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ObjectiveThe use of medical cannabis among people with epilepsy (PWE) has been garnering increasing interest. In this scoping review, we aimed to summarize the literature on recreational/non-medical cannabis (NMC) use in PWE, focusing on the experience, habits, and beliefs of PWE regarding NMC.MethodsFour databases (OVID Medline, OVID Embase, Ovid APA PsycInfo, and Web of Science) were searched for studies describing NMC use in PWE. NMC was defined as cannabis products procured from sources other than by prescription. Studies that consisted in original research and that detailed the experience, habits, and/or beliefs of PWE regarding NMC use were included in the analysis. Data pertaining to study identification, demographics, NMC use, and epilepsy characteristics were extracted. Descriptive statistical analyses and reflexive thematic analyses were performed to map these data.ResultsIn total, 3,228 records were screened, and 66 were included for analysis: 45 had mainly adult samples, whereas 21 had mainly pediatric samples. Most studies were published after 2010, originated from the USA, and were cross-sectional. The median number of PWE using cannabis in these studies was 24.5 (1–37,945). No studies showcased elderly PWE, and most had predominantly Caucasian samples. The lifetime prevalence of NMC use in PWE was variable, ranging between 0.69 and 76.8%. Factors frequently associated with NMC use in PWE were male sex, younger adult age, and lower education status. Children with epilepsy took NMC primarily for seizure control, using high CBD/THC ratios, and only orally. Adults with epilepsy took NMC for various reasons including recreationally, using variable CBD/THC ratios, and predominantly through smoking. The majority of PWE across all studies perceived that NMC aided in seizure control. Other aspects pertaining to NMC use in PWE were rarely reported and often conflicting.ConclusionThe literature on NMC use in PWE is sparse and heterogeneous, with many salient knowledge gaps. Further research is necessary to better understanding the experience, habits, and beliefs of PWE pertaining to NMC.

Cortical spreading depolarization (CSD) is recognized as a cause of transient neurological symptoms (TNS) in various clinical entities. Although scientific literature has been flourishing in the field of CSD, it remains an underrecognized pathophysiology in clinical practice. The literature evoking CSD in relation to subdural hematoma (SDH) is particularly scarce. Patients with SDH frequently suffer from TNS, most being attributed to seizures despite an atypical semiology, evolution, and therapeutic response. Recent literature has suggested that a significant proportion of those patients’ TNS represent the clinical manifestations of underlying CSD. Recently, the term Non-Epileptical Stereoytpical Intermittent Symptoms (NESIS) has been proposed to describe a subgroup of patients presenting with TNS in the context of SDH. Indirect evidence and recent research suggest that the pathophysiology of NESIS could represent the clinical manifestation of CSD. This review should provide a concise yet thorough review of the current state of literature behind the pathophysiology of CSD with a particular focus on recent research and knowledge regarding the presence of CSD in the context of subdural hematoma. Although many questions remain in the evolution of knowledge in this field would likely have significant diagnostic, therapeutic, and prognostic implications.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Background and ObjectiveFrailty 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.MethodsWe 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.ResultsForty-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.DiscussionThe 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.

