Joseph, Boney

Significance Millions of people affected by epilepsy may undergo surgical resection of the epileptic tissues to stop seizures if such epileptic foci can be accurately delineated. High-frequency oscillations (HFOs), existing in electroencephalography, are highly correlated with epileptic brain, which is promising for guiding successful neurosurgery. However, it is unclear whether and how pathological HFOs can be differentiated to localize the epileptogenic tissues given the presence of various nonepileptic high-frequency activities. Here, we show morphological and source imaging evidence that pathological HFOs can be identified by the concurrence of epileptiform spikes. We describe a framework to delineate the underlying epileptogenicity using this biomarker. Our work may offer translational tools to improve treatments by noninvasively demarking pathological activities and hence epileptic foci.

AbstractAimsLong‐term lithium therapy (LTLT) has been associated with kidney insufficiency in bipolar disorder (BD). We aimed to investigate the risk factors of chronic kidney disease (CKD) development and progression among BD patients receiving LTLT.MethodsWe included adult patients with BD on LTLT (≥1 year) who were enrolled in the Mayo Clinic Bipolar Biobank, Rochester, Minnesota. We reviewed electronic medical records to extract information related to lithium therapy and kidney‐related data to assess changes in the estimated glomerular filtration rate (eGFR). CKD severity was assessed based on eGFR.ResultsAmong 154 patients who received LTLT, 41 patients (27%) developed CKD, of whom 20 (49%) patients continued lithium (continuers) and 19 (46%) discontinued it (discontinuers). The median time to stage 3 CKD development was 21.7 years from the start of Li treatment. Type‐2 diabetes mellitus and benzodiazepine use were independent predictors for CKD development in the survival analysis, after controlling for age. The subsequent CKD progression rate did not differ between continuers and discontinuers (mean GFR 48.6 vs. 44.1, p = 0.13) at the end of follow‐up duration (mean duration: 3.5 ± 4.4 years for continuers and 4.9 ± 5.3 years for discontinuers).ConclusionCKD was observed in one fourth of patients with BD receiving LTLT. There was no significant difference in the progression of CKD among Li continuers versus discontinuers, at the mean follow‐up duration of 4.2 years, after the CKD diagnosis. Progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone.

Abstract Background Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. Methods Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. Results A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. Conclusions Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.

Abstract Noninvasive wearable devices have great potential to aid the management of epilepsy, but these devices must have robust signal quality, and patients must be willing to wear them for long periods of time. Automated machine learning classification of wearable biosensor signals requires quantitative measures of signal quality to automatically reject poor‐quality or corrupt data segments. In this study, commercially available wearable sensors were placed on patients with epilepsy undergoing in‐hospital or in‐home electroencephalographic (EEG) monitoring, and healthy volunteers. Empatica E4 and Biovotion Everion were used to record accelerometry (ACC), photoplethysmography (PPG), and electrodermal activity (EDA). Byteflies Sensor Dots were used to record ACC and PPG, the Activinsights GENEActiv watch to record ACC, and Epitel Epilog to record EEG data. PPG and EDA signals were recorded for multiple days, then epochs of high‐quality, marginal‐quality, or poor‐quality data were visually identified by reviewers, and reviewer annotations were compared to automated signal quality measures. For ACC, the ratio of spectral power from 0.8 to 5 Hz to broadband power was used to separate good‐quality signals from noise. For EDA, the rate of amplitude change and prevalence of sharp peaks significantly differentiated between good‐quality data and noise. Spectral entropy was used to assess PPG and showed significant differences between good‐, marginal‐, and poor‐quality signals. EEG data were evaluated using methods to identify a spectral noise cutoff frequency. Patients were asked to rate the usability and comfort of each device in several categories. Patients showed a significant preference for the wrist‐worn devices, and the Empatica E4 device was preferred most often. Current wearable devices can provide high‐quality data and are acceptable for routine use, but continued development is needed to improve data quality, consistency, and management, as well as acceptability to patients.

Abstract Objective The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity ( I 2 = 34%, P = .19; I 2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97). Conclusion This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.