Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Mesial temporal resection following long-term ambulatory intracranial EEG monitoring with a direct brain-responsive neurostimulation system.

OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

Factors associated with medication adherence in patients with epilepsy and recommendations for improvement.

Although it is one of the most common neurological disorders, epilepsy continues to be a highly stigmatized and disabling chronic condition. Healthy People 2020 aims for improvement in the health-related quality of life and well-being of Americans, including these medically vulnerable patients. Efforts to research and improve medication adherence in this population and others with chronic conditions are an important step towards this end. The purpose of this study was to investigate factors associated with adherence and to provide recommendations for improvement. A cross-sectional survey research design was used in a convenience sample of patients receiving treatment at a tertiary epilepsy center. Adherence was measured by self-reported missed/skipped medication doses and seizure frequencies and by the presence of intractable seizures as indicated in patients' medical charts. Analysis was conducted with SPSS 21.0 on the data collected from the returned mailed surveys. Among the sample of 180 patients, most had some education beyond high school, household incomes of varying amounts, and health insurance coverage. Most of the participants were unemployed. Clinical records showed that 46% had intractable seizures. About 66% missed taking their medication on a monthly basis, with "forgetfulness" being the primary reason. Adherence (seizure frequency) was associated with being employed (P=.028). Adherence (complying with medication treatment plan) was also associated with "medication reminders" (P=.002) and educational attainment (P=.008). The findings indicate a continued need to explore the complex issue of adherence. The findings also highlight the need for health education and other public health and medical professionals to design effective strategies to connect patients with employment opportunities and other resources. Efforts are also needed to help provide information and build skills among patients with epilepsy that would lead to improved medication adherence and management.

Patient perception of generic antiepileptic drugs in the Midwestern United States.

OBJECTIVE: Concerns have been raised about the safety of switching from a branded antiepileptic drug (AED) to a generic AED. The goal of the study described here was to understand patients' experiences with generic AEDs in the Midwestern United States. METHODS: A one-page, six-item survey was mailed to 356 patients to determine patients' awareness of the existence and their usage of generic AEDs. RESULTS: Twenty-eight percent (27.8%) of respondents (N=179) reported breakthrough seizures they believed were a direct result of the switch from a brand to a generic AED, and 33.7% reported side effects due to the switch. Thirty-one percent (31.2%) returned to a brand-name AED as a result. Sixty-nine percent (68.8%) reported being unaware that some pharmacies switch to generic AEDs without a patient's or physician's consent, and 78.7% expressed concern over this. CONCLUSION: A significant percentage of patients reported that generic AEDs were responsible for breakthrough seizures and increased side effects. A significant percentage of patients also reported switching back to a brand-name AED and expressed concern over pharmacies switching to generic AEDs without a patient's or physician's consent.

Exercise and epilepsy: a survey of Midwest epilepsy patients.

Obesity and lack of physical activity are an increasing problem. In addition to common barriers to physical activity, people with epilepsy also face fear of exercise-induced seizures, medication side effects, and, often, confusing advice regarding the safety of exercise. To explore barriers faced by people with epilepsy, we mailed a survey to 412 adult patients with epilepsy from an epilepsy center in Kansas. Survey items assessed patients' exercise habits, attitudes regarding exercise, and barriers to exercise. Forty-seven percent completed the survey. Most respondents reported that they did exercise, though most did so 3 or fewer days per week and at light intensity. Respondents who reported seizures as a barrier to exercise did not exercise with less frequency or intensity than those who did not report seizures as a barrier, but these respondents reported greater fear of seizures. Patient-specific education about the benefits of exercise needs to be initiated by physicians.

Assessment of quality of life among the elderly with epilepsy.

As the elderly represent the most rapidly growing population in the United States, it is critical that physicians are capable of managing their chronic illnesses, including epilepsy. Optimal treatment of epilepsy integrates an understanding of health-related quality of life (HRQOL), yet limited information is available to guide HRQOL issues among the elderly. This study found that seniors with epilepsy do not have poorer HRQOL compared with general epilepsy populations. However, when compared with general populations without epilepsy, seniors with epilepsy report a significantly lower HRQOL across all domains. Multiple factors may uniquely affect HRQOL among elderly populations with epilepsy: aging, comorbid conditions, and epilepsy variables. However, to our knowledge, no one instrument addresses all of these aspects. The development of HRQOL instruments specifically for an elderly population with epilepsy may be useful and needed.

Epilepsy patients' perceptions about stigma, education, and awareness: preliminary responses based on a community participatory approach.

As individuals directly impacted by their experience of epilepsy and others' responses to it, epilepsy patients' opinions about education and awareness issues are needed. A community-based participatory approach was used to develop a survey of public and patient attitudes and perceptions about epilepsy, which was administered to persons with epilepsy. The majority of the 165 respondents (34% response rate) indicated they perceive misperceptions and stigma related to epilepsy in the general public, which they thought could be ameliorated through educational interventions. Respondents indicated potential avenues of educational intervention for the general public as well as for those with epilepsy, with recommended content and intervention type depending on target audience. The community-based participatory research process and the patients' perceptions gathered through the resulting survey indicate potential activities for overcoming stigma and increasing education and awareness related to epilepsy.

Pattern and frequency of use of complementary and alternative medicine among patients with epilepsy in the midwestern United States.

Complementary and alternative medicine (CAM) is recognized to be commonly used by patients, yet there have been few studies regarding the scope of CAM use by patients with epilepsy. This study assessed usage and perceptions of CAM by patients with epilepsy in the midwest of the United States. A 25-item survey was administered to adult patients with epilepsy, and data were collected from 228 patients. The survey collected demographics, specific CAM usage, adverse effects of CAM therapy, and perceptions of the effectiveness of CAM. Thirty-nine percent reported using CAM; 25% reported using CAM specifically for their epilepsy. Prayer/spirituality was the most commonly used form of CAM (46%), followed by "mega" vitamins (25%), chiropractic care (24%), and stress management (16%). CAM use is common among midwestern patients with epilepsy, although the pattern of use may be slightly different than in other regions of the United States and elsewhere.