Enduring Language Deficits in Children of Women With Epilepsy and the Potential Role of Intrauterine Exposure to Antiepileptic Drugs

Abstract, originally published in Epilepsia

Objective: Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9-13 years in comparison with their peers, and its relationship with intrauterine AED exposure.

Methods: We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records.

Results: The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% confidence interval [CI] = -8.8 to -0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = -13.8 to -0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (-14.7, 95% CI = -23.1 to -6.4, P = .001) as compared to carbamazepine.

Significance: Intrauterine exposure to phenobarbitone and valproate impairs language development in children with epilepsy, with effects persisting into the second decade.

The Evolution of Self-Injurious Behaviors in People With Intellectual Disability and Epilepsy: A Follow-up Study

Abstract, originally published in Seizure

Purpose: Longitudinal studies of the evolution of Self-Injurious Behaviors (SIBs) in people with Intellectual Disability (ID) and epilepsy are not common. This study aimed to analyze the evolution (in terms of remission and persistence) and changes in the type, localization, frequency, and intensity of SIBs.

Methods: SIBs were assessed in a sample of 52 people with ID and epilepsy, and re-evaluated after a seven-year interval, using the “Scale for the Assessment of Self-Injurious Behaviors”. The scale was administered to caregivers (parents or health professionals) through a semi-structured interview conducted by a specifically trained psychologist.

Results: The most frequent types of SIBs identified were: self-biting, self-hitting with objects, self-hitting with hand, object-finger in cavities. The main localizations of SIBs were: hands, mouth, head and cheeks. SIBs were found to be maintained after seven years, for type, localization, frequency, and intensity, in 90.4% of the sample. SIB types were stable over time, as were the affected areas. Global SIB frequency and intensity scores were found to be unchanged. Finally, a positive correlation was found between the frequency of SIBs and levels of intellectual disability. SIBs (frequency and intensity) and seizure frequency showed no correlation.

Conclusion: Given the negative impact of self-injurious behaviors (SIBs) on the adaptation and quality of life of people with intellectual disability and epilepsy, we believe that further studies on biological, psychological and environmental aspects are needed in order to identify any potential factors that might explain the persistence of SIBs and to find effective interventions to reduce them.

Machine Learning From Wristband Sensor Data for Wearable, Noninvasive Seizure Forecasting

Abstract, originally published in Epilepsia

Objective: Seizure forecasting may provide patients with timely warnings to adapt their daily activities and help clinicians deliver more objective, personalized treatments. Although recent work has convincingly demonstrated that seizure risk assessment is in principle possible, these early approaches relied largely on complex, often invasive setups including intracranial electrocorticography, implanted devices, and multichannel electroencephalography, and required patient-specific adaptation or learning to perform optimally, all of which limit translation to broad clinical application. To facilitate broader adaptation of seizure forecasting in clinical practice, noninvasive, easily applicable techniques that reliably assess seizure risk without much prior tuning are crucial. Wristbands that continuously record physiological parameters, including electrodermal activity, body temperature, blood volume pulse, and actigraphy, may afford monitoring of autonomous nervous system function and movement relevant for such a task, hence minimizing potential complications associated with invasive monitoring and avoiding stigma associated with bulky external monitoring devices on the head.

Methods: Here, we applied deep learning on multimodal wristband sensor data from 69 patients with epilepsy (total duration > 2311 hours, 452 seizures) to assess its capability to forecast seizures in a statistically significant way.

Results: Using a leave-one-subject-out cross-validation approach, we identified better-than-chance predictability in 43% of the patients. Time-matched seizure surrogate data analyses indicated forecasting not to be driven simply by time of day or vigilance state. Prediction performance peaked when all sensor modalities were used, and did not differ between generalized and focal seizure types, but generally increased with the size of the training dataset, indicating potential further improvement with larger datasets in the future.

Significance: Collectively, these results show that statistically significant seizure risk assessments are feasible from easy-to-use, noninvasive wearable devices without the need of patient-specific training or parameter optimization.

