The Clinical Characteristics and Outcomes of Infantile Seizures in the First Year of Life: A Single-Center Study.

BACKGROUND: Epilepsy has a high incidence among infants during their first year of life, yet the prognosis can vary significantly. Although considerable research has been conducted on infantile spasms, studies examining infantile-onset epilepsy, excluding infantile spasms, remain limited, particularly concerning the factors influencing outcomes. Therefore, our study aims to elucidate seizure control, developmental outcomes, and prognostic factors in infants with epilepsy during their first year of life, within a single-center study in Malaysia. METHODS: We retrieved data from patients who experienced seizures before age 12 months and were followed for over two years, using electronic patient records at Hospital Raja Perempuan Zainab II in Kelantan, a state in Malaysia's east coast. We retrospectively reviewed these records and assessed clinical outcomes based on the last follow-up. RESULTS: Of 75 patients, 61 (81.3%) achieved good seizure control or remission. At the last follow-up, 24 (32%) exhibited developmental delay, whereas 19 (25.3%) displayed abnormal neuroimaging. Patients with abnormal background electroencephalographic (EEG) activity, as well as abnormal radiological findings, were more likely to experience poor seizure control and unfavorable developmental outcomes (P < 0.05). CONCLUSIONS: Our study underscores that most infants with epilepsy can achieve seizure remission. However, poor seizure control and developmental delay are associated with abnormal EEG background and characteristics, as well as neuroimaging abnormalities. The management of infantile-onset epilepsies may necessitate substantial resources and precise interventions to enhance overall outcomes.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

Clinical and electroencephalographic characteristics of 34 infant with onset of epileptic spasms before three months of age.

Epileptic spasms (ES) occur mostly between age 3 months and 24 months. ES beginning before 3 months of age were called early-onset ES in previous studies. The aim of this study was to identify clinical and electroencephalographic characteristics of patients with ES onset before 3 months of age. In total, 34 ES patients were retrospectively identified at Children's Hospital of Chongqing Medical University from January 1, 2020 to October 1, 2022. Our patients had diverse etiologies, including genetic (32.3 %), genetic-structural (11.8 %), structural-acquired (11.8 %), structural-congenital (8.8 %), and metabolic (5.9 %), with 29.4 % of patients having unknown etiology. Some patients experienced ES in clusters (either symmetrical or flexional) that occurred most often during awakening after sleep, and a minority of ES were characterized as isolated or asymmetrical, occurred during sleep, and could also manifest as relatively subtle. Approximately 35.3 % of patients also experienced other seizure types concurrently, including 10 focal seizures and 2 generalized seizures, and only half of the focal seizures had structural causes. The other seizure types occurred alone or sequentially with ES. Interictal electroencephalography revealed hypsarrhythmia or its variants, multifocal discharge, or burst suppression. 18 patients had no seizures lasting for more than 2 months, however, at the last follow-up visit, 5 of them had relapsed. All patients had different degrees of psychomotor retardation.

Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma.

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

The evolution of epilepsy surgery in tuberous sclerosis in Sweden: A national registry study.

PURPOSE: This study aimed to characterize the Swedish cohort of surgically treated patients with TSC and explore differences in preoperative investigation and outcome over time. METHODS: Data on patient and seizure characteristics were retrieved from the Swedish National Epilepsy Surgery Register. Two-year follow-up results were compared between the years 1997-2010 and 2011-2018. Preoperative investigations were re-evaluated. RESULTS: Eighteen tuberectomies and seven callosotomies were identified. Seizure freedom after tuberectomy was achieved in 11 % (1/9) 1997-2010 and 56 % (5/9) 2011-2018. The number of tuberectomies increased each decade. Patients operated on in 1997-2010 had higher seizure frequency (median 175 seizures/month vs. 102) and incidence of infantile spasms (4/9 vs. 1/9, none after 2011). There was a trend towards surgery at a younger age (median 86 months 1997-2010 vs. 48 months 2011-2018). None with >200 seizure/month, SEGA, or history of infantile spasms achieved seizure freedom. Two patients underwent anterior callosotomy (1992 and 1994) and became free of drop attacks. Five callosotomies were performed between 2011 and 2013, one patient became free of drop attacks. Two complications with new neurological deficits were reported. The median age at surgery was higher in the callosotomy group (14 years) than in the tuberectomy group (5 years). CONCLUSION: Seizure freedom after tuberectomy in patients with TSC has increased over time in our cohort. Signs of a heavier disease burden were more frequently observed 1997-2010 and associated with worse outcomes. Callosotomy operations were prevalent at the beginning of the 2010s.

