Epilepsy is a common and debilitating neurological disease. When medication cannot control seizures in up to 40% of cases, surgical resection of epileptogenic tissue is a clinically and cost- effective therapy to achieve seizure freedom. To simultaneously resect minimal yet sufficient cortex, exquisite localization of the epileptogenic zone (EZ) is crucial. However, localization is not straightforward, given relative difficulty of capturing seizures, constraints of the inverse problem in source localization, and possible disparate locations of symptomatogenic vs. epileptogenic regions. Thus, attention has been paid to which state of vigilance best localizes the EZ, in the hopes that one or another sleep-wake state may hold the key to improved accuracy of localization. Studies investigating this topic have employed diverse methodologies and produced diverse results. Nonetheless, rapid eye movement sleep (REM) has emerged as a promising sleep-wake state, as epileptic phenomena captured in REM may spatially correspond more closely to the EZ. Cortical neuronal asynchrony in REM may spatially constrain epileptic phenomena to reduce propagation away from the source generator, rendering them of high localizing value. However, some recent work demonstrates best localization in sleep-wake states other than REM, and there are reports of REM providing clearly false localization. Moreover, synchronistic properties and basic mechanisms of human REM remain to be fully characterized. Amidst these uncertainties, there is an urgent need for recording and analytical techniques to improve accuracy of localization. Here we present a systematic review and quantitative analysis of pertinent literature on whether and how REM may help localize epileptogenic foci. To help streamline and accelerate future work on the intriguing anti-epileptic properties of REM, we also introduce a simple, conceptually clear set-theoretic framework to conveniently and rigorously describe the spatial properties of epileptic phenomena in the brain.

Study Objectives To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3. Methods Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2-5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS. Results 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p=0.0091). All 5 SWS contributed about 45% of their localizations to converge onto 17.0±15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p=0.0006) and most discordant (39.3% vs. 29.6%, p=0.0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p=0.0059). Conclusions REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an “omni-concordant core” of source localizations shared by all 5 SWS is surrounded by a “penumbra” of source localizations shared by some but not all SWS. Uniquely, REM spares this core to “move” source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.

Background: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes. Methods: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v. placebo for 5 d), managed as outpatients, were prospectively assessed 3 months and 1 year after their positive test result. They completed detailed neurologic/neuropsychiatric symptom questionnaires, the telephone version of the Montreal Cognitive Assessment (T-MoCA), the Kessler Psychological Distress Scale (K10) and the EuroQol EQ-5D-3L (measure of quality of life). Close informants completed the Mild Behavioural Impairment Checklist (MBI-C) and the Informant Questionnaire on Cognitive Decline in the Elderly. We also tracked use of health care services and neurologic investigations. Results: The cohort consisted of 198 participants (87 female [43.9%] median age 45 yr, interquartile range 37–54 yr). Of the 179 participants with symptom assessments, 139 (77.6%) reported at least 1 neurologic symptom, the most common being anosmia/dysgeusia (99 [55.3%]), myalgia (76 [42.5%]) and headache (75 [41.9%]). Forty patients (22.3%) reported persistent symptoms at 1 year, including confusion (20 [50.0%]), headache (21 [52.5%]), insomnia (16 [40.0%]) and depression (14 [35.0%]); 27/179 (15.1%) reported no improvement. Body mass index (BMI), a history of asthma and lack of full-time employment were associated with the presence and persistence of neurologic/neuropsychiatric symptoms; female sex was independently associated with both (presence: odds ratio [OR] adjusted for age, race, BMI, history of asthma and neuropsychiatric history 5.04, 95% confidence interval [CI] 1.58 to 16.10). Compared to participants without persistent symptoms, those with persistent symptoms had more hospital admissions and family physician visits, and worse MBI-C scores and less frequent independence for instrumental activities at 1 year (83.8% v. 97.8%, p = 0.005). Patients with any or persistent neurologic symptoms had worse psychologic distress (K10 score ≥ 20: adjusted OR 12.1, 95% CI 1.4 to 97.2) and quality of life (median EQ-5D-3L visual analogue scale rating 75 v. 90, p < 0.001); 42/84 (50.0%) had a T-MoCA score less than 18 at 3 months, as did 36 (42.9%) at 1 year. Participants who reported memory loss were more likely than those who did not report such symptoms to have informant-reported cognitive-behavioural decline (1-yr MBI-C score ≥ 6.5: adjusted OR 15.0, 95% CI 2.42 to 92.60). Interpretation: Neurologic/neuropsychiatric symptoms were commonly reported in surviv...