Infantile epileptic spasms syndrome: a cohort study of 88 children.

BACKGROUND: This study aimed to investigate and analyze the risk factors for non-etiology-specific infantile spasms (IS) and unrelieved clinical symptoms after treatment. METHODS: Eighty-eight children with IS who were treated at our hospital from March 2018 to December 2021 were included in the study. The children were divided into etiology-specific (n = 46) and nonetiology-specific (n = 42) groups, based on the diagnostic results, and remission (n = 45) and nonremission (n = 43) groups, based on clinical outcomes after treatment. The clinical data from patients in the etiology-specific and nonetiology-specific groups and the remission and nonremission groups were compared. Risk factors for non-etiology-specific IS were identified using logistic regression analysis. RESULTS: Gender, family history, birth status, and metabolic abnormalities were significantly different between the etiology-specific and non-etiology-specific groups. Gender and metabolic abnormalities were risk factors for nonetiology-specific IS. Family history, birth status, metabolic abnormalities, and brain magnetic resonance imaging were significantly different between the remission and nonremission groups, and different etiologies were risk factors for unrelieved symptoms after treatment. CONCLUSION: The occurrence of nonetiology-specific IS is associated with gender and metabolic abnormalities in children. After medication, unrelieved IS symptoms are associated with etiologies.

Neurodevelopmental Outcomes of a Cohort of Children with Tuberous Sclerosis Complex with Epileptic Spasms.

The neurodevelopmental outcomes in children with tuberous sclerosis complex (TSC) with epileptic spasms remain underdiagnosed and might be responsible for significant morbidity and mortality burdens, even after spasms abate. The study was a cross-sectional study over 18 months at a tertiary care pediatric hospital, involving 30 children with TSC who had epileptic spasms. They were assessed with Diagnostic and Statistical Manual of Mental Disorders-5 criteria for autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID), and childhood psychopathology measurement schedule (CPMS) for behavioral disorders. The median age at onset of epileptic spasms was 6.5 (1-12) months, and the age at enrolment was 5 (1-15) years. Of 30 children, 2 (6.7%) had only ADHD, 15 (50%) had only ID/GDD (global developmental delay), 4 (13.3%) had ASD and ID/GDD, 3 (10%) had ADHD and ID/GDD, and 6 (20%) had none. The median intelligence quotient/development quotient (IQ/DQ) score was 60.5 (20-105). CPMS assessment revealed significant behavioral abnormalities in almost half the children. Eight (26.7%) patients were completely seizure-free for at least 2 years, 8 (26.7%) had generalized tonic-clonic seizures, 11 (36.6%) had focal epilepsy, and 3 (10%) had evolved into Lennox-Gastaut syndrome. A high proportion of neurodevelopment disorders, including ASD, ADHD, ID/GDD, and behavioral disorders were seen in this pilot study with a small cohort of children with TSC with epileptic spasms.

Age at onset in patients with Lennox-Gastaut syndrome: Correlations with clinical manifestations.

The aim of the current study was to investigate the age at onset in patients with Lennox-Gastaut Syndrome (LGS). We also investigated the clinical and EEG characteristics of these patients in different age groups. This was a retrospective study. All patients with a diagnosis of LGS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 through 2020. 300 patients had LGS. Age at onset was 3.3 ± 4.1 years (minimum = 0 and maximum = 21 years). In 10 patients (3%) LGS started at age 14 years or above. Epileptic spasms were more often observed in those with an age at onset below one year (8%) compared with those with an age at onset of 1 to 8 years (0.7%) [Odds Ratio (OR) = 10.32]. Intellectual disability was less frequently observed in those with an age at onset of 8 years and above (68%) compared with those with an age at onset of 1 to 8 years (90%) (OR = 0.33). Tonic-clonic seizures were more often observed in those with an age at onset of 8 years and above (83%) compared with those with an age at onset of 1 to 8 years (55%) (OR = 2.87). While age at onset of LGS in the majority of patients is below 8 years, in some patients the syndrome begins in their late childhood or even during adolescence. Age at onset of LGS has significant correlations with the clinical manifestations of the syndrome.

Response to treatment and outcomes of infantile spasms in Down syndrome.

