Examining the impacts of the COVID-19 pandemic on the well-being and virtual care of patients with epilepsy

Abstract, originally published in Epilepsy & Behavior

Objective: The emergence of SARS-CoV-2 (COVID-19) as a novel coronavirus resulted in a global pandemic that necessitated the implementation of social distancing measures. These public health measures may have affected the provision of care for patients with epilepsy. Social isolation may have also adversely affected well-being and quality of life due to informal and formal support networks becoming less accessible. The purpose of this qualitative study was to examine the lived experiences of patients with epilepsy and to see how their quality of life and healthcare has been affected by the COVID-19 pandemic.

Methods: From April 27 to May 15, 2020 we performed remote interviews with 18 participants who had virtual appointments with their healthcare providers and were enrolled in the Calgary Comprehensive Epilepsy Program registry. Interviews were recorded and transcribed, after which transcripts were analyzed and coded into relevant themes using NVivo 12.

Results: Three broad themes emerged throughout the interviews:1) impact of pandemic on informal and formal support systems; 2) impact of pandemic on healthcare provision; and 3) concerns about the impact of the pandemic on personal situations and society in the future. Participants reported anxiety and stress about decreased social engagement and activity cessations. Although face-to-face appointments were preferred, virtual care was well-received. Common concerns about the future included securing employment and burnout from balancing family responsibilities. Some patients also feared they would be stigmatized as society adapted to the situation.

Significance: This study highlights the need for additional research in anticipation of the implementation of remote medicine in the management and treatment of epilepsy. It also highlights the tenacity of those living with epilepsy during difficult periods despite social and familial pressures. Raising awareness during this time about the lives and experiences of epilepsy patients can help challenge misconceptions and stigma in the workplace and wider society.

Psychosocial Long-Term Outcome in Patients With Psychogenic Non-Epileptic Seizures

Abstract, originally published in Seizure

Purpose: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up.

Methods: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL.

Results: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up.

Conclusion: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and quality of life.

Review Assesses Whether Seizures in Models of Rare Neurodevelopmental Disorders Are Similar to Those Seen in Humans

Abstract, originally published in Neuroscience

Genetic neurodevelopmental disorders – that often include epilepsy as part of their phenotype – are a heterogeneous and clinically challenging spectrum of disorders in children. Although seizures often contribute significantly to morbidity in these affected populations, the mechanisms of epileptogenesis in these conditions remain poorly understood. Different model systems have been developed to aid in unraveling these mechanisms, which include a number of specific mutant mouse lines which genocopy specific general types of mutations present in patients. These mouse models have not only allowed for assessments of behavioral and electrographic seizure phenotypes to be ascertained, but also have allowed effects on the neurodevelopmental alterations and cognitive impairments associated with these disorders to be examined. In addition, these models play a role in advancing our understanding of these epileptic processes and developing preclinical therapeutics. The concordance of seizure phenotypes – in a select group of rare, genetic, neurodevelopmental disorders and epileptic encephalopathies – found between human patients and their model counterparts will be summarized. This review aims to assess whether models of Rett syndrome, CDKL5 deficiency disorder, Fragile-X syndrome, Dravet syndrome, and Ohtahara syndrome phenocopy the seizures seen in human patients.

Study Highlights the Treatment Burden in Children With Epilepsy and Comorbidities

Abstract, originally published in Epilepsy Research

Objective: We conducted a long-term follow-up of a cohort of children with newly diagnosed unprovoked seizures to assess treatment with antiepileptic drugs (AEDs), neuroleptics, antidepressants and medication for attention deficit hyperactivity disorder (ADHD) with special attention to the impact of comorbidities on the use of such medication.

Methods: Our study cohort comprised 769 children (28 days-18 years), living in Stockholm Sweden, with a first unprovoked seizure identified between 2001 and 2006. Information on neurodevelopmental comorbidities and Cerebral Palsy (CP) at seizure onset was collected from medical records. Information on treatment with AEDs, neuroleptics, antidepressants and ADHD medication was retrieved by linkage to the Swedish National Prescription Registry between 2005 and 2014. The association between comorbidities and drug treatments was assessed by odds ratios (OR) with 95 % confidence intervals (CI), adjusted for age and sex.

