Approved: “WHO Global Actions on Epilepsy and Other Neurological Disorders”

From the November 2020 International League Against Epilepsy E-Newsletter

ILAE is pleased to announce that on 12th November 2020 during the 73rd World Health Assembly, Member States unanimously approved a Resolution to develop a 10-year Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders.

The Resolution requests that the WHO develop a broad-ranging Ten-year Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders to include action on:

• Expanding universal health coverage to address the current significant gaps in the promotion of physical and mental health, and the prevention, early detection, care, treatment and rehabilitation of epilepsy and other neurological disorders

• Addressing the social, economic, educational and inclusion needs of persons and families living with these diseases

• Strengthening inter-sectoral collaboration with sectors beyond health, particularly education and employment, to promote equal opportunities for people living with epilepsy and/or other neurological disorders and with other sectors to develop more inclusive legislation and address stigma and discrimination

A new name for Psychogenic Nonepileptic Seizures?

In collaboration with the ILAE PNES Task Force and the Functional Neurological Disorders Society (FNDS), the American Epilepsy Society PNES SIG will host two informative discussions around the name of the disorder most commonly known as psychogenic nonepileptic seizures (PNES). The intent is to discuss the essential elements for naming a disorder, as well as whether there should be a push for one, rather than many, names.

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.

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.

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).

Epilepsy in Morocco Realities, Pitfalls and Prospects

Summary, originally published in Epilepsia

The World Health Organization (WHO) estimates that about 50 million people of all ages have epilepsy and nearly 85% of whom live in low- and middle-income (LMICs) countries. In Morocco, epilepsy is one of the major neurological health conditions, with an estimated prevalence of 1.1%.

The management of patients is difficult due to multiple factors. The lack of neurologists whose number is currently 180, the uneven distribution of neurologists who are concentrated in large cities, 43% of whom are in Rabat and Casablanca alone; the low involvement of general practitioners in the management of epilepsy; the frequent consultation of traditional healers; and the low coverage of social security all contribute to the treatment gap.

Several factors contribute to progress: the increasing number of neurologists compared to previous years, the creation of well-equipped new academic centers and small units of general neurology, in addition to the disuse of several antiepileptic drugs.

However, much work remains to be done against the use of many forms of traditional practices and the low involvement of general practitioners in the management of epilepsy. This is the first study on epilepsy conducted in Morocco.

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.

Systematic Review of EEG Findings in 617 Patients Diagnosed With COVID-19

Abstract, originally published in Seizure

Objective: We performed a systematic review of the literature to synthesize the data on EEG findings in COVID-19. Frontal EEG patterns are reported to be a characteristic finding in COVID-19 encephalopathy. Although several reports of EEG abnormalities are available, there is lack of clarity about typical findings.

Methods: Research databases were queried with the terms “COVID” OR “coronavirus” OR “SARS” AND “EEG”. Available data was analyzed from 617 patients with EEG findings reported in 84 studies.

Results: The median age was 61.3 years (IQR 45-69, 33.3 % female). Common EEG indications were altered mental status (61.7 %), seizure-like events (31.2 %), and cardiac arrest (3.5 %). Abnormal EEG findings (n = 543, 88.0 %) were sub-classified into three groups: (1) Background abnormalities: diffuse slowing (n = 423, 68.6 %), focal slowing (n = 105, 17.0 %), and absent posterior dominant rhythm (n = 63, 10.2 %). (2) Periodic and rhythmic EEG patterns: generalized periodic discharges (n = 35, 5.7 %), lateralized/multifocal periodic discharges (n = 24, 3.9 %), generalized rhythmic activity (n = 32, 5.2 %). (3) Epileptiform changes: focal (n = 35, 5.7 %), generalized (n = 27, 4.4 %), seizures/status epilepticus (n = 34, 5.5 %). Frontal EEG patterns comprised of approximately a third of all findings. In studies that utilized continuous EEG, 96.8 % (n = 243) of the 251 patients were reported to have abnormalities compared to 85.0 % (n = 311) patients who did not undergo continuous EEG monitoring (?2 = 22.8, p =< 0.001).

