CURE Epilepsy Discovery: Funding Basic Mechanisms Research Drives Momentum Toward a CURE

Key Points:

  • For 25 years, CURE Epilepsy has been funding breakthrough research to advance science to find a cure for epilepsy. A key focus of our research grants has been understanding the basic biological mechanisms that result in epilepsy, which provides foundational knowledge that will ultimately lead to a cure for epilepsy.
  • One initiative funded by CURE Epilepsy, the Infantile Spasms (IS) Initiative, brought together a diverse team of medical and scientific experts to rapidly advance IS research and was the first initiative of its kind in the field of epilepsy.
  • John Swann of Baylor College of Medicine, whose work is discussed herein, was one of the grantees involved in the IS Initiative. He has progressed his initial discoveries, demonstrating the importance of funding basic mechanisms research to put us one step closer to a cure.
  • Basic research provides hope for a cure for the epilepsies; by better understanding the mechanisms that cause seizures, we can develop curative treatments for the epilepsies.

 

Deep dive

Twenty-five years ago, CURE Epilepsy was founded finding a cure for epilepsy and related seizure disorders, which now impacts 3.4 million Americans and 65 million people worldwide. The founders saw a need to push the research community to think differently about epilepsy research. This resulted in a paradigm shift for the community, moving from seeking treatments and therapies that would control seizures to focusing on innovative approaches that would advance science and find a cure for epilepsy. Achieving this goal would provide freedom from seizures and the negative side effects of medications. The organization determined that it could have the largest impact by focusing on understanding the basic biological mechanisms underlying the causes of epilepsy. Understanding is the first step in the scientific process, where researchers study the brain to gain a better understanding of why and how seizures are caused. These findings create foundational knowledge that may translate to new ideas to treat epilepsy and eventually preclinical and clinical trials. Clinical trials may ultimately lead to improved and potential cures. Hence, while the benefits of basic epilepsy research are not immediate, the rewards that basic research provides in terms of our understanding epilepsy are unparalleled.

Since 1998, CURE Epilepsy has funded over 280 research grants, and many have addressed the need to learn more about the basic biological mechanisms that underlie epilepsy. Many of these grants have formed the basis for further study, learning, and advancements that may lead us to a cure. One example of this is within infantile spasms (IS), a rare and particularly severe form of epilepsy, with approximately 90% of cases diagnosed in the first year of life. Infantile spasms manifest as sudden, jerking movements of the arms and legs, and are often accompanied by an irregular brainwave pattern on the electroencephalogram (EEG) called hypsarrhythmia.[1]These seizures are also often accompanied by significant cognitive and physical deterioration.[2] Current therapies for IS are effective in only half of the children with IS [3] and are associated with negative side effects, highlighting the need to find better and more effective treatments.

In 2013, CURE Epilepsy launched the Infantile Spasms Initiative, with $4 million in funding. The IS Initiative employed a multi-disciplinary and multi-location team science approach to study the basic biological mechanisms underlying IS, search for biomarkers and novel drug targets, and develop improved treatments. Work done as part of the IS Initiative proved successful across multiple dimensions and led to more than 19 publications. More about the IS Initiative can be found here.[4]

Understanding the basic biological mechanisms underlying IS was a key focus of the IS Initiative. One example of the IS Initiative’s success in understanding a key underlying basic mechanism is from the team led by Dr. John Swann of Baylor College of Medicine.[1] Dr. Swann and his team discovered that treatment with a derivative of the growth hormone insulin-like growth factor 1 (IGF-1) called (1-3) IGF-1 reduced spasms and irregular brain wave patterns on the EEG in an animal model. Adding this compound to vigabatrin, an FDA-approved treatment for IS, reduced the dose of vigabatrin required to eliminate the spasms. Adding this compound to vigabatrin, an FDA-approved treatment for IS reduced the dose of vigabatrin required to eliminate the spasms. Reducing the dosage also decreased the risk of serious side effects, including the potential for irreversible peripheral vision loss. The Swann lab patented this combination treatment and used the discovery to obtain two National Institutes of Health (NIH) grants. The NIH grants enabled Dr. Swann to build on the discoveries from the CURE Epilepsy-funded IS Initiative. In a subsequent study, data from Dr. Swann’s team revealed that the levels IGF-1 itself were lower in brain tissue from both a rat model and from infants with IS. Data also indicated that reduced expression of IGF-1 in the rat model affected the biological pathways critical for neurodevelopmental processes.[6]

