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Background and ObjectivesThis systematic review with meta-analysis (PROSPERO: CRD42021249336) was performed to estimate the pooled lifetime prevalence of bipolar symptoms (BS) and bipolar disorder (BD) in people with epilepsy (PWE).MethodsA search was performed on June 5, 2021, in 4 databases (MEDLINE/PubMed, Ovid EMBASE, Ovid APA PsycInfo, and Web of Science) for original research reporting on BS/BD in PWE, with no restriction on language or time of publication. Inclusion criteria were as follows: (1) original research, (2) cross-sectional study design component, (3) reported lifetime prevalence of BS/BD or enough information to calculate an estimate, and (4) reported the method by which participants were deemed bipolar. Studies based on an exclusively pediatric population were excluded. To calculate pooled lifetime prevalence of BS/BD, 2 meta-analytic random-effects models were fitted, one for BS and the other for BD. Risk of bias was assessed using a standardized appraisal tool for studies reporting prevalence. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsA total of 750 records were screened and 17 studies were included for analysis: 7 provided prevalence estimates for only BS, 8 for only BD, and 2 for both BS and BD. After outlier exclusion and subgroup analysis using screening method as a moderator, the pooled prevalence of BS in PWE was 12.3% (95% CI 10.6%–14.1%) (7,506 PWE). The pooled prevalence of BD in PWE was 4.5% (95% CI 2.2%–7.4%) (48,334 PWE). Considerable heterogeneity was present, more so for BD than for BS, and could be explained through differences in population demographics and study methodology.DiscussionThis study's main limitation was regarding the certainty of evidence. However, our estimates of prevalence should prompt further research on BS/BD in PWE. Given the significant morbidity associated with BD, clinicians should carefully screen PWE for BS.

Background:Caring for women with epilepsy (WWE) during pregnancy poses unique challenges. We conducted an audit of the care our epilepsy clinic provided to pregnant WWE.Methods:We performed a retrospective study on all pregnancies followed by an epileptologist at a Canadian tertiary care centre’s epilepsy clinic between January 2003 and March 2021. Among 81 pregnancies in 53 patients, 72 pregnancies in 50 patients were analyzed to determine patient-related, follow-up-related, antiseizure-medication-related, and child-related pregnancy characteristics. Univariate analyses were performed to explore if these characteristics were associated with disabling seizure occurrence during pregnancy.Results:Most pregnancies were intended (72%) and occurred in women who used folic acid pre-pregnancy (76%) and who followed recommended blood tests for antiseizure medication (ASM) levels (71%). In 49% of pregnancies, ASM dosage was modified; 53% of these modifications were made in response to ASM blood levels. Most often used ASMs were lamotrigine (43%), followed by carbamazepine (32%) and levetiracetam (13%). One child was born with a thyroglossal duct cyst; our congenital malformation rate was thus 2%. Disabling seizures occurred in 24% of pregnancies. Exploratory analyses suggested that disabling seizure occurrence during pregnancy was associated with younger patient age (p = 0.018), higher number of ASMs used during pregnancy (p = 0.048), lamotrigine usage in polytherapy (p = 0.008), and disabling seizure occurrence pre-pregnancy (p = 0.027).Conclusion:This Canadian audit provides an in-depth description of pregnancies benefiting from specialized epilepsy care. Our results suggest an association between disabling seizure occurrence during pregnancy and lamotrigine usage in polytherapy that warrants further evaluation.

The photoparoxysmal response (PPR) is defined as the occurrence of generalized spike, spike-wave or polyspike-wave discharges consistently elicited by intermittent photic stimulation (IPS). PPR is not well studied in Sub-Saharan African people. We prospectively studied the epidemiological, clinical, and EEG characteristics of PPR among consecutive patients recorded at the clinical neurophysiology unit of Fann University Hospital (Dakar, Senegal). Among 6,808 EEG recordings including 3,065 pathological EEGs, we collected 56 EEGs with PPR (0.8% of all recorded EEGs and 1.8% of anormal EEGs), from 31 women and 25 men (sex ratio: 0.8). The mean age was 13.3 years (range: 8 months to 59 years). The peak of photosensitivity was found in the range of 6 to 10 years. Of the PPR cases, 12 had clinical manifestations during IPS. Generalized epilepsy was diagnosed in 23 (41%) patients and 18 (32%) had focal epilepsies. The most epileptogenic stimulation frequencies were between 12 and 24 Hz (range: 1-28 Hz). PPR were mainly triggered during eye closure (64%), and 41 patients (73% of PPR cases) were classified as Type 4 (Waltz classification). Our results confirm lower rates of photosensitivity in African Sub-Saharan people compared with others. Although the current data do not support a role of short-term ambient light levels, subject to consistent data from larger cohorts, it may be interesting to study the probable epigenetic-mediated protective role of sunshine against photosensitivity.

