Cutaneous Adverse Reactions Associated with Antiseizure Medication: Clinical Characteristics and Implications in Epilepsy Treatment

Abstract, originally published in Epileptic Disorders

Objective: To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history.

Methods: We analyzed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls.

Results: The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p<0.001). Most cases exposed to high-risk medication, however, did not develop cross-sensitivity.

Significance: Cutaneous adverse reaction history may influence antiseizure medication use. Cross-sensitivity is more common in severe cases and most patients are affected by mild, self-limited skin rashes. Further research should consider the relevance of mild skin rashes in lifelong epilepsy treatment.

Effects of Perceived Stigma, Unemployment and Depression on Suicidal Risk in People With Epilepsy

Abstract, originally published in Seizure

Purpose: Stigma toward people with epilepsy (PWE) is common around the globe. Perceived stigma produced by mental or physical disorders may represent a significant risk factor for suicide. This study examines whether and how perceived stigma, unemployment and depression interact to influence suicidal risk in PWE.

Methods: A consecutive cohort of people with epilepsy (PWE) was recruited from the First Affiliated Hospital of Chongqing Medical University. Each patient completed the Stigma Scale for Epilepsy (SSE), the Neurological Disorders Depression Inventory for Epilepsy scale (NDDI-E) and the suicidality module of Mini-International Neuropsychiatric Interview(MINI) v.5.0.0. Spearman’s correlation and moderated mediation analysis were used to examine the associations among perceived stigma, depression, unemployment and suicidal risk.

Results: Perceived stigma was positively associated with depression severity and suicidal risk. Depression severity mediated the association between perceived stigma and suicidal risk. The indirect effect of perceived stigma on suicidal risk through depression severity was positively moderated by unemployment.

Conclusions: The effect of perceived stigma on suicidal risk can be explained by the mediation of depression severity, At the same time, getting out from the shadow of perceived stigma may help reducing suicidal risk in PWE. In addition, improving employment status of PWE may attenuate the indirect effect of perceived stigma on suicidal risk through depression severity.

Big Data Helps Assess Seizure Burden, Improve Outcomes in Pediatric Epilepsy Patients

Summary, originally published on Eurekalert

Researchers at Children’s Hospital of Philadelphia (CHOP) have demonstrated how to use standardized reporting of clinical data for seizures caused by a variety of neurological disorders, providing fundamental baseline information that can determine what methods work best for keeping seizures under control. The findings were published today in the journal Epilepsia.

In order to make improvements in epilepsy care, clinicians need a reliable and efficient method to measure outcomes. While Electronic Medical Records (EMR) are being used more frequently for research and quality improvement, important epilepsy outcome measures such as seizure frequency or quality of life are not documented in a standardized way that enables researchers to process large-scale data on the subject.

To help standardize how clinical data is recorded for epilepsy visits, the team at CHOP began using common data elements (CDEs) to ensure that relevant data is captured in a comparable way across studies and clinical visits. In this study, the researchers assessed the results from using CDEs in routine care for pediatric epilepsy over a 12-month period.

“For those of us who treat pediatric epilepsy patients, we are constantly trying to assess how we’re doing and how we can improve outcomes for our patients,” said Mark P. Fitzgerald, MD, PhD, a pediatric neurologist in the Division of Neurology at CHOP and first author of the study. “This study provides us with fundamental data that will serve as the foundation for how we treat our patients and inform how we achieve the best patient-centered outcomes possible.”

Reciprocal Burden: Adults with Drug-Resistant Epilepsy Reflect Upon Informal Caregiver Support

Abstract, originally published in Seizure

Purpose: To explore how a sample of people with uncontrolled seizures describe their experiences of receiving informal supportive care.

Methods: Using constructivist grounded theory, in-person, semi-structured interviews were conducted in 35 adults with drug-resistant epilepsy. These 20 (57%) women and 15 (43%) men were aged 18-68 years (mean= 35.6 years), with a range of verbal comprehension scores. The majority, 28 (80%) lived in nuclear family settings.

Results: Unpredictable seizures disrupted personal autonomy and generated unique challenges for everyday life. While supportive care was deemed necessary to survival, subjective reflections around the implications of care-receiving and caregiving, were ultimately experienced as mutually burdensome. Four dynamic and interactive dimensions revealed a mirrored, interactive perspective of what it meant to be a care-recipient: assuming responsibility; protecting and supervising; acknowledging reliance and setting boundaries. Care-recipience was not one-sided, but included actively hiding personal struggles as a way to shield the caregiver from the emotional and physical demands of caregiving. Relationship dynamics between caregivers and care-recipients played a major role in treatment decision-making. A clinically useful Theory of Reciprocal Burden resulted from our study.

Conclusions: This study adds an explanatory dimension to the concept of illness burden from the perspective of care-recipients. Relationship dynamics play a key role in patient-centered epilepsy care, with clinical implications for guiding supportive caregiving, fostering independence and promoting self-management strategies.