Using the learnings from the IS Initiative as a foundation, through a series of additional experiments, the team confirmed that the (1-3) IGF-1 could also cross the blood-brain barrier with much higher efficiency than the full-length IGF-1 and activate the same biological pathways as full-length IGF-1.[7] The researchers administered it to the rats in their experiment, and successfully eliminated both the spasms and the hypsarrhythmia in most rodents. This exciting finding suggests that this smaller (1-3) IGF-1 or perhaps an IGF-1-like drug may one day be used to treat IS patients immediately after the condition is diagnosed. You can read more about this study here.

Dr. Swann and his team have continued to build on the learnings initially funded through their CURE Epilepsy grant; recently, the team studied seizure progression in IS, and the impact of spasms on learning and memory.[8] Infants with IS show developmental delay and behavioral abnormalities, with only 16% of patients with IS exhibiting normal intellectual development.[9] The reasons for a delay in intellectual development could be many, though they have not yet been determined.[10,11] Additionally, the trajectory of the decline in intellectual and behavioral abilities has not yet been documented due to the variability of the condition, and limitations in assessing intellectual abilities in infants. Spasms can be subtle, making an accurate diagnosis of the exact start of the spasms challenging.[12] Hence, whether the behavioral decline is caused by or simply associated in time with seizures in IS is an area where more research is necessary. Given the difficulties of understanding this relationship between seizures and cognitive decline in infants with IS, Dr. Swann’s team used rats with a history of spasms and assessed them in a series of tests to gauge their ability to learn and remember. Swann’s team used rats with a history of spasms and assessed them in a series of memory tests to gauge their ability to learn and remember. The team also studied their brainwaves using EEG.

Previous work by Dr. Swann’s team had developed a model to simulate IS in animal models.[13] In this model, a substance known as tetrodotoxin (TTX) is infused into the brains of infant rats 10-12 days after birth which causes many of the characteristics of IS, including spasms, seen in humans.[13] The research team then used tests to examine spatial and working memory. Spatial memory helps us remember locations and the relationship between locations, and working memory helps us remember a small part of the information in our minds temporarily. To better understand the brainwaves in rats that had spasms, Dr. Swann’s team performed continuous EEG recordings for a total of seven weeks after infusion of TTX.[8] Rats with spasms were compared with rats that did not have spasms. After seven weeks of EEG recording, behavioral tests were done to test learning and memory. The study showed that rats experiencing spasms showed impairment on the behavioral tests, pointing to issues in learning and memory, which are also seen in infants with IS.[8] EEG analysis showed that there was an increase in spasms for two weeks, and after the two weeks, spasms stabilized.[8] Seizure progression in epilepsy has long been a topic of intense research. The current study suggests that like other seizure disorders[14,15], there may be a critical period in IS when there is a gradual increase in spasm intensity over time. A better understanding of seizure progression patterns in IS could lead to clues about therapies, management, and prognosis. This work from Dr. Swann’s lab is unique as the team did rigorous EEG monitoring and behavioral analysis; these techniques are time and labor-intensive, and seizures in IS have not been studied this deeply before.[8] The neurological mechanisms that underlie memory disturbances and seizure progression in IS are not fully known. So, seizures could be correlated with the learning deficits, but exact details are not clear. Additional research using EEG monitoring coupled with behavioral analysis in the same animals could provide clarity into the relationship.

In conclusion, basic research provides a foundational understanding of underlying biology of a disease process from which cures for the epilepsies will be found. CURE Epilepsy has been funding basic research for 25 years with the sole mission of finding a cure for epilepsy. Dr. Swann’s work as part of the IS Initiative is one example of how strategic, long-term investment in basic research can advance our knowledge by leaps and bounds.

