Predictors of objective treatment adherence in adolescents with epilepsy: The important role of motivation.

OBJECTIVE: Adolescents with epilepsy are at heightened risk for suboptimal anti-seizure medication (ASM) adherence; however, there is a paucity of adherence interventions for this age group. The current study aimed to identify a comprehensive and novel set of predictors of objective, electronically-monitored ASM adherence in adolescents with epilepsy. METHODS: Participants included 104 adolescents (13-17 years old; M = 15.36 ± 1.40), diagnosed with epilepsy and their caregivers. Cross-sectional data were collected from adolescents, caregivers, healthcare providers, and medical chart reviews, including demographics (i.e., age, race/ethnicity, sex, insurance status), the COVID-19 pandemic (i.e., participation before versus during), seizure characteristics (i.e., presence and severity), ASM side effects (Pediatric Epilepsy Side Effects Questionnaire), adherence motivation (1-item 6-point Likert scale item), and adherence barriers (Pediatric Epilepsy Medication Self-Management Questionnaire). Electronically-monitored adherence data was collected via the AdhereTechTM pill bottle or the Vaica SimpleMedTM pillbox over 30 days. RESULTS: Adolescents demonstrated suboptimal adherence at 78 ± 31.6%, despite high ASM adherence motivation (M = 4.43 ± .94) and minimal adherence barriers (M = 35.64 ± 3.78). Hierarchical multiple regression, which included non-modifiable sociodemographic and medical variables (Block 1) and behaviorally modifiable psychosocial variables (Block 2) was significant, F(12,87) = 3.69, p < .001. Specifically, having private insurance (versus Medicaid or public insurance; t = -2.11, p = .038) and higher adherence motivation (t = 2.91, p = .005) predicted higher objective ASM adherence. CONCLUSION: Routine assessment of adherence predictors is vital for the promotion of adherence among adolescents with epilepsy. Adolescent adherence motivation may be an important element of multi-component interventions focused on improving ASM adherence in adolescents with epilepsy.

Investigation of the low glutamate diet as an adjunct treatment for pediatric epilepsy: A pilot randomized controlled trial.

INTRODUCTION: Current dietary therapies for epilepsy have side effects and are low in nutrients, which would make an alternative dietary treatment, which addresses these issues, advantageous. One potential option is the low glutamate diet (LGD). Glutamate is implicated in seizure activity. Blood brain barrier permeability in epilepsy could enable dietary glutamate to reach the brain and contribute to ictogenesis. OBJECTIVE: to assess the LGD as an adjunct treatment for pediatric epilepsy. METHODS: This study was a nonblinded, parallel, randomized clinical trial. The study was conducted virtually due to COVID-19 and registered on clinicaltrials.gov (NCT04545346). Participants were eligible if they were between the ages of 2 and 21 with ≥4 seizures per month. Baseline seizures were assessed for 1-month, then participants were allocated via block randomization to the intervention month (N=18), or a wait-listed control month followed by the intervention month (N=15). Outcome measures included seizure frequency, caregiver global impression of change (CGIC), non-seizure improvements, nutrient intake, and adverse events. RESULTS: Nutrient intake significantly increased during the intervention. No significant differences in seizure frequency were observed between intervention and control groups. However, efficacy was assessed at 1-month compared to the standard 3-months in diet research. Additionally, 21% of participants were observed to be clinical responders to the diet. Overall health (CGIC) significantly improved in 31%, 63% experienced ≥1 non-seizure improvements, and 53% experienced adverse events. Clinical response likelihood decreased with increasing age (0.71 [0.50-0.99], p=0.04), as did the likelihood of overall health improvement (0.71 [0.54-0.92], p=0.01). DISCUSSION: This study provides preliminary support for the LGD as an adjunct treatment before epilepsy becomes drug resistant, which is in contrast to the role of current dietary therapies in drug resistant epilepsy.

[Possibilities of optimizing therapy in COVID-19 survivors with focal epilepsy]. / Vozmozhnosti optimizatsii terapii u patsientov s fokal'noi epilepsiei, perenesshikh COVID-19.