Background. Transient neurological symptoms (TNS) frequently occur in patients with subdural hematomas (SDH) often posing diagnostic dilemna. Most of those patients will receive a diagnosis of provoked seizures despite negative workup and atypical evolution. Objective. To accumulate evidence about the existence of the distinct NESIS etiology for patients presenting with TNS post SDH, its pathophysiology and optimal management. Methods. An initial single-center, retrospective, case-control study of patients with TNS post-SDH revealed statistically significant clinical and semiological distinctions between cases (negative EEG) and controls (EEG with ictal or interictal activity). Those differences combined with a thorough review of literature led to the creation of a clinical screening score predictive of a negative EEG. When tested retrospectively, the score showed promise in detecting NESIS for patients with TNS. Its predictive value was replicated in a subsequent single-center, retrospective study. Results. In the first study, fifty-nine patients with SDH-associated TNS were included (39 cases and 20 controls). Demographic characteristics were comparable in both groups. Dysphasia and prolonged episodes were associated with a negative EEG. Clonic movements, impaired awareness, positive symptomatology, complete response to antiepileptic drugs and mortality were associated with a positive EEG. Using semiological variables, we created a scoring system with a 96.6% sensitivity and 100% specificity in predicting case group patients. In the second study, 22 patients with TNS and chronic SDH were included. Presumptive NESIS occurred in 13 patients (59%), EEG-proven epilepsy in 4 patients. NESIS patients did not respond to standard anti-epileptic drugs contrary to non-NESIS TNS (14% vs 100%). The differences between both groups support the existence of an alternative etiology than seizures for TNS in our population. We proposed the term NESIS to describe this subgroup and hypothesize that cortical spreading depolarization (CSD) could be its underlying pathophysiology. Relevant studies support the existence of specific treatments (including Topiramate) targeting CSD. Conclusion. With these results in mind, we aim to carry out a prospective randomized clinical trial to assess the efficacy of Topiramate compared to a conventional AED (LEV), known to have little impact on CSD, in a NESIS sub-group. We believe the recognition of this distinct entity, the understanding of its underlying pathophysiology and the creation of a validated clinical screening score can have important prognostic, paraclinical and therapeutic impact in the care we provide to such patients.

Objective:To evaluate the effectiveness and tolerability of brivaracetam (BRV) in a refractory epilepsy population in an outpatient clinical setting.Methods:Retrospective medical information system review and self-report questionnaire for all patients treated with BRV until the end of 2017.Results:Thirty-eight patients were included, 73.7% female and mean age 36.2. The mean number of antiepileptic drugs (AEDs) for previous use was 8.9, and for current use was 2.5. Mean seizure frequency in the last 3 months was 12 per month. At 3, 6, 12, and 15 months, the 50% responder rates were 36.1%, 32%, 41.2%, and 45.5%, respectively. Patients took BRV for a median duration of 8.25 months, ranging from 7 days to 60 months. Retention rate was 75.0%, 72.0%, 59.2%, and 47.9% at 3, 6, 12, and 15 months, respectively. Overall, the main reasons for discontinuation were adverse events (AEs) (52.3%), lack of efficacy (35.3%), or both (11.8%). The rate of total AEs was 60.5% according to medical records and 85.7% according to questionnaire, including mostly tiredness, psychiatric, and memory complaints. Psychiatric side effects occurred in 31.6% according to medical records and 47.4% according to questionnaire results, which is higher than previously reported and persisted throughout the study period.Conclusions:BRV appears to be a useful and safe add-on treatment, even in a very refractory group of patients. In this real-life clinical setting, psychiatric AEs were found at a higher rate than previously published.

Background Transient neurological symptoms (TNS) are frequent in patients with subdural hematomas (SDH) and many will receive a diagnosis of epilepsy despite a negative workup. Objective To explore if patients with TNS and a negative epilepsy workup (cases) evolved differently than those with a positive EEG (controls), which would suggest the existence of alternative etiologies for TNS. Methods We performed a single-center, retrospective, case-control study of patients with TNS post-SDH. The demographics and clinical and semiological features of cases and controls were compared. The outcome and response to antiepileptic drugs were also assessed and a scoring system developed to predict negative EEG. Results Fifty-nine patients with SDH-associated TNS were included (39 cases and 20 controls). Demographic characteristics were comparable in both groups. Dysphasia and prolonged episodes were associated with a negative EEG. Clonic movements, impaired awareness, positive symptomatology, complete response to antiepileptic drugs, and mortality were associated with a positive EEG. Using semiological variables, we created a scoring system with a 96.6% sensitivity and 100% specificity in predicting case group patients. The differences observed between both groups support the existence of an alternative etiology to seizures in our case group. We propose the term NESIS (NonEpileptic, Stereotypical, and Intermittent Symptoms) to refer to this subgroup and hypothesize that TNS in these patients might result from cortical spreading depolarization. Conclusion We describe NESIS as a syndrome experienced by SDH patients with specific prognostic and therapeutic implications. Independent validation of this new entity is now required.