 

 

Literature Cited:

  1. Gibbs EL, Fleming MM, Gibbs FA. Diagnosis and prognosis of hypsarhythmia and infantile spasms Pediatrics. 1954 Jan;13:66-73.
  2. Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms J Child Neurol. 1991 Oct;6:355-364.
  3. Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, et al. Response to treatment in a prospective national infantile spasms cohort Ann Neurol. 2016 Mar;79:475-484.
  4. Lubbers L, Iyengar SS. A team science approach to discover novel targets for infantile spasms (IS). Epilepsia Open. 2021;6:49-61.
  5. Swann J, Lee, CL., Le, JT. and Frost Jr, JD. , inventor; Combination therapies for treating infantile spasms and other treatment resistant epilepsies 2022.
  6. Ballester-Rosado CJ, Le JT, Lam TT, Mohila CA, Lam S, Anderson AE, et al. A Role for Insulin-like Growth Factor 1 in the Generation of Epileptic Spasms in a murine model Ann Neurol. 2022 Jul;92:45-60.
  7. Yamamoto H, Murphy LJ. Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action J Endocrinol. 1995 Jul;146:141-148.
  8. Le JT, Ballester-Rosado CJ, Frost JD, Jr., Swann JW. Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms Epilepsia. 2022 Dec;63:3078-3089.
  9. Hrachovy RA, Frost JD, Jr. Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/West syndrome) J Clin Neurophysiol. 2003 Nov-Dec;20:408-425.
  10. Wirrell EC, Shellhaas RA, Joshi C, Keator C, Kumar S, Mitchell WG. How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium Epilepsia. 2015 Apr;56:617-625.
  11. Osborne JP, Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, et al. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification Epilepsia. 2010 Oct;51:2168-2174.
  12. Lux AL, Osborne JP. A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group Epilepsia. 2004 Nov;45:1416-1428.
  13. Lee CL, Frost JD, Jr., Swann JW, Hrachovy RA. A new animal model of infantile spasms with unprovoked persistent seizures Epilepsia. 2008 Feb;49:298-307.
  14. Jeavons PM, Bower BD. The natural history of infantile spasms Arch Dis Child. 1961 Feb;36:17-22.
  15. Golomb MR, Garg BP, Williams LS. Outcomes of children with infantile spasms after perinatal stroke Pediatr Neurol. 2006 Apr;34:291-295.

Risk of Sudden Unexpected Death in Epilepsy (SUDEP) with Lamotrigine (Lamictal ®) and Other Sodium Channel Modulating Antiseizure Medications

Abstract found on Wiley Online Library

Objective: In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti-seizure medication (NaM-ASM), could increase risk of sudden death in patients with structural or ischaemic cardiac disease, however its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear.

Methods: This retrospective, nested case-control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM-ASM use were compared between cases and controls at time of admission, and survival analyses from time of admission up to 16?years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors.

Results: Proportions of cases and controls prescribed lamotrigine (p=0.166), one NaM-ASM (p=0.80) or ?2NaM-ASMs (p=0.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR]=0.56; p=0.054), one NaM-ASM (aHR=0.8; p=0.588) or ?2 NaM-ASMs (aHR=0.49; p=0.139) at EMU admission were not at increased SUDEP risk up to 16?years following admission. Active tonic-clonic seizures at EMU admission associated with >2-fold SUDEP risk, irrespective of lamotrigine (aHR=2.24; p=0.031) or NaM-ASM use (aHR=2.25; p=0.029). Sensitivity analyses accounting for incomplete ASM data at follow-up suggest undetected changes to ASM use are unlikely to alter our results.

Significance: This study provides additional evidence that lamotrigine and other sodium channel-modulating anti-seizure medications are unlikely to be associated with an increased long-term risk of SUDEP, up to 16?years post epilepsy monitoring unit admission.

Is the Antiparasitic Drug Ivermectin a Suitable Candidate for the Treatment of Epilepsy?