Results: Eight years after the index seizure, 31 % of the children were on AEDs, and this was more common among children with any of the comorbidities studied (OR; 4.0 95 % CI 2.9-5.6) compared to those without such comorbidities, and within this group of comorbidities particularly for those with CP (OR; 5.2 95 % CI: 2.9-9.3). Children with neurodevelopmental comorbidity or CP at baseline were more likely to receive neuroleptics (ORs 8 years after the index seizure; 6.9, 95 % CI: 2.4-19.8), antidepressants (OR; 2.3, 95 % CI: 1.0-5.5) and ADHD medication (OR; 3.6, 95 % CI: 1.8-7.2) than children without the studied comorbidities.

Conclusion: Children with seizures in combination with neurodevelopmental comorbidities or cerebral palsy (CP), especially CP, have a more frequent use of antiepileptic drugs, neuroleptics, antidepressants, and ADHD medication up to 13 years following the initial seizure than children without comorbidity. Our data highlight the treatment burden in children with epilepsy and comorbidities.

Risk of Seizure Recurrence From Antiepileptic Drug Withdrawal Among Seizure-Free Patients for More Than Two Years

Abstract, originally published in Epilepsy and Behavior

Objective: The aim of this study was to determine the outcome of antiepileptic drug (AED) withdrawal in patients who were seizure-free for more than two years.

Methods: Patients with epilepsy who were seizure-free for at least two years and decided to stop AED therapy gradually were followed up every two months for seizure relapse. The inclusion criteria were as follows: (1) diagnosis of epilepsy, defined as the following conditions: (1) at least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome; (3) patients remained seizure-free for at least 24 consecutive months during AED therapy; and (3) patients expressed a desire to discontinue AED therapy gradually and agreed to return for regular follow-ups. The time to a seizure relapse and predictive factors were analyzed by survival methods, including sex; age at seizure onset; number of episodes; seizure-free period before AED withdrawal; duration of follow-up after AED withdrawal; AED tapering off period (taper period); results from brain magnetic resonance (MRI); electroencephalogram (EEG) after drug withdrawal; EEG before drug withdrawal; seizure type (classified as generalized, partial, or multiple types based on history); and the number of AEDs administered for long-term seizure control. A log-rank test was used for univariate analysis, and a Cox proportional hazard model was used for multivariate analysis.

Results: We selected 94 patients (58 men, 36 women). The relapse ratio was 29.8%. Univariate analysis and multivariate Cox regression analysis indicated that withdrawal times and multiple AEDs, as well as the seizure-free period before withdrawal and abnormal EEG after drug withdrawal were significantly correlated with seizure recurrence and were significant independent predictive factors, with a hazard ratio of 0.839 and 3.971, 0.957, and 3.684, respectively.

Significance: The relapse rate in our study was similar to commonly reported overall rates for epilepsy. Distinguishing variables, such as withdrawal times, multiple AEDs, seizure-free period before withdrawal, and abnormal EEG after drug withdrawal, need to be considered when choosing to withdraw from AEDs. Therefore, our recommendation is that after two years of seizure-free survival, patients could consider withdrawal unless they have hippocampal sclerosis (HS).

Predictors of High School Dropout, Anxiety, and Depression in Genetic Generalized Epilepsy

Abstract, originally published in Epilepsia

Affective disorders are overrepresented in epilepsy, and people with epilepsy may be at risk of dropping out from school.

The aim of the present study was to assess factors influencing high school dropout, anxiety, and depression in genetic generalized epilepsy (GGE).

