Association Between Frailty and Antiseizure Medication Tolerability in Older Adults With Epilepsy.

BACKGROUND AND OBJECTIVE: Frailty is an important aspect of biological aging, referring to the increased vulnerability of individuals with frailty to physical and psychological stressors. While older adults with epilepsy are an important and distinct clinical group, there are no data on frailty in this population. We hypothesize that frailty will correlate with the seizure frequency and especially the tolerability of antiseizure medications (ASMs) in older adults with epilepsy. METHODS: We recruited individuals aged 60 years or older with active epilepsy from 4 Canadian hospital centers. We reported the seizure frequency in the 3 months preceding the interview, while ASM tolerability was quantified using the Liverpool Adverse Events Profile (LAEP). We applied 3 measures of frailty: grip strength as a measure of physical frailty, 1 self-reported score (Edmonton frail score [EFS]), and 1 scale completed by a healthcare professional (clinical frailty scale [CFS]). We also administered standardized questionnaires measuring levels of anxiety, depression, functional disability, and quality of life and obtained relevant clinical and demographic data. RESULTS: Forty-three women and 43 men aged 60-93 years were recruited, 87% of whom had focal epilepsy, with an average frequency of 3.4 seizures per month. Multiple linear regression and zero-inflated negative binomial regression models showed that EFS and CFS scores were associated with decreased ASM tolerability, each point increase leading to 1.83 (95% CI: 0.67-4.30) and 2.49 (95% CI: 1.27-2.39) point increases on the LAEP scale, respectively. Neither the EFS and CFS scores nor grip strength were significantly associated with seizure frequency. The EFS was moderately correlated with depression, anxiety, quality of life, and functional disability, demonstrating the best construct validity among the 3 tested measures of frailty. DISCUSSION: The EFS was significantly, both statistically and clinically, associated with ASM tolerability. It also showed multiple advantages in performance while assessing for frailty in older adults with epilepsy, when compared with the 2 other measures of frailty that we tested. Future studies must focus on what role the EFS during epilepsy diagnosis may play in ASM selection among older adults with epilepsy.

Psychogenic nonepileptic seizures in Latin America: A survey describing current practices.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are one of the most common differential diagnoses of epilepsy. This study provides an overview of diagnostic and treatment services for patients with PNES across Latin America. METHODS: In 2017-2018, clinicians practicing in Latin America with responsibilities for patients with PNES were contacted to respond to a survey regarding the management of this disorder developed by the International League Against Epilepsy (ILAE) PNES Task Force. RESULTS: Three hundred and sixty responses from 17 Latin American countries were analyzed. Most respondents were neurologists (81%) under 40 years of age (61%). Fifty-seven percent of professionals stated that they personally diagnose PNES, but only 33% stated that they provide follow-up, and only 20% that they recommend treatment. Many participants (54%) characterized themselves as either unfamiliar with the diagnosis or inexperienced in arranging treatment. Most respondents reported having access to brain magnetic resonance imaging (MRI; 88%) and routine electroencephalogram (EEG; 71%), 64% have the access to video-EEG longer than 8 h, and 54% of professionals performed video-EEG to confirm PNES diagnoses. Although cognitive-behavioral therapy was recognized as the treatment of choice (by 82% of respondents), there was little access to it (60%). In contrast, a high proportion of respondents reported using antidepressant (67%), antiseizure (57%), and antipsychotic medications (54%) as treatments for PNES. SIGNIFICANCE: This study reveals several deficiencies in the diagnosis and treatment of patients with PNES in Latin America. The barriers are reinforced by lack of knowledge among the specialists and poor healthcare system support. There is inadequate access to prolonged video-EEG and psychotherapy. An inappropriate use of antiseizure medicines seems commonplace, and there are low follow-up rates by neurologists after the diagnosis. Multidisciplinary guidelines are required to improve the approach of patients with PNES.

Practice Guidelines for Canadian Neurophysiology Laboratories During the COVID-19 Pandemic.

The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.

Development and validation of the Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19).

OBJECTIVE: No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). METHODS: An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (≥18 years old) who underwent epilepsy surgery ≥1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity. RESULTS: Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach ⍺ range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments. SIGNIFICANCE: The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings.

The Concept of an Epilepsy Brain Bank.

Epilepsy comprises more than 40 clinical syndromes affecting millions of patients and families worldwide. To decode the molecular and pathological framework of epilepsy researchers, need reliable human epilepsy and control brain samples. Brain bank organizations collecting and supplying well-documented clinically and pathophysiologically tissue specimens are important for high-quality neurophysiology and neuropharmacology studies for epilepsy and other neurological diseases. New development in molecular mechanism and new treatment methods for neurological disorders have evoked increased demands for human brain tissue. An epilepsy brain bank is a storage source for both the frozen samples as well as the formaldehyde fixed paraffin embedded (FFPE) tissue from epilepsy surgery resections. In 2014, the University of Saskatchewan have started collecting human epilepsy brain tissues for the first time in Canada. This review highlights the necessity and importance of Epilepsy Brain bank that provides unique access for research to valuable source of brain tissue and blood samples from epilepsy patients.