Abstract found on PubMed

There are only a few drugs that can seriously lay claim to the title of “wonder drug” and ivermectin, the world’s first endectocide and forerunner of a completely new class of antiparasitic agents, is among them. Ivermectin, a mixture of two macrolytic lactone derivatives (avermectin B1a and B1b in a ratio of 80:20), exerts its highly potent antiparasitic effect by activating the glutamate-gated chloride channel that is absent in vertebrate species. However, in mammals, ivermectin activates several other Cys-loop receptors, including the inhibitory GABAA and glycine receptors and the excitatory nicotinic acetylcholine receptor of brain neurons. Based on these effects on vertebrate receptors, ivermectin has recently been proposed to constitute a multifaceted wonder drug for various novel neurological indications, including alcohol use disorders, motor neuron diseases, and epilepsy. This review critically discusses the preclinical and clinical evidence of anti-seizure effects of ivermectin and provides several arguments why ivermectin is not a suitable candidate drug for the treatment of epilepsy. First, ivermectin penetrates the mammalian brain poorly, so it does not exert any pharmacological effects via mammalian ligand-gated ion channels in the brain unless it is used in high, potentially toxic doses or the blood-brain barrier is functionally impaired. Second, ivermectin is not selective but activates numerous inhibitory and excitatory receptors. Third, the preclinical evidence for anti-seizure effects of ivermectin is equivocal and, at least in part, ED50 s in seizure models are in the range of the LD50 . Fourth, the only robust clinical evidence of anti-seizure effects stems from the treatment of patients with onchocerciasis in which the reduction of seizures is due to a reduction in microfilariae densities but not a direct anti-seizure effect of ivermectin. We hope that this critical analysis of available data will avert that the unjustified hype associated with the recent use of ivermectin to control COVID-19 recurs also in neurological diseases such as epilepsy.

Study Identifies Cause for Mysterious Cases of Epilepsy in Children

Article published by Science Daily

Epilepsy is present in 4% of the population, and is among the most common brain disorders in children. Modern medicine can prevent most seizure recurrences, but approximately 20% of patients do not respond to treatment. In these cases, the reason may originate in patches of damaged or abnormal brain tissue known as “malformations of cortical development” (MCD), which results in a diverse group of neurodevelopment disorders.

Surgical resection or removal of the patch can cure the seizures, and epilepsy surgery to improve neurological outcomes is now a key part of the modern medical armamentarium, but what causes the patches has largely remained a mystery.

Writing in the January 12, 2023 issue of Nature Genetics, researchers at University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine, collaborating with an international consortium of more than 20 children’s hospitals worldwide, report a significant breakthrough in understanding the genetic causes of MCD.

The team conducted intensive genomic discovery using state-of-art somatic mosaic algorithms developed by the National Institutes of Health-sponsored Brain Somatic Mosaicism Network, of which UC San Diego is a member.

“We tried our best to detect mutations in as little as 1 percent of cells,” said co-first author Xiaoxu Yang, PhD, a postdoctoral scholar in Gleeson’s lab. “Initially we failed. To solve these problems, we needed to develop novel artificial intelligence methods to overcome barriers in sensitivity and specificity.”

The team ultimately identified 69 different genes carrying somatic brain mutations, the majority of which have never previously reported in MCD.

Parents Need Guidance Managing Sleep Issues in Children with Epilepsy

Article published by HCP Live

Georgia Cook, PhD, Department of Psychology, Health and Professional Development, Centre for Psychological Re search, Faculty of Health and Life Sciences, Oxford Brookes University, and investigators aimed to understand the experience of parents with children who live with epilepsy. These children often face issues with sleep, but there’s very little insight on how parents and caretakers are affected, or how they manage the sleep disturbances of their children.

The neurological condition is characterized by recurrent seizures, with 0.32%–0.55% of children under the age of 18 having a diagnosis. In addition to problems with sleep, it’s also common for these children to have behavioral, cognitive, attention, academic, and psychosocial deficits, which has been shown to reduce their quality of life when compared with those who don’t have epilepsy.

