Epilepsy Surgery in Infants up to 3 Months of Age: Safety, Feasibility, and Outcomes: A Multicenter, Multinational Study

Summary, originally published in Epilepsia

Objective: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on “ultra-early” epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study’s goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months.

Methods: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications.

Results: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19–104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1–3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections).

Significance: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Pediatric Epilepsy and Psychoeducational Interventions: A Review of the Literature

Abstract, originally published in Epilepsy & Behavior

For many individuals, living with epilepsy is truly a family affair throughout the life span. When it comes to childhood epilepsy, the unpredictability of seizure patterns, comorbid conditions, the risk of sudden unexpected death in epilepsy (SUDEP), and societal stigma can be emotionally taxing on children and their primary caregivers.

To this end, this article proposes to review psychoeducational interventions provided to primary caregivers of children with an epilepsy diagnosis and the impact of such interventions on general parental coping skills. There were three main themes identified (1) caregivers’ knowledge and self-efficacy about seizure management; (2) parental epilepsy-related fears, anxiety, and stress; (3) parental sleep quality and SUDEP psychoeducation.

Overall, considering research limitations, providing epilepsy-related psychoeducational interventions to primary caregivers of children with epilepsy seems to have promising evidence in the literature. After receiving such interventions, the studies show that caregivers’ psychosocial outcomes improved; they become more empowered to manage their children’s seizures and advocate for their children’s psychosocial needs.

A Children’s Epilepsy Diagnosis Aid: Development and Early Validation Using a Bayesian Approach

Abstract, originally published in Epilepsy & Behavior

Introduction: The diagnosis of epilepsy in children is difficult and misdiagnosis rates can be as much as 36%. Diagnosis in all countries is essentially clinical, based on asking a series of questions and interpreting the answers. Doctors experienced enough to do this are either scarce or absent in very many parts of the world so there is a need to develop a diagnostic aid to help less-experienced doctors or non-physician health workers (NPHWs) do this. We used a Bayesian approach to determine the most useful questions to ask based on their likelihood ratios (LR), and incorporated these into a Children’s Epilepsy Diagnosis Aid (CEDA).

Methods: Ninety-six consecutive new referrals with possible epilepsy aged under 10 years attending a pediatric neurology clinic in Khartoum were included. Initially, their caregivers were asked 65 yes/no questions by a medical officer, then seen by pediatric neurologist and the diagnosis of epilepsy (E), not epilepsy (N), or uncertain (U) was made. The LR was calculated and then we selected the variables with the highest and lowest LRs which are the most informative at differentiating epilepsy from non-epilepsy. An algorithm, (CEDA), based on the most informative questions was constructed and tested on a new sample of 47 consecutive patients with a first attendance of possible epilepsy. We calculated the sensitivity and specificity for CEDA in the diagnosis of epilepsy.

Results: Sixty-nine (79%) had epilepsy and 18 (21%) non-epilepsy giving pre-test odds of having epilepsy of 3.83. Eleven variables with the most informative LRs formed the diagnostic aid (CEDA). The pre-test odds and algorithm were used to determine the probability of epilepsy diagnosis in a subsequent sample of 47 patients. There were 36 patients with epilepsy and 11 with nonepileptic conditions. The sensitivity of CEDA was 100% with specificity of 97% and misdiagnosis 8.3%.

Conclusion: Children’s Epilepsy Diagnosis Aid has the potential to improve pediatric epilepsy diagnosis and therefore management and is particularly likely to be useful in the many situations where access to epilepsy specialists is limited. The algorithm can be presented as a smartphone application or used as a spreadsheet on a computer.

Phenotypic Analysis of Catastrophic Childhood Epilepsy Genes

Featuring the work of former CURE Epilepsy grantee Dr. Scott Baraban

Abstract, originally published in Communications Biology

Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Local field potential recordings (LFP) were used to screen ?3300 larvae. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.

Study: ‘Rethink’ Use of Antiseizure Medications after Hospital Discharge in Neonates

Summary, originally published on healio.com

Researchers observed no difference in functional neurodevelopment or epilepsy among children aged 24 months regardless of whether antiseizure medication was discontinued or maintained in infants at discharge once seizures ceased.

Results of the comparative effectiveness study were published in JAMA Neurology.

“These results support discontinuing antiseizure medications (ASMs) for most neonates with acute symptomatic seizures prior to discharge from the hospital, an approach that may represent an evidence-based change in practice for many clinicians,” Hannah C. Glass, MDCM, MAS, a pediatric neurologist, founding codirector of the neurointensive care nursery and director of neonatal critical care services at the University of California, San Francisco Benioff Children’s Hospital, and colleagues wrote.

Quality of Life at 6 Years in Children Treated for West Syndrome with Hormonal Therapy

Abstract, originally published in Epilepsy & Behavior

Introduction: West syndrome is a severe epileptic encephalopathy occurring in infancy. Majority of affected children suffer from poor epilepsy control in later life and are dependent on care-givers for daily living. There is no previous study evaluating the Quality of Life (QOL) in children suffered from WS.

Method: A prospective cohort study was performed at six years in a group of children with West syndrome, followed up in the Sri Lanka Infantile Spasm Study (SLISS). The quality of life was evaluated using Sri Lankan Health-Related Quality-of-Life Index for school children (SLHRQ-S), an age-specific, primary caregiver proxy-rated, validated questionnaire for Sri Lankan children with epilepsy. Information on epilepsy, medication, and daily activities was obtained from the parents.