Objective The study of seizure onset and termination patterns has the potential to enhance our understanding of the underlying mechanisms of seizure generation and cessation. It is largely unclear whether seizures with distinct onset patterns originate from varying network interactions and terminate through different termination pathways. Methods We investigated the morphology and location of 103 intracranial EEG seizure onset and termination patterns from 20 patients with drug-resistant focal epilepsy. We determined if seizure onset patterns were associated with specific termination patterns. Finally, we looked at network interactions prior to the generation of distinct seizure onset patterns by calculating directed functional connectivity matrices. Results We identified nine seizure onset and six seizure termination patterns. The most common onset pattern was Low-Voltage Fast Activity (36 %), and the most frequent termination pattern was Burst Suppression (44 %). All seizures with fast (>13 Hz) termination patterns had a fast (>13 Hz) onset pattern type. Almost any onset pattern could terminate with the Burst Suppression and rhythmic Spike/PolySpike and Wave (rSW/rPSW) termination patterns. Seizures with a fast activity onset had higher inflow to the seizure onset zone from other regions in the gamma and high gamma frequency ranges prior to their generation compared to seizures with a slow onset. Significance Our observations suggest that different mechanisms underlie the generation of different seizure onset patterns although seizure onset patterns can share a common termination pattern. Possible mechanisms underlying these patterns are discussed.

Background:Intervention time (IT) in response to seizures and adverse events (AEs) have emerged as key elements in epilepsy monitoring unit (EMU) management. We performed an audit of our EMU, focusing on IT and AEs.Methods:We performed a retrospective study on all clinical seizures of admissions over a 1-year period at our Canadian academic tertiary care center’s EMU. This EMU was divided in two subunits: a daytime three-bed epilepsy department subunit (EDU) supervised by EEG technicians and a three-bed neurology ward subunit (NWU) equipped with video-EEG where patients were transferred to for nights and weekends, under nursing supervision. Among 124 admissions, 58 were analyzed. A total of 1293 seizures were reviewed to determine intervention occurrence, IT, and AE occurrence. Seizures occurring when the staff was present at bedside at seizure onset were analyzed separately.Results:Median IT was 21.0 (11.0–40.8) s. The EDU, bilateral tonic–clonic seizures (BTCS), and the presence of a warning signal were associated with increased odds of an intervention taking place. The NWU, BTCS, and seizure rank (seizures were chronologically ordered by the patient for each subunit) were associated with longer ITs. Bedside staff presence rate was higher in the EDU than in the NWU (p < 0.001). AEs occurred in 19% of admissions, with no difference between subunits. AEs were more frequent in BTCS than in other seizure types (p = 0.001).Conclusion:This study suggests that close monitoring by trained staff members dedicated to EMU patients is key to optimize safety. AE rate was high, warranting corrective measures.

Over a third of patients suffering from epilepsy continue to live with recurrent disabling seizures and would greatly benefit from personalized seizure forecasting. While electroencephalography (EEG) remains most popular for studying subject-specific epileptic precursors, dysfunctions of the autonomous nervous system, notably cardiac activity measured in heart rate variability (HRV), have also been associated with epileptic seizures. This work proposes an unsupervised clustering technique which aims to automatically identify preictal HRV changes in 9 patients who underwent simultaneous electrocardiography (ECG) and intracranial EEG presurgical monitoring at the University of Montreal Hospital Center. A 2-class k-means clustering combined with a quantitative preictal HRV change detection technique were adopted in a subject- and seizure-specific manner. Results indicate inter and intra-patient variability in preictal HRV changes (between 3.5 and 6.5 min before seizure onset) and a statistically significant negative correlation between the time of change in HRV state and the duration of seizures (p

