Epilepsy Clinicians Research Articles

Artificial Intelligence: Fundamentals and Breakthrough Applications in Epilepsy

Artificial intelligence, machine learning, and deep learning are increasingly being used in all medical fields including for epilepsy research and clinical care. Already there have been resultant cutting-edge applications in both the clinical and research arenas of epileptology. Because there is a need to disseminate knowledge about these approaches, how to use them, their advantages, and their potential limitations, the goal of the 2023 Merritt-Putnam Symposium and of this synopsis review of that symposium has been to present the background and state of the art and then to draw conclusions on current and future applications of these approaches through the following: (1) Initially provide an explanation of the fundamental principles of artificial intelligence, machine learning, and deep learning. These are presented in the first section of this review by Dr Wesley Kerr. (2) Provide insights into their cutting-edge applications in screening for medications in neural organoids, in general, and for epilepsy in particular. These are presented by Dr Sandra Acosta. (3) Provide insights into how artificial intelligence approaches can predict clinical response to medication treatments. These are presented by Dr Patrick Kwan. (4) Finally, provide insights into the expanding applications to the detection and analysis of EEG signals in intensive care, epilepsy monitoring unit, and intracranial monitoring situations, as presented below by Dr Gregory Worrell. The expectation is that, in the coming decade and beyond, the increasing use of the above approaches will transform epilepsy research and care and supplement, but not replace, the diligent work of epilepsy clinicians and researchers.

Impact of intellectual and developmental disability on quality-of-life priorities in adults with epilepsy

ObjectiveAdults living with intellectual and developmental disability (IDD) and epilepsy (IDD-E) face challenges in addition to those faced by the general population of adults with epilepsy, which may be associated with distinct priorities for improving health-related quality of life (HR-QOL). This study sought to (1) conduct a survey of HR-QOL priorities identified by adults with IDD-E and caregivers, and (2) perform an exploratory cross-sectional comparison to adults with epilepsy who do not have IDD. MethodsThis cross-sectional study recruited 65 adults with IDD-E and 134 adults with epilepsy without IDD and caregivers. Using a three-step development process, 256 items from existing quality-of-life scales recommended by the American Academy of Neurology (AAN) were rated by patients/caregivers for their importance as HR-QOL priorities. HR-QOL items identified as critical to the majority of the sample of adults with IDD-E were reported. Health-related quality of life priorities were compared between adults with IDD-E and adults with epilepsy without IDD. ResultsHealth-related quality of life was significantly lower in adults with IDD-E. Health-related quality of life domains identified as critical priorities by adults with IDD-E included seizure burden, anti-seizure medication side effects, seizure unpredictability, and family impact. Priorities for improving HR-QOL differed between adults with and without IDD-E, with concerns about family impact, difficulty finding appropriate living conditions, inadequate assistance, and difficulty transitioning from pediatric-to-adult care valued significantly more among those with IDD-E. SignificanceIntellectual and developmental disability is an important determinant of HR-QOL among adults with epilepsy. We report HR-QOL priorities identified by adults with IDD-E and their caregivers. These results may help epilepsy clinicians and researchers develop tailored strategies to address priorities of the patient with IDD-E/caregiver community.

Pediatric and adult epileptologist perspectives and experiences of pediatric to adult epilepsy care transition: “Saying goodbye and opening a door.”

We aimed to describe perspectives of transition and transfer of adolescents and young adults with childhood-onset epilepsy from pediatric to adult care from the viewpoints of both pediatric and adult epileptologists. Telephone semi-structured interviews with pediatric (n = 15) and adult (n = 11) epileptologists at leading U.S. epilepsy centers were used to collect data about the transition process. Interviews were audio-recorded, transcribed, systematically coded using thematic analysis by two independent researchers, and subsequently checked for agreement during regular meetings. Participants were on average 46 years old (SD = 7.4), 50% male, 91% Non-Hispanic and 85% Caucasian; all had completed a formal epilepsy or clinical neurophysiology fellowship (mean = 11 years since terminal training) and were employed at a comprehensive epilepsy center. Three interrelated themes regarding epileptologists’ perspectives of epilepsy transition and transfer of care were evident: (1) the process is unnatural and disruptive, (2) clinicians make the best of challenges, and (3) the epilepsy transition process includes a spectrum of broad needs some of which are unique to epilepsy care while others are common to other chronic diseases. Despite challenges, epilepsy clinicians spontaneously expressed stress, empathy, and commitment to providing the best possible care.