Art and psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are episodes of seizure-like symptoms that are not associated with epileptiform discharges on electroencephalogram (EEG). They can be remarkably difficult to distinguish from epileptic seizures: both may involve alterations in mental status and behavior, sensory or perceptual disturbances, as well as simple or complex motor patterns. Pictorial expressions of PNES have always attracted attention from the lay public and medical practitioners alike, by showing the rich variety of semiologies seen in the condition and its differences with epileptic seizures. In this article, we present two new contemporary artistic descriptions by the Canadian artist Iris Hauser about PNES. The depictions highlight key signs seen in PNES such as "eyes closed during events", "the hyperextension of the back and limbs", and the "claw-like finger posturing". We believe that the drawings can provide a valuable educational component in the initial assessment of patients suspected of having PNES as a training tool to identify and refer patients for more advanced testing.

Evaluation of wait times for assessment and epilepsy surgery according the geographic area of residence in the province of Saskatchewan, Canada.

PURPOSE: The aim of this study was to determine and compare the waiting times for surgical assessment, neuropsychological testing and epilepsy surgery between people with epilepsy who live in cities with available neurologists vs not. METHODS: We reviewed all cases referred for epilepsy surgery between 2007 and 2017 at the Saskatchewan Epilepsy Program Royal University Hospital (SEP) (n = 98; Saskatchewan, Canada). Mann-Whitney U test was used to compare wait times from first diagnosis of epilepsy to epilepsy surgery between patients who live in cities with neurologists (mainly urban areas) vs cities without neurologists (mainly rural areas). RESULTS: The mean age of patients who enrolled in SEP was 37.8 ± 12.8 years. The median wait time from date of epilepsy diagnosis to referral was 9.5 years in Saskatoon and Regina (cities with available neurologists) and 14 years in other areas of Saskatchewan (small cities and rural areas with no available neurologists) (p = 0.03). The median wait time from date of epilepsy diagnosis to first consult with the epileptologist was 10 years in Saskatoon and Regina and 15.5 years in other areas of Saskatchewan (p = 0.03). The median wait time from date of first diagnosis to epilepsy surgery was 13.2 years in Saskatoon and Regina and 18.2 years in other areas of Saskatchewan (p = 0.05). CONCLUSION: A notable difference was observed in surgical wait times between patients who live in cities with available neurologists compared with people living in rural areas and cities with no neurologists. This suggests that delayed surgical treatment for epilepsy is related with the availability of neurologists.

Atypical language localization in right temporal lobe epilepsy: An fMRI case report.

We report a 41- year-old, left-handed patient with drug-resistant right temporal lobe epilepsy (TLE). Presurgical fMRI was conducted to examine whether the patient had language functioning in the right hemisphere given that left-handedness is associated with a higher prevalence of right hemisphere dominance for language. The fMRI results revealed bilateral activation in Broca's and Wernicke's areas and activation of eloquent cortex near the region of planned resection in the right temporal lobe. Due to right temporal language-related activation, the patient underwent an awake right-sided temporal lobectomy with intraoperative language mapping. Intraoperative direct cortical stimulation (DCS) was conducted in the regions corresponding to the fMRI activation, and the patient showed language abnormalities, such as paraphasic errors, and speech arrest. The decision was made to abort the planned anterior temporal lobe procedure, and the patient instead underwent a selective amygdalohippocampectomy via the Sylvian fissure at a later date. Post-operatively the patient was seizure-free with no neurological deficits. Taken together, the results support previous findings of right hemisphere language activation in left-handed individuals, and should be considered in cases in which presurgical localization is conducted for left-hand dominant patients undergoing neurosurgical procedures.

Diagnostic Accuracy of the Ambulatory EEG vs. Routine EEG for First Single Unprovoked Seizures and Seizure Recurrence: The DX-Seizure Study.

Background: The DX-Seizure study aims to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio) of the ambulatory EEG in comparison with the first routine EEG, and a second routine EEG right before the ambulatory EEG, on adult patients with first single unprovoked seizure (FSUS) and define the utility of ambulatory EEG in forecasting seizure recurrence in these patients after 1-year follow-up. Methods: The DX-Seizure study is a prospective cohort of 113 adult patients (≥18-year-old) presenting with FSUS to the Single Seizure Clinic for evaluation. These patients will be assessed by a neurologist/epileptologist with the first routine EEG (referral EEG) and undergo a second routine EEG and ambulatory EEG. The three EEG (first routine EEG as gold standard) will be compared and evaluated their diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) with respect of epileptiform activity and other abnormalities. One-year follow-up of each patient will be used to assess recurrence of seizures after a FSUS and the utility of the ambulatory EEG to forecast these recurrences. Discussion: To the best of our knowledge, this will be the first study to prospectively examine the use of ambulatory EEG for a FSUS in adults and its use for prediction of recurrence of seizures. The overarching goal is to improve diagnostic accuracy with the use of ambulatory EEG in patients with their FSUS. We anticipate that this will decrease incorrect or uncertain diagnoses with resulting psychological and financial cost to the patient. We also anticipate that an improved method to predicting the recurrence of seizures will reduce the chances of repeated seizures and their consequences.