One hundred and ten people with GGE aged 19-40 years underwent a clinical interview, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Potential predictors of high school dropout were analyzed with logistic regression, and factors influencing total HADS score were analyzed with linear regression. Having felt excluded because of epilepsy was significantly associated with high school dropout (odds ratio 7.80, P = .009), as was total HADS score (odds ratio 1.22, P = .005). If a participant was currently employed or undergoing education, previous high school dropout was less likely (odds ratio 0.07, P = .005).

High school dropout was associated with increased current anxiety and depression (β = 0.32, P = .005). Epilepsy severity (current drug resistance, current polytherapy, and active generalized tonic-clonic seizures) was not associated with high school dropout, nor with total Hospital Anxiety and Depression Scale score. The issue of stigma in epilepsy must be thoroughly addressed in comprehensive care and may be as important as seizure control when it comes to education and quality of life.

Epilepsy Research News: November 2020

This month’s research news includes a study that highlights the importance of adherence to antiepileptic drug regimens and controlling seizures to reduce the risk of sudden unexplained death in epilepsy (SUDEP). We also highlight an advancement in understanding and preventing temporal lobe epilepsy, utilizing an animal model.

Additionally, we share a study that highlights the difficulty that can be faced in diagnosing sometimes subtle seizures associated with focal epilepsy, and we present findings on the development of a new tool to help ease what can be a challenging transition from pediatric/adolescent to adult care for individuals with epilepsy.

In other news, a new FDA alert was issued to avoid the use of lamotrigine/Lamictal in people with cardiac conduction disorders, ventricular arrhythmias, or cardiac disease or abnormality.

These studies and the FDA alert are summarized below.

Research Highlights

Preventing SUDEP
Polytherapy, especially the use of three or more antiepileptic drugs, is correlated with a substantially decreased risk for SUDEP according to a nationwide study conducted in Sweden. The study also demonstrated a link between statin use and a decreased risk for SUDEP. “These results provide support for the importance of medication adherence and intensified anti-epileptic drug treatment for patients with poorly controlled generalized tonic-conic seizures in the efforts to reduce SUDEP risks and suggest that comedication with statins may reduce risks,” the researchers wrote.

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Understanding & Treating Temporal Lobe Epilepsy
A team of researchers has found that an amino acid produced by the brain could play a crucial role in preventing cell loss and seizures associated with temporal lobe epilepsy. Utilizing an animal model of temporal lobe epilepsy, the research team found that administration of the amino acid D-serine prevented cell loss characteristic of temporal lobe epilepsy and reduced the number and severity of seizures.

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Focal Epilepsy & Delayed Diagnosis
A new study shows that it can take on average two years for physicians to recognize the early signs of focal epilepsy, particularly in patients with seizures that do not involve uncontrolled movements of their arms and legs. Subtler cases are often not diagnosed until they have progressed to disruptive “motor” seizures, say the study authors, which can cause the unrestrained, whole-body spasms often portrayed in popular culture. Researchers believe the impact of earlier diagnosis in focal epilepsy patients goes beyond more timely treatment of patients; some study participants reported having one or more car accidents before their diagnosis. The researchers estimate that for every 13 early diagnoses, one car accident, equating to an estimated 1,816 annually worldwide, could be prevented.

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Transitioning to Adulthood with Epilepsy
Clinicians at Michigan Medicine have developed an assessment tool to help doctors ensure adolescents and young adults with epilepsy have the skills and confidence they need to take control of seizures and health care. Through a customized screening tool for 16 to 26-year-olds, doctors are effectively able to monitor their patients’ development of knowledge and self-management skills regarding their condition. This tool allows providers to proactively address gaps in readiness that may impact long term health outcomes.

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FDA Alert for Lamotrigine
The FDA has issued a new warning advising against the use of lamotrigine/Lamictal in people with cardiac conduction disorders, ventricular arrhythmias, or cardiac disease or abnormality. People currently taking lamotrigine should consult their healthcare provider. Do not stop taking lamotrigine without talking to your healthcare provider as doing so can cause serious problems.