According to this study, sleep and epilepsy have a complex and bidirectional relationship and have been described as ‘unfortunate bedfellows’. Epilepsy exacerbates the struggle to initiate sleep (settling and falling asleep), maintenance of sleep (experiencing night or early morning wakings), duration of sleep, daytime sleepiness and sleep anxiety.

The qualitative investigation included interviews of 9 mothers from 2018. The focus was to capture parental perceptions and experiences related to their child’s sleep habits, their management, the impact of sleep difficulties on the child and their family, and available support.

“Mothers were aware of the links between sleep and seizures, yet felt that they lacked guidance about how to address or improve their child’s sleep, including from their healthcare teams,” they wrote. “This appeared to heighten maternal anxieties and feelings of ‘helplessness’. This finding emphasizes the need to ensure adequate help and support is available to help support healthy sleep in children with epilepsy, as identified in previous work.”

Epilepsy Research News: January 2023

This issue of Epilepsy Research News includes summaries of articles on:

 

Genetic Testing for Epilepsy Improves Patient Outcomes

Genetic testing in patients with epilepsy can inform treatment and lead to better outcomes in many cases, according to a new study. The study, led and funded by the genetic testing company Invitae, included patients referred for genetic testing between 2016 and 2020 whose testing revealed a positive molecular diagnosis. The investigators asked the patient’s healthcare providers how the results of the genetic test impacted the patient’s treatment plan and outcomes. Of the 418 children and adults with epilepsy who were included in the study, nearly half saw changes in their treatment plans such as a change in medication or referral to a specialist, after genetic testing revealed new information about their condition. The study also found that of 167 patients with follow-up information available, treatment changes were associated with improved patient outcomes including a reduction or elimination of seizures. The authors concluded that results support the use of genetic testing to guide the clinical management of epilepsy to improve patient outcomes. Learn more about genetic testing for epilepsy here.

Learn More

 

New Tools to Map Seizures and Improve Epilepsy Treatment

A new “tool” – a statistical model – has been developed to help doctors find precisely where seizures originate in the brain to increase the possibility of treating that specific region. Localizing where seizures begin is usually a costly and time-consuming process that can often require days to weeks of invasive monitoring. In this study, researchers aimed to shorten the time it takes to locate the seizure onset zone by studying patients’ brains, both when they weren’t having seizures and when their brains were stimulated with quick electrical pulses, to quickly create maps predicting where seizures begin. In the 65 patients studied, the model predicted the location of the onset of seizures and the ultimate success of surgical intervention with 79% accuracy. The researchers noted that this tool might be used to help clinicians identify the area where seizures begin in a less time-consuming process.

Learn More

 

Gene Therapy for Epilepsy

A recently published study shows that a potential new treatment can prevent seizures in mice by clearing the accumulation of a protein in the brain known as the tau protein. Researchers at Macquarie University recently found that accumulation of tau protein can lead to neurons becoming hyperexcited. Hyperexcited neurons that fire continuously can result in seizures and cognitive decline. In the newly published study, the researchers developed a gene therapy that uses a brain enzyme known as p38y to prevent this accumulation. When treated with the new gene therapy, mice with uncontrolled epilepsy had a better chance of survival in addition to reduced seizure susceptibility. The researchers note that their next step is to conduct a more detailed study in the laboratory, in hopes of eventually preparing the treatment for a possible clinical trial.

Learn More

 

World Health Organization (WHO) Focuses on Improving the Lives of People with Epilepsy

A technical brief published by the World Health Organization (WHO) called Improving the Lives of People with Epilepsy sets out the actions required to deliver an integrated approach to epilepsy care and treatment with the goal of meeting the multifaceted needs of people with epilepsy. In summary, the brief highlights the importance of:

 

  • Integrated services across the life-course, particularly at the primary care level

  • Access to anti-seizure medicines

  • Resources and training for the health and social services workforce

  • Anti-stigma and discriminatory legislation and practices; promoting and respecting the human rights and full social inclusion of people with epilepsy, their families and caregivers.

