Epilepsia

BackgroundEpilepsy is a common neurologic disorder characterized by recurrent, unprovoked seizures. Epilepsy manifests as different seizure types and epilepsy types, which have important implications for treatment and prognosis. Electronic health record systems containing longitudinal data on large epilepsy cohorts can be valuable resources for clinical research. However, detailed epilepsy phenotypes are poorly captured by structured data such as diagnostic codes and are instead buried in unstru...

ImportanceTracking and predicting seizure frequency in patients with epilepsy is important for prognostication and therapy management. Interictal spikes have been proposed as a biomarker of seizure burden, but their association with seizure frequency has not been well quantified across epilepsy subtypes. ObjectiveTo measure the association between spike rate and seizure frequency and how this varies by epilepsy subtype. Design, Setting and ParticipantsWe studied 3,614 consecutive routine outpa...

Annotating seizure onset and spread in intracranial EEG is essential for epilepsy surgical planning, yet manual annotation is unreliable and cannot scale to large datasets. We introduce Neural Dynamic Divergence (NDD), an unsupervised framework that detects seizure activity by measuring deviation from patient-specific baseline neural dynamics using autoregressive models. NDD requires no labeled training data and adapts to individual patients, channels, and brain states. Validating against expert...

About half of patients who undergo epilepsy surgery for drug-resistant epilepsy have seizure recurrence, supporting the need for approaches that more accurately identify the epileptogenic zone, defined as the brain areas whose removal causes cessation of seizures. Altered network connectivity has emerged as a candidate biomarker of the epileptogenic zone, but how connectivity is altered in the epileptogenic zone remains uncertain, with prior studies reporting inconsistent results. We hypothesize...

BackgroundPathogenic KCNQ2 variants are the most common genetic cause of neonatal-onset epilepsies, with phenotypes ranging from self-limited (familial) neonatal epilepsy (SeL(F)NE) to severe developmental and epileptic encephalopathy (KCNQ2-DEE). Sodium channel blockers (SCBs) have shown promise for seizure control in these disorders, but their impact on neurodevelopmental outcomes and possible relationship with timing of initiation remain incompletely understood. MethodsWe leveraged a large, ...

Epilepsy is among the most prevalent neurological disorders, affecting millions of individuals worldwide at every stage of life. Characterised by recurrent seizures, epilepsy can significantly disrupt daily functioning, education, employment, and overall quality of life. Despite advances in neuroimaging, current approaches often overlook the individualised nature of brain disruptions in epilepsy. Here, we introduce an individualised functional Magnetic Resonance Imaging (fMRI) framework, Adjuste...

BackgroundPersons with epilepsy are at increased risk of depression/anxiety. Older antiseizure medications (ASMs) had drug-drug interactions that complicated pharmacotherapy of depression/anxiety; newer ASMs lack this drawback but can have psychiatric side effects. Anxiety/depression are increasingly recognized and treated pharmacologically. We hypothesized that the likelihood of treatment with selective serotonin uptake inhibitors (SSRI) would have increased in adult-onset epilepsy when prescri...

ObjectiveQuantitative assessment of extent of tissue resection following epilepsy surgery requires accurate delineation of the resection cavity on postoperative MRI. Current methods for resection cavity masking are time-consuming and labour-intensive, while existing automated approaches exhibit variable segmentation accuracy, particularly on extra-temporal resections. We developed MELD-PostOp, a deep learning tool trained and evaluated on a large, international, heterogeneous cohort to automatic...

Effective connectivity of the human insula, mainly assessed at rest using cortico-cortical evoked potentials (CCEPs), is not yet fully characterized at high-resolution. Here, we significantly extend prior CCEP studies of the insula by leveraging an extensive multicenter CCEP database and fine-grained anatomical atlases of the insula. We analyzed CCEP datasets from 897 patients with refractory focal epilepsy (459 females, age: 26{+/-}14 years) explored by stereo electroencephalography and with a...

BackgroundEpilepsy affects approximately 50 million individuals worldwide, with nearly one-third developing drug-resistant epilepsy (DRE). The centromedian nucleus of the thalamus (CM) and the brainstem are integral components of seizure-modulating networks and represent promising targets for neuromodulation. This study aimed to map structural connectivity between CM and specific brainstem nuclei using probabilistic tractography and to evaluate whether connectivity patterns correlate with seizur...

