Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology.

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE as well as 60 age and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, on the other hand, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, while hippocampal functional topographies were unaffected. Leveraging MRI proxies of MTL pathology, we furthermore observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic, but again not semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, while episodic processes are supported by a network involving both the hippocampus and neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.

Interictal stereo-electroencephalography features below 45 Hz are sufficient for correct localization of the epileptogenic zone and postsurgical outcome prediction.

OBJECTIVE: Evidence suggests that the most promising results in interictal localization of the epileptogenic zone (EZ) are achieved by a combination of multiple stereo-electroencephalography (SEEG) biomarkers in machine learning models. These biomarkers usually include SEEG features calculated in standard frequency bands, but also high-frequency (HF) bands. Unfortunately, HF features require extra effort to record, store, and process. Here we investigate the added value of these HF features for EZ localization and postsurgical outcome prediction. METHODS: In 50 patients we analyzed 30 min of SEEG recorded during non-rapid eye movement sleep and tested a logistic regression model with three different sets of features. The first model used broadband features (1-500 Hz); the second model used low-frequency features up to 45 Hz; and the third model used HF features above 65 Hz. The EZ localization by each model was evaluated by various metrics including the area under the precision-recall curve (AUPRC) and the positive predictive value (PPV). The differences between the models were tested by the Wilcoxon signed-rank tests and Cliff's Delta effect size. The differences in outcome predictions based on PPV values were further tested by the McNemar test. RESULTS: The AUPRC score of the random chance classifier was .098. The models (broad-band, low-frequency, high-frequency) achieved median AUPRCs of .608, .582, and .522, respectively, and correctly predicted outcomes in 38, 38, and 33 patients. There were no statistically significant differences in AUPRC or any other metric between the three models. Adding HF features to the model did not have any additional contribution. SIGNIFICANCE: Low-frequency features are sufficient for correct localization of the EZ and outcome prediction with no additional value when considering HF features. This finding allows significant simplification of the feature calculation process and opens the possibility of using these models in SEEG recordings with lower sampling rates, as commonly performed in clinical routines.

Real-world practices in reproductive health and counselling for women with epilepsy: A Canadian perspective.

Canadian women of reproductive potential living with epilepsy present unique care challenges due to the complex interplay of hormones, seizures, and medications. This study explores reproductive health practices and counselling for women with epilepsy. Through a questionnaire developed by the Canadian League Against Epilepsy women with epilepsy (WWE) workgroup, we are the first to report demographic and real-world practice characteristics of Canadian healthcare professionals providing care for WWE with specific focus on family planning, birth plans, and postpartum care counselling. Among respondents, 76.9% routinely reviewed contraception with patients and an intrauterine device (IUD) was the most popular recommended method (85.3%). With regards to preconception planning, 50% of respondents routinely had a preconception drug level prior to pregnancy. A significant proportion, 44.9%, reported not communicating a neurology-informed birth plan to obstetrical health practitioners. The majority recommended breastfeeding for WWE on anti-seizure medications (92.3%) and regularly provided safety counselling for women in the postpartum period (84.6%). Overall, our study demonstrates that Canadian practice patterns conform reasonably well to existing evidence and guidelines, although important gaps in care exist.

Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies.

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Real-world practices for the care of women with epilepsy during pregnancy: A Canadian perspective.

OBJECTIVE: Approximately 150,000 Canadian women live with epilepsy, a population that presents with unique challenges. Our objective was to capture demographic and real-world practice characteristics of Canadian healthcare professionals providing care for women with epilepsy (WWE) with specific focus on reproductive considerations to identify potential gaps in knowledge and care. METHODS: A questionnaire developed by the Canadian League Against Epilepsy WWE workgroup was distributed to Canadian healthcare professionals from February 2021 to October 2022 to capture participant demographic characteristics and practice patterns in key areas of the reproductive cycle in WWE. RESULTS: A total of 156 participants completed the questionnaire, most being physicians (81.4%), epilepsy specialists (69.0%), and those who cared for adult patients (86.5%), with a significant proportion based at an academic center (65.4%). The majority of participants counselled on folic acid supplementation (89.7%). Participants selected lamotrigine and levetiracetam most frequently for either focal or generalized epilepsies during pregnancy. Additionally, 85.9% performed therapeutic drug monitoring during pregnancy. Almost all practitioners always or often counseled WWE on valproic acid on the benefits of switching to a less teratogenic medication (96.2%). Some geographic variability in practice patterns was noted with valproic acid being one of the top three medications selected for patients with generalized epilepsies in Western regions, although participants in Eastern regions had brivaracetam more commonly included as one of their top three agents for this population. SIGNIFICANCE: This is the first report of real-world Canadian practices in epilepsy care for women in pregnancy. Overall, our study reports that Canadian practice patterns conform well to current evidence and best-practice guidelines. Important variations in antiseizure medication selection across different regions were identified.

Evaluation of the "non-epileptic" patient in a tertiary center epilepsy clinic.

PURPOSE: The epilepsy clinic at the Montreal Neurological Institute receives a high volume of referrals. Despite most patients assessed in the clinic eventually being diagnosed with epilepsy, other disorders causing alteration of consciousness or paroxystic symptoms that could be misdiagnosed as seizures are seen frequently. The incidence and clinical characteristics of such patients have not yet been determined. We aimed to determine the proportion and clinical characteristics of patients referred to our epilepsy clinic who had a final diagnosis other than epilepsy. METHODS: We performed a retrospective chart analysis of consecutive patient referrals to the epilepsy clinic from January 2013 to January 2015, inclusively. RESULTS: Four hundred four patient referrals were evaluated, 106 (or 26%) had a final diagnosis other than epilepsy. Referrals came primarily from general practitioners and nonneurology specialists. Although most patients had a normal routine electroencephalography (EEG) prior to the clinic visit, sleep-deprived EEG and cardiac investigations were rarely performed. Patients received a final diagnosis other than epilepsy after 1 to 2 visits in 92% of cases and with minimal paraclinical investigations. Prolonged video-EEG recording was required in 27% of patients. The most common diagnoses were syncope (33%), psychiatric symptoms (20%), followed by migraine (10%), and psychogenic nonepileptic seizures (9%). CONCLUSIONS: A significant proportion of patients seen in our tertiary care epilepsy clinic is in fact, not patients with epilepsy. Enhanced knowledge of these differential diagnosis and important anamnesis components to rule out seizures will help improve guidelines for referral to Epilepsy clinic and cost-effectively optimize the use of paraclinical investigations.

Electroencephalography-functional magnetic resonance imaging for clinical evaluation in focal epilepsy.

OBJECTIVE: We aimed to evaluate the contribution of simultaneous recording of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in the diagnosis of epilepsy syndrome, localization of the epileptogenic zone (EZ), and decision-making regarding surgical treatment. METHODS: We performed a retrospective study to evaluate patients with focal epilepsy who underwent EEG-fMRI. Two evaluators assessed epilepsy syndrome, presumed focus, and surgical candidacy and defined confidence levels. They assessed these clinical characteristics first without EEG-fMRI and then including EEG-fMRI to assess how the results of EEG-fMRI changed the evaluations. We also determined how the clinical evaluation was affected by the concordance level between the blood oxygen level-dependent (BOLD) response and the presumed focus location, and by the confidence level of the BOLD response itself based on the t-value of the primary and secondary clusters. RESULTS: Fifty-one scans from 48 patients were included. The BOLD map affected 66.7% of the evaluations by altering evaluation items (epilepsy syndrome, presumed focus, or surgical candidacy) or their confidence levels. EEG-fMRI results increased the confidence levels of epilepsy syndrome, presumed focus, or surgical candidacy in 47.1% of patients but reduced clinical confidence in these features in 11.8%. More specifically, the confidence levels increased for epilepsy syndrome in 28.5%, identification of presumed focus in 33.9%, and determination of surgical candidacy in 29.4%. The BOLD signal confidence level, whether high or low, did not influence these clinical factors. SIGNIFICANCE: Previous studies have emphasized the utility of EEG-fMRI for the localization of the epileptogenic zone. This study demonstrated the potential of EEG-fMRI to influence clinical confidence when determining epilepsy syndrome, the presumed epileptic focus, and surgical candidacy.

Four Atypical Cases of Subclinical Rhythmic Electroencephalogram Discharge of Adults: Case Series and Review.

SUMMARY: Subclinical rhythmic EEG discharge of adults is an uncommon variant that represents a diagnostic challenge in the clinical practice because it can be mistaken for an electrographic seizure. We present a case series of four patients who underwent EEG because of suspicious events or an unclear medical history of epilepsy. In all cases, the EEG revealed atypical features including focal and asymmetric distribution, presentation during NREM and REM sleep, rhythmic activity in the delta range with a notched appearance and blocked by eyes opening.

Development of a stereo-EEG based seizure matching system for clinical decision making in epilepsy surgery.

Objective.The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography (SEEG) datasets can allow comparing new patients to past similar cases and making clinical decisions with the knowledge of how cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients impractical. We aim to develop an automated system that electrographically and anatomically matches seizures to those in a database. Additionally, since features that define seizure similarity are unknown, we evaluate the agreement and features among experts in classifying similarity.Approach.We utilized 320 SEEG seizures from 95 consecutive patients who underwent epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score. As our primary outcome, we developed and validated an automated seizure matching system by employing patient data marked by independent experts. Secondary outcomes included the inter-rater agreement (IRA) and features for classifying seizure similarity.Main results.The seizure matching system achieved a median area-under-the-curve of 0.76 (interquartile range, 0.1), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman's rho = 0.75,p< 0.001). Additionally, the moderate IRA confirmed the practicality of our approach with an agreement of 73.9% (7%), and Gwet's kappa of 0.45 (0.16). Further, the interoperability of the system was validated on seizures from five centers.Significance.We demonstrated the feasibility and validity of a SEEG seizure matching system across patients, effectively mirroring the expertise of epileptologists. This novel system can identify patients with seizures similar to that of a patient being evaluated, thus optimizing the treatment plan by considering the results of treating similar patients in the past, potentially improving surgery outcome.

Anterior Cingulate Epilepsy: A Review.

SUMMARY: In this review, the semiology, and characteristics of noninvasive investigations suggestive of anterior cingulate and anterior midcingulate epilepsy are detailed by the authors. The clinical presentation is representative of a recently recognized rostrocaudal gradient of functional connectivity with seizures of the anterior cingulate cortex manifesting emotional and interoceptive aura followed by a hyperkinetic or complex motor seizures. The few reports of anterior midcingulate epilepsy show a trend toward a higher proportion of sensory auras and premotor semiology. Ictal pouting, vocalizations, and, in particular, laughter are strong indicators of epilepsy arising or spreading to this region. Although scalp EEG was traditionally thought to provide little information, the data provided in this review demonstrate that most patients will have abnormalities over the frontal or frontotemporal regions. Frontotemporal abnormalities at least interictally provide valuable information regarding lateralization. The etiology of epilepsy arising from the anterior cingulate region seems to be most frequently secondary to focal cortical dysplasia (FCD), followed by neoplasms and vascular lesions, particularly cavernomas, although one cannot rule out a publication bias. Findings of nuclear medicine imaging is seldomly reported but both positron emission tomography and ictal single-photon computed tomography can identify the generator or the network often showing abnormalities extending to the frontal regions. The few available magnetoencephalography (MEG) studies reveal mixed results, sometimes providing false lateralization of the focus. Anterior cingulate epilepsy is difficult to recognize, but the features summarized in this review should prompt suspicion in clinical practice.

Eslicarbazepine for focal epilepsy and acute intermittent porphyria.

Porphyrias are rare genetic disorders which cause a deficiency in the enzymes involved in the biosynthesis of heme. The treatment of epilepsy in patients with acute intermittent porphyria can be difficult since many anticonvulsants can increase heme synthesis and trigger porphyric attacks. We report a patient with focal epilepsy successfully treated with eslicarbazepine without exacerbation of porphyria.

Ictal asystole with intercurrent cardiopathy: a complex combination leading to delayed diagnosis.

Ictal asystole is a rare epileptic phenomenon, though usually self-limiting, which has been associated with an increased risk of sudden death in epileptic patients. Although early recognition is desirable, the diagnosis can be delayed until prolonged video-EEG monitoring is completed. We report a case of ictal asystole in a 74-year-old patient with co-morbid cardiac conditions leading to a delay in diagnosis of approximately 10 years. Indeed, multiple cardiac investigations and EEGs failed to reveal that the recurrent syncope was seizure induced. A detailed description of the case with an emphasis on the prolonged diagnostic process, as well as the clinical and EEG findings, is provided. This case highlights the complexity of the diagnosis of some ictal asystole cases and the need to perform continuous video-EEG monitoring for confirmation. [Published with video sequence].