Death of a loved one: A potential risk factor for onset of functional seizures.

Functional seizures (FS) are a symptom of Functional Neurological Disorder (FND), the second most common neurological diagnosis made worldwide. Childhood trauma is associated with the development of FS, but more research is needed to truly understand the effects of trauma on FS onset. A sample of 256 responses by adults with FS to the Childhood Traumatic Events Scale were analyzed using a Cox proportional hazard model. When investigating each unique childhood traumatic exposure and its associated self-reported severity together, experiencing death of a loved one and experiencing violence were significantly associated with FS onset, suggesting reduced time from trauma exposure to first FS. Death of a loved one in childhood is often overlooked as an influential risk factor for future development of serious mental illnesses such as FS. In this study we show death of a loved one in childhood should be considered as an influential traumatic experience and recommend FND researchers examine its prevalence in patient histories and the potential effects on attachment-related processes and clinical treatment formulations. We recommend future studies incorporate loss of a loved one during childhood (before age 18) in both quantitative and qualitative assessments of persons with FND.

The Financial Burden of Functional Neurological Disorders.

PURPOSE OF REVIEW: Functional neurological disorder (FND) is a common and severely debilitating condition lacking clinical ownership, existing between neurology and psychiatry. This article reports the findings of recent research investigating the economic costs of FND diagnosis and management. We define what the costs are, why they exist, and suggest actionable steps to reduce them. RECENT FINDINGS: The financial burden of FND exists across the globe characterized by high healthcare utilization resulting in exorbitant direct and indirect costs for the patient, healthcare system, and society. Inadequate medical education and stigmatization of the disorder prolong the time to diagnosis, during which cyclical utilization of inpatient and emergency department services drive up costs. Despite being cost-effective, lack of accessible treatment compounds the issue, leaving patients without a reliable exit. Recent findings support an increased awareness and the need for a cultural shift to overcome the financial burden associated with this underserved population.

Functional Seizure Clinics: A Proposed Financially Viable Solution to the Neurologist Supply and Demand Mismatch.

Background and Objectives: Projections from recent studies suggest that by 2025, there will not be enough neurologists to meet the demand in 41 states. In this study, we investigate the financial impact and improved access to care for persons with epilepsy that is possible by implementing a multidisciplinary treatment clinic for persons with functional seizures (FS), previously referred to as psychogenic nonepileptic seizures, thus separating those patients out of an epilepsy clinic. Methods: This observational retrospective study used real-time data of 156 patients referred to an FS clinic integrated into a tertiary care epilepsy center to simulate its effect on epilepsy division access and finances. Access was measured using simulations of the number of return patient visits (RPVs) and new patient visits (NPVs) of patients with FS to a dedicated epilepsy clinic, based on survey results inquiring about the standard of care without the FS clinic. Finances were simulated using the resultant access multiplied by respective wRVU and reimbursement per CPT code. Results: Treatment of 156 patients with FS in a multidisciplinary FS clinic resulted in 343 newly opened NPVs, reimbursement of $102,000, and 1,200 wRVUs in our dedicated epilepsy clinic. There were 686 RPVs, $103,000 in reimbursement, and 1,320 wRVUs. Relative to the total number of NPVs with epilepsy clinic epileptologists, 343 NPVs represent a biennial 15.5% increase in available new patient visit slots. Discussion: Our findings describe the financial viability of integrating a treatment clinic for persons with FS by directing them to FS-specialized treatment and thereby increasing access for patients with probable epilepsy to the dedicated epilepsy clinic. This study provides a potential solution to the national mismatch in the supply and demand of neurologists and an initial framework to use for those who wish to establish or integrate FS services in their institution.

Impact of COVID vaccine and comorbidities in patients receiving casirivimab-imdevimab monoclonal antibody during SARS-CoV-2 B.1.617.2 (Delta) surge: A real-world study.

