.5-41.7%) with number needed to treat being 4. The adverse effects were comparable in both the groups. Conclusions High-dose prednisolone (4 mg/kg/d) was more effective than low-dose prednisolone (2 mg/kg/d) in achieving spasm cessation at 14-days (as per parental reports) in children with infantile spasms. [ABSTRACT FROM AUTHOR]

Objectives: To assess the neurodevelopmental outcome of West syndrome (WS) in Indian children, who differ in their clinical profile from the western population. Materials and Methods: This cross-sectional study enrolled children aged 2--5 years with prior diagnosis of WS between November 2013 and March 2015. They were assessed for epilepsy outcome and developmental outcome using developmental profile 3 (DP3) and vineland adaptive behavioral scale II (VABS II). Results: Sixty-one children were enrolled. Perinatal asphyxia (40.9%), neonatal hypoglycemia (14.8%), and neonatal meningitis (9.8%) were predominant causes among the children with known etiology. Favorable epilepsy outcome (seizure freedom for >6 months) was observed in 29/61 patients (47.5%). Moderate to severe developmental delay was observed in 55/61 children (91.8%). Favorable developmental outcome (GDS by DP3 >70) was observed in just 5/61 (8%) patients. Conclusions: This study highlights the high prevalence of developmental delay in this population of children with WS, with adverse perinatal events being the most common etiology. [ABSTRACT FROM AUTHOR]

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) (P value < .05). Mean serum homocysteine level (13.9 vs 7.8 μmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls (P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms. [ABSTRACT FROM AUTHOR]

Background: The modified Atkins diet (MAD) has been used predominantly in older children, adolescents, and adults. There is a paucity of data on the use of the MAD in refractory epilepsy in young children. Objectives: This study was planned to evaluate the efficacy and tolerability of the MAD in refractory epilepsy in young children. Methods: This study recruited children aged 9 months to 3 years with refractory seizures. Children received MAD for 6‑month with the on‑going anticonvulsant medications being continued unchanged. Reduction in seizure frequency was the primary outcome measure. Adverse effects were also studied. Results: Thirty‑one children with daily seizures were studied with a median age of 18‑month (range 9–30 months). West syndrome was the most common epilepsy syndrome (26, 86.6%). Twenty‑one children remained on diet at 3 months and 13 at 6 months. The children who achieved >50% seizure reduction were 17 (54.8%) at 3 months and 9 (29%) at 6 months. Refusal to eat was a significant problem seen in eight children. Three children discontinued the diet due to adverse effects. Conclusion: The MAD was found to be feasible, effective, and well‑tolerated. [ABSTRACT FROM AUTHOR]