Difficulties with Mathematics Experienced by Adults with Epilepsy in Daily Life: An Online Study

Abstract found on PubMed

Objective: Mathematics encompass a variety of skills, broadly grouped into basic numeracy to complex secondary mathematical skills. In children with epilepsy difficulties with mathematics are common and related to a multicomponent working memory capacity. Little is known about mathematical skills of adults with epilepsy in daily life. Hence, we aimed to compare basic and secondary mathematical skills of adults with epilepsy to controls, examine relations between mathematical skills and working memory, and explored relationships between mathematical skills and epilepsy variables (age of onset, seizure frequency, and anti-seizure medication).

Methods: Eighty-four people with epilepsy and 86 healthy controls completed questionnaires on their subjective experience of using mathematics and working memory skills in daily life: The Dyscalculia Checklist (DC) and Working Memory Questionnaire (WMQ; including attention, storage, and executive scales), respectively. Questionnaires also collected demographic and epilepsy variables.

Results: Adults with epilepsy reported greater difficulties in basic and secondary mathematical skills on the DC compared with controls. Only one epilepsy variable, a younger age of epilepsy onset, related to higher DC scores (greater mathematical difficulties), but was not significantly related in regression analyses. Instead, the WMQ explained 33% of the variance on the DC; the poorer storage and attention (but not executive) on the WMQ were associated with the higher DC score, when demographic and epilepsy variables were accounted for.

Significance: Adults with epilepsy reported significant difficulties with mathematics in daily life, which were not explained by epilepsy variables but by poor working memory. While our findings suggest that daily difficulties with mathematics may be comorbid with epilepsy rather than epilepsy related, it is important to be cognizant of mathematical difficulties experienced by patients with epilepsy as they have potential to impact understanding of numerical information provided in patient care, such as risks associated with different epilepsy treatments.

The Association of Multiple Chronic Conditions and Healthcare Expenditures Among Adults with Epilepsy in the United States

Abstract found on PubMed

Rationale: Epilepsy is a frequent neurologic condition with important financial strains on the US healthcare system. The co-occurrence of multiple chronic conditions (MCC) may have additional financial repercussions on this patient population. We aimed to assess the association of coexisting chronic conditions on healthcare expenditures among adult patients with epilepsy.

Methods: We identified a total of 1,942,413 adults (?18 years) with epilepsy using the clinical classification code 83 from the MEPS-HC (Medical Expenditure Panel Survey Household Component) database between 2003 and 2014. Chronic conditions were selected using the clinical classification system (ccs), and categorized into 0, 1, or 2 chronic conditions in addition to epilepsy. We computed unadjusted healthcare expenditures per year and per individual (total direct healthcare expenditure, inpatient expenditure, outpatient expenditure, prescription medication expenditure, emergency room visit expenditure, home healthcare expenditure and other) by number of chronic conditions. We applied a two-part model with probit (probability of zero vs non-zero cost) and generalized linear model (GLM) gamma family and log link (for cost greater than zero) to examine the independent association between chronic conditions, and annual expenditures per individual, generating incremental costs with 0 chronic condition as reference.

Results: Over half of the patients with epilepsy had at least two chronic conditions (CC). Yearly, for each patient with one and two chronic conditions, unadjusted total healthcare expenditures were two times ($10,202; 95 %CI $6,551-13,853) to nearly three times ($21,277; 95 %CI $12,971-25,583) higher than those with no chronic conditions ($6,177; 95 %CI $4,895-7,459), respectively. In general healthcare expenditures increased with the number of chronic conditions for pre-specified cost categories. The incremental (adjusted) total healthcare expenditure increased with the number of chronic conditions (1CC vs 0 CC: $3,238; 95 %CI $524-5,851 p-value = 0.015 and ?2 CC vs 0 CC: $8,145; 95 %CI $5,935-10,895 p-value < 0.001). In general, for all cost categories, incremental healthcare expenditures increased with the number of chronic conditions with the largest increment noted between those with 2 CC and those with 0 CC for inpatient ($2,025: 95 %CI $867-3,1830), outpatient ($2,141; 95 %CI $1,321-2,962), and medication ($1,852; 95 %CI $1,393-2,310).