Objective To evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers. Methods The offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography. Results In GDM vs. control mothers, maternal glycated haemoglobin (A 1C , mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% ( p =0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate ( p =0.078), in neonates born to GDM mothers compared to controls. Conclusion In contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers.

The goal was to evaluate whether there was neurodevelopmental deficits in newborns born to mothers with gestational diabetes mellitus (GDM) compared to control newborns born to healthy mothers.Forty-six pregnant women (21 controls and 25 GDM) were recruited. Electroencephalogram (EEG) was recorded in the newborns within 48 h after birth. The EEG signal was quantitatively analyzed using power spectral density (PSD); coherence between hemispheres was calculated in paired channels of frontal, temporal, central and occipital regions.The left centro-occipital PSD in control newborns was 12% higher than in GDM newborns (p = 0.036) but was not significant after adjustment for gestational age. While coherence was higher in the frontal regions compared to the occipital regions (p 0.001), there was no difference between the groups for the fronto-temporal, frontal-central, centro-occipital and tempo-occipital regions.Our results support that EEG differences between groups were mainly modified by gestational age and less by GDM status of the mothers. However, there is a need to confirm this result with a higher number of mother-newborns. Quantitative EEG in GDM newborns within 48 h after birth is feasible. This study emphasizes the importance of controlling blood glucose during GDM to protect infant brain development.

Background: Resection of the epileptogenic insular cortex is surgically challenging. We sought to evaluate the potential of Gamma Knife® surgery (GKS) for the treatment of pharmacoresistant insular cortex epilepsy (ICE) in patients who underwent GKS between 2005 and 2010. Adverse events and effects on seizure frequency were assessed. Methods: Three cases of refractory ICE were treated by GKS between 2005 and 2010. Results: Case 1 had refractory nonlesional ICE, proven by depth electrodes only partially helped by a left posterior insulectomy. Case 2 had refractory ICE due to a left insular cavernoma. Case 3 had refractory ICE, confirmed by an invasive study but complicated by transient dysphasia from contusion of Wernicke's area. The marginal and maximum radiation doses delivered were 20 and 40 Gy, respectively. Treatment volume ranged from 1.2 to 3.2 cm3. Two out of 3 patients experienced significant seizure reduction and the third had a worthwhile improvement (follow-up 30-76 months). Complete antiepileptic drug withdrawal was un-fortunately not possible. Complications included transient lightheadedness and new-onset seizures responsive to medical treatment, both in the same patient. Conclusion: GKS is a promising technique for selected drug-resistant ICE patients. Additional observations are necessary.

Object Hypothalamic hamartomas (HHs) are congenital lesions typically presenting with medically refractory epilepsy. Open or endoscopic surgical procedures to remove or disconnect the hamartoma have been reported to be effective but are associated with significant morbidity. The authors of studies on Gamma Knife surgery for HHs have reported an encouraging rate of epilepsy resolution with minimal side effects. At the Centre Hospitalier Universitaire de Sherbrooke, the authors have undertaken a prospective observational study of the outcomes of patients who underwent radiosurgery for HHs. Methods Patients were included in the study if they had an HH, refractory epilepsy, and no other suspected seizure focus. After radiosurgery, seizure status was assessed every 3 months and reported using the Engel Classification. Quality of life evaluation was performed annually using a standardized questionnaire, and neuropsychological evaluation was performed after 2 years. Results Nine patients were included in the study. They ranged in age from 12 to 57 years. Epilepsy began in infancy in all cases and was refractory to standard antiepileptic drugs. The patients received an average of 2 antiepileptic drugs before undergoing radiosurgery. Using the Régis Classification, 6 patients had smaller hamartomas (Grade I–III) and underwent treatment of the entire lesion, using a margin dose of 14–20 Gy. Treatment volume ranged from 0.3 to 1.0 ml. Three patients had larger lesions (Grade IV–VI) for which a radiosurgical disconnection was attempted, targeting the area of attachment to the hypothalamus. For those patients, the margin dose was 15 or 16 Gy, with treatment volume ranging from 0.8 to 1.8 ml. In all patients, the radiation dose received by the optic pathways was kept below 10 Gy. Disconnection led to no improvement in epilepsy (Engel Class IV). Four patients in whom the entire lesion was treated are now seizure free (Engel Class I), with another having only rare seizures (Engel Class II). Quality of life and verbal memory were improved in those patients with more than 3 years of follow-up. No adverse event occurred after radiosurgery. Conclusions Radiosurgery safely and effectively controlled the epileptic disorder in patients with HHs when the entire lesion could be targeted. Radiosurgical disconnection is ineffective and cannot be recommended.