Clinical Characteristics of Epilepsy in Resource-limited Communities in Punjab, Northwest India

Abstract, originally published in Epilepsia

Objectives: To describe clinical characteristics of a community-based epilepsy cohort from resource-limited communities in Punjab, Northwest India.

Methods: The cohort was gathered following a two-stage screening survey. We cross-sectionally examined and followed-up the cohort for one year. A panel of neurologists assigned seizure types, syndromes and putative aetiologies and categorized drug?responsiveness.

Results: The cohort of 240 included 161 (67.1%) men, 109 (45.4%) illiterates and 149 (62.1%) unemployed. Current age was > 18 years in 155 (64.6%) but age at epilepsy onset was < 18 years in 173 (72.1%). Epilepsies due to structural and metabolic causes were diagnosed in 99 (41.3%), but syndromic assignments were not possible in 97 (40.4%). After one year, drug-resistant epilepsy was established in 74 (30.8%). Perinatal events (n=35; 14.6%) followed by CNS infections (n=32; 13.3%) and traumatic brain injury (n=12; 5.0%) were common risk factors. Most of those with CNS infections (n=19; 63.3%), perinatal antecedents (n=23; 76.7%) and other acquired risk factors (n=27; 90.0%) presented with epilepsy due to structural and metabolic causes . Perinatal events were the putative aetiology for nearly 40.7% of generalized epilepsies due to structural and metabolic causes and 28.2% of all epilepsies with onset < 10 years.

Significance: Existing classifications schemes should be better suited to field conditions in resource-limited communities in low- and middle-income countries. The finding of drug resistant epilepsy in nearly at least a third in a community-based sample underscores an unmet need for enhancing services for this segment within healthcare systems. Perinatal events, CNS infections and head injury account for a third of all epilepsies and hence, preventative interventions focusing on these epilepsy risk factors should be stepped up.

The Virus Moved Female Faculty to the Brink. Will Universities Help?

Article, originally published in the New York Times

The pandemic is a new setback for women in academia who already faced obstacles on the path to advancing their research and careers.

Whatever big plans Lisa Warner had for the year, the pandemic scrambled them. It forced online the biochemistry classes she taught as an assistant professor at Boise State University in Idaho, and it temporarily shut down her laboratory. Her 4-year-old son’s day care closed, and Dr. Warner felt her productivity wane. She feared for her chances of receiving tenure, the long-term job security that most early-career academics ardently pursue, by the 2024 deadline in her contract.

Around the same time, Maria Fernanda Escallón, an assistant professor of anthropology at the University of Oregon and mother to a 3-year-old daughter, was working from a walk-in closet and occasionally a backyard shed to steal quiet moments away from the demands of caregiving. She was trying to write a book, one of many publications she feels she will need to secure tenure.

Late at night, she swapped horror stories of lost time and depleted research over email with other women faculty.

“I hope the administration realizes that anything they do now to alleviate this issue for caregivers will directly impact how the professoriate will look five to 10 years from now — how diverse it will be, and how many women will be in positions of power within academia,” Dr. Escallón said.

Risk-Benefit Assessment of Treatment of Epileptic Women of Childbearing Age With Valproic Acid

Abstract, originally published in Seizure

Aim: Valproic acid (VPA) is a widely used anti-epileptic drug (AED) of demonstrated efficacy. However, its teratogenic effects have resulted in many regulatory agencies recommending that it should not be administered to women of childbearing age unless they are taking contraceptives. The aim of this study was to determine the willingness of candidate patients to change their treatment and to monitor the evolution of their attitude.

Methods: We identified patients aged between 15 and 45 years old who had been diagnosed with epilepsy and were being treated with VPA. A shared decision-making visit was arranged, during which variables related to their epilepsy were recorded. The patients were informed about the teratogenic effects of VPA and the risks/benefits of a change in treatment. The patient, or legal guardian, then freely chose the course of treatment that they wished to follow. On a follow-up visit, six months later, seizure control and tolerance to the chosen treatment were recorded. The variables related to each patient’s willingness to their change treatment were analysed.