Opportunities and Challenges for MicroRNA-Targeting Therapeutics for Epilepsy

Abstract, originally published in Trends in Pharmacological Sciences

Epilepsy is a common and serious neurological disorder characterized by recurrent spontaneous seizures. Frontline pharmacotherapy includes small-molecule antiseizure drugs that typically target ion channels and neurotransmitter systems, but these fail in 30% of patients and do not prevent either the development or progression of epilepsy. An emerging therapeutic target is microRNA (miRNA), small noncoding RNAs that negatively regulate sets of proteins. Their multitargeting action offers unique advantages for certain forms of epilepsy with complex underlying pathophysiology, such as temporal lobe epilepsy (TLE). miRNA can be inhibited by designed antisense oligonucleotides (ASOs; e.g., antimiRs). Here, we outline the prospects for miRNA-based therapies. We review design considerations for nucleic acid-based approaches and the challenges and next steps in developing therapeutic miRNA-targeting molecules for epilepsy.

New Research Could Lead to Better Treatment for Epilepsy

Abstract, originally published on

Scientists have discovered that the way in which neurons are connected within regions of the brain can be a better indicator of disease progression and treatment outcomes for people with brain disorders such as epilepsy.

Many brain diseases lead to cell death and the removal of connections within the brain. In a new study, published in Human Brain Mapping, a group of scientists, led by Dr Marcus Kaiser from the School of Medicine at the University of Nottingham, looked at epilepsy patients undergoing surgery.

They found that changes in the local network within brain regions can be a better predictor of disease progression, and also whether surgery will be successful or not.

The team found that looking at connectivity within regions of the brain showed superior results to the current approach of only observing fiber tract connectivity between brain regions. Dividing the surface of the brain into 50,000 network nodes of comparable size, each brain region could be studied as a local network with 100-500 nodes. These local networks showed distinct changes compared to a control group not suffering from epileptic seizures.

Missed, Mistaken, Stalled: Identifying Components of Delay to Diagnosis in Epilepsy

Abstract, originally published in Epilepsia

A substantial proportion of individuals with newly diagnosed epilepsy report prior seizures, suggesting a missed opportunity for early epilepsy care and management. Consideration of the causes and outcomes of diagnostic delay is needed to address this issue. We aimed to review the literature pertaining to delay to diagnosis of epilepsy, describing the components, characteristics, and risk factors for delay.

We undertook a systematic search of the literature for full-length original research papers with a focus on diagnostic delay or seizures before diagnosis, published 1998-2020. Findings were collated, and a narrative review was undertaken. Seventeen papers met the inclusion criteria. Studies utilized two measures of diagnostic delay: seizures before diagnosis and/or a study-defined time between first seizure and presentation/diagnosis. The proportion of patients with diagnostic delay ranged from 16% to 77%; 75% of studies reported 38% or more to be affected. Delays of 1 year or more were reported in 13%-16% of patients. Seizures prior to diagnosis were predominantly nonconvulsive, and usually more than one seizure was reported. Prior seizures were often missed or mistaken for symptoms of other conditions. Key delays in the progression to specialist review and diagnosis were (1) “decision delay” (the patient’s decision to seek/not seek medical review), (2) “referral delay” (delay by primary care/emergency physician referring to specialist), and (3) “attendance delay” (delay in attending specialist review). There were few data available relevant to risk factors and virtually none relevant to outcomes of diagnostic delay.

This review found that diagnostic delay consists of several components, and progression to diagnosis can stall at several points. There is limited information relating to most aspects of delay apart from prevalence and seizure types. Risk factors and outcomes may differ according to delay characteristics and for each of the key delays, and recommendations for future research include examining each before consideration of interventions is made.


Knowledge and Attitudes Toward Epilepsy Among Libyan People With and Without Epilepsy in a Tertiary Medical Center

Abstract, originally published in Epilepsy & Behavior

Background: Although patients with epilepsy (PWE) constitute a considerable sector of the population in Benghazi, there is no adequate knowledge about this disease.

Objectives: To assess knowledge and attitudes toward epilepsy among Libyan people who live in Benghazi city.

Methods: A cross-sectional prospective hospital-based study was conducted in the year 2020, from June to August. The participants were adults, PWE were included as well as people without epilepsy (NEP). Participants were interviewed through a twelve-item questionnaire related to knowledge which included definition, causes, manifestations, first aids, treatment options, and curability. In addition, attitudes toward epilepsy were tested by questions that include immediate actions when seeing a patient seizing, and whether or not PWE can drive, work, marry, and conceive).

Data analysis: Data were processed by the statistical software (SPSS) version 18.0. Differences between categorical variables were tested by Chi square and P value at 0.05, which has been considered statistically significant.

Results: The total number of the interviewees was 156. The mean age was 43 ± 14 SD years (18-76 years), 105 (67%) were males. Twenty-eight (18%) of the participants were PWE, while the remaining 128 (82%) were NEP. Ninety-nine (64%) and 145 (92%) of the participants answered correctly regarding definition and manifestations of epilepsy, respectively. The participants with Bachelor degree and post graduate level have shown a better understanding of definitions and treatments of epilepsy (P = 0.000). They also had better attitudes toward PWE in terms of their ability to conceive (P = 0.002).PWE had better knowledge about manifestations and first aids of epilepsy compared to NEP, though they did not have differences in attitude compared to NEP. Participants’ knowledge about epilepsy was mainly obtained from friends (41; 26%), patients (40; 26%), and media (37; 24%). A major portion of participants 94 (60%) did not feel satisfactory about their own information about epilepsy.