Background:Epileptiform electroencephalogram (EEG) asymmetries are not uncommon in juvenile myoclonic epilepsy (JME) and can contribute to the misdiagnosis of this syndrome. The objective of this study is to further characterize patients with focal or asymmetric epileptiform electroencephalographic abnormalities and more specifically in terms of response to treatment. Controversial data exists in the literature concerning this issue.Methods:We retrospectively reviewed clinical and EEG data of a group of consecutive JME patients followed at our Epilepsy Service. The first EEG available for each patient was reviewed blindly by two independent electroencephalographers.Results:Twenty-eight patients with JME were identified: 11 (39.3%) were resistant to at least one appropriate anti-epileptic drug (AED), including valproate, lamotrigine, topiramate or levetiracetam. All patients except two had generalized epileptiform abnormalities. Overall, EEG asymmetries were detected in 57.1% of the cases. The proportion of EEG asymmetries between AED-sensitive group (52.9%) and AED-resistant group (63.5%) did not reach statistical significance. Concordance between examiners for identification of EEG asymmetries was good. Analysis of patients with and without asymmetries showed no statistically significant differences in comparisons of age, family history of seizure, presence of polyspike and slow wave, photosensitivity and timing of EEG related to the onset of treatment.Conclusion:Asymmetric electroencephalographic abnormalities are frequent in patients with JME. These features should not be misinterpreted as being indicative of partial epilepsy. In our group, asymmetries were not associated with resistance to treatment.

Background: Transient neurological symptoms in patients with subdural hematoma (SDH) are often attributed to secondary epilepsy despite a negative workup. We believe a significant proportion of these patients could rather suffer from cortical spreading depolarization (CSD). Methods: We performed a retrospective case-control study of patients with transient neurological symptoms post-SDH evacuation between 1996 and 2017. The clinical features of patients with negative EEG were compared to those with positive EEG (ictal or interictal abnormalities) and a clinical scoring system was created. Results: 59 patients were included, 20 (34%) with a positive EEG. Speech-related symptoms (OR 4.8, p=0.018) and prolonged episodes (OR 23.1, p=0.001) were associated with a negative EEG. Clonic movements (OR 0.014, pConclusions: We believe that the differences observed between both groups were driven by the presence of CSD rather than seizure in the case group. Our proposed scoring system can help predict EEG results and may be useful to identify CSD in future trials.

Objective: To determine the accuracy of the clinical history performed by epileptologists in the identification of seizures in patients with suspected temporal lobe epilepsy. Methods: The clinical and EEG telemetry (EEGT) monitoring data of 88 patients with suspected refractory temporal lobe seizures referred for evaluation of epilepsy surgery were prospectively evaluated. All clinical events obtained by history in these patients were adjudicated as being a seizure or not by two blinded (without access to EEG data) independent epileptologists. Each clinical event was then matched with the corresponding clinical event recorded with EEG telemetry in the epilepsy monitoring unit (gold standard). Sensitivity, specificity, overall accuracy, predictive value, and interrater agreement for the clinical assessment were obtained. Results: Of 357 clinically different events, 175 (49%) were reproduced in the epilepsy monitoring unit. Only 10 events were misidentified by history as being a seizure or not, resulting in an overall clinical accuracy of 94%. Epileptologists’ sensitivity for seizure identification was 96% (95% CI 92, 98%) but specificity was only 50% (95% CI 22, 79%). Accuracy for complex partial seizures and generalized seizures was higher than for simple partial seizures (SPS). Misidentification occurred only with SPS and nonepileptic events. Agreement beyond chance among epileptologists was good. Conclusion: In this selected group of patients with temporal lobe epilepsy, seizure identification by clinical history is highly accurate. Epileptologists rarely miss seizures (high sensitivity) but more often overcall nonepileptic events as seizures (low specificity).

