DaT3M: A Data Tracker for Multi-faceted Management of Multi-site Clinical Research Data Submission, Curation, Master Inventorying, and Sharing.

Managing research data is an important and challenging aspect of clinical studies, especially for multi-site collaboratives. To address this challenge, we designed, developed and deployed a multi-faceted, multi-level interactive data tracker (DaT3M) for multi-site clinical research data submission, curation, master inventorying, and sharing. Components of DaT3M include data overview, data portal, data status panel, data query engine, and data downloader.

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk.

The association of serotonin reuptake inhibitors and benzodiazepines with ictal central apnea.

Objective: Ictal (ICA) and postconvulsive central apnea (PCCA) have been implicated in sudden unexpected death in epilepsy (SUDEP) pathomechanisms. Previous studies suggest that serotonin reuptake inhibitors (SRIs) and benzodiazepines (BZDs) may influence breathing. The aim of this study was to investigate if chronic use of these drugs alters central apnea occurrence in patients with epilepsy.

Insular resection may lead to autonomic function changes.

Objective: The aim of this study was to determine if insular damage is associated with markers of autonomic dysfunction.

Methods: We studied patients who underwent temporal lobe and/or insular resections for epilepsy surgery between April 2010 and June 2015 at University Hospitals Cleveland Medical Center (UHCMC). Presurgical T1-weighted MPRAGE, standard T1, T2 and FLAIR sequences were compared with postsurgical MRI by a neuroradiologist and classified as type 0 (no involvement of insula), type 1 (minimal involvement of insular margin), type 2 (insular involvement <25%), and type 3 (insular involvement ≥25%).

Ictal laryngospasm monitored by video-EEG and polygraphy: a potential SUDEP mechanism.

A 56-year-old man with refractory bitemporal epilepsy was monitored in the Epilepsy Monitoring Unit (EMU). In a video-EEG captured seizure, brief oroalimentary automatisms were followed by increased inspiratory effort, accompanied by prominent, visible tracheal movements and audible inspiratory stridor. The patient's oxygen saturation rapidly declined to 62%; persistent severe hypoxemia ended with spontaneous effective respiration commencing at seizure end.

The incidence and significance of periictal apnea in epileptic seizures.

Objective: The aim of this study was to investigate periictal central apnea as a seizure semiological feature, its localizing value, and possible relationship with sudden unexpected death in epilepsy (SUDEP) pathomechanisms.

Methods: We prospectively studied polygraphic physiological responses, including inductance plethysmography, peripheral capillary oxygen saturation (SpO ), electrocardiography, and video electroencephalography (VEEG) in 473 patients in a multicenter study of SUDEP. Seizures were classified according to the International League Against Epilepsy (ILAE) 2017 seizure classification based on the most prominent clinical signs during VEEG.

ODaCCI: Ontology-guided Data Curation for Multisite Clinical Research Data Integration in the NINDS Center for SUDEP Research.

Sudden Unexpected Death in Epilepsy (SUDEP) is the leading mode of epilepsy-related death. The Center for SUDEP Research (CSR) is an NINDS-funded Center Without Wall's initiative aimed at prospectively creating a comprehensive clinical research resource for SUDEP. This resource consists of a growing set of data and biological samples of a statistically significant cohort of patients at an elevated risk, best represented by the Epilepsy Monitoring Unit (EMU) patient population.

Amygdala and hippocampus are symptomatogenic zones for central apneic seizures.

Objective: To identify limbic sites of respiratory control in the human brain, and by extension, the symptomatogenic zone for central apnea.

Methods: We used direct stimulation of anatomically, precisely placed stereotactic EEG electrodes to analyze breathing responses. We prospectively studied 3 patients who were explored with stereotactically implanted depth electrodes.

Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures.

Objective: To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it.

Methods: We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death.

Results: Three patients (two definite and one probable) had SUDEP.

Left-insular damage, autonomic instability, and sudden unexpected death in epilepsy.

We analyzed the only two sudden unexpected death in epilepsy (SUDEP) cases from 320 prospectively recruited patients in the three-year Prevention and Risk Identification of SUDEP Mortality (PRISM) project. Both patients had surgically refractory epilepsy, evidence of left insular damage following previous temporal/temporo-insular resections, and progressive changes in heart rate variability (HRV) in monitored evaluations prior to death. Insular damage is known to cause autonomic dysfunction and increased mortality in acute stroke.

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

Background: A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers.

Sudden unexpected death in epilepsy: Identifying risk and preventing mortality.

Premature death among individuals with epilepsy is higher than in the general population, and sudden unexpected death is the most common cause of this mortality. A new multisite collaborative research consortium, the Center for sudden unexpected death in epilepsy (SUDEP) Research (CSR), has received major funding from the National Institutes of Health (NIH) to examine the possible biologic mechanisms underlying this potentially preventable comorbidity and develop predictive biomarkers for interventions that could lower SUDEP incidence. This inaugural report describes the structure of the CSR, its priorities for human and experimental research, and the strategic collaborations and advanced tools under development to reduce this catastrophic outcome of epilepsy.