Three decades after its introduction as an adjuvant therapeutic option in the management of selective drug-resistant epilepsy cases (DRE), vagus nerve stimulation (VNS) retains growing interest. An implantable device was first approved for epilepsy in Europe in 1994 and in the United States (US) in 1997. Subsequent modifications improved the safety and the efficacy of the system. The most recent application of vagal neurostimulation is represented by transcutaneous devices that are claimed to have strong therapeutic potential. In this review, we sought to analyze the most meaningful available data describing the indications, safety and efficacy of the different approaches of VNS in clinical practice. Therefore, we identified studies reporting VNS efficacy and/or safety in epilepsy and its comorbidities from January 1990 to February 2020 from various databases including PubMed, Scopus, Cochrane, US government databases and VNS manufacturer published resources. In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the patients. However, some clinically relevant differences have been reported with specific factors such as epilepsy etiology or type, patient age as well as the delay of VNS therapy onset. VNS efficacy on seizure frequency has been demonstrated in both children and adults, in lesional and non-lesional cases, in focal and generalized epilepsies, on both seizures and epilepsy comorbidities. Regarding the latter, VNS can lead to an improvement of about 25-35 % in depression scores, 35 % in anxiety scores and 25 % in mood assessment scores. If non-invasive devices are undeniably safer, their efficacy is limited due to the scarcity of large cohort studies and the disparity of methodological approaches (study design and stimulation parameters). Overall, we believe that there is a progress margin for improving the safety of implantable devices and, above all, the effectiveness of the various VNS approaches.

Calcium and magnesium are divalent multipotent ions playing a major role in metabolism, excitability and neuroglial plasticity. Because of these multiple properties, their deficiency induces complex brain processes leading to acute or even lasting disorders in excitability and neural networks. These ions are usually prescribed in clinical contexts of neuronal hyperexcitability such as preeclampsia and chronic stress. Our aim was to evaluate whether magnesium at 20 mg/kg and calcium at 100 mg/kg could improve the memory prognosis in the kainic model of mesial temporal epilepsy in mice. The animals were organized into 6 groups: control group (without kainate), reference group (GR) without administration of ions, groups treated with magnesium or calcium from the third day (respectively G1m, G1c), groups treated with magnesium or calcium from the third week (respectively G2m, G2c). The mice treated by ions performed better than GR mice, but magnesium was more effective. Memory (short term-long term) was differently affected by kainate or improved by magnesium-calcium. In addition, magnesium demonstrated an increasing therapeutic effect over time while calcium had an acute and apparently decreasing action in the G1c group that received calcium early.

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004–2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. Results: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). Conclusions: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes.

As a dynamical system, the brain constantly modulates its state and epileptic seizures have been hypothesized to be low dimensional periodic states of the brain. With this assumption, seizures have previously been investigated to identify patterns of these recurrent states; however, these attempts have generated conflicting results. These discrepant observations led us to reconsider the dynamic of state transitions during seizures.Using intracerebral recordings of 17 refractory epilepsy patients assessed prior to surgery, we studied ictal states with several state-of-the-art methods in order to investigate their dynamics. Global states were identified based on distinct functional connectivity measures in the time domain, frequency domain, and phase-space. We further investigated the state transitions in different brain regions locally using a univariate measure based on dynamical system analysis named the Recurrence Plot (RP).For the ictal period, we detected lower global state transition rates compared to pre- and post-ictal periods (p 0.05 for seizure-free (SF) and p 0.05 for non-seizure-free (NSF) groups post-surgery); however, the structure of RPs pointed towards higher state transition rates in some regions like the seizure-onset-zone (p 0.001 for SF and p 0.05 for NSF group). Moreover, a direct comparison of state transition dynamics between SF and NSF patients revealed different patterns for local state transitions between SF and NSF patients (p 0.05 for seizure-onset-zone while p 0.05 for other regions) and no significant difference in global state transition rates (p 0.05).Our findings pointed to distinct dynamics for state transitions at different spatial scales. While the pattern of global state transitions led to the conclusion that the brain changes state less frequently during ictal activity, locally, it experienced a higher rate of state transition. Furthermore, our results for different patterns of state transitions in the seizure-onset-zone between SF and NSF patients could have a practical application in predicting surgical outcome.