AIM: To estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long-term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland. METHOD: This was a 10-year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long-term outcomes. RESULTS: The prevalence of infantile spasms in Down syndrome was 3.0% during the study period. Fifty-four infants were identified with median age of spasm onset at 201 days (interquartile range [IQR] 156-242). Spasm cessation was achieved in 88% (n=46) at a median of 110 days (IQR 5-66). The most common first-line medications were prednisolone (n=20, 37%), vigabatrin (n=18, 33.3%), and sodium valproate (n=9, 16.7%). At follow-up (median age 23.7mo; IQR 13.4-40.6), 25% had ongoing seizures and 85% had developmental concerns. Treatment within 60 days did not correlate with spasm cessation. Seventeen children (31%) experienced medication side effects, with vigabatrin accounting for 52%. INTERPRETATION: Prednisolone is an effective and well-tolerated medication for treating infantile spasms in Down syndrome. Despite the high percentage of spasm cessation, developmental concerns and ongoing seizures were common.

Cardiometabolic outcomes in children and adolescents with West syndrome.

BACKGROUND: West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published. METHODS: In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy (< 2 years), early childhood (2-6 years), and childhood/adolescence (6-18 years). RESULTS: The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [p = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [p < 0.001], hypertriglyceridemia 71 % vs. 40 % [p = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [p = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [p < 0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients (p = 0.008, p = 0.001, and p = 0.037, respectively), and higher triglyceride levels during early childhood (p = 0.050), with no significant group differences during childhood/adolescence. CONCLUSIONS: Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation.

Current medico-psycho-social conditions of patients with West syndrome in Japan.

OBJECTIVE: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan. METHODS: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset. RESULTS: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%. SIGNIFICANCE: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.

West Syndrome in Children With Congenital Zika Virus Infection.

Congenital Zika infection has been linked with a characteristic phenotype including neurologic sequelae. However, West syndrome has not been previously well described as a consequence. We aim to show this association through a retrospective descriptive study performed in Ecuador. Among 147 infants with congenital Zika infection, 7.5% suffered from West syndrome. Vigabatrin seems to be effective to control the spasms.

Epilepsy in adult patients with tuberous sclerosis complex.

OBJECTIVES: Little is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic. MATERIALS AND METHODS: We collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities. RESULTS: Out of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug-resistant; 59 (32.8%) seizure-free, at a median age of 18 years. 22% of the seizure-free patients (13/59) discontinued medication. Median age at seizure onset was 9 months. Seventy-six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p < 0.001) and subependymal nodules (SENs) (p < 0.001) were more frequent in those who developed epilepsy. Cognitive functioning was lower (p < 0.001) and psychiatric disorders more frequent (p = 0.001). We did not find significant differences regarding age, gender, mutation and tubers/SENs in seizure-free vs drug-resistant individuals. Intellectual disability (p < 0.001) and psychiatric disorders (p = 0.004) were more common among drug-resistant patients. CONCLUSIONS: Epilepsy in TSC can be a lifelong disorder, but one-third of individuals reach seizure freedom by early adulthood. In the long term, age at epilepsy onset has a crucial role in drug resistance and in developing intellectual disability, both in drug-resistant and drug-sensible patients. Patients with drug-refractory seizures tend to develop psychiatric issues, which should be recognized and adequately treated.

Patterns of Brain Injury in Perinatal Arterial Ischemic Stroke and the Development of Infantile Spasms.

INTRODUCTION: Perinatal arterial ischemic stroke (PAIS) underlies approximately 10% of infantile spasms (IS). We aim to identify patterns of brain injury in ischemic stroke that may predispose infants to infantile spasms. METHODS: Sixty-four perinatal arterial ischemic stroke patients were identified meeting the following inclusion criteria: term birth, magnetic resonance imaging (MRI) showing ischemic stroke or encephalomalacia in an arterial distribution, and follow-up records. Patients who developed infantile spasms (PAIS-IS) were analyzed descriptively for ischemic stroke injury patterns and were compared to a seizure-free control group (PAIS-only). Stroke injury was scored using the modified pediatric ASPECTS (modASPECTS). RESULTS: The PAIS-IS (n = 9) group had significantly higher modASPECTS than the PAIS-only (n = 16) group (P = .002, Mann-Whitney). A greater proportion of PAIS-IS patients had injury to deep cerebral structures (67%) than PAIS-only (25%). CONCLUSION: Infarct size was significantly associated with infantile spasms development. Results support theories implicating deep cerebral structures in infantile spasms pathogenesis. This may help identify perinatal arterial ischemic stroke patients at risk of infantile spasms, facilitating more timely diagnosis.

