Toward individualized prediction of seizure recurrence: Hippocampal neuroimaging features in a cohort of patients from a first seizure clinic.

PURPOSE: We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis. METHODS: Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time. RESULTS: Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017). CONCLUSION: We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.

Opioid Prescribing in Canada following the Legalization of Cannabis: A Clinical and Economic Time-Series Analysis.

PURPOSE: On 17 October 2018 recreational cannabis became legal in Canada, thereby increasing access and reducing the stigma associated with its use for pain management. This study assessed total opioid prescribing volumes and expenditures prior to and following cannabis legalization. METHODS: National monthly claims data for public and private payers were obtained from January 2016 to June 2019. The drugs evaluated consisted of morphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, oxycodone, tramadol, and the non-opioids gabapentin and pregabalin. All opioid volumes were converted to a mean morphine equivalent dose (MED)/claim, which is analogous to a prescription from a physician. Gabapentin and pregabalin claims data were analyzed separately from the opioids. Time-series regression modelling was undertaken with dependent variables being mean MED/claim and total monthly spending. The slopes of the time-series curves were then compared pre- versus post-cannabis legalization. RESULTS: Over the 42-month period, the mean MED/claim declined within public plans (p < 0.001). However, the decline in MED/claim was 5.4 times greater in the period following legalization (22.3 mg/claim post vs. 4.1 mg/claim pre). Total monthly opioid spending was also reduced to a greater extent post legalization ($Can267,000 vs. $Can95,000 per month). The findings were similar for private drug plans; however, the absolute drop in opioid use was more pronounced (76.9 vs. 30.8 mg/claim). Over the 42-month period, gabapentin and pregabalin usage also declined. CONCLUSIONS: Our findings support the hypothesis that easier access to cannabis for pain may reduce opioid use for both public and private drug plans.

Document-Engineering Methodology in Health Care: An Innovative Behavioral Science-Based Approach to Improve Patient Empowerment.

Engaging patients in their treatment and making them experts of their condition has been identified as a high priority across many medical disciplines. Patient empowerment claims to improve compliance, patient safety, and disease outcome. Patient empowerment may help the patient in shared decision making and in becoming an informed partner of the health care professional. We consider patient empowerment to be in jeopardy if written medical information for patients is too complex and confusing. We introduce document-engineering methodology (DEM) as a new tool for the health care industry. DEM tries to implement principles of cognitive science and neuroscience-based concepts of reading and comprehension. It follows the most recent document design techniques. DEM has been used in the aviation, mining, and oil industries. In these very industries, DEM was integrated to improve user performance, prevent harm, and increase safety. We postulate that DEM, applied to written documents in health care, will help patients to quickly navigate through complex written information and thereby enable them to better comprehend the essence of the medical information. DEM aims to empower the patient and help start an informed conversation with their health care professional. The ultimate goals of DEM are to increase adherence and compliance, leading to improved outcomes. Our approach is innovative, as we apply our learning from other industries to health care; we call this cross-industry innovation. In this manuscript, we provide illustrative examples of DEM in three frequent clinical scenarios: (1) explaining a complex diagnosis for the first time, (2) understanding medical leaflet information, and (3) exploring cannabis-based medicine. There is an urgent need to test DEM in larger clinical cohorts and for careful proof-of-concept studies, regarding patient and stakeholder engagement, to be conducted.

A prospective pilot study of cognitive impairment and mood in adults with first seizure, new-onset epilepsy, and newly diagnosed epilepsy at time of initial seizure presentation.

INTRODUCTION: This is an observational prospective cohort study of cognition and mood in individuals presenting to a tertiary neurology clinic with first unprovoked seizure (FS), new-onset epilepsy (NOE), and newly diagnosed epilepsy (NDE). Our aim was to understand the cognitive profile of these three diagnostic groups at the time of first presentation. Follow-up was obtained to evaluate any association between cognition at presentation and subsequent clinical course. METHODS: Forty-three participants (age: 18-60 years) were recruited with FS (n = 17), NOE (n = 16), and NDE (n = 10). Clinical details, neuropsychological testing, and screening for mood disorders were obtained at the time of presentation to clinic. Seizure recurrence was evaluated at clinic follow-up at least 6-12 months following the initial presentation. RESULTS: In all groups, general intelligence (intelligence quotient [IQ]) was consistent with population norms, but more than half of participants (55.8%) were impaired in at least one cognitive domain. The most commonly impaired domain in all diagnostic groups was visuospatial and visuoconstruction suggesting that it may be a sensitive marker of early cognitive impairment. Those with epilepsy (NOE and NDE) at initial presentation were more likely to be impaired than those with FS, particularly on tests of attention, working memory, and processing speed. Seven participants with FS converted to NOE (FSNOE) at follow-up. They were more likely to be impaired on tests of memory than those with FS who did not convert to NOE. On mood screening, 21% of participants scored moderate or severe for depressive symptoms, and 25.6% of participants scored moderate or severe for anxiety symptoms. DISCUSSION: Cognitive impairment and mood changes are common at first seizure presentation and mirror the pattern seen in chronic epilepsy. This cooccurrence of symptomatology at disease onset prior to prolonged antiepilepsy drug exposure suggests a shared underlying disease mechanism and carries important clinical implications for effective diagnosis and management of epilepsy. Furthermore, early cognitive testing may become a clinical biomarker and enable the prediction of an individual's clinical course.

