Opinion Piece: When It Comes to People Like My Daughter, One Size Does Not Fit All

Opinion Piece, published in The New York Times

My daughter, Lauren, turned 40 last month. She is happy and healthy. And that is nothing short of a miracle.

These brutal seizures would continue, poorly controlled, for the next 19 years, roiling her developing brain and necessitating an ever-shifting regimen of medications with punishing side-effects, of surgeries and hospitalizations. More than once, we feared we would lose her.

Lauren’s doctors finally found a cocktail of medications that would work to subdue the seizures, but the battering her brain took from the ordeal left her with significant developmental deficits.

Today, Lauren faces another battle, not with epilepsy or the toll it’s taken, but with policy changes that could deny her and others with intellectual disabilities the life they choose in concert with their families and loved ones.

The issue is federal Medicaid funding to states, which helps underwrite residential facilities for people with intellectual disabilities, and the conviction of some advocates and policymakers that larger settings like Misericordia should be discouraged.

Household Poverty, Schooling, Stigma and Quality of Life in Adolescents With Epilepsy in Rural Uganda

Abstract, originally published in Epilepsy and Behavior

Background: Epilepsy remains a leading chronic neurological disorder in Low- and Middle-Income Countries. In Uganda, the highest burden is among young rural people. We aimed to; (i) describe socio-economic status (including schooling), and household poverty in adolescents living with epilepsy (ALE) compared to unaffected counterparts in the same communities and (ii) determine the factors associated with the overall quality of life (QoL).

Methods: This was a cross-sectional survey nested within a larger study of ALE compared to age-matched healthy community children in Uganda. Between Sept 2016 to Sept 2017, 154 ALE and 154 healthy community controls were children were consecutively recruited. Adolescents recruited were frequency and age-matched based on age categories 10-14 and 15-19 years. Clinical history and standardized assessments were conducted. One control participant had incomplete assessment and was excluded. The primary outcome was overall QoL and key variables assessed were schooling status and household poverty. Descriptive and multivariable linear regression analysis were conducted for independent associations with overall QoL.

Results: Mean (SD) age at seizure onset was 8.8 (3.9) years and median (IQR) monthly seizure burden was 2 (1-4). Epilepsy was associated with living in homes with high household poverty; 95/154 (61.7%) ALE lived in the poorest homes compared to 68/153 (44.5%) of the healthy adolescents, p = 0.001. Nearly two-thirds of ALE had dropped out of school and only 48/154 (31.2%) were currently attending school compared to 136/153 (88.9%) of healthy controls, p < 0.001. QoL was lowest among ALE who never attended school (p < 0.001), with primary education (p = 0.006) compared to those with at least secondary education. Stigma scores [mean(SD)] were highest among ALE in the poorest [69.1(34.6)], and wealthy [70.2(32.2)] quintiles compared to their counterparts in poorer [61.8(31.7)], medium [68.0(32.7)] and wealthiest [61.5(33.3)] quintiles, though not statistically significant (p = 0.75). After adjusting for covariates, ALE currently attending school had higher overall QoL compared to their counterparts who never attended school (β = 4.20, 95%CI: 0.90,7.49, p = 0.013). QoL scores were higher among ALE with ≥secondary education than those with no or primary education (β = 10.69, 95%CI: 1.65, 19.72).

Conclusions: Adolescents living with epilepsy (ALE) in this rural area are from the poorest households, are more likely to drop out of school and have the lowest quality of life (QoL). Those with poorer seizure control are most affected. ALE should be included among vulnerable population groups and in addition to schooling, strategies for seizure control and addressing the epilepsy treatment gap in affected homes should be specifically targeted in state poverty eradication programs.

Stress increases susceptibility to pentylenetetrazole-induced seizures in adult zebrafish

Abstract, originally published in Epilepsy & Behavior

Stress is the body’s reaction to any change that requires adaptive responses. In various organisms, stress is a seizure-related comorbidity. Despite the exposure to stressors eliciting aversive behaviors in zebrafish, there are no data showing whether stress potentiates epileptic seizures in this species.

Here, we investigated whether a previous exposure to an intense acute stressor positively modulates the susceptibility to seizures in pentylenetetrazole (PTZ)-challenged zebrafish.

The conspecific alarm substance (CAS) was used to elicit aversive responses (3.5 mL/L for 5 min), observed by increased bottom dwelling and erratic movements. Then, fish were immediately exposed to 7.5 mM PTZ for 10 min to induce seizure-like behaviors. Stress increased the seizure intensity, the number of clonic-like seizure behaviors (score 4), as well as facilitated the occurrence of score 4 episodes by decreasing the latency in which fish reached the score 4. Moreover, fish with heightened anxiety showed increased susceptibility to PTZ, since positive correlations between anxiety- and seizure-like behaviors were found. Overall, since CAS also increased whole-body cortisol levels in zebra fish, our novel findings show a prominent response to PTZ-induced seizures in previously stressed zebrafish. Moreover, we reinforce the growing utility of zebrafish models to assess seizure-related comorbidities aiming to elucidate how stress can affect epileptic seizures in vertebrates.

Yale study gets closer to understanding causes of severe treatment-resistant epilepsy

Article, originally published by Yale Daily News

A recent study by researchers at the Yale School of Medicine found that mice injected with similar gene mutations as humans who have some severe forms of epilepsy also exhibited very similar brain malformations as the humans.

The researchers investigated two severe epilepsy disorders that result from two neurodevelopmental disorders called focal cortical dysplasia and tuberous sclerosis complex. These severe forms of biological epilepsy appear in humans shortly after birth, leading to sudden recurrent seizures and brain damage. These forms of severe epilepsy are not easily treatable with normal anti-epilepsy medications. The similar brain malformations from the mutations in both the human and mice brains helped the scientists identify the protein, called HCN4, and the molecular pathway, called mTOR, that are key factors in causing these epilepsies, thereby helping them get closer to finding treatments for the conditions.

“About 35 to 40 perecent of patients with epilepsy are resistant to medication,” Dennis Spencer, an expert in Epilepsy Surgery at the Yale School of Medicine, told the News. “[Epilepsy is] very heterogeneous and so many patients who have epilepsy are resistant to medication and the medications that are used today are also quite heterogeneous.”

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.