The severe epilepsy syndromes of infancy: A population-based study.

OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.

Epileptic Spasms in a Large Hypothalamic Hamartoma Cohort.

INTRODUCTION: Hypothalamic hamartoma is rarely associated with epileptic spasms. We describe epileptic spasms in a large cohort of hypothalamic hamartoma patients. METHODS: We performed a retrospective chart review between March 2011 and March 2020 to identify patients with hypothalamic hamartoma and epilepsy. RESULTS: We identified 114 patients with hypothalamic hamartoma and epilepsy, only 3 male patients (2.6%) also had epileptic spasms. The epileptic spasms developed between 6 and 18 months of age. Epileptic spasms resolved with oral prednisolone in 1 and with vigabatrin in the second patient. The third patient continued epileptic spasms despite multiple antiepileptic drugs and partial resection of hypothalamic hamartoma. All 3 patients underwent laser-ablation of hypothalamic hamartoma at the age of 14, 29, and 63 months. The seizure burden decreased by 100%, 84%, and 93% at follow-up (3-47 months). CONCLUSIONS: Epileptic spasms are rare in hypothalamic hamartoma patients and early laser-ablation could potentially treat epileptic spasms and all other seizure types associated with hypothalamic hamartoma.

Molecular diagnosis of epileptic encephalopathy of the first year of life applying a customized gene panel in a group of Argentinean patients.

OBJECTIVE: The aim of this study was to perform a molecular characterization of 17 Argentinean pediatric patients with diagnosis of having epileptic encephalopathies (EEs) of the first year of life without known etiology, applying next-generation sequencing (NGS). METHODS: We included 17 patients with EE with age of onset under 12 months without known etiology after ruling out structural abnormalities, metabolic disorders, and large chromosomal abnormalities. They presented with the following clinical phenotypes: Dravet syndrome (DS; n: 7), epilepsy of infancy with migrating focal seizures (EIMFS; n: 3), West syndrome (WS; n: 2), and undetermined epileptic encephalopathy (UEE; n: 5). Neurologic examinations, seizure semiology, brain magnetic resonance imaging, and standard electroencephalography (EEG) or video-EEG studies were performed in all cases. Using a custom amplicon strategy, we designed an NGS panel to study 47 genes associated with EEs. RESULTS: Pathogenic variants were detected in 8 cases (47%), including seven novel pathogenic variants and one previously reported as being pathogenic. The pathogenic variants were identified in 6 patients with DS (SCN1A gene), one with EIMFS (SCN2A gene), and one with UEE (SLC2A1 gene). Nonrelevant variants were identified in the patients with WS. CONCLUSION: We demonstrated the feasibility of an NGS-gene panel approach for the analysis of patients with EE in our setting. A genetic diagnosis was achieved in nearly 50% of patients, 87% of them presenting with nonpreviously reported variants. The early identification of the underlying causative genetic alteration will be a valuable tool for providing prognostic information and genetic counselling and also to improve therapeutic decisions in Argentinean patients.

The patterns of response of 11 regimens for infantile spasms.

Infantile spasms (ISs) is a devastating form of an early infantile epileptic encephalopathy. The patterns of response of multiple regimens, and the difference in response rates for the cases who receive first-line therapies on time versus those who receive them after non-first-line therapies are unknown. We performed a study involving 314 ISs cases aiming to investigate the patterns of response of 11 regimens, and the difference in response rates for the cases received first-line therapies as first two regimens versus those who received other drugs prior to first-line options. As a result, the efficacy of each regimen was: the foremost two regimens; 36.99%, third; 10.27%, fourth; 6.16%, fifth; 5.48%, and from the sixth regimen onwards, each additional regimen added ≤ 2% probability of seizure freedom. There was a statistically significant difference in seizure freedom rates between cases received first-line therapies as first or second regimen versus those who received them later. Our study revealed for the first time that in ISs cases, seizure freedom is likely to be observed within the first five regimens, and an early administration of first-line therapies is superior to non-first-line options. These results will aid in management of ISs cases.

Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience.