Co-designing Integrated Care Using Participatory Action Research [PAR]: The Epilepsy Partnership in Care [EPiC] Project

Introduction: Concepts of “Co-design”, “Co-creation”, “Co-production” are currently used by those promoting innovation to improve integration of healthcare services. They each reflect a practice where both the consumer and the provider of a service/product work together, in partnership, to make something happen. In response to the fragmentation of traditional health services Integrated Care has become a core value of current and emerging health service reforms worldwide. Models of Integrated Care are promoting enhanced co-ordination of care for individuals, better continuity across organisational boundaries and healthcare sectors and improved efficiencies and use of limited health care resources. While Integrated Care is high on the health reform agenda, this does not mean it is actually happening. Using epilepsy as a probe, the National Clinical Care Programme for Epilepsy in collaboration with academic partners from RCSI, Maynooth and Dublin City Universities is conducting a project entitled “Epilepsy Partnership in Care (EPiC)” to explore and advance the integration of care and services provided. Aim: The EPiC Project aims to: realise the promise of Integrated Care for people with epilepsy in Ireland. develop a fine-grained understanding of the provision of services and the experience(s) of living with epilepsy. identify and act on opportunities for promoting better integration of epilepsy services and care. Methods: Ethnographic field work (in-depth interviews, observational field work and focus groups) initially explored Integrated Care in the Irish epilepsy domain. This involved engagement with people with epilepsy (PWE), families, carers, community resource officers, healthcare providers from multiple health services (epileptologists, epilepsy specialist nurses, health service managers, general practitioners, community nurses) at various sites across Ireland ranging from the patient living room to the hospital ward. From this field word, four contexts for creating participatory action research (PAR) teams were identified. Results: 32 people with epilepsy, 6 community resource officers, 4 consultant epileptologists, 13 epilepsy specialist nurses, 3 intellectual disability sector nurses, 3 general practitioners, 2 health service managers and 1 epilepsy service manager have participated in the project. The exploration has elucidated the full range of actors involved in the epilepsy ecosystem, and the nature of their interactions with each other and their surroundings. Evidence of (expert epilepsy clinicians), gaps in (role confusion), and challenges to (competing priorities) integration of epilepsy care have emerged as have opportunities for advancing it through PAR research. Four PAR teams (Community Care; Education; Adolescent Transition; Telephone Advice) were formed into collaborative partnerships between people who receive and deliver epilepsy care and iteratively explored the meaning of Integrated Care while simultaneously identifying both opportunities for and challenges to achieving sustainable integrated care. Conclusion: The EPiC project recognises people with epilepsy in the context of their whole lives not just their medical condition. It is collaboratively observing and cataloguing the diversity of needs, and experiences within the epilepsy care domain in Ireland from the day-to-day life of the person with epilepsy to the experiences of those who deliver services and care. EPiC will create the conditions for intelligently designing and implementing integrated care.

Obtaining structured clinical data from unstructured data using natural language processing software

ABSTRACT
 BackgroundFree text documents in healthcare settings contain a wealth of information not captured in electronic healthcare records (EHRs). Epilepsy clinic letters are an example of an unstructured data source containing a large amount of intricate disease information. Extracting meaningful and contextually correct clinical information from free text sources, to enhance EHRs, remains a significant challenge. SCANR (Swansea University Collaborative in the Analysis of NLP Research) was set up to use natural language processing (NLP) technology to extract structured data from unstructured sources.
 IBM Watson Content Analytics software (ICA) uses NLP technology. It enables users to define annotations based on dictionaries and language characteristics to create parsing rules that highlight relevant items. These include clinical details such as symptoms and diagnoses, medication and test results, as well as personal identifiers.
 