OBJECTIVE: To study the effect of phenosanoic acid therapy on the frequency of seizures, asthenia and quality of life of adult patients with focal epilepsy who had a new coronavirus infection caused by SARS-CoV-2. MATERIAL AND METHODS: The data of 20 patients with focal epilepsy who suffered COVID-19 and received therapy with phenosanic acid (Dibufelon) were studied. The frequency of epileptic seizures, the severity of asthenia and the quality of life were evaluated according to clinical scales. RESULTS: Significant decrease in the frequency of bilateral tonic-clonic seizures and focal seizures with loss of consciousness was recorded. There was a significant improvement in the quality of life. There was no significant dynamics of asthenia against the background of taking the drug phenosanic acid in patients. CONCLUSION: The preparation of phenosanic acid can be an effective means of add-on therapy in patients with epilepsy who have undergone COVID-19.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.

BACKGROUND: Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal. RESULTS: The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P  < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio = 7.384, 95% confidence interval = 1.732-31.488, P  = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P  = 0.143). CONCLUSIONS: PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

Satisfaction among persons with epilepsy towards physical consultation versus online video consultation for follow-up.

PURPOSE: Telemedicine gained popularity in the setting of the COVID-19 pandemic. We aimed to study the satisfaction levels of persons with epilepsy (PWE) with online video consultation (OVC) and physical consultation (PC). METHODS: This was a cross-sectional questionnaire-based study conducted in a tertiary referral care center for epilepsy in India. All PWE who had availed of both OVC and PC were included. Those who did not give consent to a questionnaire were excluded. A questionnaire was given to assess patients' satisfaction regarding OVC and PC. Scores for each question for both OVC and PC were compared. RESULTS: One hundred and forty-one patients who had PC earlier and later availed of OVC from December 2020 to July 2021 formed the cohort. Seventy one patients who responded to the questionnaire were included. 49% and 51% of the patients belonged to urban and rural regions respectively. 8.5% of the patients were off anti-seizure medications (ASM), while 5.6% and 85.9% were on single and multiple ASMs respectively. There were no differences between PC and OVC regarding ease of getting the appointment, privacy during a consultation, patients' perceived chances of missing consultations, and overall comfort and experience on either type of consultation. Physical consultation scored more than OVC in patients' satisfaction with the time doctor spent with them, an opportunity to communicate their queries well, clarifications received from the doctor, and the likelihood of patients recommending the particular type of consultation to others(p < 0.05). CONCLUSIONS: Online video consultation can be a satisfactory alternative to PC and can improve patient satisfaction if some of the issues in OVC are addressed properly.

Safety and Tolerability of COVID-19 Vaccine in Children With Epilepsy: A Prospective, Multicenter Study.

BACKGROUND: We designed this study to investigate the effects of the coronavirus disease 2019 (COVID-19) vaccine on epileptic seizures, as well as its adverse effects, in children with epilepsy (<18 years). METHODS: This anonymous questionnaire study involved a multicenter prospective survey of outpatients and inpatients with epilepsy (＜18 years) registered in epilepsy clinics in eight hospitals in six cities of Shandong Province. RESULTS: A total of 224 children with epilepsy were included in the study. Fifty of them experienced general adverse events after vaccination. The most common local adverse events were pain or tenderness at the injection site. The most common systemic adverse effects were muscle soreness and headache. No severe adverse events were reported. There were no significant differences in the number of antiseizure medications (P = 0.459), gender (P = 0.336), etiology (P = 0.449), age (P = 0.499), duration of disease (P = 0.546), or seizure type (P = 0.475) between the patients with and without general adverse events. We found that the risk of seizure after vaccination was decreased in children who were seizure free for more than six months before vaccination. There was no significant difference in the number of seizures during the first month before vaccination, the first month after the first dose, and the first month after the second dose (P = 0.091). CONCLUSION: The benefits of vaccination against COVID-19 outweighed the risks of seizures/relapses and severe adverse events after vaccination for children with epilepsy.

Pilot randomized controlled clinical trial of an adherence social norms intervention for adolescents with epilepsy.