Significance: EEG abnormalities are common in COVID-19 related encephalopathy and correlates with disease severity, preexisting neurological conditions including epilepsy and prolonged EEG monitoring. Frontal findings are frequent and have been proposed as a biomarker for COVID-19 encephalopathy.

Learnings From 30 Years of Reported Efficacy and Safety of Vagus Nerve Stimulation (Vns) for Epilepsy Treatment: A Critical Review

Abstract, originally published in Seizure

Three decades after its introduction as an adjuvant therapeutic option in the management of selective drug-resistant epilepsy cases (DRE), vagus nerve stimulation (VNS) retains growing interest. An implantable device was first approved for epilepsy in Europe in 1994 and in the United States (US) in 1997. Subsequent modifications improved the safety and the efficacy of the system. The most recent application of vagal neurostimulation is represented by transcutaneous devices that are claimed to have strong therapeutic potential. In this review, we sought to analyze the most meaningful available data describing the indications, safety and efficacy of the different approaches of VNS in clinical practice. Therefore, we identified studies reporting VNS efficacy and/or safety in epilepsy and its comorbidities from January 1990 to February 2020 from various databases including PubMed, Scopus, Cochrane, US government databases and VNS manufacturer published resources. In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the patients. However, some clinically relevant differences have been reported with specific factors such as epilepsy etiology or type, patient age as well as the delay of VNS therapy onset. VNS efficacy on seizure frequency has been demonstrated in both children and adults, in lesional and non-lesional cases, in focal and generalized epilepsies, on both seizures and epilepsy comorbidities. Regarding the latter, VNS can lead to an improvement of about 25-35 % in depression scores, 35 % in anxiety scores and 25 % in mood assessment scores. If non-invasive devices are undeniably safer, their efficacy is limited due to the scarcity of large cohort studies and the disparity of methodological approaches (study design and stimulation parameters). Overall, we believe that there is a progress margin for improving the safety of implantable devices and, above all, the effectiveness of the various VNS approaches.

Anti-Seizure Medication Use During Pregnancy and Risk of ASD and ADHD in Children

Abstract, originally published in Neurology

Objective: To determine whether children born to women who use anti-seizure medications (ASMs) during pregnancy have higher risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) independent of confounding factors.

Methods: We used Swedish-register data (n = 14,614 children born 1996-2011 and followed through 2013) to examine associations in children of women with epilepsy, using the largest sample to date and adjusting for a range of measured confounders. We examined maternal-reported first-trimester use of any ASM (22.7%); and the 3 most commonly reported individual drugs (valproic acid, 4.8%; lamotrigine, 6.8%; and carbamazepine, 9.7%). We identified ASD with ICD-10 diagnoses and ADHD with ICD-10 diagnoses or filled prescriptions of ADHD medication.

Results: Examination of individual drugs revealed that after adjustment for confounding, use of valproic acid was associated with ASD (Hazard Ratio = 2.30, 95% CI = 1.53-3.47) and ADHD (HR = 1.74, 95% CI = 1.28-2.38). Whereas a small, non-statistically significant association with ASD (HR = 1.25, 95% CI = 0.88-1.79) and ADHD (HR = 1.18, 95% CI = 0.91-1.52) remained for reported use of carbamazepine, confounding explained all of the associations with lamotrigine (HRASD = 0.86, 95% CI = 0.67-1.53; HRADHD = 1.01, 95% CI = 0.67-1.53).

Conclusions: We found no evidence of risk related to exposure to lamotrigine, whereas we observed elevated risk of autism spectrum disorder and ADHD related to maternal use of valproic acid. Associations with carbamazepine were weak and not statistically significant. Our findings add to a growing body of evidence that suggest that certain anti-seizure medications may be safer than others in pregnancy.

Lennox–Gastaut Syndrome: Perspective of a Parent and a Physician

Abstract, originally published in Neurology and Therapy

This article is co-authored by a parent of a 32-year-old male patient with Lennox–Gastaut syndrome (LGS) and his epileptologist. It discusses the parent’s experience of having a child with LGS from diagnosis through living day-to-day with the disease and the physician’s perspective when treating this devastating epilepsy syndrome. The patient’s mother, who is his legal representative, provided written consent for publication of this article.