Early communication is key - Designing a new communication tool to immediately empower people with psychogenic nonepileptic seizures.

INTRODUCTION: Patient empowerment and shared decision-making has been increasingly recognized as key factors for a favorable prognosis. This is particularly true in complex brain disorders such as psychogenic nonepileptic seizures (PNES) which go along with several challenges. People with PNES (PW-PNES) often feel lost in the healthcare system. Early clear communication is one of the few favorable prognostic variables. Our goal was to design a new ultrashort user-friendly communication tool allowing immediate patient empowerment. METHODS: We conceptualized a design thinking process with patient engagement of PW-PNES. Together with a larger group of PW-PNES, we developed a comprehensive user-friendly 1-page document summarizing the key features of PNES. We applied document engineering (DE) as a cognitive science-based new methodology. Document engineering is well established in the aviation, oil, and mining industries and measurably reduces comprehension and performance errors. RESULTS: The design thinking process encompassed 5 phases (empathize, ideate, define, prototype, and test). A prototype of a 1-page document, the 1-Pager-PNES, was created which contained the essential 7 domains organized in a simple structure such as a promise-question-answer (PQA) format. Information was kept poignant, complete, easy-to-read integrating cognitive principles to optimize navigation. The prototype "1-Pager-PNES" was subsequently tested in a 7-member focus group. All patients expressed significant improvement in understanding their disease and felt immediately empowered. Implementing their specific feedbacks, reiterative testing, and involving PNES experts resulted in the final version of the "1-Pager-PNES". CONCLUSION: A promising new communication tool reduced to 1-page only is introduced which improves patient guidance and enables better coping mechanisms with this complex disease. The patient/user is empowered quickly through finding answers to pressing questions. Our study is unique for three reasons: 1) it engaged patients in the developing process, 2) it produced a tool for immediate communication for PW-PNES, which follows principles of human behavior and cognitive science, and 3) it used cross-industry thinking. Despite all limitations, we consider our small pilot study an inspiration for future studies with focus on patient empowerment through user-friendly documents.

Anxiety and Depression in Adult First Seizure Presentations.

OBJECTIVE: To define the prevalence of psychiatric symptoms of anxiety and depression in patients at the time of their first seizure presentation to a neurologist. METHODS: Our pilot study uses a cohort approach with multimodal data (clinical, social, structural [3T magnetic resonance imaging], and functional [electroencephalogram]). We screened 105 patients referred to the Halifax First Seizure Clinic between 2014 and 2016 and 51 controls. All participants completed two screening questionnaires: Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder 7-Item. After applying the exclusion criteria, the study population consisted of 57 patients with unprovoked first seizure and 31 controls. The prevalence of anxiety and depression was based on cutoff scores of >15 and >14 respectively. RESULTS: Unprovoked first seizure patients showed higher prevalence of depression (33%) compared with control (6%) with an odds ratio (OR) of 2.75 (95% confidence interval [CI], 0.72-10.5). There was no significant difference in the prevalence of anxiety between control subjects (9.7%) and unprovoked first seizure patients (23%). Subcategory analysis conducted after diagnosis confirmation revealed significantly increased OR of depression in patients diagnosed with new-onset epilepsy (OR, 11.6; 95% CI, 2.1-64.0) and newly diagnosed epilepsy (OR, 20.0; 95% CI,2.2-181), but not first seizure only patients (OR, 2.2; 95% CI,0.28-17.6) compared with control. CONCLUSIONS: Our study supports a bidirectional relationship between the first seizure and depression. Prevalence rate of depression increased with duration of undiagnosed epilepsy at the time of first clinical assessment.

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted.

Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?

Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled "Epilepsy as a Network Disorder." This was the fourth in a series of conferences, the "Fourth International Halifax Conference and Retreat". This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy.

A pilot study of reduction in healthcare costs following the application of intensive short-term dynamic psychotherapy for psychogenic nonepileptic seizures.