Results: A total of 60 patients, with a median age of 32.7 years, were included in the study. Of these, 25 (41.7%) suffered some form of intellectual disability. Only one (1.7%) had poor seizure control. After the initial visit, 41 patients (68%) opted to continue with the VPA treatment, six opted to stop receiving VPA, and 13 decided to switch to another AED. The median age of the patients who opted to change treatment was significantly lower than that of those who opted to continue with the VPA treatment (29.1 vs. 34.4, p = 0.024). The absence of intellectual disability (p = 0.047) and a length of treatment of less than five years (0.016) were both significantly associated with the decision to change treatment. Of the 19 patients who changed treatment, nine (47%) returned to the initial treatment with VPA.

Conclusions: Despite being informed of the teratogenic risk associated with VPA, a significant number of patients and legal guardians opted to continue with this treatment; the reasons given for this were the low possibility of pregnancy and the risk of breakthrough seizures. In almost half the cases studied, the pharmacological alternatives to VPA were poorly tolerated and did not provide a good level of seizure control.

SARS-CoV-2 Pandemic and Epilepsy: The Impact on Emergency Department Attendances for Seizures

Abstract, originally published in Seizure

Introduction: The risk of acquiring SARS-CoV-2 in a hospital setting and the need of reorganizing the Emergency Departments (EDs) to cope with infected patients have led to a reduction of ED attendances for non-infectious acute conditions and to a different management of chronic disorders.

Methods: We performed a retrospective study evaluating the frequency and features of ED attendances for seizures during the lockdown period (March 10th-April 30th 2020) in the University Hospital of Trieste, Italy. We studied the possible pandemic impact on the way patients with seizures sought for medical assistance by comparing the lockdown period to a matched period in 2019 and to a period of identical length preceding the lockdown (January 18th-March 9th 2020).

Results: A striking decrease in total emergency department (ED) attendances was observed during lockdown (4664) compared to the matched control (10424) and to the pre-lockdown (9522) periods. A similar reduction, although to a lesser extent, was detected for seizure attendances to the ED: there were 37 during lockdown and 63 and 44 respectively during the two other periods. Intriguingly, during the lockdown a higher number of patients attended the ED with first seizures (p = 0.013), and more EEGs (p = 0.008) and CT brain scans (p = 0.018) were performed; there was a trend towards more frequent transport to the ED by ambulance (p = 0.061) in the lockdown period.

Conclusions: Our data suggest that the pandemic has affected the way patients with seizures access the Health Care System.

Researchers Develop Wearable Device for Predicting Epileptic Seizures

Article, originally posted on MedicalXPress.com

Ben-Gurion University of the Negev researchers have developed Epiness, a device for detecting and predicting epileptic seizures based on machine-learning algorithms. The wearable device can generate an advanced warning about an upcoming seizure that will be sent to a smartphone up to an hour prior to its onset. The system was out-licensed for further development and commercialization to NeuroHelp, a startup company that was recently founded by BGN Technologies, the technology transfer company of BGU and Dr. Oren Shriki, of BGU’s Department of Cognitive and Brain Sciences and NeuroHelp’s scientific founder.

Epiness is a seizure prediction and detection device that is based on a new, ground-breaking combination of EEG-based monitoring of brain activity together with proprietary machine-learning algorithms. The device combines a wearable EEG device with state-of-the-art software that minimizes the number of necessary EEG electrodes and optimizes electrode placement on the scalp. The sophisticated machine-learning algorithms are designed to filter noise that is not related to brain activity, extract informative measures of the underlying brain dynamics, and distinguish between brain activity before an expected epileptic seizure and brain activity when a seizure is not expected to occur.

