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Epilepsy Research

Elsevier BV

All preprints, ranked by how well they match Epilepsy Research's content profile, based on 14 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Attributional bias in epilepsy: differences between genetic generalised epilepsy, temporal lobe epilepsy and healthy controls

Pytelova, V.; Gatialova, E.; Zalud, J.; Modrak, M.; Ksirova, E.; Kalinova, M.; Kalina, A.; Marusic, P.; Amlerova, J.

2026-04-29 neurology 10.64898/2026.04.28.26351955 medRxiv
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BackgroundAttributional bias, a tendency to overinterpret others intentions as hostile (rather than situational or accidental), represents a component of social cognition and may affect everyday functioning. Neural models link attributional processing to fronto-temporal circuits and the default mode network, which are frequently altered in epilepsy. Difficulties in social participation and employment are common in people with epilepsy, and maladaptive attributional styles may contribute to these challenges. Attributional bias has not been systematically compared across epilepsy syndromes. MethodsWe examined attributional bias in 96 participants comprising 26 individuals with genetic generalised epilepsy (GGE), 27 with temporal lobe epilepsy (TLE), and 43 healthy controls (HC). Attributional style was assessed using the Ambiguous Intentions Hostility Questionnaire. Depressive symptoms were evaluated using the Neurological Disorders Depression Inventory in Epilepsy. Group differences were analysed, and potential clinical and demographical correlates were explored. ResultsThe GGE group exhibited higher hostility bias scores than HC (95% CI: 0.12-0.38, adjusted p = 0.014), whereas the difference between TLE and HC groups was moderate and not statistically significant (95% CI: 0.12-0.58, adjusted p = 0.059). Higher blame scores were positively associated with depressive symptoms (p = 0.016). Disease duration, seizure frequency, and antiseizure medication were not significantly associated with attributional bias. ConclusionsThese findings suggest that some individuals with genetic generalised epilepsy are more likely to interpret ambiguous situations as hostile. Altered attributional style may represent an under-recognised factor contributing to social difficulties in people with epilepsy and warrants further investigation as a potential target for psychosocial interventions. HighlightsO_LISome people with epilepsy are more prone to interpret social situations as hostile. C_LIO_LIHigher depression scores correlate with a tendency to blame external factors for misfortunes. C_LIO_LIDisease duration, antiseizure medication, and seizure frequency do not seem to influence the attributional bias. C_LI

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Central-positive complexes in ECT-induced seizures: Evidence for thalamocortical mechanisms

Huels, E. R.; Hickman, L. B.; Ching, S.; Lenze, E. J.; Farber, N. B.; Avidan, M. S.; Hogan, R. E.; Palanca, B. J. A.

2020-05-04 psychiatry and clinical psychology 10.1101/2020.04.28.20072520 medRxiv
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Electroconvulsive therapy (ECT) relies on the electrical induction of generalized seizures to treat major depressive disorder and other psychiatric illnesses. These planned procedures provide a clinically relevant model system for studying neurophysiologic characteristics of generalized seizures. We recently described novel central-positive complexes (CPCs), which were observed during ECT-induced seizures as generalized, high-amplitude waveforms with maximum positive voltage over the vertex. Here, we performed a systematic characterization of 6,928 CPC ictal waveforms recorded in 11 patients undergoing right unilateral (RUL) ECT. Analyses of high-density 65-electrode EEG recordings during these 50 seizures allowed evaluation of these CPCs across temporal, spatial, and spectral domains. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. Total duration of CPCs positively correlated with the time required for return of responsiveness after ECT treatment (r = 0.39, p = 0.005). The rate of CPCs showed a frequency decline consistent with an exponential decay (median 0.032 (IQR 0.053) complexes/second). Gamma band (30-80 Hz) oscillations correlated with the peak amplitude of CPCs, which was also reproducible across seizures, with band power declining over time (r = -0.32, p < 10-7). The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Our findings demonstrated CPC characteristics that were invariant to participant, stimulus charge, time, and agent used to induce general anesthesia during the procedure. Consistent with ictal waveforms of other generalized epilepsy syndromes, CPCs showed topographic distribution over the fronto-central regions, predictable intra-seizure frequency decline, and correlation with gamma-range frequencies. Furthermore, source localization to the medial thalamus was consistent with underlying thalamocortical pathophysiology, as established in generalized epilepsy syndromes. The consistency and reproducibility of CPCs offers a new avenue for studying the dynamics of seizure activity and thalamocortical networks.

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Paradoxical relief after seizures: a diagnostic signal distinguishing functional/dissociative from epileptic seizures

Masharani, A.; Koreki, A.; Marcelo, M.; Shalfrooshan, K.; Diamos, M.-A.; Santucci, C.; Pillai, K.; Bindman, D.; O'Sullivan, S.; Rugg-Gunn, F.; Sidhu, M.; Yogarajah, M.