INTRODUCTION: A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE METHODS: An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented. RESULTS: Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy. CONCLUSIONS: Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints.

Epilepsy and Neurodevelopmental Comorbidities in Tuberous Sclerosis Complex: A Natural History Study.

BACKGROUND: We studied the natural history, genotype influence, and inter-relationship of epilepsy and neuropsychiatric disorders in tuberous sclerosis complex. METHODS: Patients were identified using the TSC Natural History Database, the largest repository of longitudinally studied patients enrolled by the TSC Clinics Consortium. RESULTS: A cohort of 1657 TSC Natural History Database patients was analyzed. Eighty-eight percent patients (91% TSC2 vs 82% TSC1; P = 0.002) had epilepsy; TSC2 was more frequent with epilepsy onset at age less than two years (TSC2 82% vs TSC1 54%; P < 0.001) and infantile spasms (TSC2 56% vs TSC1 27%; P < 0.001). Frequency of intellectual disability (intelligence quotient less than 70) was higher when epilepsy coexisted (P < 0.001), but was not impacted by genotype (P = 0.08). Severe intellectual disability (intelligence quotient less than 50) was associated with epilepsy onset at age less than two years (P = 0.007), but not with the epilepsy duration (P = 0.45). Autism was diagnosed in 23% and was associated with epilepsy (P < 0.001), particularly with epilepsy onset at age less than two years (P = 0.02) but not with genotype (P = 0.06). Attention-deficit/hyperactivity disorder (age greater than four years) was diagnosed in 18% and was associated with epilepsy (P < 0.001), but genotype made no difference. Nine percent had anxiety (age greater than seven years) and 6% had depression (age greater than nine years), but neither showed association with epilepsy or genotype. CONCLUSIONS: Epilepsy is associated with intellectual disability, and when epilepsy begins before age two years the frequency and severity of intellectual disability is much higher. Epilepsy is also associated with autism and attention-deficit/hyperactivity disorder but not with anxiety and depression. Additional trials, blinded, prospective, and adequately powered, will help clarify if early and effective treatment of epilepsy may also mitigate intellectual disability, autism, and attention-deficit/hyperactivity disorder.

Early epilepsy in children with Zika-related microcephaly in a cohort in Recife, Brazil: Characteristics, electroencephalographic findings, and treatment response.

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

Impact of therapeutic hypothermia on infantile spasms: an observational cohort study.

AIM: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome. RESULTS: Forty-two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1-40.0wks]). The aetiology for infantile spasms was identified in almost two-thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138). INTERPRETATION: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants. WHAT THIS PAPER ADDS: The incidence of infantile spasms and patient characteristics in the southern region of the Republic of Ireland is similar to internationally published data. None of the infants with a history of mild hypoxic-ischemic encephalopathy (HIE) developed infantile spasms. The risk of infantile spasms was higher in infants with severe HIE. Infantile spasms were more frequent in infants with severe HIE not treated with therapeutic hypothermia.

IMPACTO DE LA HIPOTERMIA COMO TRATAMIENTO EN LOS ESPASMOS INFANTILES: UN ESTUDIO DE COHORTE OBSERVACIONAL: OBJETIVO: Establecer la incidencia de los espasmos infantiles en niños de la República de Irlanda y comparar la incidencia de los espasmos infantiles antes y después de la introducción de la hipotermia terapéutica en niños con encefalopatía hipóxico-isquémica (EHI). MÉTODO: Niños nacidos entre 2003 y 2015 y diagnosticados con espasmos infantiles (espasmos epilépticos con o sin hipsarritmia) en los primeros 2 años de vida fueron identificados por medio de auditorías de reportes de electroencefalográficos y listas de pacientes de neurólogos infantiles. Datos sobre los nacidos vivos se obtuvieron de la base de datos estadística del hospital regional. Las historias clínicas de los casos de espasmos infantiles fueron revisadas para obtener datos demográficos, resultados diagnósticos, respuesta a tratamiento, curso de la enfermedad y resultados del desarrollo. RESULTADOS: Fueron identificados 42 niños con espasmos infantiles. La incidencia acumulada de los espasmos infantiles por encima de los 2 años fue de 4,01 por 10.000 nacidos vivos. La diferencia debida al sexo fue mínima (22 masculinos, 20 femeninos) y la mayoría nacieron en o cercano a término, con edad gestacional entre 30,0 y 41,8 semanas (media (rango Intercuartil) 39,6 semanas (38,1-40,0 semanas). La etiología de espasmos infantiles fue identificada en dos tercios de los casos, siendo EHI la causa más común (7 de 42). Otras causas incluyeron anormalidades cromosómicas y monogénicas (8 de 42). Los espasmos infantiles ocurrieron en los grados moderados y severos de EHI con incidencia significativamente mayor en aquellos casos severos de EHI (p=0,029). Los niños con EHI severo que no recibieron hipotermia terapéutica tuvieron una probabilidad seis veces mayor de desarrollar espasmos infantiles comparados con aquellos quienes la recibieron, pero la diferencia no era estadísticamente significativa (4 de 16 vs 1 de 14, p=0,138). INTERPRETACIÓN: Este estudio proporciona información detallada acerca de los espasmos infantiles antes y después de la introducción de la hipotermia terapéutica. La severidad de la EHI es un factor de riesgo para el desarrollo de los espasmos infantiles. La introducción de la hipotermia terapéutica puede haber tenido un impacto, pero el efecto fue difícil de determinar en esta cohorte debido al pequeño número de recién nacidos.