BACKGROUND: Several randomized trials and real-world studies depicted the role of monoclonal antibody infusion in reducing hospitalization, and halting progression from asymptomatic to symptomatic COVID pneumonia, viral titer, and death. No data exists to show outcomes of patients who received casirivimab-imdevimab infusion based on their vaccination status and underlying comorbidities. This study aims to provide outcomes of casirivimab-imdevimab treatment during the SARS-CoV-2 B1.617.2 (Delta) surge among fully vaccinated and not fully vaccinated individuals. METHODS: COVID-19-positive patients who received casirivimab-imdevimab infusion during the Delta surge were analyzed to compare their underlying comorbidities and the rate of 28-days all-cause and COVID-related ED visits or hospitalization, among fully vaccinated and not fully vaccinated individuals. RESULTS: A total of 3,586 patients received casirivimab-imdevimab infusion. COVID-related hospitalizations were directly related to the number of comorbidities (OR:1.745, 95 % CI:1.469-2.074). Vaccinated patients with ≥3 comorbidities had lower rates of 28-day COVID-related ED visits or hospitalization (p = 0.044) and those with ≥4 comorbidities had lower rates of 28-day All-cause ED visits or hospitalization (p = 0.029). Hypertension (OR:2.418, 95 %CI:1.341-4.360), immunocompromised state (OR:5.250, 95 %CI: 1.912-14.417), age ≥ 65 (OR:4.045, 95 %CI:2.224-7.358) increased the probability of hospitalization due to COVID and being fully vaccinated lowered the likelihood of hospitalization (OR: 0.472, 95 %CI: 0.239-0.933). Vaccinated patients had a lower length of COVID-related hospitalization (2 days vs 4.5 days, p < 0.001). CONCLUSION: COVID vaccination status and comorbidities are significant predictors of outcomes after casirivimab-imdevimab treatment. Despite having higher comorbidities, patients who were fully vaccinated at the time of casirivimab-imdevimab infusion had a lower length of hospitalization and reduced 28-day COVID ED visits or hospitalizations. Future trials should also compare outcomes based on the patient's vaccination status.

Suicide in Deep Brain Stimulation for Parkinson's Disease: A Retrospective Case-Control Study.

Deep brain stimulation (DBS), a treatment of Parkinson's disease (PD), has been associated with suicidality. We conducted a case-control study comparing suicide in four pairs of cohorts: PD patients with DBS or not, epilepsy patients with resection surgery or not, subjects with BMI≥30 with bariatric surgery or not, and patients with chronic kidney disease with transplantation or not. PD patients with DBS demonstrated a lower risk of suicide relative to PD patients without DBS. Findings from other elective surgeries indicate that patients receiving operative treatments do not possess predictable differences in suicide rates relative to their medically managed counterparts.

Exploring the influence of telehealth on patient engagement with a multidisciplinary Non-Epileptic Seizure (NES) Clinic during the COVID-19 pandemic.

The ILAE task force has identified a gap in treatment access for patients with nonepileptic seizures (NES) [1]. Access to multidisciplinary treatment clinics for adults with NES is limited with only 18 institutions delivering care across the United States [2]. Patient engagement has been low in the University of Colorado, NES Clinic treatment program despite our clinic's status as the only clinic of its kind in the mountain west. We analyzed patient factors of those who engaged in treatment before and after COVID-19 regulations were imposed and found a 23.6% increase in treatment engagement using telehealth. Those who engaged using telehealth were more likely to be of white race, of non-Hispanic ethnicity, publicly insured, employed, have a Charlson Comorbidity Index (CCI) of zero, a daily seizure rate of 0-1, did not have suicidal ideation or attempts, and live greater than 25 miles from the NES clinic. Delivering NES treatment via telehealth reduced the logistical and psychological barriers to initiating recovery and with a severe lack of accessible treatments for patients with NES, barrier reduction is necessary. This study describes patient factors that result in higher engagement with NES treatment using telehealth and emphasizes the importance of telehealth utilization to improve access to available treatment.

Assessing the hidden burden of psychiatric disease in patients with nonepileptic seizures.