 ApproachTo use ICA to build a pipeline to accurately extract detailed epilepsy information from clinic letters.
 MethodsWe used ICA to retrieve important epilepsy information from 41 pseudo-anonymized unstructured epilepsy clinic letters. The 41 letters consisted of 13 ‘new’ and 28 ‘follow-up’ letters (for 15 different patients) written by 12 different doctors in different styles. We designed dictionaries and annotators to enable ICA to extract epilepsy type (focal, generalized or unclassified), epilepsy cause, age of onset, investigation results (EEG, CT and MRI), medication, and clinic date. Epilepsy clinicians assessed the accuracy of the pipeline.
 ResultsThe accuracy (sensitivity, specificity) of each concept was: epilepsy diagnosis 98% (97%, 100%), focal epilepsy 100%, generalized epilepsy 98% (93%, 100%), medication 95% (93%, 100%), age of onset 100% and clinic date 95% (95%, 100%).
 Precision and recall for each concept were respectively, 98% and 97% for epilepsy diagnosis, 100% each for focal epilepsy, 100% and 93% for generalized epilepsy, 100% each for age of onset, 100% and 93% for medication, 100% and 96% for EEG results, 100% and 83% for MRI scan results, and 100% and 95% for clinic date.
 Conclusions ICA is capable of extracting detailed, structured epilepsy information from unstructured clinic letters to a high degree of accuracy. This data can be used to populate relational databases and be linked to EHRs. Researchers can build in custom rules to identify concepts of interest from letters and produce structured information. We plan to extend our work to hundreds and then thousands of clinic letters, to provide phenotypically rich epilepsy data to link with other anonymised, routinely collected data.

Commentary: Epilepsia's Wada survey.

The potential equivalence of non-invasive approaches for establishing language and memory representation to invasive methods (e.g., Wada testing, cortical simulation mapping) in epilepsy surgery candidates is an important topic of discussion, and we thank the editors of EPILEPSIA for the opportunity to present our rationale as to why we consider it premature to make broad pronouncements that invasive approaches should be abandoned. Our comments were intended to be balanced, acknowledging the differences in backgrounds and skills across epilepsy surgery programs, and thus were couched in probabilistic rather than absolute terms to reflect this variability. We recognize that the readership poll on the initial controversy dialogue was never intended to be scientific, and indeed, the sample size is insufficient to allow any broad generalizations. The goals of such polls, however, are to encourage greater participation of EPILEPSIA readers on topics for which there is a lack of consensus, and the equivalence of invasive and non-invasive measures of language and memory during preoperative evaluation is such a topic. No exchanges will convince persons with strongly held beliefs to abandon them, although commentary and dialogue are important to articulate the clinical rationale behind choice of methods. From our perspective, the survey questions addressing the persuasiveness of our clinical rationale could be improved upon, and perhaps future EPILEPSIA controversy authors could supply several questions similar to what is typically necessary in continuing education courses. For example, neither Papanicolaou nor our manuscript directly addressed the necessity of Wada testing as part of the evaluation for temporal lobe epilepsy, but rather, discussed whether existing non-invasive approaches to language and memory provide information that is sufficiently equivalent to Wada results so that Wada testing itself becomes unnecessary, a comparison that was explicitly probed regarding MEG and fMRI vs. intracranial grids. That over half of responders indicated intracranial grids are still necessary for cortical localization despite MEG and fMRI is a valuable data point reflecting diverse clinical practice. It would be interesting to have included a question as to whether MEG and fMRI were sufficiently developed so that Wada testing should be fully abandoned across all epilepsy programs. While we never argued whether Wada testing should or should not be performed on all temporal lobe epilepsy surgical candidates, the survey findings that no European responders felt that the Wada is necessary reflects the greater emphasis of using fMRI to minimize Wada testing by epilepsy clinicians in Europe in the epilepsy literature. We reassert our belief, though, that it is premature to develop position statements asserting that the Wada test (or stimulation mapping) is unnecessary due to the availability of non-invasive measures of language and memory fMRI or MEG since non-invasive approaches have important limitations that are not always fully appreciated or acknowledged by non-expert users, and that such a position does not reflect the opinion of many clinicians who actively manage and follow epilepsy patients to optimize their epilepsy care.