IMPACTO DA HIPOTERMIA TERAPÊUTICA NOS ESPASMOS INFANTIS: UM ESTUDO DE COORTE OBSERVACIONAL: OBJETIVO: Estabelecer a incidência de espasmos infantis em crianças da República da Irlanda e comparar a incidência de espasmos infantis antes e após a introdução da hipotermia terapêutica em lactentes com encefalopatia hipóxica-isquêmica (EHI). MÉTODO: Crianças nascidas entre 2003 e 2015 e diagnosticadas com espasmos infantis (espasmos epilépticos com ou sem hipsarritmia) nos primeiros 2 anos de vida foram identificadas por meio de checagem dos relatórios de eletroencefalografia e listas de pacientes de neurologia pediátrica. Dados sobre nascidos vivos foram obtidos nas bases de dados estatísticas dos hospitais regionais. Prontuários médicos sobre casos de espasmos infantis foram revisados quanto a dados demográficos, resultados diagnósticos, resposta ao tratamento, curso da doença, e resultado desenvolvimental. RESULTADOS: Quarenta e dois lactentes com espasmos infantis foram identificados. A incidência cumulativa de espasmos infantis até os dois anos de idade foi 4,01 por 10.000 nascidos vidos. Diferenças devida ao sexo foram mínimas (22 meninos, 20 meninas) e a maior parte dos lactentes nasceu próximo ao termo, com idades gestacionais variando de 30,0 41,8 semanas (mediana [intervalo interquartil] 39,6 sem [38,1-40,0sem]). A etiologia dos espasmos infantis foi identificada em dois terços dos casos, com a EHI sendo a causa mais comum (7 em cada 42). Outras causas incluíram anormalidades cromossômicas e monogenéticas (8 em 42). Os espasmos infantis aconteceram em graus moderados a severos de EHI, com incidência significantemente maior naqueles com EHI severa (p=0,029). Lactentes com EHI severa que não receberam hipotermia terapêutica tinham seis vezes mais probabilidade de desenvolver espasmos infantis comparados com os que receberam, mas a diferença não foi estatisticamente significativa. (4 em16 vs 1 em 24, p=0,138). INTERPRETAÇÃO: Este esudo fornece informação detalhada sobre espasmos infantis antes e após a introdução de hipotermia terapêutica. A severidade da EHI é um fator de risco para o desenvolvimento de espasmos infantis. A introdução de hiportermia terapêutica por ter tido um impacto, mas o efeito foi difícil de assegurar nesta coorte devido ao pequeno número de lactentes.

Does Co-occurred Cerebral Palsy Change the Prognosis of West Syndrome?