Nonepileptic seizures are commonly associated with psychiatric comorbidities, and specifically PTSD. Despite increased prevalence of psychiatric disease noted on referral of patients to our dedicated clinic for nonepileptic seizures, we found even higher rates of comorbid psychiatric disease or significant symptomatology after our initial clinic intakes, whereby patients are formally evaluated by a behavioral health provider, in addition to an epileptologist. After intake, an additional 21% of patients were identified as having PTSD or significant trauma-related symptoms, an additional 7% of patients were identified with significant anxiety or panic-related symptoms, and an additional 11% of patients were identified with significant depressive symptoms. While highly effective treatment of nonepileptic seizures remains elusive, well-developed treatment paradigms with proven efficacy exist for depression, anxiety, and PTSD. Eliciting these psychiatric comorbidities and pursuing targeted treatments, especially for those patients that do not have easy access to providers with dedicated expertise in the management of nonepileptic seizures, may be a more easily scalable and implementable treatment modality for these patients.

Validation of a predictive calculator to distinguish between patients presenting with dissociative versus epileptic seizures.

Dissociative seizures (also known as psychogenic nonepileptic seizures) are a common functional neurological disorder that can be difficult to distinguish from epileptic seizures. Patients with dissociative seizures provide diagnostic challenges, leading to delays in care, inappropriate care, and significant healthcare utilization and associated costs. The dissociative seizure likelihood score (DSLS) was developed by Kerr and colleagues at UCLA to distinguish between patients with epileptic seizures and dissociative seizures based on clinical and medication history as well as features of seizure semiology. We validated this calculator at the University of Colorado, which is a Level 4 National Association of Epilepsy Center. The DSLS accurately predicted the diagnosis in 81% of patients, despite local variability in the factors associated with epileptic versus dissociative seizures between the two populations. The DSLS can be a useful tool to assist with history taking and may have important utility for clinical decision making with these difficult to distinguish patient populations.

Would people living with epilepsy benefit from palliative care?

Palliative care (PC) is an approach to the care of persons living with serious illness and their families that focuses on improving quality of life and reducing suffering by addressing complex medical symptoms, psychosocial needs, spiritual well-being, and advance care planning. While PC has traditionally been associated with hospice care for persons with cancer, there is now recognition that PC is relevant to many noncancer diagnoses, including neurologic illness, and at multiple points along the illness journey, not just end of life. Despite the recent growth of the field of neuropalliative care there has been scant attention paid to the relevance of PC principles in epilepsy or the potential for PC approaches to improve outcomes for persons living with epilepsy and their families. We believe this has been a significant oversight and that PC may provide a useful framework for addressing the many sources of suffering facing persons living with epilepsy, for engaging patients and families in challenging conversations, and to focus efforts to improve models of care for this population. In this manuscript we review areas of significant unmet needs where a PC approach may improve patient and family-centered outcomes, including complex symptom management, goals of care, advance care planning, psychosocial support for patient and family and spiritual well-being. When relevant we highlight areas where epilepsy patients may have unique PC needs compared to other patient populations and conclude with suggestions for future research, clinical, and educational efforts.

Sex Effects on Coping, Dissociation, and PTSD in Patients With Non-epileptic Seizures.

PURPOSE OF REVIEW: Sex differences in non-epileptic seizures (NES) are of interest, as the diagnosis is more frequent in women than men (3:1 ratio). This paper reviews clinical findings regarding sex differences in NES through selective literature review and compares coping measures between women and men in our NES clinic. RECENT FINDINGS: Some distinguishing clinical features of NES in women and men are reported in the literature. However, we found few sex differences in demographics and coping. In our population, avoidance and dissociation were strongly related to one another and significantly related to co-occurring PTSD diagnosis, which was seen in over 50% in both sexes. Our findings confirm a high prevalence of PTSD in patients with NES, suggesting that comorbid PTSD may override sex differences in accounting for use of avoidant and dissociative coping. These findings raise the possibility that NES may, at times, represent an extreme variant in dysfunctional coping in patients with PTSD.

Analysis of cutaneous allergic reactions in clinical trials of eslicarbazepine acetate.