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Inhibiting Epileptic Activity in the Brain

Abstract, originally published in Neurobiology of Disease featuring the work of CURE Grantee Dr. Jeffrey Loeb

Epileptic seizures often originate in small, localized areas of the brain where neurons abnormally fire in unison. These electrical impulses disrupt proper brain functioning and cause seizures. But what makes regions where seizures start different from parts of the brain where electrical impulses remain normal? More importantly, what prevents these epileptic centers from growing?

The answer to these questions may lie in a new discovery by researchers at the University of Illinois Chicago. In non-CURE funded work, CURE Grantee Dr. Jeffrey Loeb and his colleagues found that a protein — called DUSP4 — was increased in healthy brain tissue directly adjacent to epileptic tissue. Their research suggests that boosting levels of DUSP4 could be a novel way of preventing or treating epilepsy.

Their findings are reported in the journal Neurobiology of Disease.

“If epileptic brain regions spread throughout the brain with nothing to stop them, the seizures would overwhelm the brain, it would not be survivable,” said Loeb, UIC professor and head of neurology and rehabilitation at the College of Medicine and corresponding author on the study. “We wondered if there were natural ways that epileptic brain areas are quarantined. We searched for genes at the border between epileptic and normal brain tissue that may help prevent the spread of epilepsy.”

Sunflower Syndrome: A Poorly Understood Photosensitive Epilepsy

Abstract, originally published in Developmental Medicine and Child Neurology

Sunflower syndrome is a rare photosensitive epilepsy which has received little attention in recent medical literature. The historical cases documenting the epilepsy’s stereotyped handwaving motion in front of light characterized the behavior as self-inducing seizures via mimic of stroboscopic effect. However, the relationship between handwaving episodes and attendant generalized electroencephalogram abnormalities, and an appreciation of the compulsive attraction the sun and other light sources hold for these patients, suggest the handwaving motion may be a part of the seizure rather than a mechanism of self-induction. The lack of awareness of Sunflower syndrome often leads to misdiagnosis. The seizures are often refractory to traditional anticonvulsant medication, and patients resort to behavioral intervention, such as hats and sunglasses, to reduce handwaving episodes. Further study is required to determine the syndrome’s natural history and to identify more effective treatment options.

Incidence of Potential Adverse Events During Hospital-Based Ketogenic Diet Initiation Among Children with Drug-Resistant Epilepsy

Abstract, originally published in Epilepsia

Objective: Due to the possibility of serious adverse events (AE), patients are commonly admitted to hospital for 3–5 days for ketogenic diet (KD) initiation. This study examined the incidence of potential AE during admission for KD initiation to investigate the possibility of safely initiating a KD at home.

Methods: Children with drug-resistant epilepsy (DRE) who were admitted to hospital for five days for KD initiation were retrospectively studied.

Results: A total of 66 children (59% female) were analyzed. The mean age at the initiation of the KD was 48.0±38.4 months and the mean weight was 14.6±6.3 kilograms. The median number of anticonvulsant medications used at the time of KD initiation was 3. The etiology of the DRE was structural in 4.5%, hypoxic ischemic encephalopathy in 10.6%, genetic/metabolic in 31.8%, acquired in 10.6% and unknown in 42.2%. The potential AE occurred in 28.7% of patients, including hypoglycemia (20%), hypoactivity (6.1%), somnolence (3%), and vomiting (7.6%). A univariate analysis of the clinical characteristics of the AE and no AE groups showed a statistically significant difference in weight (P = 0.003) and age (P = 0.033). The concurrent use of topiramate was found to have a near significant association (P = 0.097) between the groups. The groups’ urine ketone levels on all five days were compared and a statistically significant difference was found on day three (P = 0.026). A statistically significant difference in the serum bicarbonate levels (P = 0.038) was found between the patients taking topiramate and those not taking it.

Significance: The incidence of adverse events during admission for ketogenic diet initiation was found to be low. The adverse events either required no intervention or were easily managed with simple interventions. Thus, it may be possible to initiate a ketogenic diet at home if the parents are adequately prepared and monitored.