Network meta‐analysis and the comparison of efficacy and tolerability of anti‐epileptic drugs for treatment of refractory focal epilepsy

We read with interest the recent paper on network meta-analysis [1] in which efficacy and tolerability of selected anti-epileptic drugs in people with refractory focal epilepsy were compared. Whilst network meta-analysis may be a powerful tool, the validity of the results must depend on the selection of studies included. In this respect, we are curious about several methodological points. The authors include some studies but not others that are of the same nature. The authors deem as appropriate doses those that most experienced epilepsy clinicians would consider unusual and the results that emerge would be considered misleading by most experienced epilepsy clinicians. Only one of the four drugs the authors suggest have efficacy and tolerability in focal epilepsies would be accepted as such by experienced epilepsy clinicians. Their recommendation of vigabatrin in this category is most surprising, given the significant adverse effects associated with its use. The paper illustrates the importance of ensuring that the results of any complex statistical process should always be checked against actual clinical experience. The authors selected for comparison only people receiving doses of the target drugs which they deemed appropriate. Despite the authors’ claim that they chose the selected doses based on their clinical experience, the choice seems arbitrary, is out of keeping with clinical experience and is not based on any stated evidence. For instance, only someone with little clinical experience of oxcarbazepine would consider doses over 1800 mg day−1 as appropriate. The dose of 2400 mg is poorly tolerated by most people. It is also unlikely that many people would tolerate doses of topiramate over 300 mg day−1. Several relevant studies were not included, without clear explanation. For instance, a key lacosamide study [2] was not included. The same apply for studies with topiramate [3] and levetiracetam [4]. Two relevant lamotrigine studies [5, 6] were also excluded. One could suggest that these were excluded as they were crossover studies, but then other crossover studies were included, such as a levetiracetam study [7]. It is imperative that consistent criteria are applied for study selection if this type of analysis is to be meaningful. The authors conclude that in their mixed-treatment network meta-analysis, levetiracetam, vigabatrin, sodium valproate and gabapentin emerge as the anti-epileptic drugs with the best combination of short term efficacy and tolerability. As experienced epilepsy clinicians having seen many thousands of patients, we do not consider that valproate and gabapentin should be considered as first line anti-epileptic drugs for people with focal epilepsy, whilst any epilepsy clinician would know that the risk of visual field loss with vigabatrin is far too high to contemplate its regular use. The authors’ recommendation on valproate appears to emanate from one old study comparing vigabatrin with valproate, in which a small number of people with epilepsy not controlled by carbamazepine were given either valproate or vigabatrin [8]. It is not clear why better quality data [9] were omitted from the analysis. For these reasons, the conclusions cannot be considered particularly helpful. The need for answers to the questions the authors set out to address remains. One important thing to remember is that epilepsy, a symptom-complex, is not a single disease but a collection of many different conditions for which the current clinical trials paradigm is completely inappropriate [10, 11].

Transitional services for adolescents with epilepsy in the UK: A survey

PurposeTo survey the current transitional epilepsy services in tertiary paediatric neurology centres in the UK within the principles of transitional care for young people with epilepsy. MethodsAn online web-based questionnaire was sent to the lead epilepsy clinicians in tertiary paediatric neurology centres on behalf of the British Paediatric Epilepsy Group, the specialist epilepsy group of the British Paediatric Neurology Association (BPNA). A transition clinic was defined as a ‘clinic or service that provided joint paediatric and adult supervision of care from paediatric to adult services’. ResultsTwenty-three centres were approached of which18 responded and 15 of which provided auditable data. The clinics were held between three and 12 times per year, mostly in the afternoon and sited equally between the paediatric and adult centre. Approximately three to five new, and three to eight follow up patients were seen in each clinic. Most clinics accepted new referrals with a minimum age of 14 and a maximum of 20 years. Most young people were seen only once in a transition clinic before then being promoted into the adult epilepsy service. Very few clinics accepted direct referrals from the GP. Adult, slightly more than the paediatric team provided out-of-hospital advice after the young person was seen in the transition clinic. ConclusionsYoung people with epilepsy are a challenging, but interesting group and their care at this time may have a potentially irreversible impact on their life. Their progress from paediatric to adult services should be a dynamic, gradual and smoothly transitioned process to optimise their care. Although recommended by the National Institute for Health and Clinical Excellence (NICE) and the National Services Framework (NSF), the findings of this survey would suggest an un-met need of this population.