Mutation in the ß-tubulin gene TUBB4A results in epileptic encephalopathy associated with hypomyelinated leucodystrophy: Unexpected findings reveal genetic mosaicism.

INTRODUCTION: Epileptic encephalopathies (EEs) are a group of heterogeneous epileptic syndromes characterized by early-onset refractory seizures, specific EEG abnormalities, developmental delay or regression and intellectual disability. The genetic spectrum of EE is very wide with mutations in a number of genes having various functions, such as those encoding AMPA ionotropic and glutamate receptors as well as voltage-gated ion channels. However, the list of EE-responsible genes could certainly be enlarged by next-generation sequencing. PATIENTS AND METHODS: The present study reports a clinical investigation and a molecular analysis by the whole exome sequencing (WES) and pyrosequencing of a patient's family affected by epileptic spasms and severe psychomotor delay. RESULTS: Clinical and radiological investigations revealed that the patient presented clinical features of severe and drug-resistant EE-type infantile epileptic spasm syndrome that evolved to Lennox Gastaut syndrome with radiological findings of hypomyelinated leukodystrophy. The results of WES revealed the presence of a novel heterozygous c.466C>T mutation in exon 4 of the TUBB4A gene in the patient. This transition led to the replacement of arginine by cysteine at position 156 (p.R156C) of the conserved helix 4 among the N-terminal domain of the TUBB4A protein. Bioinformatic tools predicted its deleterious effects on the structural arrangement and stability of the protein. The presence of the mutation in the asymptomatic father suggested the hypothesis of somatic mosaicism that was tested by pyrosequencing of DNA from two tissues of the patient and her father. The obtained results showed a lower rate of mutated alleles in the asymptomatic father compared with the affected daughter in both lymphocytes and buccal mucosa cells, confirming the occurrence of paternal mosaicism. The phenotypic features of the patient were also compared with those of previously described patients presenting TUBB4A mutations. CONCLUSIONS: Our study is the first to report a disease-causing variant in the TUBB4A gene in a patient with EE associated with hypomyelinated leucodystrophy. In addition, we expanded the phenotypic spectrum associated with the TUBB4A gene.

Infantile spasms caused by NEXMIF mutation: A case report and literature review.

BACKGROUND: Infantile spasms are rare epileptic syndromes associated with neurodevelopment and genes. The NEXMIF gene, identified as KIDLIA, KIAA2022 or Xpn, is a gene of unknown biological identity located on the q13.2 X chromosome. CASE DESCRIPTION: We presented a 4-month-old infant with a diagnosis of infantile spasms with NEXMIF mutation. Clinical manifestations include psychomotor retardation, loss of consciousness, and seizures. After oral therapy with vigabatrin, sodium valproate, and levetiracetam, the syndrome was alleviated and no recurrence was observed during one month of follow-up. CONCLUSIONS: A loss-of-function mutation in the NEXMIF gene has been reported. There are few reports on this mutation worldwide. This study provides a new idea for the clinical treatment of infantile spasms.

Nutritional vitamin B12 deficiency-associated Infantile epileptic spasms syndrome: Clinico-neurophysiological presentation, response to treatment, and neurodevelopmental outcome.

INTRODUCTION: Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. METHODS: In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables. RESULTS: Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p<0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p<0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p<0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p<0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml). CONCLUSIONS: Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology.

Inaccuracies in Parental Reporting of Treated Epileptic Spasms: Both Under- and Over-Reporting.

BACKGROUND: The purpose of this study was to evaluate the accuracy of parental reporting of epileptic spasms (ES) after 14 days of appropriate medical therapy for new-onset ES by comparison with extended video electroencephalography (vEEG) monitoring results. METHODS: Fifty-eight patients were identified from August 2019 to February 2021 with new-onset ES, confirmed on vEEG. Patients were initiated on appropriate treatment (high-dose steroids or vigabatrin). After two weeks of therapy, patients underwent overnight (18 to 24 hours) vEEG monitoring in the epilepsy monitoring unit. Parental reporting of presence or absence of ES on admission was compared with results of vEEG monitoring. RESULTS: The 58 patients ranged in age from three to 20 months (average 7.8 months). An underlying etiology was identified in 78%, whereas 22% patients had unknown etiology. The overall accuracy of parental reporting was 74% (43 of 58) when compared with results of vEEG within 14 to 18 days of starting therapy. Of these, 65% (28 of 43) reported ES resolution and 35% (15 of 43) reported continued ES. Of the 26% (15 of 58) families who were incorrect at two-week follow-up, 67% (10 of 15) reported resolution of ES. However, a minority of families, 33% (five of 15), who continued to report spasms clinically, were inaccurate. CONCLUSIONS: Although a majority of inaccurate parental reports at two weeks of treatment were due to unrecognized ES (a widely known phenomenon), a minority were conversely inaccurate due to persistent over-reporting of ES. This fact highlights the importance of correlating parental history with objective vEEG monitoring, to prevent inappropriate escalation of medication therapy.

