The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence.

Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.

Abnormal functional connectivity of the posterior hypothalamus and other arousal regions in surgical temporal lobe epilepsy.

OBJECTIVE: This study sought to characterize resting-state functional MRI (fMRI) connectivity patterns of the posterior hypothalamus (pHTH) and the nucleus basalis of Meynert (NBM) in surgical patients with mesial temporal lobe epilepsy (mTLE), and to investigate potential correlations between functional connectivity of these arousal regions and neurocognitive performance. METHODS: The study evaluated resting-state fMRI in 60 patients with preoperative mTLE and in 95 healthy controls. The authors first conducted voxel-wise connectivity analyses seeded from the pHTH, combined anterior and tuberal hypothalamus (atHTH; i.e., the rest of the hypothalamus), and the NBM ipsilateral (ipsiNBM) and contralateral (contraNBM) to the epileptogenic zone. Based on these results, the authors included the pHTH, ipsiNBM, and frontoparietal neocortex in a network-based statistic (NBS) analysis to elucidate a network that best distinguishes patients from controls. The connections involving the pHTH and ipsiNBM from this network were included in age-corrected pairwise region of interest (ROI) analysis, along with connections between arousal structures, including the pHTH, ipsiNBM, and brainstem arousal regions. Finally, patient functional connectivity was correlated with clinical neurocognitive testing scores for IQ as well as attention and concentration tests. RESULTS: The voxel-wise analysis demonstrated that the pHTH, when compared with the atHTH, showed more widespread functional connectivity decreases in surgical mTLE patients when compared with controls. It was also observed that the ipsiNBM, but not the contraNBM, showed decreased functional connectivity in mTLE. The NBS analysis uncovered a perturbed network of frontoparietal regions, the pHTH, and ipsiNBM that distinguishes patients from controls. Age-corrected ROI analysis revealed functional connectivity decreases between the pHTH and bilateral superior frontal gyri, medial orbitofrontal cortices, rostral anterior cingulate cortices, and inferior parietal cortices in mTLE when compared with controls. For the ipsiNBM, there was reduced connectivity with bilateral medial orbitofrontal and rostral anterior cingulate cortices. Age-corrected ROI analysis also demonstrated upstream connectivity decreases from controls between the pHTH and the brainstem arousal regions, cuneiform/subcuneiform (CSC) nuclei, and ventral tegmental area, as well as the ipsiNBM and CSC nuclei. Reduced functional connectivity was also detected between the pHTH and ipsiNBM. Lastly, neurocognitive test scores for attention and concentration were found to be positively correlated with the functional connectivity between the pHTH and ipsiNBM, suggesting worse performance associated with connectivity perturbations. CONCLUSIONS: This study demonstrated perturbed resting-state functional connectivity of arousal regions in surgical mTLE and is one of the first investigations to demonstrate decreased functional connectivity of the pHTH with frontoparietal regions and other arousal regions. Connectivity disturbances in arousal regions may contribute to neurocognitive deficits in surgical mTLE patients.

Evaluation of the effects of repeated disinfection on medical exam gloves: Part 1. Changes in physical integrity.

COVID-19 has created shortages of personal protective equipment. In resource-constrained situations, limited cycles of disinfection and extended use of gloves is recommended by the U.S. Centers for Disease Control and Prevention to conserve supplies. However, these guidelines are based on limited evidence. In this study, serial cycles of hand hygiene were performed on gloved hands using an ethanol-based hand rub (six and 10 cycles), 0.1% sodium hypochlorite (bleach) solution (10 cycles), or soap and water (10 cycles) on latex and nitrile medical exam gloves from the United States and India. A modified water-leak test evaluated glove integrity after repeated applications of these disinfecting agents. When aggregated, dilute bleach demonstrated the lowest difference between treatment and control arms: -2.5 percentage points (95% CI: -5.3 to 0.3) for nitrile, 0.6 percentage points (95% CI: -2.6 to 3.8) for non-powdered latex. For U.S.-purchased gloves tested with six and 10 applications of ethanol-based hand rub, the mean difference in failure risk between treatment and control gloves was within the prespecified non-inferiority margin of five percentage points or less, though some findings were inconclusive since outside the margin. The aggregated difference in failure risk between treatment and control was 3.5 percentage points (0.6 to 6.4) for soap and water, and 2.3 percentage points (-0.5 to 5.0) and 5.0 percentage points (1.8 to 8.2) for 10 and 6 applications of ethanol-based hand rub, respectively. Most leaks occurred in the interdigital webs (35%) and on the fingers (34%). This indicates that some combinations of glove types and disinfection methods may allow for extended use. Ten applications of dilute bleach solution had the least impact on glove integrity. However, the majority of glove and exposure combinations were inconclusive. Additional testing of specific glove and disinfectant combinations may inform future strategies to guide extended use during glove shortages. Additional considerations, not evaluated here, include duration of use, disinfectant chemical permeation, and the effects of hand temperature, movement, and manipulation of instruments on glove integrity.

Evaluation of the effects of repeated disinfection on medical exam gloves: Part 2. Changes in mechanical properties.

Many healthcare professionals have been forced, under acute shortages, to extend medical exam gloves beyond their intended single use. Despite limited available literature, the CDC proposed a set of guidelines for repeated exam gloves use, indicating a maximum number of treatments for three widely available disinfectants. This study examines how these treatments affect the mechanical properties of latex and nitrile gloves. Furthermore, an acceptability threshold is proposed for changes in tensile property, specifically elastic modulus, as an indication of degradation. This proposed criterion was also applied to similar studies available in the literature to determine applicability and aid in recommendation development. Three different latex glove brands and three nitrile brands were exposed to repeated treatments of an alcohol-based hand rub, diluted bleach, or soap and water. Tensile tests of samples cut from untreated and treated gloves were performed to assess the change in elastic modulus induced by each treatment. The findings suggest that latex gloves performed well within the CDC recommended guidelines of six repeated treatments for an ethanol-based hand rub and 10 repeated treatments of either dilute bleach or soap and water. Nitrile exam gloves, on the other hand, showed significant changes in elastic modulus, with more inconclusive results among brands. This was especially true for treatment with dilute bleach and soap and water. Further research is needed to investigate the effects of disinfection products on the mechanical integrity of nitrile exam gloves. The results support the use of five repeated treatments of ethanol-based hand rub for nitrile exam gloves, a lower threshold than currently recommended by the CDC. This research also supports that the CDC recommendation of 10 repeated treatment with soap and water is appropriate for latex exam gloves, but not for nitrile exam gloves. Occupational safety and health professionals involved in the selection of disposable exam gloves for infection control should consider the compatibility of the glove polymer type with available disinfectants, especially if extended use with repeated disinfection becomes necessary.