2026-08-31 neurology 10.64898/2026.08.27.26360607 medRxiv
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Objective: To determine whether paradoxical relief, feeling unusually better after a seizure compared to before it, is more common after functional/dissociative seizures (FDS) than epileptic seizures (ES), quantify its diagnostic accuracy, and explore its relationship with preictal symptoms. Methods: Consecutive patients admitted to a tertiary epilepsy unit for prolonged inpatient EEG monitoring underwent a structured clinical interview on admission, before final multidisciplinary diagnostic classification. Preictal dissociative and autonomic/somatic symptom burden was assessed using items adapted from established questionnaires. Diagnostic classification incorporated clinical history, seizure semiology, video electroencephalography findings, and collateral information. Patients with dual or indeterminate diagnoses were excluded. Associations with paradoxical relief were examined using logistic regression, followed by an exploratory mediation analysis. Results: Of 176 patients assessed, 66 with FDS and 65 with ES were included. Paradoxical relief was reported by 46/66 patients with FDS (69.7%) and 10/65 with ES (15.4%; unadjusted odds ratio [OR] 12.65, 95% confidence interval [CI] 5.57 to 31.09). As a diagnostic signal for FDS, paradoxical relief had 69.7% sensitivity (95% CI 57.1 to 80.4), 84.6% specificity (95% CI 73.5 to 92.4), a positive likelihood ratio of 4.53 (2.51 to 8.19), and a negative likelihood ratio of 0.36 (0.24 to 0.52). FDS diagnosis remained independently associated with paradoxical relief after adjustment (OR 10.59, 95% CI 3.42 to 38.06). In a parallel mediation analysis, dissociative symptom burden showed a significant indirect effect, accounting for 19.5% of the association between diagnostic group and relief, whereas the indirect effect through somatic/autonomic symptom burden was not significant. Significance: Paradoxical relief is substantially more common after FDS than ES and may provide a simple, clinically useful diagnostic signal. Its absence does not exclude FDS, and the finding requires external validation. The association with dissociative symptoms is exploratory and supports prospective investigation of whether relief reflects transient resolution of a disturbed, disembodied preictal state.

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Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Zeicu, C.; Legouhy, A.; Scott, C. A.; Oliveira, J. F. A.; Winston, G.; Duncan, J. S.; Vos, S. B.; Thom, M.; Lhatoo, S.; Zhang, H.; Harper, R. M.; Diehl, B.

2023-03-17 neurology 10.1101/2023.03.16.23287369 medRxiv
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Abstract and key wordsO_ST_ABSObjectivesC_ST_ABSSudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA). Methods73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG. ResultsBilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort. Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI values vs the non-apnea FBTCS group (p=0.004). SignificanceIndividuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

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Determinants of quality of life in Latin American people with drug-resistant epilepsy: A cross-sectional, correlational study

Diaz-Torres, M. A.; Buzo-Jarquin, E. G.; Rodriguez-Martinez, A. C.; de Leon-Altamira, D. L.; Padilla-Rivas, G.; Castillo-Torres, S. A.; Olivas-Reyes, J. E. G.; Cisneros-Franco, M.

2020-07-04 neurology 10.1101/2020.07.03.20146019 medRxiv
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One third of people with epilepsy (PWE) continue to have seizures despite adequate antiepileptic drug treatment. This condition, known as drug-resistant epilepsy (DRE) significantly impairs their social, family and work environment. The aims of this study were to assess the quality of life (QoL) in PWE with DRE and to investigate which factors are associated with a better QoL. This was a cross-sectional observational study of 133 Latin American PWE. QoL was assessed with the Spanish version of the Quality of Life with Epilepsy questionnaire (QOLIE-10). Independent clinical variables were analyzed with non-parametric statistics and their association with QoL was investigated with multiple linear regression. Poor quality of life was found in 25.8% of PWE. A low number of antiepileptic drugs (AEDs) was the major factor associated with better quality of life, closely followed by seizure frequency. We conclude that careful selection of AED treatment may contribute to improving both seizure control and QoL.

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Cognitive Impairment Among People with Epilepsy in Peru

Allen, S. E.; Phillips, C.; Wardle, M. T.; Moyano, L. M.; Bustos, J. A.; Rojas, L. L.; Reto, N.; Bolivar, L. M.; O'Neal, S.; Garcia, H. H.; Cysticercosis Working Group in Peru (CWGP),

2026-08-31 neurology 10.64898/2026.08.28.26361672 medRxiv
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Objective: Cognitive impairment is a common comorbidity among people with epilepsy (PWE) and is associated with disability and reduced quality of life. We characterized the burden of cognitive impairment and identified factors associated with cognitive performance in a large, population-based cohort of PWE living in Northern Peru, a region highly endemic for Taenia solium where neurocysticercosis (NCC) is a common cause of acquired epilepsy. Methods: PWE enrolled in a population-based cohort in Northern Peru between 2007 and 2020 completed the Mini-Mental State Examination (MMSE) at enrollment. Cognitive impairment was defined as an MMSE score <24. Demographic and clinical data, including epilepsy characteristics and NCC status, were collected. Negative binomial regression was used to identify factors associated with the number of MMSE errors. Results: Among 764 participants, the mean MMSE score was 26.4 (SD 4.2), and 16.4% met criteria for cognitive impairment. Memory and attention were the most affected domains. In multivariable analysis, older age and lower educational attainment were independently associated with poorer cognitive performance. Conclusion: In this large, community-based cohort from Northern Peru, approximately 1 in 6 PWE had abnormal global cognition on the MMSE, with memory and attention most affected. These findings underscore the importance of incorporating cognitive evaluation and management into comprehensive epilepsy care, particularly in resource-limited settings where cognitive morbidity may be underrecognized. Given the potential for cognitive difficulties to compound disability and adversely affect quality of life, identifying and addressing cognitive morbidity may be especially important in populations already facing substantial barriers to epilepsy care.

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Healthcare Equity in Epilepsy Surgery: Equivalent Outcomes Between NAEC-IV Public Safety-Net and Tertiary Academic Centers in a Major Metropolitan Area

Lam, J.; Mehta, V.; Russin, J.; Millett, D.; Shaw, S.; Liu, L.; Lee, B.; Kalayjian, L.; Armacost, M.; Gong, H.; Heck, C.; Lee, D.; Liu, C.

2024-11-04 neurology 10.1101/2024.11.04.24316317 medRxiv
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Access to and delivery of quality surgical epilepsy care remains a challenge in both safety-net and private hospital systems. Underserved populations are more likely to utilize safety-net hospital systems, but there are few data on epilepsy surgery outcomes in this setting. We aimed to analyze and compare surgical epilepsy care in a safety-net versus private hospital system. We prospectively collected evaluation and treatment data in patients undergoing resective surgery for epilepsy at a safety-net hospital system and a collaborating private hospital system between 2010-2017. Seizure characteristics, pre-surgical evaluation, perioperative complications, and seizure outcomes were prospectively recorded. Data from 102 patients in the safety-net and 145 patients in the private hospital system were analyzed. There were higher proportions of African American (p=.02) and Hispanic patients (p= .03) in the safety-net hospital system. There was no difference in mean time from epilepsy onset to surgery between groups (p=.54). The presurgical evaluation was equivalent (p>.18), except for more frequent use of magnetoencephalography in the private system (p=.02). Seizure freedom outcomes were excellent, and complication rates were low with no significant differences between groups (p=.95 and p>.22, respectively). However, patients from safety-net hospital systems were more likely to be lost to follow up (p=.04). Quality and equitable surgical epilepsy care can be delivered in a safety-net hospital system despite the higher-minority demographics and intrinsic factors of safety-net hospitals. Partnership of safety-net hospital systems with established comprehensive epilepsy centers and the expansion of these services is essential for healthcare equity in modern epilepsy care.

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The predictive value of interictal scalp EEG findings in aiding the detection of malformations of cortical development in temporal lobe epilepsy and impact on surgical planning

Fuchs, J. W.; Shlobin, N. A.; Hopkins, B. S.; Husain, Z.; Cloney, M. B.; Tyrtova, E.; Farooque, P.; Templer, J. W.; Bandt, S. K.

2021-05-14 neurology 10.1101/2021.05.08.21256883 medRxiv
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BackgroundComplete resection of focal malformations of cortical development (MCD) has been recognized as crucial for the success of epilepsy surgery. However, many of these lesions escape detection using even state-of-the-art epilepsy protocol MRI imaging. This study evaluates the concurrence of radiographic and histopathologic findings of MCD in patients with refractory temporal lobe epilepsy (TLE) and defines the predictive value of EEG findings in the detection of MCD. Materials and MethodsPre-operative MRI, scalp VEEG, and post-operative surgical pathology reports from 34 consecutive patients treated for refractory TLE by surgical resection over a ten year period were included in analysis. Radiographic findings of MCD were correlated with histopathologic findings of MCD and compared against pre-operative interictal scalp EEG findings. Results66.7% of focal cortical dysplasias (FCD) identified on pathology and all cases of mild MCD (mMCD) were missed on pre-operative MRI. The description of a rhythmic or continuous interictal abnormality on pre-operative VEEG corresponds to a sensitivity of 73.1% and a specificity of 62.5% in detecting either FCD or mMCD. Of the patients who had a radiographically occult FCD, 80% had either a continuous or rhythmic interictal abnormality described in the interpretation of their pre-operative VEEG. ConclusionThis study highlights the high prevalence of MCDs in refractory TLE and the high rate of missed MCDs on pre-operative MRI. Findings here suggest that pre-operative scalp EEG may be able to provide additional information in the pre-operative detection of MCDs and therefore inform surgical decision making.

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A Study On Clinical Profile And Semiology In Complex Partial Seizures And Its Radiological Correlation

Balasubramani, N. P.; S, E.; M, T.

2021-05-29 neurology 10.1101/2021.05.26.21257846 medRxiv
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BackgroundEpilepsy is the second most common and frequently encountered neurological disorder which poses huge threat to known healthcare systems worldwide also causing financial, socio economic burden to the community. Complex Partial Seizures are a form of focal epileptic seizures that may impair consciousness. Aim and objectivesOur motivation for the study was to understand the extent of patients with complex partial seizures associated with medial temporal lobe sclerosis. Materials and methodsWe performed a cross sectional study about patients with complex partial seizures in Thanjavur medical college and hospital about their clinical profile and neuro-radiological correlation. Statistical analysis and resultsThrough our multimodal study with EEG, MRI on N=118 (female / male, age range, Most common age group-10-20 years, mean age of 23 years, SD-14 years, 66% males), we observed that atypical febrile seizures and fever provoked seizures has more association (18%) to complex partial seizures and to medial temporal lobe sclerosis in comparison to 12% in an earlier study. ConclusionWe believe this study summarizes the complex partial seizure features, origin, and their link to Medial Temporal lobe Sclerosis in our subject pool from Thajavur, India. LimitationThere are some limitations to our study, especially with no video EEG monitoring and no invasive EEG recording. We aim to improve them in our future studies.

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Mean Dynamics Index: a useful tool to identify motor psychogenic non epileptic seizures.

Winer, R.; Shahkoohi, S. S.; Herskovitz, M.

2024-02-08 neurology 10.1101/2024.02.07.24302379 medRxiv
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Timely and accurate diagnosis of Psychogenic Non-Epileptic Seizures (PNES) is crucial. Aside from potential diagnostic delays, patients with PNES often undergo unnecessary pharmacological or invasive treatments. Presently, effective bedside tools for distinguishing PNES from epileptic seizures (ES) remain elusive, and the gold standard diagnosis relies primarily on patient history and prolonged video EEG monitoring. In this study, we developed a simple clinical tool - the Mean Dynamic Index (MD) - to differentiate PNES from ES. We divided the body into five anatomical regions: the head and face, two upper extremities, and two lower extremities. Due to limited movement potential, the trunk was excluded from consideration. Among these five areas, only actively involved regions were considered in the score calculation. Each distinct motor feature observed contributed a point to the regional summation, with each regions score comprising the Regional Dynamic Index (RDI). The Mean Dynamic Index (MDI) represents the average of all RDIs. Sixty consecutive patients admitted to the VEEG monitoring unit were evaluated. Of these, 15 patients presented primarily with motor symptoms. Eight were diagnosed with PNES, while seven had epileptic seizures. The mean MDI was 1.2{+/-}0.4 in the PNES group and 2.8{+/-}0.77 in the ES group (p<0.001). The mean MDI/duration ratio was 0.31{+/-}0.38 for PNES and 3.5{+/-}2.4 for ES (p < 0.003). An MDI score of 1.665 yielded a specificity of 87.5% and sensitivity of 100% for diagnosing ES. A low MDI score (<1.66) in motor seizures indicates limited variability in the movement profile of each body part, suggesting a PNES etiology. Additionally, as the MDI/time ratio decreases, PNES becomes more likely. Furthermore, we observed that an RDI of 3 or higher completely differentiated between PNES and ES. These findings offer a valuable bedside tool for distinguishing between the two conditions.

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A novel mouse model of focal limbic seizures that reproduces behavioral impairment associated with cortical slow wave activity

Sieu, L.-A.; Singla, S.; Sharafeldin, A.; Chandrasekaran, G.; Valcarce-Aspegren, M.; Niknahad, A.; Fu, I.; Doilicho, N.; Gummadavelli, A.; McCafferty, C. P.; Crouse, R. B.; Perrenoud, Q.; Picciotto, M.; Cardin, J. A.; Blumenfeld, H.

2021-05-06 neuroscience 10.1101/2021.05.05.442811 medRxiv
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Patients with focal temporal lobe seizures often experience loss of consciousness. In humans, this loss of consciousness has been shown to be positively correlated with EEG neocortical slow waves, similar to those seen in non-REM sleep. Previous work in rat models of temporal lobe seizures suggests that decreased activity of subcortical arousal systems cause depressed cortical function during seizures. However, these studies were performed under light anesthesia, making it impossible to correlate behavior, and therefore consciousness, to electrophysiologic data. Further, the genetic and molecular toolkits allowing for precise study of the underlying neural circuitry are much more developed in mice than in rats. Here, we describe an awake-behaving, head-fixed mouse model of temporal lobe seizures with both spared and impaired behavior reflecting level of consciousness. Water-restricted mice were head-fixed on a running wheel and trained to associate an auditory stimulus to the delivery of a drop of water from a dispenser. To investigate the effect of seizures on behavior, seizures were electrically induced by stimulating either the left or right hippocampus via a chronically-implanted electrode, while mice were performing the task. Behavior was measured by monitoring lick responses to the auditory stimulus and running speed on the wheel. Further, local field potentials (LFP) signals were simultaneously recorded from hippocampus and orbitofrontal cortex (OFC). Induced focal seizures were 5-30s in duration, and repeatable for several weeks (n=20 animals). Behavioral responses showed a decrease in lick rate to auditory stimulus, and decreased running speed during seizures (p<0.01, n=20 animals). Interestingly, licking response to sound could vary from being impaired to normal during seizures. We found that behavioral impairment is correlated with large amplitude cortical slow-wave activity in frontal cortex, as seen in patients with temporal lobe seizures. These results suggest that induced focal limbic seizures in the mouse can impair consciousness and that the impaired consciousness is correlated with depressed cortical function resembling slow wave sleep. This novel mouse model has similar characteristics with previously studied rat models and human temporal lobe seizures. By leveraging the genetic and molecular techniques available in the mouse, this model can be used to further uncover fundamental mechanisms for loss of consciousness in focal seizures.

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A systematic review to assess seizure risk with chloroquine therapy in persons with epilepsy

Pati, S.

2020-04-14 neurology 10.1101/2020.04.09.20056358 medRxiv
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BackgroundThe goal of this systematic review is to assess the published literature for seizure risk with chloroquine therapy in persons with and without epilepsy. With the COVID-19 pandemic, there is a desperate need for therapy against the SARS CoV-2 virus. Chloroquine is one proposed medication that has received substantial public attention. However, drug labeling in the package insertion states that persons with epilepsy have the risk of chloroquine provoking seizures, and this has increased questions and anxiety in the epilepsy community. MethodsPubMed (1970 to March 27, 2020) and the Embase (1970 to March 27, 2020) were searched with the terms chloroquine and seizure or epilepsy. Selected studies were reviewed, and the adverse drug reaction was classified. ResultsOnly nine out of 27 studies were deemed eligible for systematic analysis. Out of the nine studies, only one was a prospective study (N=109), two were case series (N=6), and the remaining 6 were case reports. The dose of chloroquine ranged between 100-500 mg/day, except in one patient, the seizure was after taking 1000 mg. The strength of causality for the drug causing seizures in healthy and persons with epilepsy was mostly possible or unlikely, and none were certain. The only clinical trial that evaluated seizure risk with chloroquine failed to find any significant relation. ConclusionAlthough the drug insertion label states an increased risk of seizure, the systematic review highlights that such a statement is not supported by any class I studies but by anecdotal case reports. The only randomized clinical study revealed that seizures were not associated with an increased blood level of chloroquine or its metabolite. The present systematic review should provide reassurance to busy clinicians and persons with epilepsy that chloroquine, if prescribed to treat COVID-19, lacks any substantial evidence to suggest that the medication increases the risk of seizure.

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Integrating the cognitive sequelae after temporal lobe surgery into daily life: a mixed methods approach to the consequences of average to severe memory decline

Taube, J.; Middendorf, D.; Taube, G.; Francke, E.; Reinecke, C.; Helmstaedter, L.; Borger, V.; Racz, A.; Surges, R.; Helmstaedter, C.

2026-08-05 neurology 10.64898/2026.08.03.26359089 medRxiv
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Background: Temporal lobe epilepsy surgery (TLS) is an effective treatment for drug-resistant focal epilepsy but is often associated with cognitive decline. A key unresolved question is how to distinguish average from severe memory loss and how these levels differentially affect everyday life. We addressed this question applying patient-derived norms of memory decline and conducting qualitative inter-views with patients experiencing expected or unexpectedly severe memory loss. Methods: Regression-based normative change criteria for postoperative verbal memory loss were derived from a single-center cohort of 806 patients. Two matched groups of four patients each were selected from the severe memory de-cline (SMD; below the 5th percentile) and average memory decline (AMD; 20th - 75th percentile) ranges. In-depth, semi-structured narrative interviews were analyzed using qualitative content analysis with a combined deductive-inductive ap-proach. Results: AMD narratives emphasized recovery, with surgery integrated into a con-tinuing sense of self. In contrast, SMD descriptions focused on persistent symp-toms, continued treatment, and illness despite meaningful seizure reduction. Pa-tients with SMD also reported limited information, insufficient psychological preparation or postoperative cognitive rehabilitation. Conclusions: Whereas AMD was generally manageable and successfully integrat-ed into everyday life, SMD disrupted identity, autonomy, and expected life trajecto-ries. Current surgical pathways appear to address these cognitive sequelae insufficiently. Improved expectation management, together with structured preoperative counseling and postoperative rehabilitation, may facilitate adaption to memory de-cline and improve long-term functioning and quality of life after surgery.

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Seizure Semiology and Response to Treatment in a Pediatric Cohort with SCN2A Variants: A Parent Report

O'Connor, J. B.; Kirschenblatt, E. B.; Laux, L.; Berg, A. T.; Misra, S. N.; Millichap, J. J.

2023-02-24 neurology 10.1101/2023.02.23.23286378 medRxiv
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We examined seizure semiology and response to medications in 28 children (9 female, 19 male) with likely pathogenic and pathogenic SCN2A-related epilepsy. Parents reported seizure onset, seizure semiology, genetic variants, therapies used for seizures, and response to treatment. 27 children experienced defined seizures and 1 reported no seizure history. The most common initial seizures were focal or hemi-convulsions (n=8). Tonic seizures were the most common reported seizure type while febrile and atonic or drop seizures were the least common. Most patients experienced multiple seizures daily or were entirely seizure-free, with no difference based on age at seizure onset. The proportion of effective trials of the 8 most commonly reported medications ranged from 4 of 26 trials (levetiracetam) to 5 of 10 trials (valproic acid). Phenytoin was the most commonly reported effective treatment (N=4). Topiramate was reported to be the most effective treatment in combination with another treatment (N=6). We found a wide phenotypic spectrum of SCN2A-related disorders and a possible correlation between genotype and seizure onset, semiology, and treatment response. Gain-of-function mutations in early-onset SCN2A epilepsies responded well to sodium channel blockers. Further exploration of SCN2A pathogenic variants are needed to identify mediation mechanisms of action in SCN2A-related epilepsy.

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Understanding Seizures in Malan Syndrome Through Caregiver Reports: A Cross-Sectional Study

Dubey, S.; Hunter, S.; Delagrammatikas, C.; Pinero, G.; Elumalai, V.; Zafar, M. S.

2025-06-14 neurology 10.1101/2025.06.13.25329538 medRxiv
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Malan syndrome is an ultra-rare Overgrowth-Intellectual Disability syndrome caused by pathogenic NFIX variants, characterized by intellectual disability, postnatal overgrowth, and dysmorphic features. Seizures in Malan syndrome remain poorly understood. We surveyed caregivers of 53 individuals with Malan syndrome. Overall, 55% had seizures or EEG abnormalities. Seizures occurred in 47%, with 28% experiencing drug-resistant epilepsy. The median seizure onset was at age 3 years. Epilepsy classifications included focal (40%) and unknown-onset tonic-clonic seizures (48%). Generalized tonic-clonic (8%), myoclonic (8%), and epileptic spasms (4%) were also reported. Status epilepticus was common (44%). Valproic acid was the most used anti-seizure medication, with variable efficacy. This study represents the largest cohort to date, providing detailed descriptions of seizures in Malan syndrome, and lays a foundation for future research phenotyping epilepsy in affected individuals. Clinicians should maintain a high suspicion of seizures and monitor closely for status epilepticus in individuals with Malan syndrome.

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Psychiatric morbidity among patients living with epilepsy at a tertiary referral hospital in western Kenya: A cross-sectional study

Odhiambo, A. A.; Kinyanjui, D. W. C.; Momanyi, R. K.

2026-07-14 psychiatry and clinical psychology 10.64898/2026.07.11.26357815 medRxiv
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Background Psychiatric comorbidities commonly have a negative impact on epilepsy outcomes. However, they are continuously ignored in routine epilepsy care, with focus directed more towards seizure control. There is paucity of data on the burden of psychiatric morbidity among those living with epilepsy in Kenya. This study sought to determine the prevalence and associated factors of psychiatric morbidity among patients living with epilepsy at a tertiary referral hospital in Western Kenya. Methods This was a descriptive cross-sectional study. Consecutive sampling was used to recruit participants, with a sample size of 278. Data were collected using a structured pretested sociodemographic and clinical characteristics questionnaire, and the Mini International Neuropsychiatric Interview (MINI), and analyzed using STATA version 16. Pearson Chi-square test/Fishers Exact test and logistic regression were used to assess relationships at bivariate and multivariate levels respectively. Results The prevalence of psychiatric morbidity was 52.2%. Major depressive disorder was the most prevalent (36%), followed by anxiety disorders (26.2%), psychotic disorders (16.9%), and suicidality (15.1%). Casual/self-employment (aOR=2.590, p=0.020), seizure-related physical trauma (aOR=4.032, p=0.004), antiepileptic polytherapy (aOR=4.280, p=0.001), frequent seizures (aOR=3.801, p<0.001), and comorbid medical conditions (aOR=5.478, p=0.047) were independent predictors of psychiatric morbidity. Having attained a tertiary level of education was protective against psychiatric morbidity (aOR=0.221, p=0.036). Conclusion More than half of the patients living with epilepsy had at least one psychiatric comorbidity. Routine psychiatric screening and integration of mental health services in epilepsy care is essential to improve clinical outcomes.

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Are medical students aware of SUDEP? A survey in Turkey

ASLAN, F. S.; ISMAYILOVA, A.; HASANLI, S.; ANGELOPOULOU, E.; BAYDILI, K. N.; AKYUZ, E.

2023-07-16 neurology 10.1101/2023.07.14.23292665 medRxiv
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ObjectiveSudden unexpected death in epilepsy (SUDEP) has been recognized as an important cause of death in patients with epilepsy. In order to inform patients with epilepsy and their relatives correctly, it is necessary to increase the awareness of students about SUDEP from the early stages of medical education. The aim of this study was to identify the level of knowledge and awareness of medical students in Turkey about SUDEP. MethodsMedical students (23{+/-}7 years old; n=793) in Turkey participated in the online SUDEP awareness survey. The survey included demographic evidence, followed by questions about their awareness of epilepsy, seizure knowledge and about the definition, awareness of SUDEP. ResultsThe majority of medical students (95%) claimed that they had heard about epileptic seizures. Half of the participants (49.9%) mentioned that they had heard about tonic-clonic seizures. However, two-thirds of the students (67%) have never heard about SUDEP, while 85% of the students stated that they did not have sufficient knowledge about SUDEP. Concerning the potential prevention of SUDEP, 80.8% of the students did not know about this topic. Furthermore, most participants (82%) expressed their interest and willingness to learn about SUDEP. ConclusionKnowledge about SUDEP plays a key role in identifying patients at risk and informing patients and their relatives. The limited awareness of SUDEP in medical education may pose risks for patients diagnosed with epilepsy and their relatives, and the effective incorporation of lectures and training in SUDEP into the curriculum of medical school is of paramount importance.

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Cenobamate as add-on treatment for SCN8A development and epileptic encephalopathy

Gjerulfsen, C. E.; Oudin, M.; Furia, F.; Gverdtsiteli, S.; Johannessen Landmark, C.; Trivisano, M.; Aledo-Serrano, A.; Morcos, R.; Previtali, R.; Veggiotti, P.; Ricci, E.; Rubboli, G.; Gardella, E.; Moller, R.

2024-10-19 neurology 10.1101/2024.10.17.24312949 medRxiv
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ObjectivesDevelopmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. Commonly used antiseizure medications (ASMs) for SCN8A-related disorders, caused by gain-of-function variants, are sodium channel blockers. The use of such ASMs is often not enough to gain satisfactory seizure control. In this retrospective study, the effect of cenobamate was assessed in patients with SCN8A-DEE. MethodsAcross multiple centers and through a collaboration with the patient advocacy organization International SCN8A Alliance, patients with SCN8A-DEE treated with cenobamate for [&ge;]3 months were identified. Data were obtained once from patients caregivers or treating physicians through a RedCap survey. The functional effects of the included patients SCN8A variants were determined by functional tests published in the literature or functionally classified by prediction tools. ResultsTwelve patients (2-25 years, 8 females) with presumed gain-of-function SCN8A variants were treated with cenobamate for a mean period of 8.6 months (range 3-27 months). Countable motor seizures were reduced in 12/12 (100%) patients. Seven experienced a seizure reduction above 75% of which two patients achieved seizure freedom. A 25-50% and 50-75% decrease was observed in three and two patients, respectively. An increase in seizure-free days/patient was also reported. Rescue medication was decreased in 83% of patients, and non-seizure-related improvements (increased alertness, better sleep, improved muscle tone) were observed in 58%. Adverse effects were reported by 33%; half resolved spontaneously or by the reduction of concomitant ASMs. SignificanceOur data suggest, that cenobamate is a promising and safe treatment for SCN8A- DEE, even during early infancy. As a possible precision approach to treatment, cenobamate effectively reduced seizure burden and ameliorated non-seizure-related symptoms. Similar results may be achieved in cohorts of patients with gain-of-function variants encoding other sodium channels. Key pointsO_LIPatients with DEE caused by pathogenic GOF variants in SCN8A are commonly treated with sodium channel blockers, often without satisfying seizure control. C_LIO_LIAdjunctive cenobamate improved seizure frequency in 12/12 patients (2-25 years, 8 females) with SCN8A-DEE of which two achieved seizure freedom. C_LIO_LIAn increase in seizure-free days/patient, non-seizure-related improvements (e.g. increased alertness), and a decrease in rescue medication was also observed. C_LIO_LICenobamate is a promising and safe treatment for SCN8A-DEE, even during early infancy. C_LIO_LISimilar results may be achieved in patients with gain-of-function variants encoding other sodium channels. C_LI

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Patient Perceptions of a Seizure Service Dog in the Epilepsy Monitoring Unit

ERNST, L. D.; Madani, B.; Zhu, D.; McCaskill, M.; Kellogg, M. A.

2026-05-01 neurology 10.64898/2026.04.30.26352073 medRxiv
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ObjectiveSeizure dogs are service animals trained to respond supportively to seizures in people with epilepsy; some are also trained to detect seizure-specific scents, particularly ictal volatile organic compounds (VOCs). This survey study examines feasibility and safety of incorporating a seizure service dog (SSD) into an inpatient setting, as well as patient perceptions of having an SSD in the Epilepsy Monitoring Unit (EMU). MethodsOur SSD underwent specialized training for seizure response and seizure recognition based on seizure-specific VOCs, and accompanied his epileptologist owner in the EMU on rounds for over four years prior to the study. We administered surveys to patients hospitalized in the EMU before and after interactions with a trained seizure dog. The surveys assessed the patients comfort with the dog, perceived usefulness of service dogs, safety, and tolerability. Select case examples are also presented in which seizure dog spontaneously alerted prior to epileptic seizures; seizures later confirmed by independent EEG review. ResultsPatient responses underscored overall high enthusiasm for seizure dog therapy, with 93% of participants reporting feeling "very comfortable" or "extremely comfortable" with a seizure dog present. No adverse concerns or negative experiences were reported by participants. 91% reported personally experiencing benefits of working with the seizure dog, citing emotional and comfort benefits during their hospitalization. 94% of participants were comfortable with physical contact with the dog or had no proximity preference. ConclusionThese findings suggest that seizure service dogs can be safely integrated into the inpatient EMU setting and have potential to enhance patient care and emotional well-being during EMU monitoring. Summary PointsO_LITotal of 98 patients admitted to EMU were surveyed about opinions regarding seizure dogs and comfort with integration of seizure dog in EMU setting, with 35 patients completing post-test surveys after interacting with the seizure dog. C_LIO_LI93% of surveyed EMU patients completing post-test surveys felt very or extremely comfortable with the seizure dog; no negative experiences or safety concerns were reported. C_LIO_LI91% reported personally experiencing emotional benefits of working with the seizure dog. C_LIO_LISelect case examples demonstrate that the trained seizure dog in our study may be able to spontaneously identify epileptic seizures. C_LI

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Interruption of rat absence seizures by auditory stimulation

McCafferty, C. P.; Zheng, X.; Tung, R.; Gruenbaum, B. F.; Blumenfeld, H.

2025-10-13 neuroscience 10.1101/2025.10.10.681637 medRxiv
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Absence seizures are episodes of impaired consciousness and responsiveness that impact an individuals ability to interact with the world around them. Childhood absence epilepsy, a condition defined by these seizures, can have profound effects on childrens social, educational, and psychological development. Absence seizures are accompanied by a distinctive electrographic signature called a spike-wave discharge. The impairment of consciousness associated with a spike-wave discharge can be variable: some people maintain responsiveness during some absence seizures, and some rodent oscillations resembling spike-wave discharges may not have any behavioral impact. We previously observed that spike-wave discharges in the Genetic Absence Epilepsy Rat from Strasbourg model sometimes terminated shortly after presentation of a conditioned auditory stimulus. In this study we found that these terminations were caused by the stimuli and that they occurred after approximately 50% of stimuli. We also found that the probability of a spike-wave discharge being interrupted depended on stimulus timing, degree of conditioning, and electrographic signal power. These data provide insight into the factors that determine the mechanisms of absence seizure termination, with possible implications for therapy.