PURPOSE: The purpose of this study was to examine preliminary evidence of intensive short-term dynamic psychotherapy (ISTDP) as a treatment option for psychogenic nonepileptic seizures (PNES) in terms of impact on healthcare costs, emotional wellbeing, and somatic symptoms. METHOD: Drawn from a sample of patients treated in a tertiary psychiatric service over a nine-year period, this naturalistic pilot study compared within-group changes from pretreatment with each year up to three years posttreatment, in physician visits, physician costs, hospital admissions, and overall hospital costs. RESULTS: Twenty-eight patients with PNES received ISTDP with average treatment duration of 3.6 sessions. Healthcare costs significantly reduced in follow-up compared with those in baseline, with patient costs falling below the healthy population means, and reductions in healthcare costs compared with those in baseline by 88% in year one, 90% in year two, and 81% in year three. This was accompanied by significant reductions in symptoms and interpersonal problems. CONCLUSION: These preliminary findings indicate the potential for short-term and long-term healthcare savings and improvements in emotional wellbeing, for patients with PNES from the application of ISTDP. Further research evaluating the impact of ISTDP on seizure reduction and comparing this approach with control conditions is warranted.

Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study.

BACKGROUND: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. METHODS: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged ≥ 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. RESULTS: Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. CONCLUSIONS: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged ≥ 60 years with newly diagnosed epilepsy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

Early electroencephalography in patients with Emergency Room diagnoses of suspected new-onset seizures: Diagnostic yield and impact on clinical decision-making.

PURPOSE: To assess the utility of acute electroencephalography (EEG) performed in the emergency room (ER) and its impact on subsequent management of patients with new-onset seizures. Adults who recover fully in the ER following suspected isolated new-onset seizures are usually discharged to the neurology clinic for further review. An EEG at that stage may be normal. We sought to assess the feasibility and yield of early EEG in the ER setting, its impact on management. METHODS: A prospective study from January 2008 to January 2011 of patients diagnosed by ER physicians with uncomplicated suspected first episodes of unprovoked convulsive seizures. All patients underwent routine 30-min EEG in the ER prior to discharge and specialist review was arranged in the epilepsy clinic within 2 weeks of presentation. Management decisions were at the discretion of the treating neurologist. Seizure recurrence was assessed during a follow up period between 9 months and 3 years. RESULTS: 136 patients were included in the study (92 males). Mean age was 32 years (range 16-73). Forty had abnormal EEGs: 16 focal epileptiform discharges, 12 focal slowing, 10 generalized spike-wave discharges and 2 generalized slowing. Using multivariate analysis, those with abnormal EEG (51% vs 11%, p = 0.003) and abnormal MRI (53% vs 28%, p < 0.001) were more likely to be commenced on anticonvulsant therapy. Abnormal MRI (p = 0.001) was independently associated with a higher risk of recurrence. CONCLUSIONS: Following an ER diagnosis of new-onset uncomplicated seizure, early EEG had a high diagnostic yield. Abnormal EEG and abnormal MRI significantly contributed to decision-making regarding treatment at specialist review. Abnormal MRI was associated with significantly higher risks of subsequent seizures.

Canadian epileptologists' counseling of drivers amidst guideline inconsistencies.

BACKGROUND: Epilepsy is a common medical condition for which physicians perform driver fitness assessments. The Canadian Medical association (CMA) and the Canadian Council of Motor transportation administrators (CCMTA) publish documents to guide Canadian physicians' driver fitness assessments. OBJECTIVES: We aimed to measure the consistency of driver fitness counseling among epileptologists in Canada, and to determine whether inconsistencies between national guidelines are associated with greater variability in counseling instructions. METHODS: We surveyed 35 epileptologists in Canada (response rate 71%) using a questionnaire that explored physicians' philosophies about driver fitness assessments and counseling practices of seizure patients in common clinical scenarios. Of the nine scenarios, CCMTA and CMA recommendations were concordant for only two. Cumulative agreement for all scenarios was calculated using Kappa statistic. Agreement for concordant (two) vs. discordant (seven) scenarios were split at the median and analyzed using the Wilcoxon signed rank sum test. RESULTS: Overall the agreement between respondents for the clinical scenarios was not acceptable (Kappa=0.28). For the two scenarios where CMa and CCMta guidelines were concordant, specialists had high levels of agreement with recommendations (89% each). A majority of specialists disagreed with CMa recommendations in three of seven discordant scenarios. The lack of consistency in respondents' agreement attained statistical significance (p<0.001). CONCLUSIONS: Canadian epileptologists have variable counseling practices about driving, and this may be attributable to inconsistencies between CMa and CCMta medical fitness guidelines. This study highlights the need to harmonize driving recommendations in order to prevent physician and patient confusion about driving fitness in Canada.

Efficacy and safety of pregabalin in refractory focal epilepsy with and without comorbid anxiety disorders - results of an open-label, parallel group, investigator-initiated, proof-of-concept study.