OBJECTIVEFor patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone may be more arduous than for other types of epilepsy and frequently requires information from multiple noninvasive presurgical modalities and intracranial EEG (icEEG). In this prospective, blinded study, the authors assessed the clinical added value of magnetic source imaging (MSI) in the presurgical evaluation of patients with NLRFE.METHODSThis study prospectively included 57 consecutive patients with NLRFE who were considered for epilepsy surgery. All patients underwent noninvasive presurgical evaluation and then MSI. To determine the surgical plan, discussion of the results of the presurgical evaluation was first undertaken while discussion participants were blinded to the MSI results. MSI results were then presented. MSI influence on the initial management plan was assessed.RESULTSMSI results influenced patient management in 32 patients. MSI results led to the following changes in surgical strategy in 14 patients (25%): allowing direct surgery in 6 patients through facilitating the detection of subtle cortical dysplasia in 4 patients and providing additional concordant diagnostic information to other presurgical workup in another 2 patients; rejection of surgery in 3 patients originally deemed surgical candidates; change of plan from direct surgery to icEEG in 2 patients; and allowing icEEG in 3 patients deemed not surgical candidates. MSI results led to changed electrode locations and contact numbers in another 18 patients. Epilepsy surgery was performed in 26 patients influenced by MSI results and good surgical outcome was achieved in 21 patients.CONCLUSIONSThis prospective, blinded study showed that information provided by MSI allows more informed icEEG planning and surgical outcome in a significant percentage of patients with NLRFE and should be included in the presurgical workup in those patients.

Introduction The photoparoxysmal response (PPR) is defined as the occurrence of generalized spike, spike-wave or polyspike-wave discharges consistently elicited by intermittent photic stimulation (IPS). PPR is not well studied in the African black subject Method We prospectively studied the epidemiological, clinical and EEG characteristics of PPR among consecutive epileptic patients seen in the EEG laboratory at Fann University Hospital at Dakar in Senegal. Result Among 3065 pathological EEGs for one year, we collected 56 EEGs (1.8%) with PPR, including 31 women and 25 men (sex ratio: 0.8). The mean age was 13.3 years (range: 8 months to 59 years). The peak of photosensitivity was found in the range of 6 to 10 years. Of the PPR cases, 40 were not known epileptic, of whom 12 had had clinical manifestations during IPS. 23% of patients were classified with generalized epilepsy, followed by 17% of focal epilepsy. The most epileptogenic stimulation frequencies are between 12 and 24 Hz. PPR were obtained most often when the eyes are closed (64%) and 41 patients (73% of patients) were classified as Type 4 (Waltz classification). Conclusion Our results suggests lower rates of photosensitivity in sub-Saharan people compared with Caucasians. Therefore, subject to consistent larger cohorts data, it would be interesting to study a probable epigenetic protective value of sunshine against photosensitivity.

Taenia solium neurocysticercosis (NCC) is a major cause of neurological morbidity in the world. Variability in the neuropathology and clinical presentation of NCC often make it difficult to diagnose and manage. Diagnosis of NCC can be challenging especially in endemic and resource-limited countries where laboratory and imaging techniques are often lacking. NCC management can also be challenging as current treatment options are limited and involve symptomatic agents, antiparasitic agents, or surgery. Although antiparasitic treatment probably reduces the number of active lesions and long-term seizure frequency, its efficacy is limited and strategies to improve treatment regimens are warranted. Treatment decisions should be individualized in relation to the type of NCC. Initial measures should focus on symptomatic management, with antiparasitic therapy only to be considered later on, when appropriate. Symptomatic treatment remains the cornerstone in NCC management which should not only focuses on epilepsy, but also on other manifestations that cause considerable burden (recurrent headaches, cognitive decline). Accurate patients’ categorization, better antiparasitic regimens, and definition of new clinical outcomes for trials on NCC could improve management quality and prognosis of NCC. Prevention strategies targeting tapeworm carriers and infected pigs are yielding good results in local models. If local elimination of transmission is confirmed and replicated, this will open the door to cysticercosis eradication efforts worldwide., Video abstract