Ocular motility as a measure of cerebral dysfunction in adults with focal epilepsy.

OBJECTIVE: Using objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. METHODS: We recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. RESULTS: Compared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). SIGNIFICANCE: Patients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy.

Can seizure-related heart rate differentiate epileptic from psychogenic nonepileptic seizures?

OBJECTIVES: We aimed to (1) determine if seizure-related heart rate (HR) differentiates epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES); (2) define the most useful point of the following HR measurements: preictal, ictal-onset, maximal-ictal, or postictal; and (3) delineate the optimal HR cutoff points (absolute HR and relative HR increase) to differentiate ES from PNES. METHODS: All video-electroencephalography (VEEG) recorded at an Australian tertiary hospital from May 2009 to November 2015 were retrospectively reviewed. Baseline (during rest and wakefulness), 1-min preictal, ictal-onset, maximal-ictal, and 1-min postictal HR were measured for each ES and PNES event. Events lasting <10 s or with uninterpretable electrocardiogram (ECG) due to artifacts were excluded. Receiver operating characteristic curve analysis was performed to assess the diagnostic accuracy of HR reflected by the area under the curve (AUC). RESULTS: Video-electroencephalography of 341 ES and 265 PNES from 130 patients were analyzed. The AUC for preictal, ictal-onset, maximal-ictal, and postictal HR were found to have poor differentiation between all types of ES and PNES. However, comparing bilateral tonic-clonic ES and PNES, AUC for absolute maximal-ictal HR was 0.84 (95% confidence interval [CI]: 0.73-0.95) and for absolute postictal HR was 0.90 (95% CI: 0.81-1.00) indicating good diagnostic discrimination. Using Youden's index to diagnose tonic-clonic ES, the optimal cutoff point for absolute maximal-ictal HR was 114 bpm (sensitivity: 84%, specificity: 82%) and for absolute postictal HR was 90 bpm (sensitivity: 91%, specificity: 82%). CONCLUSION: These findings suggest that seizure-related HR is useful in differentiating bilateral tonic-clonic ES from PNES. Based on the AUC, the best diagnostic measurements are maximal-ictal and postictal HR.

Ex-SPECTing Success: predictors of successful SPECT radiotracer injection during pre-surgical video-EEG admissions.

OBJECTIVES: To determine predictors of successful ictal Single Photon Emission Computed Tomography (SPECT) injections during Epilepsy Monitoring Unit (EMU) admissions for patients undergoing presurgical evaluation for drug resistant focal epilepsy. METHODS: In this retrospective study, consecutive EMU admissions were analysed at a single centre between 2019-2021. All seizures that occurred during the admission were reviewed. 'Injectable seizures' occurred during hours when the radiotracer was available. EMU-level data were analysed to identify factors predictive of an EMU admission with a successful SPECT injection (successful admission). Seizure-level data were analysed to identify factors predictive of an 'injectable seizure' receiving a SPECT injection during the ictal phase (successful injection). A multivariate generalised linear model was used to identify predictive variables. RESULTS: 125 EMU admissions involving 103 patients (median 37 years, IQR27.0-45.5) were analysed. 38.8% of seizures that were eligible for SPECT (n=134) were successfully injected; this represented 17.4% of all seizures (n=298) that occurred during admission. Unsuccessful admissions were most commonly due to a lack of seizures during EMU-SPECT (19.3%) or no 'injectable seizures' (62.3%). Successful EMU-SPECT was associated with baseline seizure frequency >1 per week (95%CI 2.1-3.0, p <0.001) and focal PET hypometabolism (95%CI 2.0-3.7, p <0.001). On multivariate analysis, the only factor associated with successful injection was patients being able to indicate they were having a seizure to staff (95%CI 1.0-4.4, p=0.038). SIGNIFICANCE: Completing a successful ictal SPECT study remains challenging. Baseline seizure frequency of >1 per-week, a PET hypometabolic focus and a patient's ability to indicate seizure onset were identified as predictors of success. These findings may assist EMUs in optimising their SPECT protocols, patient selection, and resource allocation.

Prospective multisite cohort study of patient-reported outcomes in adults with new-onset seizures.

OBJECTIVE: New-onset seizures affect up to 10% of people over their lifetime, however, their health economic impact has not been well-studied. This prospective multicenter study will collect patient-reported outcome measures (PROMs) from adults with new-onset seizures seen in six Seizure Clinics across Melbourne, Australia and The University of Colorado, USA. METHODS: Approximately 450 eligible patients will be enrolled in the study at or following their initial attendance to Seizure Clinics at the study hospitals. Inclusion criteria for the study group are those with new-onset acute symptomatic seizures, new-onset unprovoked seizures, and new-onset epilepsy. Inclusion criteria for the three comparator groups are those with noncardiac syncope, those with psychogenic nonepileptic seizures, as well as published PROMs data from the Australian general population. Exclusion criteria are those aged less than 18 years, those with a preexisting epilepsy diagnosis, and those with intellectual disabilities or other impairments which would preclude them from comprehending and completing the questionnaires. Patients will complete eight online questionnaires regarding the effect that their seizures (or seizure mimics) have had on various aspects of their life. These questionnaires will be readministered at 6 and 12 months. Patients with new-diagnosis epilepsy will also be asked to share the reasons why they have accepted or declined antiseizure medications. ANALYSIS: Primary outcome measures will be quality of life, work productivity, informal care needs, and mood, at baseline compared to 6 and 12 months later for those with new-onset seizures and comparing these outcomes to those in the three comparator groups. Secondary outcomes include mapping of QoLIE-31 to the EQ-5D-5L in epilepsy, modelling indirect costs of new-onset seizures, and exploring why patients may or may not wish to take antiseizure medications. SIGNIFICANCE: These data will form an evidence-base for future studies that examine the effectiveness of various healthcare interventions for new-onset seizure patients. ETHICS AND DISSEMINATION: This study is approved by the Alfred Health Human Research Ethics Committee (SERP: 52 538, Alfred HREC: 307/19), the Austin Health Human Research Ethics Committee (HREC/59148/Austin-2019), and the Colorado Multiple Institutional Review Board (COMIRB) (COMIRB #20-3028). ANZCTR TRIAL REGISTRATION NUMBER: ACTRN12621000908831.

Significance of mannose-binding lectin deficiency and nucleotide-binding oligomerization domain 2 polymorphisms in Staphylococcus aureus bloodstream infections: a case-control study.

BACKGROUND: Pathways coordinated by innate pattern recognition receptors like mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2 (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus) bloodstream infections (BSI) in animal models, but human data are limited. Here, we investigated the role of MBL deficiency and NOD2 mutations in the predisposition to and severity of S. aureus BSI. PATIENTS AND METHODS: A matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2 polymorphisms were analyzed. RESULTS: After adjusting for potential confounders, MBL deficiency (<0.5 µg/ml) was found less frequently in cases than controls (26 vs. 41%, OR 0.4, 95% confidence interval (CI) 0.20-0.95, p=0.04) as were low producing MBL genotypes (11 vs. 23%, OR 0.2, 95% CI 0.08-0.75, p=0.01), whereas NOD2 polymorphisms were similarly distributed. Cases with NOD2 polymorphisms had less organ dysfunction as shown by a lower SOFA score (median 2.5 vs. 4.5, p=0.02), whereas only severe MBL deficiency (<0.1 µg/ml) was associated with life-threatening S. aureus BSI (OR 5.6, 95% CI 1.25-24.85, p=0.02). CONCLUSIONS: Contrary to animal model data, our study suggests MBL deficiency may confer protection against acquiring S. aureus BSI. NOD2 mutations were less frequently associated with multi-organ dysfunction. Further human studies of the innate immune response in S. aureus BSI are needed to identify suitable host targets in sepsis treatment.