An elderly woman speaks with her doctor, who is explaining the prescription.

Antiepileptic Drugs Linked to Higher Mortality in Alzheimer’s

Originally published on McKnights.com

Antiepileptic drugs are tied to higher mortality risk in people with Alzheimer’s disease, according to a new study from Finland.

The findings are concerning, as the drugs are frequently used for indications other than epilepsy in these patients, the researchers contend. This includes neuropathic pain and the behavioral and psychological symptoms of dementia.

Study data was pulled from a nationwide Finnish prescription registry of people with Alzheimer’s, including patients with and without epilepsy. Investigators found that mortality risk jumped during the first three months of antiepileptic drug treatment. In addition, users of older drugs were more likely to die when compared to those who took newer antiepileptics.

People with Alzheimer’s disease are not only more likely to be prescribed antiepileptics than those without dementia, but to be prescribed older drugs choices, wrote first author Tatyana Sarycheva, M.D., from the University of Eastern Finland.

The results held after controlling for comorbidities, sociodemographic factors and the use of other medications. Risk also remained elevated after participants with epilepsy were excluded.

The researchers cautioned that the reasons for prescribing an antiepileptic could partly explain the study results.

Abstract, published in Neurology

Objective To evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.

Methods The MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).

Results Nearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).

Conclusion In older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

Disability Benefits in Patients with Psychogenic Nonepileptic Seizures: A Survey of Physicians’ Opinions

Abstract, published in Epilepsy & Behavior 

Objectives: The aim of the current study was to gather the views of healthcare providers practicing in the field of psychogenic nonepileptic seizures (PNES) on the issue of “disability benefits eligibility and PNES”. PNES are involuntary episodes that look and feel similar to epileptic seizures but have psychological rather than neurological causes.

Methods: This was a questionnaire study that was sent to all neurologists and psychiatrists practicing in Fars province, Iran. The survey included seven questions: one question about professional qualifications, one question on the participants’ personal experience with the topic of interest (i.e., PNES), and five questions probing their opinions about the matter of interest (i.e., the issue of disability benefits eligibility in PNES).

Results: The response rate was 72%. Respondents included 32 psychiatrists and 31 neurologists. In response to the question “Do you think that patients with PNES should be counseled to avoid performing all jobs or professions as long as they have active PNES?”, 47 (75%) physicians answered “no” (22 neurologists and 25 psychiatrists). In response to the question “Do you think that patients with PNES should be qualified for disability benefits?”, 47 (75%) physicians answered “Patients with specific jobs or professions should be qualified for disability benefits” (23 neurologists and 24 psychiatrists, while no one believed that “All of them should be qualified for disability benefits”.

Conclusion: Although collection of the opinions of physicians is valuable, this is just one piece of the puzzle. Future studies should investigate the opinions of other stakeholders. More importantly, investigators should explore whether patients with PNES have any job-related difficulties.

Which Seizure Elements Do Patients Remember? A Comparison of History and Seizure Documentation

Abstract, published in Epilepsia

Objective: People with epilepsy (PWE) are frequently unable to recall the core manifestation of their disease, epileptic seizures. This means that seizure frequency is often underestimated by practitioners and that seizure classification based on reports of patients or their relatives is difficult because seizure symptoms remain unclear. The purpose of this study, therefore, was to prospectively explore patients’ memory regarding seizure elements and to assess the role of seizure types.

Methods: Ninety patients diagnosed with focal epilepsy undergoing diagnostic electroencephalography (EEG)–video monitoring were included. The ability to remember individual seizure elements was assessed using a questionnaire. Patient memory was then compared to the findings of subsequent seizure documentation during EEG?video monitoring. Seizure elements were categorized in four groups: subjective, motor, autonomic, and postictal (immediately after the seizure) elements.

Results: In all categories, the number of documented seizure elements during monitoring strongly exceeded the number of elements that were recalled. Only 45.6% of subjective elements, 5.4% of motor phenomena, 11.9% of autonomic findings, and 2.1% of postictal impairments were recalled. The ability to recall seizure elements varied significantly depending on seizure types (secondarily generalized tonic?clonic seizures [SGTCS] < complex partial seizures [CPS] < simple partial seizures [SPS]), but not on the relative timing of the element during the seizure.

Significance: Patients’ memory of seizure symptoms is almost always fragmentary. Although the rate of correctly remembered seizure elements depends on the seizure type, complete recall of a seizure is almost never obtained. Consequently, 89 of 90 patients in this cohort would only have had seizures classified as a seizure with “impaired awareness,” according to the new International League Against Epilepsy (ILAE) seizure classification.

A visibly pregnant woman looks at a prescription, which her doctor is handing to her.

New-Onset Epilepsy in Women with First-Time Seizures During Pregnancy

Abstract, published in Seizure

Introduction: In women with epilepsy, seizure frequency and severity can be affected during pregnancy by factors such as changes in anti-seizure drug, metabolism, changes in hormone levels, and medication compliance. Some women with epilepsy experience seizure worsening during pregnancy, while others have an improvement. Most epileptic seizures during pregnancy occur in women with pre-existing epilepsy, but some women can develop new-onset seizure-like episodes during pregnancy, the latter of which poses a diagnostic and therapeutic challenge for the physician.

Methods: To determine the frequency of new-onset seizures during pregnancy and the clinical course of those with new seizures, we performed a retrospective study of all women with concomitant diagnoses of pregnancy and seizures at the Johns Hopkins Medical Institutions over a five-year period.

Results: Of the 41,869 women who received pregnancy care at Johns Hopkins Medical Institutions, eighty-four women had at least one seizure-like event. Of these, eleven had no prior history of seizures and five were found to have first-time unprovoked epileptic seizures, indicated by epileptiform abnormalities on EEG. All women delivered at term with no major complications. Four of these women continued to have epileptic seizures after delivery.

Conclusions: Although new onset seizures during pregnancy were rare, most women with first-time epileptic seizures during pregnancy continued to suffer from epileptic seizures after pregnancy.

Hallucinations in People with Seizures May Point to Suicide Risk

In a study published in the journal Epilepsia, researchers from Trinity College Dublin and the Royal College of Surgeons in Ireland (RCSI) have shown, for the first time, the mental health significance of hallucinations in people with a history of seizures. Of 15,000 people living in the UK,  8% of individuals with a history of seizures report hallucinations, including experiences of hearing or seeing things that are not based in reality. And, most importantly, of that 8%, 65% also met criteria for one or more mental health disorders and 53% had one or more suicide attempt.

Although hallucinations are known to occur in some adults with seizures, they may be erroneously viewed as “incidental” symptoms of abnormal electrical activity in the brain and nothing more. The findings of this study suggest that these symptoms are not just incidental in people with seizures; they are important markers of risk for mental ill health and for suicidal behavior.

Dr. Ian Kelleher, Research Associate Professor of Psychiatry, Trinity and Senior Author of the study said: “People with epilepsy are known to be at increased risk of suicide. But among individuals with seizures, it’s hard to pick out who is most at risk. What this research shows is that people with seizures who report hallucinations are a particularly high-risk group for suicidal behavior—about half of these individuals had one or more suicide attempt. So, it’s important in epilepsy clinics to ask about hallucinations—and where someone confirms these symptoms, to carefully examine their mental state.”

Dr. Kelleher concluded: “We’ll need further research to fully understand the significance of hallucinations in people with seizures. But what’s clear from this work is that, for clinicians working with people with seizures, asking about auditory and visual hallucinations should be a routine part of their assessment.”

A doctor goes over medical information with his patient.

Prediction of the Recurrence Risk in Patients with Epilepsy After the Withdrawal of Antiepileptic Drugs

Abstract, published in Epilepsy and Behavior

Many seizure-free patients who consider withdrawing from antiepileptic drugs (AEDs) hope to discontinue treatment to avoid adverse effects. However, withdrawal has certain risks that are difficult to predict.

In this study, researchers performed a literature review, summarized the causes of significant variability in the risk of post-withdrawal recurrent seizures, and reviewed study data on the age at onset, cause, types of seizures, epilepsy syndrome, magnetic resonance imaging (MRI) abnormalities, epilepsy surgery, and withdrawal outcomes of patients with epilepsy. Many factors are associated with recurrent seizures after AED withdrawal. For patients who are seizure-free after treatment, the role of an electroencephalogram (EEG) alone in ensuring safe withdrawal is limited.

A series of prediction models for the post-withdrawal recurrence risk have incorporated various potentially important factors in a comprehensive analysis. This study focused on the populations of studies investigating five risk prediction models and analyzed the predictive variables and recommended applications of each model, aiming to provide a reference for personalized withdrawal for patients with epilepsy in clinical practice.

Trends in Hospitalization and Readmission for Pediatric Epilepsy and Underutilization of Epilepsy Surgery in the United States

Abstract, published in Seizure

Background: Previous studies have shown the healthcare utilization for medically refractory epilepsy and epilepsy surgery until 2012 with disparities according to race/ethnicity and socioeconomic status. To extend these data and add other utilization information, the research team retrospectively investigated the nationwide trends in hospitalization and readmission during 2010–2015.