OBJECTIVE: Non-adherence to anti-seizure medications (ASMs) is common for adolescents with epilepsy, with potentially devastating consequences. Existing adherence interventions in epilepsy do not meet the unique challenges faced by adolescents. Leveraging social norms capitalizes on the increased importance of peer influence while simultaneously targeting the low motivation levels of many adolescents. The current study examined the feasibility, acceptability, and satisfaction of a social norms adherence intervention in adolescents with epilepsy. METHODS: A pilot RCT of a mHealth social norms intervention was conducted with adolescents with epilepsy who demonstrated non-adherence (≤95% adherence) during baseline. Adolescents were randomized to either (1) mHealth social norms (reminders, individualized and social norms adherence feedback) or (2) control (reminders and individualized adherence feedback). Primary outcomes included feasibility, acceptability, and satisfaction. Exploratory outcomes included electronically monitored adherence, seizure severity, and health-related quality of life (HRQOL). RESULTS: One hundred four adolescents were recruited (53% female; Mage = 15.4 ± 1.4 years; 81% White: Non-Hispanic; 5% Black, 10% Bi/Multiracial; 2% White: Hispanic; 1% Other: Hispanic; 1% Bi/Multiracial-Hispanic). Forty-five percent screen-failed due to high adherence, 16% withdrew, and 38% were randomized to treatment (n = 19) or control (n = 21). Recruitment (75%), retention (78%), and treatment satisfaction were moderately high. Engagement with the intervention was moderate, with 64% of participants engaging with intervention notifications. Exploratory analyses revealed that after controlling for COVID-19 impact, the social norms intervention group maintained higher adherence over time compared to the control group. Small to moderate effect sizes were noted for seizure severity and HRQOL between groups. CONCLUSION: This pilot intervention appeared feasible and acceptable. Increases in adherence in the treatment versus control group were modest, but a future larger more adequately powered study is needed to detect effects. Notably, it appeared the COVID pandemic influenced adherence behaviors during our trial.

Adaptive behaviour in children exposed to topiramate in the womb: An observational cohort study.

OBJECTIVE: Many women with epilepsy need to continue anti-seizure medications (ASMs) throughout pregnancy. The current study investigated adaptive behaviour outcomes in children exposed to topiramate in the womb. METHOD: An observational, cross-sectional study was designed, recruiting mother-child-pairs from the UK Epilepsy and Pregnancy Register (UKEPR). Health, developmental histories and Vineland Adaptive Behaviour Scale-Third Edition (VABS-III) assessments were administered via telephone by a blinded researcher, supplemented with prospectively collected pregnancy and medication information. Topiramate monotherapy exposed children were compared to VABS-III normative data as recruitment was disrupted by the COVID-19 pandemic. RESULTS: Thirty-four women with epilepsy from 135 (25%) initially agreed to participate in the study, of whom 26 women completed telephone interviews about their children (n = 28). Children ranged from 2.5 to 17 years of age at the time of assessment. Six topiramate-exposed children were born small for gestational age, and there were significant associations between birthweight, dose and VABS-III scores. Significantly lower scores were observed in topiramate-exposed children (n = 21) with a significant dose-response relationship established after adjustment for parental educational level. Daily mean dosage was 280.21 mg, with high dosages of topiramate associated with a 12-point reduction in VABS-III scores. Additionally, four topiramate-exposed children (19.05%) had diagnoses of Autism Spectrum Disorder, which was significantly higher than UK prevalence rates (1.1%). CONCLUSIONS: The findings of poorer adaptive behaviour, higher incidence of ASD and associations with birth weight are of concern and require further validation and replication using larger prospectively-recruited samples and comparator cohorts. Implications for research and clinical practice are discussed.

A cluster-randomized trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country.

OBJECTIVE: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country. METHODS: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker. We compared the intervention group to a routine clinic-based care group in a cluster-randomized trial lasting 24 months. The primary outcome was antiseizure medication adherence, appraised from monthly pill counts. Seizure outcomes were assessed by monthly seizure aggregates and time to first seizure and impact by the Personal Impact of Epilepsy scale. RESULTS: Enrolment began on September 25, 2017 and was complete by July 24, 2018. Twenty-four clusters, each comprising ten people with epilepsy, were randomized to either home- or clinic-care. Home-care recipients were more likely to have used up their monthly-dispensed epilepsy medicine stock (regression coefficient: 0.585; 95% confidence intervals, 0.289-0.881; P = 0.001) and had fewer seizures (regression coefficient: -2.060; 95%CI, -3.335 to -0.785; P = 0.002). More people from clinic-care (n = 44; 37%) than home-care (n = 23; 19%) exited the trial (P = 0.003). The time to first seizure, adverse effects and the personal impact of epilepsy were similar in the two arms. SIGNIFICANCE: Home care for epilepsy compared to clinic care in resource-limited communities improves medication adherence and seizure outcomes and reduces the secondary epilepsy treatment gap.

Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: A multicenter, prospective study.

Objectives: Several COVID-19 vaccines list "uncontrolled epilepsy" as a contraindication for vaccination. This consequently restricts vaccination against COVID-19 in patients with epilepsy (PWE). However, there is no strong evidence that COVID-19 vaccination can exacerbate conditions in PWE. This study aims to determine the impact of COVID-19 vaccination on PWE. Methods: PWE were prospectively recruited from 25 epilepsy centers. We recorded the seizure frequency at three time periods (one month before the first vaccination and one month after the first and second vaccinations). A generalized linear mixed-effects model (GLMM) was used for analysis, and the adjusted incidence rate ratio (AIRR) with 95% CI was presented and interpreted accordingly. Results: Overall, 859 PWE were included in the analysis. Thirty-one (3.6%) and 35 (4.1%) patients were found to have increased seizure frequency after the two doses, respectively. Age had an interaction with time. The seizure frequency in adults decreased by 81% after the first dose (AIRR=0.19, 95% CI:0.11-0.34) and 85% after the second dose (AIRR=0.16, 95% CI:0.08-0.30). In juveniles (<18), it was 25% (AIRR=0.75, 95% CI:0.42-1.34) and 51% (AIRR=0.49, 95% CI:0.25-0.95), respectively. Interval between the last seizure before vaccination and the first dose of vaccination (ILSFV) had a significant effect on seizure frequency after vaccination. Seizure frequency in PWE with hereditary epilepsy after vaccination was significantly higher than that in PWE with unknown etiology (AIRR=1.95, 95% CI: 1.17-3.24). Two hundred and seventeen (25.3%) patients experienced non-epileptic but not serious adverse reactions. Discussion: The inactivated COVID-19 vaccine does not significantly increase seizure frequency in PWE. The limitations of vaccination in PWE should focus on aspects other than control status. Juvenile PWE should be of greater concern after vaccination because they have lower safety. Finally, PWE should not reduce the dosage of anti-seizure medication during the peri-vaccination period.

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies.

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

Efficacy of Valproic Acid Against Coronavirus Disease 2019 Infection or Severity: A Pilot Study.

OBJECTIVES: The purpose of the current study was to investigate whether taking valproic acid (VPA) was protective against coronavirus disease 2019 (COVID-19) infection or severity in patients with epilepsy. METHODS: This was a questionnaire study of 150 people who were taking VPA in monotherapy or polytherapy (since the start of the pandemic or longer) and also 150 people who were not taking VPA (since the start of the pandemic), registered in our epilepsy database. The data compared rates of the seropositivity and severity of infection of COVID-19 between the 2 groups. The latter was assessed, by proxy, vis-à-vis rates of hospital admission and intensive care unit admission. RESULTS: Two hundred forty-one patients were studied, including 130 (53.9%) male and 111 (46.1%) female patients. The mean age of the patients was 30.7 ± 11.4 years. The infection rate and severity of COVID-19 did not significantly differ among patients who were taking VPA and those who were not taking VPA (P = 0.587) and (P = 0.648), respectively. CONCLUSIONS: In this pilot study, no support was found for the hypothesis of a protective effect of VPA against the infectivity rate of COVID-19. Neither was there any indication of a disease-modulating effect of VPA in people with active COVID-19 infection. Larger, randomized controlled trials would be warranted to substantiate our conclusion.

Challenges for low middle-income people with epilepsy during the COVID-19 pandemic: Lessons learnt, call for action.