Anxiety disorders are prevalent in people with epilepsy and severely influence daily living and quality of life. Pregabalin (PGB) is licensed in Germany for the add on-treatment of focal epilepsy and for generalized anxiety disorder in adults. To our knowledge, PGB has not been studied before in patients with epilepsy and comorbid anxiety disorder. We included 41 adult patients with focal epilepsy in a monocentric, noncontrolled open-label study adding up to 600 mg of PGB to an antiepileptic baseline medication. Patients were allocated to two groups: patients with epilepsy plus anxiety disorder (EAG) and patients with epilepsy only (EOG). Endpoints were responder rate, seizure frequency, adverse events, and anxiety symptoms. The responder rate in the EAG was higher compared to that in the EOG (per protocol population: 9 [75.0%] vs. 2 [12.5%], p=0.001). Improvements in several psychological scales were found.

First seizure while driving (FSWD)--an underestimated phenomenon?

BACKGROUND: Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD). METHOD: Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence. RESULTS: The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour. DISCUSSION: FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

The puzzle(s) of pharmacoresistant epilepsy.

Despite the availability of >25 antiepileptic drugs, 30% of people with epilepsy do not respond to conventional agents, exhibiting pharmacoresistance (PR)--a high percentage that has not changed significantly in decades. This is not surprising given that all current pharmaceutical agents merely reduce the incidence of seizures ("antiictogenic"); they do not interfere with the natural history of epilepsy and are therefore not antiepileptogenic. The two prevailing hypotheses of pharmacoresistance, the target hypothesis and the transporter hypothesis, can only partially explain the complexity and the diversity of PR. It is a neuropharmacologic priority that we change our approach to understanding PR. Herein we suggest the need to regard PR as a complex puzzle in which the target and transporter hypotheses represent a very small piece of the whole. Indeed, we do not even know if this piece of the whole is epiphenomenal or neurobiologically causal. To grasp the whole, we need to constantly gather information (look around for other pieces) from other perspectives and insights coming from clinical, epidemiologic, neuroradiologic, genetic, and other data. A recent research workshop on PR, the 2nd Halifax International Epilepsy Conference & Retreat, chose this eclectic and all-encompassing approach. The participants were fully aware that their diverse contributions represent only still-fragmented pieces of this frustrating but clinically important puzzle.

A conceptual framework for the use of neuroimaging to study and predict pharmacoresistance in epilepsy.

Twenty percent to 49% of newly treated patients with epilepsy will develop pharmacoresistance (PR). The mechanisms leading to PR are unclear. There is currently no unifying theory to explain the variety of presentations of PR and the diversity of potential contributing factors. Etiology of seizures seems to play a critical role in at least a subset of PR. Many magnetic resonance imaging (MRI) studies in the advanced stages of epilepsy suggest a strong association between lesions such as hippocampal sclerosis and focal cortical dysplasia and PR. Unfortunately, almost all of these studies are cross-sectional and retrospective. There is a need for a new perspective on the role of preexisting lesions in the evolution of epilepsy and PR. We propose in this article to study a unique population of drug-naive patients with either first seizure or new-onset epilepsy longitudinally with advanced MRI imaging techniques, including magnetic resonance spectroscopy and diffusion tensor imaging. We hope to be able to monitor imaging findings and the development of PR early in the course of the disease in a subset of these patients with temporal lobe epilepsy (TLE). Our goal is to understand the pathogenesis of PR, to dissect changes associated with the development of PR from changes associated with chronic seizures and medication, and ultimately to predict PR at the onset of disease.

Pharmacoresistant epilepsy: unmet needs in solving the puzzle(s).

Pharmacoresistant epilepsy is a significant medical problem. The 2nd Halifax International Epilepsy Conference & Retreat identified crucial needs, which if successfully addressed, will aid in paving the way to improved lives for people with pharmacoresistant epilepsy. These are needs: (1) for an evidence-based and dynamic definition of pharmacoresistant epilepsy; (2) for a comprehensive description of the natural history of pharmacoresistant epilepsy; (3) for a comprehensive description of the complications and comorbidities of pharmacoresistant epilepsy; (4) for a rigorous delineation of the epidemiology and socioeconomic impact of pharmacoresistant epilepsy; (5) for clinically meaningful diagnostic and prognostic physiologically based electroencephalography (EEG) biomarkers; (6) for clinically meaningful diagnostic and prognostic anatomically based (MRI Imaging) biomarkers; (7) for biomolecular/biochemical mechanistic understanding of etiopathogenesis for pharmacoresistant epilepsy; (8) for representative animal models of pharmacoresistant epilepsy; (9) for new and effective drugs or other novel treatments for pharmacoresistant epilepsy; and (10) to promote continuing research and research funding targeting pharmacoresistant epilepsy.

Quality of life, anxiety and depression in adult patients after add-on of levetiracetam and conversion to levetiracetam monotherapy.

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (≥50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction.