False positive clusters in normal control samples at different z-scores and different quantitative measures (gwc = grey-white contrast; sulc = sulcal depth; lgi = local gyrification index; curv = curvature; jacobia = jacobian distance).

<p>Calculations were performed for all controls (n = 41, 82 hemispheres).</p

Multimodal results for Patient 4.

<p><b>A.</b> Sagittal T1 with pial and white matter surface tracings used for calculating cortical thickness and G–W contrast. Green circle marks area of visually identified focal cortical dysplasia. <b>B.</b> Patient's reconstructed white matter surface with area of significant cortical thickening marked in red/yellow (z>3.5, cluster-corrected) within the expert-delineated lesion margin (green tracing). <b>C.</b> Mean cortical thickness of the true positive cluster for patient (red cross, top left) and all normal control subjects in blue. <b>D.</b> Same as B, but for gray-white matter contrast. The significant cluster shows an area of significant blurring of the gray-white matter junction. EEG traces from intracranial electrodes near the dysplastic area showing focal interictal and ictal discharges (orange), compared to slightly more distant electrode locations (white), showing a co-localization of detected lesion and pathological electrophysiology. <b>E.</b> Mean gray-white matter contrast for the single patient and all control subjects. More positive values denote increased gray-white boundary blurring. <b>F.</b> Resected area after surgery (in white). Crosshair marks area of maximum thickness increase within the detected lesion. This patient is seizure free one year after surgery.</p

Summary of patient demographics and clinical profile.

<p><b>Clinical MRI:</b> diagnosis based on visual inspection of routine clinical MRI (FCD: focal cortical dysplasia; EM: encephalomalacia; PMG: polymicrogyria; HT: heterotopia); <b>Location:</b> (Lobe, R =  right hemisphere, L =  left hemisphere, B =  bilateral); <b>Scalp EEG:</b> seizure onset location based on scalp video-EEG monitoring.</p

Sensitivity and specificity for quantitatively derived areas of abnormality compared to expert-delineated lesion margins for different thresholds.

<p>Sensitivity and specificity for quantitatively derived areas of abnormality compared to expert-delineated lesion margins for different thresholds.</p

Sensitivity and specificity measures for the union (logical OR) of cortical thickness and grey-white contrast, and area-under-the-receiver-operator-curve (AuROC) calculations showing discriminability between patients and normal controls.

<p>Union measure combining thickness and contrast show superior performance.</p

Impact of the COVID-19 pandemic on people with epilepsy: findings from the US arm of the COV-E study

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we aimed to understand the impact of COVID-19 on the medical care and well-being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers. Methods: Separate surveys designed for PWE and their caregivers were circulated from April 2020 to July 2021; modifications in March 2021 included a question about COVID-19 vaccination status. Results: We received 788 responses, 71% from PWE (n = 559) and 29% (n=229) from caregivers of persons with epilepsy. A third (n = 308) of respondents reported a change in their health or in the health of the person they care for. Twenty-seven percent (n = 210) reported issues related to worsening mental health. Of respondents taking ASMs (n = 769), 10% (n= 78) reported difficulty taking medications on time, mostly due to stress causing forgetfulness. Less than half of respondents received counseling on mental health and stress. Less than half of the PWE reported having discussions with their healthcare providers about sleep, ASMs and potential side effects, while a larger proportion of caregivers (81%) reported having had discussions with their healthcare providers on the same topics. More PWE and caregivers reported that COVID-19 related measures caused adverse impact on their health in the post-vaccine period than during the pre-vaccine period, citing mental health issues as the primary reason. Significance: Our findings indicate that the impact of the COVID-19 pandemic in the US on PWE is multifaceted. Apart from the increased risk of poor COVID-19 outcomes, the pandemic has also had negative effects on mental health and self-management. Healthcare providers must be vigilant for increased emotional distress in PWE during the pandemic and consider the importance of effective counseling to diminish risks related to exacerbated treatment gaps.</div

Receiver Operator Characteristics (ROC) curve showing effects of smoothing (smoothing level [sm] in FWHM [mm]) on sensitivity and specificity for thickness at different smoothing levels.

<p>Larger area under the curve shows higher discriminability.</p

Detection sensitivity and specificity calculations for cortical surface measures calculated across patients and normal controls for different statistical thresholds (at FWHM = 5 mm).

<p>Detection sensitivity and specificity calculations for cortical surface measures calculated across patients and normal controls for different statistical thresholds (at FWHM  = 5 mm).</p

Cortical dysplasia marked by cortical thickening and gray-white boundary blurring in Patient 3.

<p><b>A.</b> Significantly increased thickening of the cortical ribbon (in red/yellow) detected by the automated quantitative approach falls within the expert-delineated area of focal cortical dysplasia (green tracing on the inflated pial surface). The area with highest z-score shows cortical thickness measures of up to 6.5 mm between white matter and pial surfaces. <b>B.</b> Calculating the T1-signal contrast at .5 mm above vs below the gray/white interface shows an area of significant blurring within the lesion. The green circle on the left shows the area of maximum blurring on a coronal volumetric MRI slice.</p

Rare genetic variation and outcome of surgery for mesial temporal lobe epilepsy

Objective: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. Methods: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. Results: Nine centers from 3 continents contributed 206 patients operated for drug-resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss-of-function (LoF) variants (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.9-3.5, p = 1.3E-09) and in genes encoding voltage-gated cation channels (OR = 2.4, 95% CI = 1.4-3.8, p = 2.7E-04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between-group differences. Interpretation: Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision-making and counseling. ANN NEUROL 2022.</p