Conclusion: Knowledge and attitudes toward epilepsy were generally satisfactory. Participants with a Bachelors degree or higher level of education had better knowledge and positive attitudes toward PWE. Patients and media are important tools to improve knowledge and attitudes about epilepsy.

Seizures and Status Epilepticus May Be Risk Factor for Cardiac Arrhythmia or Cardiac Arrest Across Multiple Time Frames

Abstract, originally published in Epilepsy & Behavior

Objective: To determine if Emergency Department (ED) or inpatient encounters for epilepsy or status epilepticus are associated with increased odds of cardiac arrhythmia or cardiac arrest over successively longer time frames.

Methods: The State Inpatient and ED Databases (from New York, Florida, and California) are statewide datasets containing data on 97% of hospitalizations and ED encounters from these states. In this retrospective, case-crossover study, we used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index cardiac arrhythmia encounters. Exposures were inpatient or ED encounters for epilepsy or status epilepticus. The case-crossover analysis tested whether an epilepsy or status epilepticus encounter within various case periods (1, 3, 7, 30, 60, 90, and 180 days prior to index encounter) was associated with subsequent ED or inpatient encounter for cardiac arrhythmia, as compared to control periods of equal length one year prior.

Results: The odds ratio (OR) for cardiac arrhythmia after an epilepsy encounter was significant at all time intervals (OR range 2.37-3.36), and highest at 1 day after epilepsy encounter (OR 3.63, 95% confidence interval [CI] 1.66-7.93, p = 0.0013). The OR after status epilepticus was significant at 7- to 180-day intervals (OR range 2.25-2.74), and highest at 60 days (OR 2.74, CI 2.09-3.61, p < 0.0001).

Significance: Epilepsy and status epilepticus events are associated with increased odds of subsequent cardiac arrhythmia or cardiac arrest over multiple chronic timeframes. Increased cardiac surveillance may be warranted to minimize morbidity and mortality in patients with epilepsy.

Psychiatric and Cognitive Characteristics of Older Adults Admitted to a Video-EEG Monitoring (VEM) Unit

Abstract, originally published in Epilepsy & Behavior

Objective: To compare the clinical, psychiatric, and cognitive characteristics of older with younger patients presenting to a video-EEG monitoring (VEM) unit.

Method: This was a retrospective case-control study involving patients admitted for VEM over a two-year period (from April 2018 to April 2020) at two comprehensive epilepsy units. Patients were categorized into an older (?60 years) and a younger (<60 years) group. Younger patients were individually matched to older adults to form a matched younger group. Diagnosis was determined by a consensus opinion of epileptologists, neurologists, and neuropsychiatrists. The main diagnostic categories were epilepsy, psychogenic nonepileptic seizures (PNES), and ‘other’ diagnosis (non-diagnostic and other nonepileptic diagnoses). Clinical psychiatric diagnoses were obtained from neuropsychiatric reports. Objective cognitive function was measured with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Subjective cognitive function was assessed using the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) cognitive subscales.

Results: Five-hundred and thirty three patients (71 older, 462 younger) aged 16-91 years were admitted to the VEM unit during the study period. There was a diagnosis of focal epilepsy in 55% of the older group and 48% of the younger group, generalized epilepsy in 3% of the older group and 10% of the younger group, and ‘other’ in 32% of the older group and 19% of the younger group. Ten percent (2 males and 5 females) of the older group were diagnosed with PNES compared to 22% of the younger group (p = 0.016). A depressive disorder was diagnosed in 34% of the older group and 24% of the younger group (p = 0.20). An anxiety disorder was diagnosed in 15% of the older group and 25% of the younger group (p = 0.15). Mild neurocognitive disorder was more common in the older group (34%) compared to the matched younger group (34% vs 3%, p < 0.001). The older group had lower mean NUCOG scores compared to the matched younger group (79.49 vs 87.73, p = <0.001). There was no evidence for a relationship between mean NUCOG score and overall subjective cognitive difficulties for the older group (r = 0.03, p = 0.83). Among older adults, those diagnosed with PNES had more experiences of childhood trauma. Measures of dissociation, depression, or general anxiety did not differ between PNES and non-PNES diagnoses in the older group.

Conclusion: Psychiatric comorbidities are common among older adults admitted for video-EEG monitoring. The psychological impact of epilepsy and risk factors for psychogenic non-epileptic seizures seen in younger patients are also applicable in the older group. The older group demonstrated more cognitive impairments than the younger group, although these were usually unrecognized by individuals. Older adults admitted to video-EEG monitoring will benefit from psychiatric and neuropsychological input to ensure a comprehensive care approach to evaluation and management.