AIM: We aimed to examine the occurrence of cerebral palsy (CP) in children with West syndrome (WS), to estimate the possible causative factors by analyzing the neuroimaging examinations of patients, to evaluate their cognitive/motor function and epileptic status and to compare the prognosis of children with double pathology of WS and CP and of those without CP. METHODS: The clinical and magnetic resonance imaging (MRI) data of 62 patients with West syndrome were evaluated. A total of 39 of 62 patients (63%) suffered from CP (CP group). The non-CP group included 23 patients. RESULTS: Abnormal MRI was found in 55/62 (89%) patients. Main anomalies were: brain malformation (21), hypoxic-ischemic encephalopathy (13), cerebrovascular insult (8), infection (7), and other anomalies (6). In the CP group, the most common MRI abnormalities included pre/perinatal hypoxia/ischemia, brain malformation, cerebrovascular insult, and infection. In the non-CP group, brain malformations were the most frequent. Significantly more negative MRIs were found in the non-CP group. More than 60% of the patients were severely cognitively impaired, almost 90% of them had CP. Not only the occurrence of intellectual disability was lower in the non-CP group, but its severity was milder as well. A total of 78% of the children with CP had a very severe motor disability. Fifty-four percent in the CP and 67% in the non-CP group had therapy-resistant epilepsy. CONCLUSION: WS has an especially unfavorable prognosis: cerebral anomaly was confirmed in 89% of our patients. CP was present in almost two-thirds of the children with WS, most of them had severe cognitive and motor deficits.

Retinal defect in children with infantile spasms of varying etiologies: An observational study.

OBJECTIVE: To determine the prevalence of retinal defect in children with infantile spasms (IS) unrelated to treatment with vigabatrin and clarify if specific primary etiologies for IS are associated with retinal defect more than others. METHODS: This was an observational cohort study including 312 patients (176 male, 136 female) with IS who were vigabatrin-naive. Participants ranged from 1.7 to 34.7 months of age (mean 8.8 months). Electroretinograms (ERGs) were performed according to the International Society for Clinical Electrophysiology of Vision. Retinal defect was identified as abnormal if the 30-Hz flicker ERG amplitude was lower than the age-corrected normal 95% prediction interval. The primary etiology for IS, as determined by the treating pediatric neurologist(s), was obtained from patient health records and classified into 1 of 9 etiologic subgroups: (1) genetic disorders alone, (2) genetic-structural disorders, (3) structural-congenital, (4) structural-acquired (perinatal), (5) structural-acquired (postnatal), (6) metabolic disorders, (7) immunologic disorders, (8) infectious, and (9) unknown causes. RESULTS: Fifty-nine of the 312 vigabatrin-naive children (18.9%) showed retinal defect and the prevalence of retinal defect was highest (24.4%) in the structural-acquired (perinatal) subgroup, which included hypoxic-ischemic defect. Retinal function compared across subgroups showed no significant difference. CONCLUSIONS: Care is required in diagnosing retinal toxicity, which would be enhanced by baseline flicker ERG in children with IS prior to starting vigabatrin.

Incidence of Hypertension Among Children Treated With Adrenocorticotropic Hormone (ACTH) or Prednisolone for Infantile Spasms.

Children with infantile spasms are often treated with hormonal therapies including adrenocorticotropic hormone (ACTH) and prednisolone. These have numerous systemic side effects including hypertension and, rarely, fatal cardiomyopathy; however, the incidence of these side effects has not been well described. This study aims to quantify the incidence and short-term sequelae of hypertension in this population. A retrospective chart review was performed at a single institution. Children 2 months to 2 years old with newly diagnosed infantile spasms treated from 2013 to 2017 were included. Variables collected included age, sex, etiology and treatment of infantile spasms, documented or missed diagnosis of hypertension, treatment of hypertension, echocardiogram results, referrals for hypertension, and persistence of hypertension 2 to 4 months after treatment. Analyses included descriptive statistics with percentiles, means, and medians. Differences between groups were assessed using Fisher exact tests. Hypertension occurred in 34/77 children (44%) during treatment with ACTH and 4/11 children (36%) during treatment with prednisolone. No child developed hypertension during treatment with nonhormonal therapies. The incidence of hypertension between ACTH and prednisolone groups was not significantly different (P = .75). The incidence of hypertension was significantly higher in the ACTH and prednisolone groups compared to the nonhormonal group (P < .001 for each). Sixteen children received echocardiograms, with no cases of cardiomyopathy. Two children had persistent hypertension at 2 months after discontinuation of hormonal therapy. Hypertension is a very common side effect of hormonal therapy for infantile spasms; however, few developed long-term hypertension and none developed cardiomyopathy. Further study is needed to determine the role of antihypertensive treatment for hormone-related hypertension.