Surgical treatment for epilepsy: the potential gap between evidence and practice

Findings from randomised controlled trials, along with more than 100 case series and observational studies, support the efficacy and safety of resective surgery and, more recently, non-resective surgical interventions for the treatment of drug-resistant epilepsy in appropriately selected individuals. There is an argument that epilepsy surgery remains underused, but the evidence to support this assertion is at times unclear. Results from longitudinal studies show a stagnant or declining rate of epilepsy surgery over time, despite the evidence and guidelines supporting its use. Some suggest that this stagnation is due to a decreasing pool of eligible surgical candidates, whereas others emphasise the numerous barriers to epilepsy surgery. Strategies exist to increase access to surgery and to improve communication about the effectiveness of this potentially life-changing procedure. Further investigation into the nature and causes of the presumed underuse of epilepsy surgery and the elaboration of strategies to address this treatment gap are necessary and pressing

Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines

Surgical treatment of drug-resistant focal epilepsy: selection, economic considerations and long-term outcomes

Epilepsy surgery can be an effective treatment for drug-resistant focal epilepsy, but requires careful selection of appropriate candidates to achieve optimal results and minimise the chance of adverse outcomes, including seizure recurrence. Long-term data on multimodal outcomes and a better appreciation of various factors influencing surgical suitability will help facilitate informed discussions between clinicians and prospective surgical candidates. This thesis includes a comprehensive analysis of a cohort of individuals who had epilepsy surgery at a tertiary neurosciences centre over the last 30 years, supplemented by data on individuals who completed presurgical evaluation at the same centre but did not proceed to surgical resection. An inability to localise the epileptogenic zone (EZ), multifocal epilepsy, or an individual choice not to have either intracranial electroencephalography or surgery were the most common reasons why people referred for presurgical evaluation did not proceed to a definitive resection. A predictive model based on demographic, imaging and electroclinical data was constructed to assist early discussions about surgical suitability. Those with normal MRI, extratemporal epilepsy and evidence of bilateral seizure onsets on video telemetry had an estimated 2.9% chance of proceeding to surgery, and people with a normal MRI brain invariably required intracranial EEG. Frontal lobe epilepsy surgery was safe and effective, with a long-term (median seven years) seizure freedom rate of 27%, and another 11% having auras only. Psychiatric comorbidity frequently improved postoperatively and paralleled seizure freedom. Focal MRI abnormality and fewer anti-seizure medications at the time of surgery could help predict a good outcome. In contrast, the site of resection and intracranial monitoring were not independently significant. Localisation of the EZ should rely on clinical features and multimodal investigation, as in our cohort frontal lobe semiology alone could correctly lateralise the EZ in only 77% and localise to a sublobar level in 52%. For those who completed presurgical evaluation but did not have surgery, under 5% had >12 months of seizure-freedom following the decision not to proceed, although a quarter had substantial improvement with further anti-seizure medication (ASM) or neurostimulation. Evaluation for epilepsy surgery was lengthy for individuals and costly for the public health system. Both duration and cost depended on what investigations were required and varied according to different routes through the presurgical pathway, especially the need for intracranial EEG. The median duration of evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9,138 (IQR £6,984-£14,868). Approximately £123,500 was spent per additional person seizure-free

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Cognitive, emotional and psychosocial functions after resective epilepsy surgery