Results: Fifty parents of initial 97 children treated for WS participated. The majority had no ongoing epilepsy (56%) at time of evaluation. The mean QOL was 67.22 (SD 15.68). Mean QOL scores for individual domains showed that physical domain was the worst affected (58.51 (SD = 22.11)). Psychological and social function domains were 68.73 (SD = 17.74) and 75.2 (SD = 14.87), respectively. Male sex (0.02), using multiple anti-seizure medications (0.00) and lower ILAE epilepsy control scale (0.02) were significantly associated with a poor quality of life. Age at onset, delay in treatment, and early spasm control were among the factors that did not influence quality of life.

Conclusion: Despite having control of their epilepsy in the majority, these children suffered from poor quality of life. The greater impact on the physical domain possibly is related to the effect of underlying pathologies.

Surgery for Drug-Resistant Epilepsy in Children

Summary, originally published on docwirenews.com

A systematic review published in Child’s Nervous System evaluated factors associated with and outcomes following hemispherotomy in children with drug-resistant epilepsy.

“Several variations of functional disconnection surgery have been described for the treatment of lateralized, hemispheric, drug-resistant epilepsy in children,” the study authors explained. “The purpose of this study is to investigate the existing literature regarding patient selection, approach, and outcomes after hemispherotomy.”

They performed a systematic review of literature published in English through February 2019. Articles were stratified based on level of evidence. Data on seizure and functional outcomes, surgical techniques, complications, and patient selection were analyzed.

“Both vertical and lateral hemispherotomy approaches result in durable, reproducible benefits to epilepsy severity and functional status in appropriately selected pediatric patients,” the researchers concluded.

Brief Video Enhances Teacher Trainees’ Knowledge of Epilepsy

Abstract, originally published in Epilepsy & Behavior

Objective: Relative to the general population, children with epilepsy (CWE) demonstrate difficulties in aspects of cognition and mental health. Previous studies have found that teachers have poor knowledge about epilepsy, which may lead to inadequate management of CWE’s comorbidities and seizures, potentially impacting CWE’s school performance, social development, and safety. The current study aimed to evaluate whether a brief training program improves teachers’ epilepsy knowledge.

Method: Participants included pre-service teachers enrolled in the Faculty of Education at Western University (London, Ontario, Canada). There were no exclusion criteria. Pre-service teachers completed a questionnaire evaluating their experiences and knowledge of epilepsy prior to, and two weeks following, the training program. The training program consisted of a 10.5-min video and booklet that described the characteristics of seizures, seizure first aid, and the cognitive, psychological, and social consequences of epilepsy.

Results: Pre-service teachers’ knowledge about epilepsy, seizure safety, and common comorbidities associated with epilepsy significantly improved after participating in the training program. Furthermore, pre-service teachers indicated greater self-reported knowledge about epilepsy and greater preparedness to handle a seizure in the classroom.

Conclusion: The results of the current study demonstrated that a brief, cost-effective training program significantly enhances teachers’ knowledge about epilepsy, seizure safety, and the comorbidities associated with epilepsy. Enhancing teachers’ knowledge about epilepsy has the potential to improve children’s academic and social success in school.

Challenges in the Treatment of a Chronic Disease: A Study of Narratives of People With Juvenile Myoclonic Epilepsy

Abstract, originally published in Seizure

Purpose: The purpose of this study was to explore how people with juvenile myoclonic epilepsy perceive the impact of treatment.

Methods: We conducted 14 interviews of participants with juvenile myoclonic epilepsy recruited with the support of the Brazilian Association of Epilepsy in 2018 in São Paulo. Thematic analysis was carried out by two investigators who independently coded the transcripts and reviewed the coding results to check for agreement.

Results: Participants’ (n = 14, 8 female) mean age was 31.4 years (SD ± 8.3) and their onset of seizures occurred at mean age 13.4 (SD ± 2.9). The answers to the interview questions revealed the paths of participants through life as they dealt with difficulties and challenges. Three interrelated themes and seven sub-themes emerged from the answers of the participants: seizure control, impact of epilepsy and attitude of others.

Conclusion: This investigation may be useful in providing insights for the interventions of health providers in caring for people with JME. Themes and sub-themes that emerged from this study are connected to important aspects of treatment that go beyond focusing solely on seizures.

The Unchanging Face of Lennox-Gastaut Syndrome in Adulthood

Abstract, originally published in Epilepsy Research

Purpose: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy characterized by the presence of multiple types of intractable seizures, cognitive impairment, and specific electroencephalogram (EEG) patterns. The aim of this study was to investigate the electroclinical features of patients with LGS during adulthood.

Methods: We retrospectively identified the medical records of 20 patients aged over 18 years with a diagnosis of LGS from 3896 patients with epilepsy.

Results: Thirteen (65 %) patients were male. The mean age of the patients was 23.4 ± 7.1 (min-max; 18-43) years, and the mean follow-up period was 5.6 ± 4.5 (min-max; 1-14) years. The etiology was identified in 11 (55 %) patients. None of the patients achieved seizure freedom. The most prevalent seizure types were atypical absences in 14 (70 %) patients, tonic seizures in 13 (65 %) patients, and atonic seizures in 11 (55 %) patients. One (5 %) patient was diagnosed as having psychogenic non-epileptic seizures. Mental retardation was reported in all patients and only half of them could walk independently. All patients had drug-resistant seizures and 16 (80 %) patients were on polytherapy. A vagus nerve stimulator was implanted into ten (50 %) patients and five reported 50-80 % seizure reduction. Ketogenic diet was administered to two (10 %) patients and epilepsy surgery was performed in two (10 %) patients with no significant benefit.

Conclusions: Paying attention to all factors of seizure outcomes, cognitive impairment, and ambulatory status, all patients were dependent on caregivers for daily living abilities. LGS has life-long persistence with poor outcomes, even during adulthood.