OBJECTIVE: The COVID-19 pandemic impacted the care of people with epilepsy (PWE). Several online surveys were conducted but there is limited data regarding the impact on low-income PWE from lower-middle income countries (LMICs) who have no access or ability to answer online surveys. The purpose of this interview was to understand the challenges faced by low-income PWE during the lockdown phase of the pandemic. METHOD: PWE visiting the epilepsy specialty outpatient department of a tertiary referral government hospital to avail of subsidized services were interviewed. In the interview, they discussed challenges in obtaining medical care, the impact on wellbeing, employment, and vaccination status during the lockdown phase of the pandemic. RESULTS: Out of the 214 PWE interviewed, 20.6% had increased seizure frequency, 28.9% did not have access to medication mainly due to travel restrictions, 30.5% reported lack of availability of medication and 50% were not able to afford the medication mainly due to loss of income. 51% were unable to have follow-up consultations. 36% reported worsening of mood and some reported impact on other aspects of wellbeing. The impact on wellbeing was significantly associated with an increase in seizure frequency (P < .05). The study revealed hesitation related to vaccines in the majority and expectations of financial support by the government and assistance for procuring medication. There was a lack of awareness about telemedicine services and the same was not adequately offered by government hospitals. SIGNIFICANCE: The study underscores the need to learn lessons from the challenging experiences of low-income PWE and create an action plan for the future to address the issues of lack of affordability of medical care and access to telemedicine. It is critical that the care of the marginalized, underrepresented PWE from lower-middle income countries is not neglected during a pandemic.

Seizure control during the COVID-19 pandemic: Correlating Responsive Neurostimulation System data with patient reports.

OBJECTIVE: To understand the impact of the Coronavirus Disease-2019 (COVID-19) pandemic on seizure frequency in persons with epilepsy with a Responsive Neurostimulation (RNS) system implanted. METHODS: Weekly long episode counts (LEC) were used as a proxy for seizures for six months pre-COVID-19 and during the COVID-19 period. Telephone surveys and chart reviews were conducted to assess patient mental health during the pandemic. The change in LEC between the two time periods was correlated to reported stressors. RESULTS: Twenty patients were included. Comparing the pre-COVID-19 period to the COVID-19 period, we found that only 5 (25%) patients had increased seizures, which was positively correlated with change in anti-seizure medications (ASM, p = 0.03) and bitemporal seizures (p = 0.03). Increased seizures were not correlated to anxiety (p = 1.00), depression (p = 0.58), and sleep disturbances (p = 1.00). The correlation between RNS-detected and patient-reported seizures was poor (p = 0.32). CONCLUSIONS: Most of our patients did not have an increase in seizures following the COVID-19 pandemic. Changes in ASM and bitemporal seizures were positively correlated to increased LEC. There was no correlation between pandemic-related stress and seizures in those found to have increased seizures. SIGNIFICANCE: This is the first study correlating RNS-derived objective LECs with patient self-reports and potential seizure risk factors during the COVID-19 pandemic.

Seizure Control in Patients with Epilepsy during the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Objective To investigate seizure control in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic. Method A systematic review and meta-analysis was conducted, and the MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies that reported seizure control in patients with epilepsy during the COVID-19 pandemic were included. Pooled proportions with 95% confidence intervals (CIs) of patients with epilepsy who experienced seizure worsening during the COVID-19 pandemic were assessed using a random-effects model. The quality of the assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Subgroup analyses were performed, excluding studies with reports of seizures worsening from caregivers. Results A total of 24 studies with 6,492 patients/caregivers were included in the meta-analysis. The pooled proportion of seizure worsening was 18.5% (95% CI: 13.9-23.6; I2=96%; p<0.01). The pooled proportion of seizure worsening in the subgroup analysis was 18.9% (95% CI: 13.5-25.0; I2=96%; p<0.01). Conclusion Although the heterogeneity was high, our results showed a relatively high incidence of seizure worsening during the COVID-19 pandemic. During the COVID-19 pandemic, physicians should be aware of the likelihood of worsening seizures in patients with epilepsy.

Clinically Relevant Interactions Between Ritonavir-Boosted Nirmatrelvir and Concomitant Antiseizure Medications: Implications for the Management of COVID-19 in Patients with Epilepsy.

Ritonavir-boosted nirmatrelvir (RBN) has been authorized recently in several countries as an orally active anti-SARS-CoV-2 treatment for patients at high risk of progressing to severe COVID-19 disease. Nirmatrelvir is the active component against the SARS-CoV-2 virus, whereas ritonavir, a potent CYP3A inhibitor, is intended to boost the activity of nirmatrelvir by increasing its concentration in plasma to ensure persistence of antiviral concentrations during the 12-hour dosing interval. RBN is involved in many clinically important drug-drug interactions both as perpetrator and as victim, which can complicate its use in patients treated with antiseizure medications (ASMs). Interactions between RBN and ASMs are bidirectional. As perpetrator, RBN may increase the plasma concentration of a number of ASMs that are CYP3A4 substrates, possibly leading to toxicity. As victims, both nirmatrelvir and ritonavir are subject to metabolic induction by concomitant treatment with potent enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital and primidone). According to US and European prescribing information, treatment with these ASMs is a contraindication to the use of RBN. Although remdesivir is a valuable alternative to RBN, it may not be readily accessible in some settings due to cost and/or need for intravenous administration. If remdesivir is not an appropriate option, either bebtelovimab or molnupiravir may be considered. However, evidence about the clinical efficacy of bebtelovimab is still limited, and molnupiravir, the only orally active alternative, is deemed to have appreciably lower efficacy than RBN and remdesivir.

A cross-sectional study of COVID-19 vaccination patterns among patients with epilepsy in Hong Kong.

OBJECTIVE: As Hong Kong faced the 5th wave of the COVID-19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination gap among patients with epilepsy. METHODS: A cross-sectional, pragmatic study of COVID-19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI). RESULTS: A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up-to-date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects. SIGNIFICANCE: A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.

Epilepsy management during difficult times

Major disruption in the delivery of healthcare services can occur in exceptional situations such as natural disasters, conflicts, periods of severe economic hardship, and epidemics. These disruptions typically affect to the greatest extent the most vulnerable segments of the population, including people with epilepsy. Inability to access healthcare services can lead to failure to undergo necessary diagnostic investigations, or to receive needed therapeutic interventions, including epilepsy surgery. Stress and other factors associated with the nature or the cause of the disruption can adversely affect seizure control status, or precipitate the occurrence of psychiatric disorders and other comorbid conditions. Failure to access antiseizure medications is a common occurrence in these situations and can result in loss of seizure control, withdrawal seizures, and status epilepticus. In this article, we provide examples of recent disruptions in healthcare and their implications for people with epilepsy. We discuss the consequences of natural disasters, conflicts, economic sanctions, and focus in greater detail on lessons learnt during the COVID-19 pandemic. We also discuss possible mitigation procedures, focusing in particular on the application of telemedicine to epilepsy care. Finally, we underline the need for governments, healthcare authorities, and international organizations to improve their preparedness to deal with exceptional situations that may arise in the future.

Prescription cannabidiol for seizure disorder management: Initial drug-drug interaction management by specialty pharmacists.

PURPOSE: To describe the presence, type, and management of drug-drug interactions (DDIs) at prescription cannabidiol (CBD) therapy initiation. METHODS: We conducted a single-center, retrospective study of patients prescribed CBD from a medical center's neurology clinic for seizure management from January 2019 through April 2020. Patients were excluded if they were enrolled in a CBD clinical trial or the insurance approval or medication fulfillment process was not completed by the center's specialty pharmacy. The primary outcomes were the numbers, types, and management of DDIs identified at the time of CBD prescribing. RESULTS: Of the 136 patients included, 109 (80%) had a DDI identified at baseline. Of the 260 DDIs, 71% (n = 184) were pharmacodynamic and 29% (n = 76) were pharmacokinetic in nature. Management of the 260 DDIs detected included counseling only (89% [n = 232 interactions]), discontinuation of the interacting agent [9% (n = 22 interactions]), and dosage change for the interacting agent [2% (n = 6 interactions]). Clobazam was the most commonly identified interacting medication (n = 63, 24%), while valproic acid accounted for 10% (n = 26) of the DDIs. The population was predominantly white (n = 115, 85%), 18 years of age or younger (n = 92, 68%), and had an indication for prescription CBD treatment of Lennox-Gastaut syndrome (n = 117, 86%). CONCLUSION: This study provides new information on the role that integrated specialty pharmacists can play in identifying and managing initial DDIs in patients starting prescription CBD.