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 (pConclusions: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.

Object This prospective observational study, conducted at the CHUS between 2005 and 2016, aims to examine the outcomes of patients who underwent radiosurgery for hypothalamic hamartomas (HHs). Method Patients were included in the study if they were diagnosed with an HH and refractory epilepsy, without any other suspected seizure focus. After radiosurgery, seizure status was assessed periodically using the Engel Classification. Neuropsychological and quality of life evaluations were performed at baseline and thereafter. A follow-up evaluation was completed ten years after the first Gamma-knife treatment. Results Thirteen patients, refractory to medical treatment, were included in the study, ranging in age from 12–57 years. Using the Regis Classification, ten patients had smaller hamartomas (Grade I-III) and underwent treatment of the entire lesion. Radiosurgical disconnection was attempted in three patients with larger lesions (Grade IV-VI). One patient was lost to follow-up, and one died from seizure complications following an open surgery for HH. Disconnection was ineffective. Gamma-knife treatment was repeated in three patients in which the first intervention had failed to reduce the seizure burden. Seven patients (58%) had a good outcome (Engel I-II), including five patients who were seizure-free after a mean time of 6.4 months. Five patients (42%) had Engel classification of III or IV. Treatment adverse events included psychotic depression (1) and radiation necrosis (1). Conclusion Radiosurgery seems to offer a better control of epilepsy secondary to HHs, principally in cases where the entire lesion can be targeted. The authors consider that radiosurgery should be attempted as a first-line surgical therapy for these patients.

Objective The primary outcome of the study was to evaluate whether women with epilepsy (WWE) of reproductive age received counselling before conception, including issues such as folate supplementation, antiepileptic drug selection (AED) and their potential teratogenic risks. Background WWE of reproductive age should be counselled regarding their condition and the potential complications of pregnancy associated with epilepsy and AEDs, considering that 50% of pregnancies are unplanned. Design/methods We retrospectively reviewed 64 consecutive medical charts of WWE between the ages of 13 and 50, who were followed prior to conception, and managed during pregnancy at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between July 1, 2003 to June 30, 2013. Twenty patients were excluded primarily due to referral to the CHUS only after conception. Forty-two patients, encompassing 62 pregnancies were included. Maternal and neonatal charts were thoroughly reviewed and information was collected on an Excel spreadsheet. The protocol was approved by the Ethics review Board of the CHUS. We described our population regarding pre-conception counselling, dose of folate supplementation taken, type, dose and quantity of AEDs, control of seizure in the year preceding pregnancy as well as throughout pregnancy, maternal and neonatal complications or malformations. We evaluated whether those who received counselling before pregnancy were less likely to be taking Valproic acid (VPA) during pregnancy, have less seizures during pregnancy and less complications during pregnancy and delivery. Results Counselling before conception was documented in 45/62 (72.6%) of medical charts. Folate supplementation before pregnancy was prescribed in 44/62 (71%) pregnancies. Risks of complications were formally documented in 27/62 (43%) of charts. There were no statistically significant differences between those receiving counselling and those that did not, in terms of seizure frequency during pregnancy, and VPA use. Interestingly, of the 15 (100%) women on an AED polytherapy, all received counselling compared to those who did not ( p = 0.006). There were no statistically significant differences regarding maternal and neonatal complications for women on polytherapy, those on VPA or women with seizure during pregnancy, compared to their counterparts. Two cases of malformations were detected and one woman died unexpectedly at 18 weeks of pregnancy. Between 2003 and 2008 there were 11/34 (32%) women on VPA compared to 2/26 (7%) between 2009 and 2013, p = 0.026. Conclusion This study has shown that the rate of counselling received by WWE at our centre was satisfactory, but remains an area that can be improved. Physicians should more actively be prescribing folate supplementation to this population due to the high rate of unexpected pregnancies. More attention should be placed in formally documenting important discussions about risks of epilepsy and AED. We plan to raise awareness of these issues to the healthcare professionals at our center who are involved in the care of WWE during their reproductive years.

