Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Epilepsy is a chronic neurological disease that represents a tremendous burden on both patients and society in general. Studies have addressed how demographic variables, socioeconomic variables, and psychological comorbidity are related to the quality of life (QOL) of people with epilepsy (PWE). However, there has been less focus on how these factors may differ between patients who exhibit varying degrees of seizure control. This study utilized data from the Managing Epilepsy Well (MEW) Network of the Centers for Disease Control and Prevention with the aim of elucidating differences in demographic variables, depression, and QOL between adult PWE. METHODS:Demographic variables, depression, and QOL were compared between PWE who experience clinically relevant differences in seizure occurrence. RESULTS:Gender, ethnicity, race, education, income, and relationship status did not differ significantly between the seizure-frequency categories (p>0.05). People with worse seizure control were significantly younger (p=0.039), more depressed (as assessed using the Patient Health Questionnaire) (p=0.036), and had lower QOL (as determined using the 10-item Quality of Life in Epilepsy for Adults scale) (p<0.001). CONCLUSIONS:The present results underscore the importance of early screening, detection, and treatment of depression, since these factors relate to both seizure occurrence and QOL in PWE.

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 (SpO2 ), 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. The putative epileptogenic zone was defined based on clinical history, seizure semiology, neuroimaging, and EEG. RESULTS:Complete datasets were available in 126 patients in 312 seizures. Ictal central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%] and 103/312 seizures [36.5%]) (P < .001). ICA was the only clinical manifestation in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 ± 4.9 s, in 56/103 (54.3%) seizures. ICA ≥60 s was associated with severe hypoxemia (SpO2 <75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA nonmotor onset semiologies were associated with ICA presence (P < .001), ICA duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe epilepsy was highly associated with ICA in comparison to extratemporal epilepsy (P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period. SIGNIFICANCE/CONCLUSIONS:ICA is a frequent, self-limiting semiological feature of focal epilepsy, often starting before surface EEG onset, and may be the only clinical manifestation of focal seizures. However, prolonged ICA (≥60 s) is associated with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more frequently seen in temporal than extratemporal seizures, and in typical temporal seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is typical, and thus it may remain unrecognized without polygraphic measurements that include breathing parameters.

OBJECTIVE:To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System. METHODS:All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS:There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1). SIGNIFICANCE/CONCLUSIONS:The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures.

OBJECTIVE:Limited data are available regarding the evolution over time of the rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy implanted with vagus nerve stimulation (VNS) therapy in the United States (from 1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation follow-up period. METHODS:Patient vital status was ascertained using the Centers for Disease Control and Prevention's National Death Index (NDI). An expert panel adjudicated classification of cause of deaths as SUDEP based on NDI data and available narrative descriptions of deaths. We tested the hypothesis that SUDEP rates decrease with time using the Mann-Kendall nonparametric trend test and by comparing SUDEP rates of the first 2 years of follow-up (years 1-2) to longer follow-up (years 3-10). RESULTS:Our cohort included 277 661 person-years of follow-up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a significant decrease in age-adjusted SUDEP rate during follow-up (S = -27 P = .008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P = .002). Sensitivity analyses confirm these findings. SIGNIFICANCE/CONCLUSIONS:Our data suggest that SUDEP risk significantly decreases during long-term follow-up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long-term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study.

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered.