Digital and technological opportunities in epilepsy: Toward a digital ecosystem for enhanced epilepsy management.

This commentary details the implications of a growing body of literature supporting several categories of supportive digital tools for the self-management of epilepsy. Although many prior review articles have focused on specific forms of digital epilepsy solutions, we propose the concept of an integrated self-management digital ecosystem. This would include categories of tools including self-management education programs, electronic diaries for self-monitoring, and automated wearables for seizure detection. Within these categories, individual interventions have been studied and made available to patients for years, but the evolution of a digital ecosystem promises the potential to integrate these tools in a manner that can meaningfully benefit patients' health. This commentary presents a discussion of the possible concerns that are preventing more widespread adoption of these digital health resources. Barriers are identified at multiple positions of the healthcare system, including the individual, the organizational, the community, and the policy levels.

Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia.

SEE SCABER AND TALBOT DOI101093/AWW264 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus. At autopsy, widespread RNA foci and dipeptide repeat protein inclusions were observed, but TDP-43 pathology was nearly absent, even in degenerating brain regions. Case 2 was a 74-year-old female with atypical frontotemporal dementia-motor neuron disease who underwent temporal lobe resection for epilepsy 5 years prior to her first frontotemporal dementia symptoms. Archival surgical resection tissue contained RNA foci, dipeptide repeat protein inclusions, and loss of nuclear TDP-43 but no TDP-43 inclusions despite florid TDP-43 inclusions at autopsy 8 years after first symptoms. These findings suggest that C9orf72-specific phenomena may impact brain structure and function and emerge before first symptoms and TDP-43 aggregation.

Seizure diaries for clinical research and practice: limitations and future prospects.

PURPOSE: An NINDS-sponsored conference in April of 2011 reviewed issues in epilepsy clinical trials. One goal was to clarify new electronic methods for recording seizure information and other data in clinical trials. METHODS: This selective literature review and compilation of expert opinion considers advantages and limitations of traditional paper-based seizure diaries in comparison to electronic diaries. KEY FINDINGS: Seizure diaries are a type of patient-reported outcome. All seizure diaries depend first on accurate recognition and recording of seizures, which is a problem since about half of seizures recorded during video-EEG monitoring are not known to the patient. Reliability of recording is another key issue. Diaries may not be at hand after a seizure, lost or not brought to clinic visits. On-line electronic diaries have several potential advantages over paper diaries. Smartphones are increasingly accessible as data entry gateways. Data are not easily lost and are accessible from clinic. Entries can be time-stamped and provide immediate feedback, validation or reminders. Data can also can be graphed and pasted into an EMR. Disadvantages include need for digital sophistication, higher cost, increased setup time, and requiring attention to potential privacy issues. The Epilepsy Diary by epilepsy.com and Irody, Inc. has over 13,000 registrants and SeizureTracker over 10,000, and both are used for clinical and research purposes. Some studies have documented patient preference and increased compliance for electronic versus paper diaries. Seizure diaries can be challenging in the pediatric population. Children often have multiple seizure types and limited reporting of subjective symptoms. Multiple caregivers during the day require more training to produce reliable and consistent data. Diary-based observational studies have the advantages of low cost, allowing locus-of-control by the patient and testing in a "real-world" environment. Diary-based studies can also be useful as descriptive "snapshots" of a population. However, the type of information available is very different from that obtained by prospective controlled studies. The act of self-recording observations may itself influence the observation, for example, by causing the subject to attend more vigilantly to seizures after changing medication. Pivotal anti-seizure drug or device trials still mostly rely on paper-based seizure diaries. Industry is aware of the potential advantages of electronic diaries, particularly, the promise of real-time transmission of data, time-stamping of entries, reminders to subjects, and potentially automatic interfaces to other devices. However, until diaries are validated as research tools and the regulatory environment becomes clearer, adoption of new types of diaries as markers for a primary study outcome will be cautious. SIGNIFICANCE: Recommendations from the conference included: further studies of validity of epilepsy diaries and how they can be used to improve adherence; use and further development of core data sets, such as the one recently developed by NINDS; encouraging links of diaries to electronic sensors; development of diary privacy and legal policies; examination of special pediatric diary issues; development of principles for observational research from diaries; and work with the FDA to make electronic diaries more useful in industry-sponsored clinical trials.

Stopping antiepileptic drugs: when and why?

After a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the bias towards continuing therapy indefinitely can be substantial. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs, but there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period, typically 1 to 2 years for children and 2 to 5 years for adults. For children, symptomatic epilepsy, adolescent onset, and a longer time to achieve seizure control are associated with a worse prognosis. In adults, factors such as a longer duration of epilepsy, an abnormal neurologic examination, an abnormal EEG, and certain epilepsy syndromes are known to increase the risk of recurrence. Even in patients with a favorable prognosis, however, the risk of relapse can be as high as 20% to 25%. Before withdrawing AEDs, patients should be counseled about their individual risk for relapse and the potential implications of a recurrent seizure, particularly for safety and driving.

Digital tools for epilepsy: Opportunities and barriers.

This review and commentary presents and discusses the major categories of digital tools that are currently available to epilepsy patients. This review synthesizes the breadth of resources that may be used to create a comprehensive self-management platform. The manuscript organizes the discussion into the following topics: self-management education programs, electronic diaries for self-monitoring, and automated wearables for seizure detection. Despite being available for many years, these tools are utilized by only a small fraction of epilepsy patients. To directly address this, the discussion section will opine on some of the possible barriers, including a lack of historical precedent or prescribing infrastructure, a lack of financial incentives, concerns about data privacy or liability, and uncertainty about the supporting evidence for these solutions.

Neuro-Oncology Practice Clinical Debate: long-term antiepileptic drug prophylaxis in patients with glioma.

Patients with primary brain tumors often experience seizures, which can be the presenting symptom or occur for the first time at any point along the illness trajectory. In addition to causing morbidity, seizures negatively affect independence and quality of life in other ways, for example, by leading to loss of driving privileges. Long-term therapy with antiepileptic drugs (AEDs) is the standard of care in brain tumor patients with seizures, but the role of prophylactic AEDs in seizure-naive patients remains controversial. In this article, experts in the field discuss the issues of AED efficacy and toxicity, and explain their differing recommendations for routine use of prophylactic AEDs.

Assessment of the Predictive Value of Outpatient Smartphone Videos for Diagnosis of Epileptic Seizures.

Importance: Misdiagnosis of epilepsy is common. Video electroencephalogram provides a definitive diagnosis but is impractical for many patients referred for evaluation of epilepsy. Objective: To evaluate the accuracy of outpatient smartphone videos in epilepsy. Design, Setting, and Participants: This prospective, masked, diagnostic accuracy study (the OSmartViE study) took place between August 31, 2015, and August 31, 2018, at 8 academic epilepsy centers in the United States and included a convenience sample of 44 nonconsecutive outpatients who volunteered a smartphone video during evaluation and subsequently underwent video electroencephalogram monitoring. Three epileptologists uploaded videos for physicians from the 8 epilepsy centers to review. Main Outcomes and Measures: Measures of performance (accuracy, sensitivity, specificity, positive predictive value, and negative predictive value) for smartphone video-based diagnosis by experts and trainees (the index test) were compared with those for history and physical examination and video electroencephalogram monitoring (the reference standard). Results: Forty-four eligible epilepsy clinic outpatients (31 women [70.5%]; mean [range] age, 45.1 [20-82] years) submitted smartphone videos (530 total physician reviews). Final video electroencephalogram diagnoses included 11 epileptic seizures, 30 psychogenic nonepileptic attacks, and 3 physiologic nonepileptic events. Expert interpretation of a smartphone video was accurate in predicting a video electroencephalogram monitoring diagnosis of epileptic seizures 89.1% (95% CI, 84.2%-92.9%) of the time, with a specificity of 93.3% (95% CI, 88.3%-96.6%). Resident responses were less accurate for all metrics involving epileptic seizures and psychogenic nonepileptic attacks, despite greater confidence. Motor signs during events increased accuracy. One-fourth of the smartphone videos were correctly diagnosed by 100% of the reviewing physicians, composed solely of psychogenic attacks. When histories and physical examination results were combined with smartphone videos, correct diagnoses rose from 78.6% to 95.2%. The odds of receiving a correct diagnosis were 5.45 times greater using smartphone video alongside patient history and physical examination results than with history and physical examination alone (95% CI, 1.01-54.3; P = .02). Conclusions and Relevance: Outpatient smartphone video review by experts has predictive and additive value for diagnosing epileptic seizures. Smartphone videos may reliably aid psychogenic nonepileptic attacks diagnosis for some people.

The effects of epilepsy and its treatments on affect and emotion.

Epilepsy creates significant morbidity, disability, and loss of productivity worldwide. Although unpredictable seizures define epilepsy, the cognitive and emotional difficulties encountered by people with epilepsy may have an even greater impact on everyday function. Epilepsy is associated with lower quality of life (QOL); while this is partially attributable to ongoing seizures, QOL is independently affected by comorbid affective disorders like depression and anxiety. These can accompany all types of epilepsy, but may be especially noteworthy in partial epilepsy syndromes with foci in the frontal or temporal lobes. There is growing evidence that epileptogenic lesions disrupt cortical networks that carry out emotional processing. In addition to epilepsy itself, treatment strategies also affect cognitive functioning and mood. Antiepileptic drugs, vagal nerve stimulation, and surgical resection have all been associated with changes in mood, emotional processing, and social cognition. Overall, the relationship between epilepsy and emotion is vastly complex; when assessing emotional difficulties in a person with epilepsy, we must consider the psychosocial impact of the disease on the patient, the underlying pathophysiology of the disease, and the effects of ongoing treatments.