Objective To evaluate the degree of temporal lobe atrophy (TLA) in elderly patients with new-onset epilepsy, and its relation to temporal epileptiform discharges. Background No etiology can be identified in as much as 30% to 50% of cases of new-onset epilepsy in the elderly, despite adequate investigation. Degenerative diseases, notably Alzheimer’s disease (AD), increase the risk of epilepsy, and are often underdiagnosed in routine clinical practice. Abnormal activity on electroencephalography (EEG) of demented epileptic individuals is most often found focally in temporal regions. Design/methods We retrospectively reviewed neuroimaging and EEG results of a consecutive cohort of 322 elders with new-onset epilepsy. The > 65 year-old patients were evaluated at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between January 2001 and October 2010. On imaging, TLA was assessed visually on axial images and graded on a 0–3 scale estimating sulcal widening and temporal horn ventricular enlargement. Measurement of the temporal horn radial width (THRW) was also acquired as a quantitative estimate of TLA. TLA was compared between subjects with epilepsy of unknown etiology (n = 127) and demented epileptic individuals of the same cohort (n = 10), as well as a healthy elderly control group (n = 31) and non-epileptic AD patients (n = 10). EEG interpretations were also analyzed, looking for correlation between temporal lobe atrophy and temporal epileptiform discharges, in the whole epileptic cohort. Results MRI (46%) or CT (93%) was available for 112 patients with epilepsy of unknown etiology. Thirty-eight percent of elderly with new-onset epilepsy of unknown cause had significant temporal atrophy, using the dichotomized 0–3 scale (0–1 vs 2–3) or THRW. This was significantly more than the healthy control group (0%) after adjustment for age and sex (p = 0.000). As expected, individuals of the same cohort with epilepsy attributed to dementia had higher prevalence of significant TLA using both THRW and the visual scale (70.4%, p = 0.026 and 76.9% p = 0.021) as did patients with established AD (70% p = 0.040 and 60% p = 0.077). EEG results were available for 297 of the 322 patients (92.2%), including 125 of the 127 subjects with epilepsy of unknown etiology. Epileptiform discharges were present in 111/297 (37.3%) and 45/125 (36%) individuals respectively, of which 68.5% and 55.5% were found in temporal leads. No correlation was found between the presence of temporal lobe atrophy, using either dichotomized THRW or the visual scale, and temporal epileptiform activity (p = 0.312 and 0.469). Conclusions A considerable proportion of elderly with new-onset epilepsy of unknown cause exhibit temporal lobe atrophy on brain imaging, which suggests that a degenerative disease such as AD could be underrecognized as a possible etiology. However, it appears there is no correlation between this atrophy and the temporal localization of epileptiform activity. Financial support University Chair.

Hypothalamic hamartomas (HHs) are congenital lesions typically presenting with medically refractory epilepsy. Open or endoscopic surgical procedures to remove or disconnect the hamartoma have been reported to be effective but are associated with significant morbidity. The authors of studies on Gamma Knife surgery for HHs have reported an encouraging rate of epilepsy resolution with minimal side effects. At the Centre Hospitalier Universitaire de Sherbrooke, the authors have undertaken a prospective observational study of the outcomes of patients who underwent radiosurgery for HHs.Patients were included in the study if they had an HH, refractory epilepsy, and no other suspected seizure focus. After radiosurgery, seizure status was assessed every 3 months and reported using the Engel Classification. Quality of life evaluation was performed annually using a standardized questionnaire, and neuropsychological evaluation was performed after 2 years.Nine patients were included in the study. They ranged in age from 12 to 57 years. Epilepsy began in infancy in all cases and was refractory to standard antiepileptic drugs. The patients received an average of 2 antiepileptic drugs before undergoing radiosurgery. Using the Régis Classification, 6 patients had smaller hamartomas (Grade I-III) and underwent treatment of the entire lesion, using a margin dose of 14-20 Gy. Treatment volume ranged from 0.3 to 1.0 ml. Three patients had larger lesions (Grade IV-VI) for which a radiosurgical disconnection was attempted, targeting the area of attachment to the hypothalamus. For those patients, the margin dose was 15 or 16 Gy, with treatment volume ranging from 0.8 to 1.8 ml. In all patients, the radiation dose received by the optic pathways was kept below 10 Gy. Disconnection led to no improvement in epilepsy (Engel Class IV). Four patients in whom the entire lesion was treated are now seizure free (Engel Class I), with another having only rare seizures (Engel Class II). Quality of life and verbal memory were improved in those patients with more than 3 years of follow-up. No adverse event occurred after radiosurgery.Radiosurgery safely and effectively controlled the epileptic disorder in patients with HHs when the entire lesion could be targeted. Radiosurgical disconnection is ineffective and cannot be recommended.