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.

CDKL5 Deficiency Disorder Without Epilepsy.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) has epilepsy as a cardinal feature. Here we report two new female patients and review six previously published patients, one male and five females, with features of CDD but who never developed epilepsy. In contrast with the classical and severe CDD phenotype, they presented with milder gross motor delays, autism spectrum disorder, and no visual cortical impairment. Prolonged video electroencephalography was normal in adult cases but showed interictal frontal-temporal bilateral spikes and sharp waves in sleep in the three-year-old girl. Causative CDKL5 variants included two likely gene damaging (nonsense and frameshift) and six missense variants, being de novo or maternally inherited from asymptomatic females with skewed X-chromosome inactivation (two missense variants). Our data indicate that a milder form of CDD without epilepsy can occur in some cases without clear correlation with specific variants in the CDKL5 gene.

Long-Term Outcome of Adrenocorticotropic Hormone Therapy in Children With New-Onset Infantile Spasms.

BACKGROUND: To investigate for pretreatment clinical variables to predict the outcome of new-onset epileptic spasms after adrenocorticotropic hormone (ACTH) therapy and to identify risk factors for poor long-term outcome. METHODS: We retrospectively studied 129 consecutive patients with infantile spasms syndrome (ISS). These patients received ACTH with antiseizure medication therapy for the first time and were regularly followed up for more than six months at our hospital. The response to treatment was assessed after two weeks of ACTH injection. Kaplan-Meier survival analysis and the multivariate Cox proportional hazard regression model were used. RESULTS: Among the 129 patients, 61 (47.3%) had a good response after two weeks of ACTH treatment. At the time of the latest follow-up, 71 (55%) patients were seizure-free (International League Against Epilepsy class1). The univariate analysis revealed that normal neurodevelopment (P = 0.018), time lag of less than one month (P = 0.026), no hypsarrhythmia on EEG (P = 0.004), and serum calcium level ≥2.50 mmol/L (P = 0.035) were significantly associated with a good response. Only a good response to ACTH therapy was significantly associated with a positive long-term outcome. The Kaplan-Meier survival analysis showed that serum calcium level ≧2.50 mmol/L was significantly associated with a positive long-term outcome (P = 0.030). Multivariate analysis confirmed that no response to ACTH therapy was an independent variable that predicted long-term seizure recurrence (P < 0.001, hazard ratio = 4.602, confidence interval = 2.252 to 9.406). CONCLUSIONS: A good response to ACTH therapy had a significant predictive value for long-term seizure outcomes. Calcium may play an important role in the treatment of ISS with ACTH.

The Epilepsy Surgery Experience in Children With Infantile Epileptic Spasms Syndrome at a Tertiary Care Center in Canada.

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.

WWOX developmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk.

OBJECTIVE: WWOX is an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX-DEE), also known as WOREE (WWOX-related epileptic encephalopathy). We analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival. METHODS: We studied 13 patients from 12 families with WWOX-DEE. Information regarding seizure semiology, comorbidities, facial dysmorphisms, and disease outcome were collected. Electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) data were analyzed. Pathogenic WWOX variants from our cohort and the literature were coded as either null or missense, allowing individuals to be classified into one of three genotype classes: (1) null/null, (2) null/missense, (3) missense/missense. Differences in survival outcome were estimated using the Kaplan-Meier method. RESULTS: All patients experienced multiple seizure types (median onset = 5 weeks, range = 1 day-10 months), the most frequent being focal (85%), epileptic spasms (77%), and tonic seizures (69%). Ictal EEG recordings in six of 13 patients showed tonic (n = 5), myoclonic (n = 2), epileptic spasms (n = 2), focal (n = 1), and migrating focal (n = 1) seizures. Interictal EEGs demonstrated slow background activity with multifocal discharges, predominantly over frontal or temporo-occipital regions. Eleven of 13 patients had a movement disorder, most frequently dystonia. Brain MRIs revealed severe frontotemporal, hippocampal, and optic atrophy, thin corpus callosum, and white matter signal abnormalities. Pathogenic variants were located throughout WWOX and comprised both missense and null changes including five copy number variants (four deletions, one duplication). Survival analyses showed that patients with two null variants are at higher mortality risk (p-value = .0085, log-rank test). SIGNIFICANCE: Biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome. The most common seizure types are focal seizures and epileptic spasms. Mortality risk is associated with mutation type; patients with biallelic null WWOX pathogenic variants have significantly lower survival probability compared to those carrying at least one presumed hypomorphic missense pathogenic variant.