Study Reveals Seizures During Menstrual Cycle Linked to Drug-Resistant Epilepsy

Summary, originally posted on EurekAlert

More frequent seizures during the menstrual cycle in women with genetic generalized epilepsy have been linked for the first time to drug-resistant epilepsy when anti-seizure medications don’t work, according to a study published in the journal Neurology.

Women with a form of genetic generalized epilepsy called catamenial epilepsy – when seizure frequency increases during their menstrual cycle – were nearly four times more likely to have drug-resistant epilepsy than women who experience no changes in frequency. In generalized epilepsy, seizures begin on both sides of the brain at the same time, while focal seizures start in only one part of the brain.

“Typically, genetic generalized epilepsy is thought to respond better to anti-seizure medications than focal epilepsy. However, previous studies suggest a minority of individuals, between 18 and 36%, with genetic generalized epilepsy, do not respond well to these medications,” said senior author Gary A. Heiman, an associate professor in the Department of Genetics in the School of Arts and Sciences at Rutgers University – New Brunswick. “It is unclear why seizures in these individuals do not respond well, and we sought to investigate why. We found a surprising association between women’s menstrual cycle and these with drug-resistant genetic generalized epilepsy. Understanding the reasons for this association could lead to alternative, personalized treatment options for at least some patients.”

Fetal Alcohol Spectrum Disorder Linked to High Prevalence of Epilepsy

Summary, originally posted in Science Daily

Fetal alcohol spectrum disorder (FASD) refers to a range of negative developmental outcomes that result from maternal drinking during pregnancy. Children with FASD can suffer from many problems, including epilepsy, and a new study has found a much higher prevalence of epilepsy or history of seizures in individuals with FASD.

For this study, researchers examined the histories of 425 individuals (254 males, 171 females), between the ages of two and 49 years, from two FASD clinics. Relationships between a confirmed FASD diagnosis and other risk factors — such as exposure to alcohol or other drugs, type of birth, and trauma — were examined for the co-occurrence of epilepsy or a history of seizures.

“This study revealed a much higher prevalence of epilepsy and seizure history in individuals with a diagnosis of FASD,” said Stephanie H. Bell, a researcher with the Centre for Neuroscience Studies at Queens University and corresponding author for the study. “In the general population, less than one percent are expected to develop epilepsy; of those with FASD, six percent had epilepsy and 12 percent had one or more seizures in their life. Subjects were more likely to have epilepsy, or a history of seizures, if exposure to alcohol had occurred in the first trimester or throughout the entire pregnancy.”

“While this report supports a growing impression that fetal alcohol exposure may predispose the immature brain to the development of epilepsy, the results do not establish a direct cause-effect relationship between FASD and epilepsy,” cautioned Dan Savage, a professor of neuroscience at the University of New Mexico who was not involved in the study. “Establishing a direct link between these clinical conditions will be a difficult challenge given our incomplete understanding of how alcohol damages the developing brain and what neuropathological changes in brain tissue lead to the development of different types of epilepsy.”

Nonetheless, Savage added that it is clear that alcohol can damage the fetal brain. “The extent to which this damage leads to adverse neurobehavioral consequences likely depends upon many factors, including the amount and patterns of drinking during pregnancy, the presence of other pregnancy risk factors, such as cigarette smoking, substance abuse, or poor prenatal care, and the presence of other diseases affecting a mother’s health, such as diabetes or high blood pressure,” he said. “As risk factors accumulate, the risk of adverse neurodevelopmental outcomes also increases.”

“This report builds on a growing body of evidence that maternal drinking during pregnancy may put a child at greater risk for an even wider variety of neurologic and behavioral health problems than we had appreciated before,” said Savage. “The consensus recommendation of scientists and clinical investigators, along with public health officials around the world, is very clear — a woman should avoid drinking during pregnancy as part of an overall program of good prenatal care that includes good nutrition, adequate exercise, sufficient rest, and proper prenatal health care.”