Idiopathic generalized epilepsy (IGE) has evidence of a strong genetic etiology. We conducted genomewide linkage analysis for genes responsible for familial IGE in French-Canadian pedigrees. Twenty families segregating autosomal dominant epilepsy were collected. Four larger IGE families sufficiently powerful for independent linkage analysis were genome-scanned and follow-up fine mapping was performed over regions with LOD scores >3.0. The genotyping of 16 smaller families was carried out at significantly linked loci for supportive linkage analysis and haplotype comparisons. One of the four families provided a significant linkage result at marker D10S1426 on chromosome 10 (two-point LOD score = 3.05, theta = 0, multipoint LOD score = 3.18). Fine mapping revealed a segregating haplotype and key recombination breakpoints, suggesting a candidate gene interval of 6.5 Mb. Multipoint linkage analyses using the additional 16 families yielded a maximum LOD score under heterogeneity of 4.23 (alpha = 0.34) at this locus. Evaluation of recombination breakpoints in these families narrowed the candidate region to 1.7 Mb. Sequencing of the two known genes in this region, NRP1 and PARD3, was negative for mutation. Replication of linkage to this locus in other cohorts of IGE families is essential to characterize the underlying genetic mechanism for the disease. © 2008 Wiley-Liss, Inc.

Background:Triphasic waves (TWs) and generalized nonconvulsive status epilepticus (GNCSE) share morphological features that may create diagnostic ambiguity.Objective::To describe electroencephalographic differences between TWs and GNCSE.Methods:We retrospectively compared the electroencephalograms (EEGs) of two groups of patients presenting with decreased level of consciousness; those with TWs associated with metabolic encephalopathy and those with GNCSE. We studied the following: demographics, etiology and EEG morphological features. All EEGs were classified blindly (TWs or GNCSE) by two expert EEGers. Agreement between experts and concordance with clinical diagnosis were measured.Results:We analysed 87 EEGs (71 patients) with TWs and 27 EEGs (13 patients) with GNCSE. Agreement between experts and concordance with clinical diagnosis were excellent. When compared to TWs, epileptiform discharges associated with GNCSE had a higher frequency (mean=2.4Hz vs 1.8Hz) (pConclusion:Certain EEG morphological criteria and the response to stimulation are very helpful in distinguishing TWs from GNCSE.