OBJECTIVES: To evaluate cutaneous allergic reactions in clinical trials of adjunctive eslicarbazepine acetate (ESL) for focal seizures. MATERIALS AND METHODS: Data were analyzed from three phase III randomized, double-blind, placebo-controlled studies of adjunctive ESL in adults (placebo, n = 426; ESL, n = 1021) and two randomized, double-blind, placebo-controlled studies (and open-label extensions [OLEs]) of adjunctive ESL in children aged 4-17 years (placebo, n = 160; ESL, n = 202; OLE, n = 337). RESULTS: Adult studies: Rash (ESL 1.9%, placebo 0.9%) and pruritus (ESL 1.2%, placebo 0.9%) were the most frequent rash-related treatment-emergent adverse events (TEAEs). Most rash-related TEAEs were mild or moderate in severity. Incidence of rash increased with increasing ESL dose, but was not higher for patients who initiated treatment with higher ESL doses. Pediatric studies: Allergic dermatitis (ESL 3.0%, placebo 0) and rash (controlled studies: ESL 1.0%, placebo 1.3%; OLE periods: ESL ≤1.2%) were the most frequent rash-related TEAEs. There was one case of DRESS in the ESL group. Most rash-related TEAEs were mild or moderate in severity and judged as not related to treatment with ESL. CONCLUSIONS: Serious skin rashes were rare during adult and pediatric clinical trials of ESL. Although the incidence of rash with ESL was low, it is important for patients/caregivers to be made aware of the potential signs and symptoms associated with serious skin rashes.

The feasibility of a multidisciplinary group therapy clinic for the treatment of nonepileptic seizures.

A high percentage of patients presenting to epilepsy centers have a functional neurological disorder with apparent seizures, ultimately diagnosed as nonepileptic seizures (NES). Meta-analyses suggest that psychological treatment is required, but this treatment is not reliably available, resulting in reentry of these patients to neurology clinics and urgent care settings, reducing access for these services to patients with epilepsy and resulting in inadequate psychological care for patients with NES. A sustainable, group therapy-focused treatment clinic for patients with NES was developed as a combined effort between the departments of neurology and psychiatry at the University of Colorado Hospital, consisting of a full psychiatric evaluation, a five-week psychoeducational group, a 12-week psychodynamic therapy group, individual therapy, medication management, and family assessment. One hundred and six patients were treated in this clinic between July 2016 and October 2018. Patient retention after referral for treatment was 89/136 (65.4%), and group therapy adherence was 89/106 (84.0%). Healthcare utilization, used as a proxy to demonstrate worth, decreased during and after treatment. Analysis of the 106 treated patients elucidates other clinical characteristics of this population, including psychiatric comorbidities and specific medication classes at time of NES diagnosis. We conclude that this clinic model is feasible for recruiting, retaining, and engaging patients in appropriate treatment for their NES.

Serum sodium levels and related treatment-emergent adverse events during eslicarbazepine acetate use in adults with epilepsy.

OBJECTIVE: To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal- (partial-) onset seizures. METHODS: This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400-1200 mg once daily), two phase 3 trials of ESL monotherapy (1200-1600 mg once daily), and their open-label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+ ]), incidences of hyponatremia-related treatment-emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. RESULTS: The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open-label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+ ] measurement ≤125 mEq/L, <9% had a >10 mEq/L decrease in [Na+ ] from baseline, <6% had a hyponatremia-related TEAE, and <2% discontinued the controlled trials due to a hyponatremia-related TEAE. Hyponatremia appeared to be more frequent in the monotherapy (vs adjunctive therapy) trials; in the controlled trials of adjunctive ESL and ESL monotherapy, incidence generally increased with increasing ESL dose. The majority of patients with an investigator-reported TEAE of "hyponatremia" or "blood sodium decreased" did not have a corresponding laboratory [Na+ ] measurement ≤125 mEq/L. Some symptoms potentially related to hyponatremia (including nausea and vomiting) were more frequent in patients with a minimum postdose [Na+ ] measurement ≤125 mEq/L. SIGNIFICANCE: Reductions in serum sodium concentrations and hyponatremia-related TEAEs occurred in a small number of patients taking ESL. Suspected hyponatremia should be confirmed and monitored via [Na+ ] measurements.

Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting from carbamazepine.

OBJECTIVE: To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046). METHODS: Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, and tolerability. Endpoints were analyzed for subgroups of patients who received CBZ (or any VGSC inhibitor [VGSCi]) during baseline versus those who received other AEDs. RESULTS: Of 365 patients in the studies, 332 were evaluable for efficacy. The higher risk of study exit in the subgroups that received CBZ (or any VGSCi) during baseline, versus other AEDs, was not statistically significant (hazard ratios were 1.49 for +CBZ vs -CBZ [P = .10] and 1.27 for +VGSCi vs. -VGSCi [P = .33]). Reductions in seizure frequency and responder rates were lower in patients who converted from CBZ or other VGSCi compared with those who converted from other AEDs. There were no notable differences in overall tolerability between subgroups, but the incidence of some adverse events (eg, dizziness, somnolence, nausea) differed between subgroups and/or between treatment periods. SIGNIFICANCE: Baseline use of CBZ or other major putative VGSC inhibitors did not appear to significantly increase the risk of study exit due to worsening seizure control, or to increase the frequency of side effects when converting to ESL monotherapy. However, bigger improvements in efficacy may be possible in patients converting to ESL monotherapy from an AED regimen that does not include a VGSC inhibitor.

Disrobing associated with epileptic seizures and forensic implications.

Little is known about the clinical aspects and medico-legal consequences of disrobing in the context of epileptic seizures. Seizure-related disrobing may occur either as an ictal automatism or during the postictal period. Some patients may experience a seizure while already in the unclothed state, engage in ictal wandering, and thereby appear in public in the nude. Two cases involving disrobing associated with seizures captured via video-monitored electroencephalography are offered. An additional case reveals the legal consequences endured by one patient who experienced a nocturnal seizure and began wandering in an unclothed state. Collectively, these cases illustrate the medical reality of seizure-related disrobing and the related adverse effects on patients' quality of life. Disrobing associated with epileptic seizures carries the potential for serious legal consequences if not properly identified as an ictal phenomenon.

New antiepileptic drugs: lacosamide, rufinamide, and vigabatrin.

OPINION STATEMENT: The treatment of epilepsy is complicated by the multiple seizure types and epilepsy syndromes needing therapy. In addition, seizures in up to 30% of epilepsy patients are resistant to available medications. The three newest antiepileptic medications (lacosamide, rufinamide, and vigabatrin) all putatively have novel mechanisms of action, which might increase the chance of treatment success in patients failing previous antiepilepsy drug trials and the chance of successful synergy with currently available medications. In our experience, all three drugs generally are well tolerated, although the risk for serious long-term complications with vigabatrin presents special challenges and precautions. Lacosamide is approved for the adjunctive therapy of complex partial seizures in adults and also is available in an intravenous formulation. Rufinamide is a new treatment option for seizures associated with Lennox-Gastaut syndrome, and although it is not FDA approved for partial seizures, it has shown efficacy for that indication as well. Vigabatrin has been approved in adults for drug-resistant complex partial seizures and in infants as a treatment option for infantile spasms.

End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: a case series of six patients.

OBJECTIVE: Specific psychological withdrawal symptoms following the cessation of treatment with many drugs that affect the central nervous system, including anxiolytics and antidepressants, have been well documented. Studies have investigated withdrawal symptoms associated with some of the older antiepileptic drugs, but the potential for withdrawal symptoms associated with newer antiepileptic drugs, including lamotrigine, has not yet been investigated. METHODS: Using a retrospective chart review, we identified six patients with epilepsy who reported transient emergent psychological symptoms during stable, chronic lamotrigine monotherapy. RESULTS: These symptoms included anxiety, emotional lability, and irritability. In each case, the symptoms resulted in marked subjective distress and reliably occurred in the 1-2h before the patients were due to take their next dose of medication. CONCLUSIONS: Lamotrigine withdrawal symptoms exist and can occur as an end-of-dose phenomenon, even in patients on stable medication doses. End-of-dose withdrawal from lamotrigine is a clinically significant adverse effect that can hamper successful treatment with this medication.