Learn More

 

Memory Impairment in Those with Epilepsy

People with chronic epilepsy often experience impaired memory. Researchers have now found a mechanism using a mouse model of epilepsy that could explain this impairment. Porous channels called ion channels within the brain allow electrically charged particles (ions) to flow into neurons, allowing neurons to communicate with each other. However, the researchers found changes in sodium ion channels within neurons of the hippocampus – an area of the brain important in learning and memory – that could lead to changes in the activity of these neurons and affect their normal function. When the researchers administered substances to restore the normal function of these channels, the firing properties of the neurons normalized, and the animals were better able to remember places they had visited. The study provides insight into the processes involved in memory retrieval. In addition, it provides support for the idea that the development of new drugs may improve the memory of epilepsy patients.

Learn More

UK Epilepsy Prevalence and Incidence Update

Article published by Epilepsy Action

A new update on the number of new cases of epilepsy and the number of people with epilepsy in the UK has found differences between the nations.

The new UK study by Wigglesworth and colleagues aimed to provide an update on the incidence of epilepsy (the number of new cases) and the prevalence (the number of people with epilepsy) in the UK between 2013-2018.

The researchers used electronic health records of around 14 million people, representing around one fifth (20%) of the UK population.

The study found that overall in the UK, just over nine people would have epilepsy in every 1,000 people each year. This means that an estimated 633,000 people are living with epilepsy in the UK.

When looking individually at England, Northern Ireland, Scotland and Wales, the team found there were slight differences.

In England, this drops to just under nine people in every 1,000 having epilepsy a year. In Scotland, this was just over 10 people, in Wales it was over 11 people and in Northern Ireland it was over 12 people.

Epilepsy Severity Mediates Association Between Mutation Type and ADHD Symptoms in Tuberous Sclerosis Complex

Abstract found on PubMed

The association between attention deficit hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load and mutation were obtained with 125 children aged 0 – 16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modelling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when IQ was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early-onset and severe epilepsy in the first two years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioural sequelae associated with ADHD from early in life, to further understanding of the association between ADHD and early-onset epilepsy across syndromic and non-syndromic populations.

Use of Newer Antiseizure Meds for Epilepsy Differs by Race, Ethnicity – Black and Hispanic Patients Had Lower Odds of Taking Second- or Third-Generation Medications

Article published by MedPage Today

Racial and ethnic minority groups are less likely to be taking newer-generation antiseizure medications (ASMs) for their epilepsy, an analysis of Medicaid data showed.

Compared with white patients, Black (adjusted OR 0.71, 95% CI 0.68-0.75), Hispanic (aOR 0.93, 95% CI 0.88-0.99), and Native Hawaiian/Pacific Islander (aOR 0.77, 95% CI 0.67-0.88) patients had lower odds of being on newer ASMs, reported Wyatt Bensken, PhD, of Case Western Reserve University in Cleveland, and co-authors.

Racial and ethnic minority groups are less likely to be taking newer-generation antiseizure medications (ASMs) for their epilepsy, an analysis of Medicaid data showed.

Of note, taking a second-generation ASM was associated with better treatment adherence (aOR 1.17, 95% CI 1.11-1.23), and those seeing a neurologist had higher odds of being on newer ASMs (aOR 3.26, 95% CI 3.13-3.41), the researchers detailed in Neurology Clinical Practiceopens in a new tab or window.

“Being on a newer, second-, and third-generation ASM may represent an important marker of quality of care for people with epilepsy,” Bensken and team wrote, citing evidence that newer ASMs opens in a new tab or window are associated with fewer side effectsopens in a new tab or window and more effective seizure control opens in a new tab or window.

“From the patterns we observed, there is the potential that a sizeable proportion of people with epilepsy may not be on an optimal ASM regimen, and the differences appear to reflect clear racial and ethnic inequities in epilepsy care,” they added.

The Epidemiology of Epilepsy in Older Adults: A Narrative Review by the ILAE Task Force on Epilepsy in the Elderly

Abstract found on PubMed

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because “epilepsy in the elderly” is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug-resistant epilepsy using the newer definitions. Many more data are needed from low-income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.