Rationale Hypothalamic hamartomas (HHs) are intrinsically epileptogenic congenital lesions typically presenting with drug resistant epilepsy. Patients affected also suffer from progressive cognitive deficits. Based upon previous studies, Gamma-knife surgery for HHs seems to be effective regarding epilepsy outcome with minimal side effects. Little data is available on the neurocognitive effect of this procedure. At the Centre Hospitalier Universitaire de Sherbrooke, we have undertaken a prospective observational study of patients who underwent radiosurgery for HHs, evaluating the response rate of seizures and the impact on cognition and quality of life. Methods Patients were included in the study if they had an HH, refractory epilepsy, and no other suspected seizure focus. After radiosurgery, seizure status was assessed every three months and reported using the Engel Classification. Neuropsychological evaluation and quality of life evaluation using a standardized questionnaire (QOLIE-89) was performed at baseline and annually thereafter. Results Twelve patients with refractory epilepsy have been included so far in the study. Age ranged from 14 to 57 years. Margin doses ranged from 14 to 20 Gy. Nine patients had smaller hamartomas (Regis classification Grade I–III) and underwent treatment of the entire lesion. Three patients had larger lesions (Grade IV–VI) for which a radiosurgical disconnection was attempted. One of them had a second treatment with full lesion coverage. Among the seven patients treated with full lesion coverage with more than two years of follow-up, five (70%) are seizure free (Engel I). One patient has only rare seizure (Engel II), and one did not improve (Engel IV). Mean time to seizure freedom was twelve months (range 4–22). Disconnection led to no or little improvement in epilepsy (Engel IV in two patients and Engel IIIa in one). Nine patients had an abnormal cognitive profile at baseline. Four of them had a second evaluation after two years, and marked improvement in multiple domains of cognition occurred in three patients, and one remained stable. We observed a tendency toward improvement of quality of life evaluated with QOLIE-89, with a median result of 53% before treatment compared to 84% one or two years after treatment ( p = 0.068). Three patients had transient psychiatric disturbances after treatment (major depression with psychotic features requiring hospitalization in two, and impulsive behavior in one). Conclusions In this prospective study of patients with refractory epilepsy associated with HHs, radiosurgery was effective in most patients when the entire lesion could be targeted. Some encouraging effects were also observed for cognition and quality of life, but this needs to be further evaluated in larger series of patients. Radiosurgical disconnection of large lesions was ineffective. Psychiatric disturbances as a possible side effect of this procedure need to be investigated further. For small HHs, radiosurgery with full lesion coverage should be a first line surgical therapy.

Objective To evaluate if published treatment guidelines had an impact on the choice of drug for the treatment of epilepsy in the elderly in the recent years. To examine baseline and follow-up data for the treated patients. Methods A retrospective cohort study was conducted at a tertiary care center to identify patients aged 65 and older with new-onset epilepsy. Clinical data and investigation results were collected from baseline to latest available follow-up. The number of patients receiving antiepileptic drugs (AEDs) considered suboptimal (phenytoin, phenobarbital, and primidone) and optimal were compared for the 2001–2005 and 2006–2010 time periods. Results A significant reduction in the proportion of patients started on a suboptimal drug was observed between the first and second time period (from 78.1% to 47.3%), mainly explained by a reduction in phenytoin use combined with a rise in levetiracetam use. One year after the index event, there was no difference between the two categories of antiepileptic drugs in terms of recurrence of seizures or change in medication. Conclusions Medications received by elderly patients newly diagnosed with epilepsy in this retrospective study were more in phase with recommendations in the latter half of the 2001–2010 decade. Nonetheless, phenytoin remained widely used.

Introduction Detailed prospective studies are scarce on gamma knife treatment for arteriovenous malformations (AVM) or cavernous angioma (CA) regarding epilepsy outcome. The objective of this study is to further investigate prospectively the effect of gamma knife on seizures and expand our knowledge to other aspects of epilepsy management: medication, cognition and quality of life. Method We included prospectively 9 consecutive patients (4 AVM and 5 CA) who underwent radiosurgery for epilepsy caused by vascular malformation at the CHUS between August 2004 and August 2009. The mean marginal radiation dose was 20 Gy. The objective of this study is to determinate the seizure outcome after radiosurgery. Patients were followed every 3 months to evaluate seizure count over time, Engel score and medication status. Quality of life (QOLIE 89) and neuropsychological evaluation were completed before the treatment and at 12 and 24 months following the intervention. Results Patients were followed for a mean period of 39 months (range from 15 to 72 months). Three patients have been seizure free for 1 year (33%). Overall 5 patients (55%) had significant improvement with an Engel score of 1 (completely seizure free or non disabling simple partial seizure only). Medication status did not change over time. The QOLIE 89 score improved by more than 25 points (on a 100 points scale) in 3 patients (43%), 2 patients (29%) reported no change and 2 patients had lower scores. Neuropsychological testing did not show any deterioration in cognition following the intervention. No adverse reaction occurred so far. Conclusion Stereotactic radiosurgery has some efficacy for the treatment of epilepsy associated with vascular malformations and improves quality of life in a majority of patients. It seems less effective than surgical lesionectomy. No cognitive or physical morbidity was observed. This treatment could be a useful alternative for vascular lesions in eloquent areas that cannot be safely removed with microsurgery.