A comparison of epilepsy self-management needs: Provider and patient perspectives

A consistent and serious empirical issue in the epilepsy self-management literature involves dropout and attrition in intervention studies. One explanation for this issue revolves around “top-down” intervention designs (i.e., interventions generated by epilepsy clinicians and researchers) and the potential for disparity with patient interests, capabilities, and perceived needs. The purpose of this study was to extend the work of Fraser et al. (2011) [19] by comparing perceptions regarding self-management problems, topics, and program design, between two subgroups of adult patients with epilepsy (n=165) and epilepsy clinicians (n=20). Results indicate differences in problem severity ratings, program emphasis (i.e., goal-setting, coping, education), and program leadership between clinicians and each patient subgroup to varying degrees. These findings highlight some of the differences in opinion between patients and clinicians and emphasize the need for patient-involved planning with regard to self-management programs. Implications and explanations are offered as points for consideration in self-management program development.

048 Lost in translation: epilepsy in KwaZulu Natal South Africa

In 2009 based at Mseleni hospital in KwaZulu Natal I was tasked to assess patients with epilepsy and to provide basic seizure education to doctors and nursing sisters in rural...

POE01 Outcome of medication change in patients with refractory epilepsy

BackgroundDespite the low probability of achieving seizure-freedom in refractory epilepsy patients and clinicians may be inclined to try new or previously untried medications. We assessed the outcome of consecutive medication...

Monday, December 3, 2007 Found in Translation – New Target for Therapies 9:00 a.m.‐11:30 a.m.

John W. Swann 1 ( 1 Pediatrics/Neuroscience, Baylor College of Medicine, Houston, TX ) Summary: Epilepsy research scientists and clinicians are collaborating in translating scientific discoveries into new therapies for the intractable epilepsies. Discoveries of clinical researchers are guiding the development of relevant animal models. Studies in these models are leading to the identification of what appear to be key molecular steps in the genesis of epilepsy. These molecular mechanisms provide new targets for the development of rationale therapies, which can be tested in these same models. As an example of the progress being made, this program will review the most recent studies of the consequences of prolonged febrile seizures in children. Potential targets for new therapies that have been discovered in models of febrile seizures, head injury, neonatal seizures and kindling will be discussed.

110 Puzzling Cases of Epilepsy

110 Puzzling Cases of Epilepsy edited by D. Schmidt and S.C. Schachter, 451 pp., Martin Dunitz, 2002, $80.80, 2002 In their 2002 volume 110 Puzzling Cases of Epilepsy , Drs. Dieter Schmidt and Steven Schachter have compiled the collective wisdom and experiences of over 100 of the world’s foremost epilepsy clinicians and researchers. Their goal in launching this effort was quite simple: to glean from the minds of the experts that one case that changed their practice or taught them an invaluable lesson that is inaccessible through any textbook or epilepsy algorithm. To accomplish this goal, they solicited a single case from a number of well-known epileptologists, instructing them to include a commentary on what they learned and how it changed their clinical practice. The resultant text is an insightful compendium of clinical vignettes, filled with unusual diagnoses, treatments, …

Cost of Illness of Epilepsy in the US: Comparison of Patient-Based and Population-Based Estimates

Purpose: To analyze the direct medical costs associated with epilepsy in the US using a cost-of-illness analysis that incorporates both a patient-based approach and a population-based approach. Methods: Patient-based or ‘bottom-up’ analysis relied on information provided by a panel of experienced epilepsy clinicians to determine the number and type of medical resources used by individuals with epilepsy. Population-based or ‘top-down’ analysis relied on cost estimates from a nationally representative sample in the 1987 National Medical Expenditure Survey. Results: The average annual cost per individual in the patient-based analysis was $1,490. The average annual cost per individual in the population-based analysis was $1,510 with average yearly costs per adult of $1,480 and $1,740 per child. New cases of epilepsy are associated with costs of $362 million for the first year of treatment; existing cases of epilepsy are estimated to cost the US nearly $2 billion. Conclusions: The results of this study indicate incident cases are more than twice as expensive as prevalent cases, and the need to properly care for epilepsy patients is increasingly important in today’s health care environment, where the emphasis is on providing effective treatments while simultaneously lowering the costs.