Results: 100,000–120,000 children were hospitalized due to epilepsy each year. Hospitalization rates and 30-day readmission rates were 214.6–262.3 per 1000 patient-years and 72.4–78.0 per 1000 discharges, respectively. 1400–2000 children with epilepsy received epilepsy surgery, but the proportions of medically refractory epilepsy were estimated as 0.8–1.2%. Disparities in patients receiving epilepsy surgery by race/ethnicity were observed during 2010–2012, but they were not after 2013. Children with higher household income levels had consistently higher proportions of receiving epilepsy surgery than those with lower levels. The hospitalization costs for epilepsy surgery were constant at $55,780–$60,813 after adjusting for healthcare cost inflation, whereas the cost for epilepsy were slightly elevated from $15,984 to $17,426.

Conclusions: This study provides novel insights into the current healthcare utilization for epilepsy and epilepsy surgery. Although the disparity of epilepsy surgery seemed to be mitigated, surgery in children with medically refractory epilepsy was still underutilized.

Healthcare Utilization and Associated Costs Following Initiation of Perampanel (Fycompa®) in Patients with Epilepsy

Abstract, published in Epilepsy & Behavior

Purpose: This study compared health service utilization and costs for patients with epilepsy before and after initiation of perampanel and compared with matched controls.

Results: Three hundred and forty-three patients treated with perampanel were identified. One hundred and eighty-three (53.4%) were male, with an average age of 39 and an average epilepsy duration of 21 years. Two hundred and eighty-seven (83.7%) were matched to controls. Inpatient admissions with a primary diagnosis of epilepsy and neurology specific outpatient appointments were significantly reduced following initiation with perampanel. Total costs attributable to epilepsy and overall secondary costs were also significantly reduced. There was no significant difference in primary care, outpatient, or general inpatient admissions. Compared with controls, there was a significant reduction in primary epilepsy admissions but a significant increase in outpatient appointments and accident and emergency contacts for patients treated with perampanel.

Conclusion: Treatment with perampanel is associated with reduced epilepsy-related inpatient admissions and accident and emergency contacts.

Study Shows that Birth Defects Attributed to Valproate (Depakote®) Do Not Involve a Genetic Component

Abstract, published in Epilepsia

Objective: Sodium valproate (VPA), the most effective antiepileptic drug for patients with genetic generalized epilepsy (GGE), that is, generalized epilepsy cause by a mutation,  dramatically increases the risk of a range of birth defects. Although the mechanisms underlying these birth defects are not known, they may involve genetic risk factors. This study aimed to develop an animal model of VPA-induced birth defects.

Results: The team used three different rat models of epilepsy, each of which had a different genetic mutation. VPA-exposed pups showed significant reductions in weight, length, and whole-body development compared with controls. Specifically, VPA treatment altered the distances between individual vertebrae in the backbone in all three rat models, more frequently than in controls.

Significance: Exposure of embryos to VPA during pregnancy results in similar developmental and morphological abnormalities in three different rat models, indicating that the genetic underpinnings of epilepsy do not contribute markedly to VPA-induced birth defects. These models may be used in future studies to investigate mechanisms involved in the pathogenesis of antiepileptic drug–induced birth defects.

The Self-Stigma of Patients with Epilepsy in Japan: A Qualitative Approach

Abstract, published in Epilepsy & Behavior

The mental health of patients with epilepsy represents a substantial public health concern in Japan. For instance, the Japanese term for epilepsy, “tenkan”, has the negative meaning of “mad” and “a violent temperament that is apt to be infatuated”. Although epilepsy is now understood as a disease caused by abnormal neuronal activity in the brain, discrimination and stigma against people with epilepsy remain deeply rooted in Japanese culture. Understandably, this stigma can have a serious impact on the psychology and behavior of individuals with epilepsy.

To our knowledge, no studies have clarified the formation process or examined the treatment of self-stigma in patients with epilepsy in Japan. Characterizing coping strategies and examining methods for reducing self-stigma will increase the understanding of the experiences of patients and facilitate effective psychiatric rehabilitation. Accordingly, the purpose of this study was to investigate the quality and degree of cognition regarding self-stigma and to examine coping strategies in patients with epilepsy living in the community.

The participants were psychiatric outpatients aged 20-65 years who had been diagnosed with epilepsy and visited this psychiatric outpatient clinic between October 1 and December 31, 2016. The researchers conducted semi-structured interviews with 20 patients who consented to participate.

The study revealed details of self-stigma in patients with epilepsy. Patients and their families are often aware of the presence of this self-stigma, but many do not know how to address it. In this study, researchers qualitatively examined self-stigma in patients with epilepsy according to patient narratives. Based on our findings, the team would like to examine intervention methods for reducing self-stigma in patients with epilepsy.