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy-not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy.

Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.

BACKGROUND AND OBJECTIVES: Early life epilepsies (epilepsies in children 1-36 months old) are common and may be refractory to antiseizure medications. We summarize findings of a systematic review commissioned by the American Epilepsy Society to assess evidence and identify evidence gaps for surgical treatments for epilepsy in children aged 1-36 months without infantile spasms. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Library were searched for studies published from 1/1/1999 to 8/19/21. We included studies reporting data on children aged 1 month to ≤36 months undergoing surgical interventions or neurostimulation for epilepsy and enrolling ≥10 patients per procedure. We excluded studies of infants with infantile spasms or status epilepticus. For effectiveness outcomes (seizure freedom, seizure frequency), studies were required to report follow-up at ≥ 12 weeks. For harm outcomes, no minimum follow-up was required. Outcomes for all epilepsy types, regardless of etiology, were reported together. RESULTS: Eighteen studies (in 19 articles) met the inclusion criteria. Sixteen prestudies/poststudies reported on efficacy, and 12 studies addressed harms. Surgeries were performed from 1979 to 2020. Seizure freedom for infants undergoing hemispherectomy/hemispherotomy ranged from 7% to 76% at 1 year after surgery. For nonhemispheric surgeries, seizure freedom ranged from 40% to 70%. For efficacy, we concluded low strength of evidence (SOE) suggests some infants achieve seizure freedom after epilepsy surgery. Over half of infants undergoing hemispherectomy/hemispherotomy achieved a favorable outcome (Engel I or II, International League Against Epilepsy I to IV, or >50% seizure reduction) at follow-up of >1 year, although studies had key limitations. Surgical mortality was rare for functional hemispherectomy/hemispherotomy and nonhemispheric resections. Low SOE suggests postoperative hydrocephalus is uncommon for infants undergoing nonhemispheric procedures for epilepsy. DISCUSSION: Although existing evidence remains sparse and low quality, some infants achieve seizure freedom after surgery and ≥50% achieve favorable outcomes. Future prospective studies in this age group are needed. In addition to seizure outcomes, studies should evaluate other important outcomes (developmental outcomes, quality of life [QOL], sleep, functional performance, and caregiver QOL). TRIAL REGISTRATION INFORMATION: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Analysis of electrocardiograms in individuals with CDKL5 deficiency disorder.

CDKL5 deficiency disorder (CDD) is an epileptic encephalopathy associated with medically refractory epilepsy. We sought to determine whether prolonged corrected QT interval (QTc) or other cardiac conduction abnormalities were seen in CDD in a clinical cohort. A cohort of individuals with CDD was evaluated in the Children's Hospital Colorado's International Foundation for CDKL5 Research designated Center of Excellence clinic with routine electrocardiograms obtained as part of routine clinical care. Retrospective review of electrocardiograms was completed. ECGs from 44 individuals (7 male, 37 female, age range 0-34.5 years) with pathogenic mutations and findings consistent with CDD were evaluated. Multiple ECGs were available from the 44 individuals obtained from 1996 to 2020. Prolonged QTc was found in two individuals (4.5%) and either resolved or was not confirmed on Holter monitor; no additional interventions were performed. A total of 11 individuals had echocardiograms for a variety of indications including unexplained tachycardia and ECG abnormalities; all were normal. Two individuals in the cohort died during the study with no abnormal findings on ECG. The incidence of prolonged QTc or other significant actionable cardiac abnormalities was rare in a cohort of individuals with CDD though was higher than the prevalence seen within the general population. Further studies in a larger, confirmatory cohort over a longer period are needed.