Conclusion: Chronic conditions are frequent among adult patients with epilepsy and are associated with a dose-response increase in healthcare expenditure, a difference driven by inpatient, outpatient, and medication prescription expenditures. Greater coordination of epilepsy care accounting for the presence of multiple chronic conditions may help lower the cost of epilepsy.

Epilepsy Center Characteristics and Geographic Region Influence Presurgical Testing in the United States

Abstract found on Wiley Online Library

Objective: Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy.

Methods: We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and U.S. Census regional data. We used Wilcoxon rank-sum, Kruskal-Wallis, and chi-square tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios of significant variables.

Results: The response rate was 100% with individual element missingness less than 11% across 342 observations undergoing univariate analysis. 278 complete observations were included in the multivariable models and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR 2.87, 95% CI 1.2 – 6.86, p = 0.018) and FDG-PET (OR 2.74, 95% CI 1.14- 6.61, p = 0.025) more commonly. For centers in the Northeast (OR 0.46, 95% CI 0.23-0.93, p = 0.031) and West (OR 0.41, 95% CI 0.19-0.87, p = 0.022), odds of performing SPECT was lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume and resources were also associated with varying individual testing rates.

Significance: Presurgical testing for drug resistant epilepsy is influenced by U.S. geographic region and other center characteristics. These findings have potential implications for comparing outcomes between U.S. epilepsy centers and may inject disparities in access to surgical treatment.

Breastfeeding While on Treatment with Antiseizure Medications: a Systematic Review from the ILAE Women Task Force

Abstract found on PubMed

We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol (Epidiolex ®), cenobamate (XCOPRI ®), clobazam (Onfi ®), eslicarbazepine-acetate (Aptiom ®), everolimus (Afinitor ®), felbamate (Felbatol ®), fenfluramine (Fintepla ®), retigabine (Trobalt ®), rufinamide (Banzel ®), stiripentol (Diacomit ®), tiagabine (Gabitril ®), and vigabatrin (Sabril ®). For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman’s specific ASM treatment.

Seizure First Aid for People with Epilepsy: Opinions and Knowledge of Caregivers and Healthcare Professionals

Abstract found on PubMed 

Objective: We investigated the opinions and knowledge of the caregivers of people with epilepsy (PWE) and the related healthcare professionals (i.e., nurses and physicians) in Iran about first aid measures for helping a person experiencing a seizure.

Methods: In this exploratory and descriptive study, we surveyed the caregivers of all PWE admitted to the epilepsy monitoring unit at Namazi Hospital, Shiraz, Iran, in May 2022. We also surveyed all the nurses at this hospital. A similar survey was distributed in the WhatsApp groups of the neurology, pediatrics, internal medicine, family physician, psychiatry, and neurosurgery physicians working at places affiliated with Shiraz University of Medical Sciences, Shiraz, Iran.

Results: In total, 583 nurses, 70 physicians, and 133 caregivers participated in this study. On most questions, more caregivers provided inappropriate responses than nurses and physicians (e.g., not timing the seizure; not loosening the clothes around the neck; not rolling the patient onto the side if unconscious). On two questions, more caregivers provided appropriate responses than nurses and physicians (i.e., not putting something into the mouth; not always calling for emergency medical services).

Conclusion: While some actions may help prevent or reduce the chance of harmful consequences of epileptic seizures, many caregivers of PWE and healthcare professionals do not apply appropriate measures to help a patient experiencing a seizure. The scientific community should develop standardized seizure first aid training programs for the general public and healthcare professionals alike.

Multi-Modal Data Integration Platform Combining Clinical and Preclinical Models of Post Subarachnoid Hemorrhage Epilepsy

Featuring the work of CURE Epilepsy PTE Initiative grantee Dr. Jeffrey Loeb and his laboratory

Abstract found on PubMed

Subarachnoid hemorrhage (SAH) is a devastating neurological injury that can lead to many downstream complications including epilepsy. Predicting who will get epilepsy in order to find ways to prevent it as well as stratify patients for future interventions is a major challenge given the large number of variables not only related to the injury itself, but also to what happens after the injury. Extensive multimodal data are generated during the process of SAH patient care. In parallel, preclinical models are under development that attempt to imitate the variables observed in patients. Computational tools that consider all variables from both human data and animal models are lacking and demand an integrated, time-dependent platform where researchers can aggregate, store, visualize, analyze, and share the extensive integrated multimodal information. We developed a multi-tier web-based application that is secure, extensible, and adaptable to all available data modalities using flask micro-web framework, python, and PostgreSQL database. The system supports data visualization, data sharing and downloading for offline processing. The system is currently hosted inside the institutional private network and holds [Formula: see text] of data from 164 patients and 71 rodents.