A patient with epilepsy charged with kidnapping, unlawful confinement, and assault causing bodily harm after seizures: Deficiencies in the legal system.

We report the rare case of a 34-year-old right-handed male who had drug-resistant epilepsy associated with a frontal cavernoma since the age of 13 who was convicted of criminal charges related to seizures. When he was 32 years old, he had a focal seizure with impaired awareness and then he tried to grab a 7-year-old girl who was in a car coming out from a dance class. He was arrested and taken to the police station. Later that day, the patient was being interrogated by a police officer when he had a hypermotor seizure at the end of the interview. He punched the policeman leading to multiple charges laid, including kidnapping, unlawful confinement, and assault causing bodily harm. He remained in jail for the next year and a half. During this time, he had epilepsy surgery for resection of the cavernoma. The patient was rendered seizure-free after resection of the cavernoma for one-year. Due to the occurrence of seizures before the alleged "kidnapping" and based upon his interview with the policeman, the patient was acquitted from all legal charges. We review available cases of non-homicidal criminality with a legal outcome in this article.

The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?

Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.

Risk factors associated with drug resistant focal epilepsy in adults: A case control study.

PURPOSE: Using an adult cohort of patients with focal epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy, which if identifiable would allow patients to receive appropriate counsel and earlier surgical treatment. METHODS: This is a case-control study nested within a cohort, 146 adult patients with focal epilepsy were included. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis. RESULTS: Seventy-one [48.6%] patients met the criteria for drug-resistant epilepsy [cases] and 75 [51.4%] patients were controls. The mean age of patients was 44.5 ± 16.4 years. The most significant variables associated with developing drug-resistant epilepsy include younger age at diagnosis [18.75 vs. 32.2, p < 0.001], years of evolution of epilepsy [22.54 vs. 16.05, p < 0.001], number of AED [4.8 vs. 2.87, p < 0.001], complex partial seizures [51 vs. 35 OR 2.9, p = 0.002], having more than one seizure per month [51 vs. 38, p = 0.009], bi-temporal focus [14 vs. 4 p = 0.008] and mesial temporal sclerosis [23 vs. 11 p = 0.01]. Good response to first AED [7 vs. 29 OR 0.2, p = 0.001] and epilepsy secondary to encephalomalacia [8 vs. 20 OR 0.35, p = 0.018] might be protective factors against drug resistant epilepsy. CONCLUSIONS: Longer time of epilepsy evolution, high frequency of seizures, complex partial seizure presentation, higher number of antiepileptic drugs, mesial temporal sclerosis and bitemporal epilepsy are predictive factors of subsequent pharmacoresistance.

Resolution of ictal bradycardia and asystole following temporal lobectomy: A case report, and review of available cases using pacemakers.

Ictal bradycardia (IB) and ictal asystole (IA) are uncommonly recognized phenomena that increase morbidity in patients with epilepsy by causing syncope and seizure-related falls. These arrhythmias are also suspected to be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We report a case of a 57-year-old male with left temporal lobe epilepsy who experienced both IB and IA. This patient was initially managed with pacemaker implantation, prior to undergoing left temporal lobectomy. Following surgery, the patient had no ongoing IB or IA on his pacemaker recordings, and his seizure control was greatly improved. His pacemaker was removed approximately one year post-operatively and he continued treatment with anti-seizure drugs (ASDs). A literature review of cases of IB and IA that were managed with pacemakers was performed. Pacemaker implantation appears to be quite effective for reducing seizure-related syncope and falls in the setting of IB/IA. Epilepsy surgery also seems to be an effective treatment option for IB/IA, as many patients are able to have their pacemakers removed post-operatively. Further investigations into the pathophysiology of IB and IA and long-term outcomes using different treatment modalities are clearly needed to help formulate treatment guidelines and, potentially, to reduce the occurrence of SUDEP in these patients.

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.

Forced normalization: A systematic review.

OBJECTIVE: Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. METHODS: We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. RESULTS: Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. SIGNIFICANCE: Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.

Deep Brain Stimulation and Drug-Resistant Epilepsy: A Review of the Literature.

Introduction: Deep brain stimulation is a safe and effective neurointerventional technique for the treatment of movement disorders. Electrical stimulation of subcortical structures may exert a control on seizure generators initiating epileptic activities. The aim of this review is to present the targets of the deep brain stimulation for the treatment of drug-resistant epilepsy. Methods: We performed a structured review of the literature from 1980 to 2018 using Medline and PubMed. Articles assessing the impact of deep brain stimulation on seizure frequency in patients with DRE were selected. Meta-analyses, randomized controlled trials, and observational studies were included. Results: To date, deep brain stimulation of various neural targets has been investigated in animal experiments and humans. This article presents the use of stimulation of the anterior and centromedian nucleus of the thalamus, hippocampus, basal ganglia, cerebellum and hypothalamus. Anterior thalamic stimulation has demonstrated efficacy and there is evidence to recommend it as the target of choice. Conclusion: Deep brain stimulation for seizures may be an option in patients with drug-resistant epilepsy. Anterior thalamic nucleus stimulation could be recommended over other targets.