ObjectiveWe developed and validated a detection-guided artifact removal framework for clinical electroencephalography (EEG). It corrects only the contaminated segments and preserves artifact-free data. ApproachThe framework employs convolutional neural network (CNN) detectors trained on the Temple University Hospital (TUH) Artifact Corpus of 150 recordings from 105 patients. For eye movement artifacts (20 second windows), it uses independent component analysis (ICA) and canonical correlation an...

SCN1A-related disorders are the single most common monogenic cause of epilepsy and represent a major focus of precision medicine efforts. In conjunction with existing prospective studies, the analysis of real-world data obtained during routine clinical care can expand upon the scale and duration of available data and contribute to the development of meaningful outcomes for clinical trials. Here, we leveraged real-world data to delineate the longitudinal disease history of 100 individuals with S...

IntroductionSleep spindles are electroencephalographic elements characteristic of non-rapid eye movement sleep generated by thalamo-cortical interactions. Spindles have been linked to some of the cognitive benefits afforded by sleep and high spindle activity is associated with increased arousal threshold (deeper sleep). Here, we demonstrate that targeting the thalamus with Transcranial Electrical Stimulation with Temporal Interference (TES-TI) can enhance spindle activity. Methods24 participant...

Topiramate (TPM) is approved for seizures and migraine prophylaxis and is used off-label for several neuropsychiatric conditions. The available dosage forms, including tablets and sprinkle capsules, are unsuitable for patients who may be unable to take medicine orally. The resulting potential treatment interruptions could have untoward consequences and underscores the importance of developing a parenteral formulation. In this study, we developed a population pharmacokinetic model of a novel, int...

ObjectiveTo delineate the phenotype of juvenile myoclonic epilepsy (JME) with a focus on obsessive-compulsive personality disorder (OCPD) using multimodal psychiatric, neuropsychological, quantitative EEG (qEEG), and structural MRI markers within a predictive-processing/free-energy framework. MethodsWe prospectively studied 65 patients with JME and 68 matched healthy controls (HC). Participants completed DSM-IV SCID I/II interviews and a neuropsychological battery assessing working memory, psyc...

Type 1 narcolepsy (NT1), a disorder caused by the loss of hypocretin/orexin transmission, is characterized by daytime sleepiness and symptoms where Rapid Eye Movement (REM) sleep, a state normally occurring from middle to late in the night, can intermingle with wakefulness. This results in cataplexy and sleep paralysis, episodes of muscle paralysis when awake, or in the generation of dream-like hallucinations and vivid dreaming, periods of visual imagery or sensory experiences that occur while a...

Developmental and epileptic encephalopathies (DEEs) are a group of severe childhood-onset neurological disorders, often caused by rare genetic variants affecting brain development and excitability. Despite advances in genomic sequencing, a substantial proportion of DEE cases remain unsolved. Here, we identify THAP12 as a novel disease-causing gene associated with autosomal recessive DEE. Whole-genome sequencing in two siblings who presented with infantile spasms and progressed to Lennox-Gastaut ...

Protocadherin-12 (PCDH12), a cell-adhesion protein belonging to the non-clustered protocadherin family, plays a crucial role in the establishment and regulation of neuronal connections and communication. Bi-allelic loss-of-function (LoF) variants in the PCDH12 gene have been associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic junction dysplasia (DMJD) syndrome, cerebral palsy, and cerebellar ataxia, often accompanied by ocular abnormalities. However, ge...

BackgroundDeep brain stimulation has emerged as an effective investigational treatment for select cases of severe Gilles de la Tourette Syndrome. Defining the optimal stimulation sites within different targets and the specific tic improvement network across targets will be important to guide neuromodulation therapies. MethodsThis retrospective multi-center cohort study analyzed stimulation locations in patients who received bilateral deep brain stimulation for Gilles de la Tourette Syndrome acr...

Visual Snow Syndrome (VSS) is a neurological condition characterized by continuous visual disturbances resembling television static across the visual field. Despite its significant impact on quality of life, objective assessment methods remain limited, with diagnosis relying primarily on subjective patient reports. Current understanding of VSS pathophysiology suggests cortical hyperexcitability, but precise mechanisms remain unclear. Here we developed an integrated protocol combining transcrania...