Clinical Relevance-Our platform supports clinical and preclinical data management. It allows users to comprehensively visualize patient data and perform visual analytics. These utilities can improve research and clinical practice for subarachnoid hemorrhage and other brain injuries.

Association of Ictal Imaging Changes [Changes Related to the Seizure] in Status Epilepticus and Neurological Deterioration

Abstract found on Wiley Online Library

Objective: In patients with status epilepticus (SE), the clinical significance of ictal changes [changes related to the seizure] on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge.

Methods: The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008–2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes.

Results: Of 261 eligible patients, 101 received at least one MRI during SE or within 7?days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n =?20) and without (n =?81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24?h and hardly seen >5?days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies.

Significance: In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.

Epilepsy Research News: September 2022

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


Recent Advances in Precision Medicine for Genetic Epilepsy

The genetic basis of many epilepsies is increasingly understood. This gives rise to the possibility of precision treatments that can be tailored to a person’s specific genetic epilepsy. CURE Epilepsy Taking Flight grantee Juliet Knowles, MD, PhD, led a collection of prominent stakeholders within the epilepsy community, including CURE Epilepsy’s Dr. Laura Lubbers, in authoring a critical review that describes recent progress, new or persistent challenges, and future directions of precision medicine for genetic epilepsies, among other things. The article states that though current medical therapy for most epilepsies remains imprecise, the epilepsy community is ready to make big steps forward in precision therapy tailored to a person’s specific genetic epilepsy because of increased access to genetic testing and counseling and advances in the ability to diagnose genetic epilepsies. The authors conclude that the future of precision medicine for genetic epilepsy looks bright if progress in this area continues in a strategic and coordinated manner.
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Mortality Rates are Higher Among Veterans with Drug Resistant Epilepsy, Prompting Need for Improved Management

According to data from an observational cohort study, US veterans with drug-resistant epilepsy have higher rates of mortality than the general population, suggesting a critical need for appropriate management of epilepsy in this population. The findings showed that lower mortality was associated with increased utilization of medical care, especially when utilizing a Veterans Affairs Epilepsy Center of Excellence compared to a neurology clinic alone. The study authors noted that the higher mortality risk might be lowered by appropriate referrals for comprehensive evaluation, adequate diagnostic testing, and optimal medication management and that adequate resources should be allocated to care for this patient group.
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Seizures and Epilepsy Risk Still High Two Years After Delta, Omicron Infections

A recent study found an increased risk among adults for epilepsy or seizures two years after COVID-19 infection. Researchers used data collected as part of a two-year retrospective cohort study to investigate the neurological and psychiatric impact of SARS-CoV-2 infections. The researchers discovered that participants who had been infected with the Delta COVID-19 variant had an increased risk for epilepsy or seizures (amongst other risks) when compared to participants who had been infected with the Alpha variant. They also found that while the death rate decreased after the emergence of the Omicron variant, the virus still carried about the same risks for psychiatric or neurological problems, including epilepsy or seizures, compared to the Delta variant. The authors note that these findings emphasize there is a need for further research into the long-term impact of COVID-19.
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Study of Potassium Channels Reveals Novel Mechanism Behind Epilepsy

Epilepsy can have a variety of causes, including genetic variants in a family of proteins that regulate potassium ions in the brain. A research team is examining the mechanisms behind the function and dysfunction of two of these proteins, the potassium ion channels KCNQ2 and KCNQ3, as well as their interactions with an antiseizure medication, to develop a new strategy to treat epilepsy. The team identified a set of mutations in these ion channels associated with early infantile epileptic encephalopathy, a severe form of childhood epilepsy, that specifically disrupts the function of these channels. The researchers took advantage of the antiseizure drug retigabine, given its mechanism of action on neuronal KCNQ channels, and demonstrated that the function of these mutated KCNQ channels can be restored. Their studies suggest that targeting the function of KCNQ channels may be an effective strategy for developing more effective therapies for epilepsy.
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Brain Abnormalities in Epilepsy Detected by New AI Algorithm

An artificial intelligence (AI) algorithm to detect subtle brain abnormalities that cause epileptic seizures has been developed. The abnormalities, known as focal cortical dysplasias (FCDs), can often be treated with surgery but are difficult to visualize on an MRI. The new algorithm is expected to give physicians greater confidence in identifying FCDs in patients with epilepsy. To develop the algorithm, the team quantified features of the brain cortex—such as thickness and folding—in more than 1,000 patient MRI scans from 22 epilepsy centers around the world. They then trained the algorithm on examples labeled by expert radiologists as either being healthy or having FCD. The study’s authors state that the algorithm automatically learns to detect lesions from thousands of MRI scans of patients and can reliably detect lesions of different types, shapes, and sizes. The algorithm can even detect many of those lesions that were previously missed by radiologists. Ultimately, the team would like this AI algorithm to help doctors confidently identify FCDs, and then use surgery to remove them, in hopes of providing a cure for epilepsy.
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Effect of Alexithymia [Problem Feeling Emotion] and Difficulty of Emotion Regulation, Neuroticism, Low Extraversion, and Suicidality on Quality of Life in Epilepsy

Abstract found on PubMed

Objective: The objective of this study was to investigate alexithymia, emotion dysregulation, suicidality, and personality traits in people with epilepsy (PWE) and to evaluate their effects on quality of life.

Materials and methods: Forty-six consecutive PWE and forty healthy control subjects (HC) were recruited for the study. Both PWE and HC were interviewed and completed the following questionnaires: Toronto Alexithymia Scale-20(TAS-20), Difficulties in Emotion Regulation Scale (DERS), Eysenck Personality Questionnaire, Suicidal Ideation Scale, Beck Depression Inventory-II, Beck Anxiety Inventory, and Quality Of Life In Epilepsy-31.

Results: TAS-20 and difficulty identifying feelings which was the subgroup of TAS-20, scores of total and non-acceptance, goals, impulse, strategies, and clarity subgroups of DERS were statistically significantly higher in PWE (p = 0.01, 0.004, 0.01, 0.07, 0.009, 0.06, 0.01, respectively). Considering the personality characteristics, neuroticism was more common in PWE, while extraversion was less common. Suicidal ideation and anxiety scores were higher in PWE than HC (p = 0.02, p = 0.003). Anxiety, suicidal ideation, neuroticism, alexithymia and emotion dysregulation had a negative relationship on quality of life. (r = -0.54, p < 0.001; r = -0.54, p < 0.001; r = -0.62, p < 0.001; r = -0.32, p = 0.02; r = -0.52, p < 0.001).

Conclusion: Difficulty identifying feelings, dysregulation of emotions especially nonacceptance, goals, impulse, strategies, and clarity are common in PWE. Anxiety, suicidal ideation, neuroticism, alexithymia, and emotion dysregulation had a negative impact on quality of life. Each of these are important for psychosocial wellbeing of our patients and must be questioned considering their effects on quality of life.

Economic Aspects of Treating Seizure Clusters

Abstract found on PubMed 

Seizure clusters may initiate a chain of events that have economic as well as clinical consequences. The potential economic consequences of seizure clusters must be weighed against the cost of medication to attenuate them. This is true both for individual patients and for society. Data needed for economic analyses include the chance that a cluster will progress to an adverse outcome, such as a need for emergency care, the costs of such an outcome, the cost of a rescue medication (RM), and the effectiveness of the RM. Indirect costs, such as lost employment for patients and caregivers, must also be considered. Several types of economic analyses can be used to determine costs and benefits of a medical intervention. There are studies comparing different RMs from an economic perspective, but there is little direct information on the costs of using an RM versus allowing clusters to run their course. However, the high expense of consequences of seizure clusters makes it likely that effective rescue medication will make economic as well as medical sense for many patients.