Epilepsy surgery is a potentially curing treatment for a selected group of patients with drug-resistant focal epilepsy. Cognitive side-effects after temporal lobe resections (TLR) are well documented but it is still difficult to predict individual memory outcome after TLR. Concerning frontal lobe resections (FLR), fewer studies have addressed the cognitive outcome. The aim of this thesis was to develop a prediction model for verbal memory decline after TLR and to further the knowledge of cognitive, emotional and psychosocial outcome after FLR for epilepsy. In Study I, regression analyses based on pre- and postoperative cognitive data from 110 patients who underwent TLR for epilepsy were made to develop a prediction model for verbal memory decline after TLR. In Study II, cognitive outcome two years after FLR for epilepsy was studied through analyses of neuropsychological data from 30 consecutive FLR patients. Study III was an interview study including 14 FLR patients and 12 of their respective relatives who were inter-viewed about experiences of emotional, cognitive and psychosocial consequences of FLR. Data were analyzed by qualitative content analysis. In Study IV, decision making after FLR was ex-plored using the Iowa Gambling Task (IGT). The same 14 FLR patients as in Study III were included. Results from study I identified left sided surgery, inclusion of hippocampus in the resection, high preoperative verbal memory function and a history of tonic-clonic seizures (TCS) as predictors of significant memory decline after TLR. The results from study II mainly showed cognitive stability two years after FLR. However, at the individual level 44% of patients had reliable decline in a verbal reasoning task. In study III, patients and relatives described positive experiences after FLR, like increased autonomy and more joy in life, but also negative ones, such as loss of energy and social withdrawal. Study IV showed that patients had problems with decision making after FLR. This was demonstrated through a failure to learn from feedback throughout the IGT. To conclude, this thesis has contributed with a prediction model which included four clinically useful predictors of memory decline after TLR. The FLR studies demonstrated mainly cognitive stability over time, positive as well as negative individual experiences of cognitive, emotional and psychosocial functions and difficulties associated with decision making. These contributions will be valuable to share with patients and their families in the preoperative counselling process preced-ing a decision about TLR or FLR

12th World Congress on Controversies in Neurology

Warszawa, 22–25 marca 2018 rok

The Value of Seizure Semiology in Epilepsy Surgery: Epileptogenic-Zone Localisation in Presurgical Patients using Machine Learning and Semiology Visualisation Tool

Background Eight million individuals have focal drug resistant epilepsy worldwide. If their epileptogenic focus is identified and resected, they may become seizure-free and experience significant improvements in quality of life. However, seizure-freedom occurs in less than half of surgical resections. Seizure semiology - the signs and symptoms during a seizure - along with brain imaging and electroencephalography (EEG) are amongst the mainstays of seizure localisation. Although there have been advances in algorithmic identification of abnormalities on EEG and imaging, semiological analysis has remained more subjective. The primary objective of this research was to investigate the localising value of clinician-identified semiology, and secondarily to improve personalised prognostication for epilepsy surgery. Methods I data mined retrospective hospital records to link semiology to outcomes. I trained machine learning models to predict temporal lobe epilepsy (TLE) and determine the value of semiology compared to a benchmark of hippocampal sclerosis (HS). Due to the hospital dataset being relatively small, we also collected data from a systematic review of the literature to curate an open-access Semio2Brain database. We built the Semiology-to-Brain Visualisation Tool (SVT) on this database and retrospectively validated SVT in two separate groups of randomly selected patients and individuals with frontal lobe epilepsy. Separately, a systematic review of multimodal prognostic features of epilepsy surgery was undertaken. The concept of a semiological connectome was devised and compared to structural connectivity to investigate probabilistic propagation and semiology generation. Results Although a (non-chronological) list of patients’ semiologies did not improve localisation beyond the initial semiology, the list of semiology added value when combined with an imaging feature. The absolute added value of semiology in a support vector classifier in diagnosing TLE, compared to HS, was 25%. Semiology was however unable to predict postsurgical outcomes. To help future prognostic models, a list of essential multimodal prognostic features for epilepsy surgery were extracted from meta-analyses and a structural causal model proposed. Semio2Brain consists of over 13000 semiological datapoints from 4643 patients across 309 studies and uniquely enabled a Bayesian approach to localisation to mitigate TLE publication bias. SVT performed well in a retrospective validation, matching the best expert clinician’s localisation scores and exceeding them for lateralisation, and showed modest value in localisation in individuals with frontal lobe epilepsy (FLE). There was a significant correlation between the number of connecting fibres between brain regions and the seizure semiologies that can arise from these regions. Conclusions Semiology is valuable in localisation, but multimodal concordance is more valuable and highly prognostic. SVT could be suitable for use in multimodal models to predict the seizure focus