Mobile health: the power of wearables, sensors, and apps to transform clinical trials.

Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies.

Interest in a digital health tool in veterans with epilepsy: results of a phone survey.

OBJECTIVE: Online tools for managing chronic health conditions are becoming increasingly popular. Perceived benefits include ease of use, low costs, and availability but are contingent on patient engagement, Internet access, and digital literacy. This article describes data collected during the recruitment phase of a study evaluating an online self-management platform for epilepsy in a U.S. Veteran population. METHODS: We used administrative data to identify and contact Veterans with a likely diagnosis of epilepsy in the Veterans Health Administration (VHA). Veterans who did not respond directly to a mailed invitation were recruited by phone to determine study interest and evaluate digital access. RESULTS: Of the 2,143 Veterans mailed study invitations, phone calls were made to 1,789 who did not specifically decline participation. Among those reached by phone (n = 1,053): 295 (28%) expressed interest in the study and an online tool, 333 (19%) reported a lack of computer and/or Internet access and 425 (40%) were not interested for other reasons. CONCLUSIONS: This study suggests an interest in online tools for managing health despite the fact that some Veterans lack computer and/or Internet access. As investment in digital health solutions grows, the VHA should prioritize the widespread provision of digital access to more Veterans.

Patients optimizing epilepsy management via an online community: the POEM Study.

OBJECTIVE: The study objective was to test whether engaging in an online patient community improves self-management and self-efficacy in veterans with epilepsy. METHODS: The study primary outcomes were validated questionnaires for self-management (Epilepsy Self-Management Scale [ESMS]) and self-efficacy (Epilepsy Self-Efficacy Scale [ESES]). Results were based on within-subject comparisons of pre- and postintervention survey responses of veterans with epilepsy engaging with the PatientsLikeMe platform for a period of at least 6 weeks. Analyses were based on both completer and intention-to-treat scenarios. RESULTS: Of 249 eligible participants enrolled, 92 individuals completed both surveys. Over 6 weeks, completers improved their epilepsy self-management (ESMS total score from 139.7 to 142.7, p = 0.02) and epilepsy self-efficacy (ESES total score from 244.2 to 254.4, p = 0.02) scores, with greatest impact on an information management subscale (ESMS-information management total score from 20.3 to 22.4, p < 0.001). Results were similar in intention-to-treat analyses. Median number of logins, postings to forums, leaving profile comments, and sending private messages were more common in completers than noncompleters. CONCLUSIONS: An internet-based psychosocial intervention was feasible to implement in the US veteran population and increased epilepsy self-management and self-efficacy scores. The greatest improvement was noted for information management behaviors. Patients with chronic conditions are increasingly encouraged to self-manage their condition, and digital communities have potential advantages, such as convenience, scalability to large populations, and building a community support network. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with epilepsy, engaging in an online patient community improves self-management and self-efficacy.

Guidelines for new antiepileptic drug evaluation.

The current evidence-based data on efficacy, safety, and administration of the 7 new antiepileptic drugs (AEDs) approved over the past 10 years by the US Food and Drug Administration to treat new-onset and refractory epilepsy in children and adults is summarized based on the recent American Academy of Neurology (AAN) guidelines. The clinical trial work still necessary as well as areas where such research would not be informative and those in which nonevidence-based strategies are needed are highlighted in efforts to provide clinicians with the most up-to-date information on treatment regimens for patients with epilepsy. The limited amount of data currently available on these newer AEDs and the existence of traditionally efficacious medications complicate therapeutic decision-making for the clinician. Neurologists are encouraged to integrate the AAN guidelines with clinical experience, opinion, and other considerations of special populations until an exhaustive set of guidelines is available for a wide variety of seizure types.

Fear sensitivity and the psychological profile of patients with psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon for both patients and their physicians. Recent work has begun to focus on the possible psychological underpinnings of this diagnosis, but few studies have focused on specific emotional pathologies. This study sought to investigate the impact of a specific emotional measure: self-reported fear sensitivity. Three patient groups (patients with PNES, patients with epilepsy, and healthy volunteers) were administered the Modified Fear Survey Schedule, along with other neuropsychological batteries. As expected, the PNES and epilepsy cohorts demonstrated elevated levels of depression, anxiety, and comorbid psychiatric conditions. The PNES group independently exhibited a statistically significant higher level of fear sensitivity compared with both patients with epilepsy and healthy volunteers. This fear-specific trait was independent of other comorbid psychological factors or psychiatric conditions. These results suggest that patients with PNES exhibit disproportionately elevated fear sensitivity on self-report measures when compared with patients with epilepsy. This finding may reflect an elevated internal "setpoint" for appraising the intensity of emotional settings.