A Novel Noninvasive Approach Based on SPECT and EEG for the Location of the Epileptogenic Zone in Pharmacoresistant Non-Lesional Epilepsy

Background and objectives: The aim of this study is to propose a methodology that combines non-invasive functional modalities electroencephalography (EEG) and single photon emission computed tomography (SPECT) to estimate the location of the epileptogenic zone (EZ) for the presurgical evaluation of patients with drug-resistant non-lesional epilepsy. Materials and Methods: This methodology consists of: (i) Estimation of ictal EEG source imaging (ESI); (ii) application of the subtraction of ictal and interictal SPECT co-registered with MRI (SISCOM) methodology; and (iii) estimation of ESI but using the output of the SISCOM as a priori information for the estimation of the sources. The methodology was implemented in a case series as an example of the application of this novel approach for the presurgical evaluation. A gold standard and a coincidence analysis based on measures of sensitivity and specificity were used as a preliminary assessment of the proposed methodology to localize EZ. Results: In patients with good postoperative evolution, the estimated EZ presented a spatial coincidence with the resection site represented by high values of sensitivity and specificity. For the patient with poor postoperative evolution, the methodology showed a partial incoherence between the estimated EZ and the resection site. In cases of multifocal epilepsy, the method proposed spatially extensive epileptogenic zones. Conclusions: The results of the case series provide preliminary evidence of the methodology's potential to epileptogenic zone localization in non-lesion drug-resistant epilepsy. The novelty of the article consists in estimating the sources of ictal EEG using SISCOM result as a prior for the inverse solution. Future studies are necessary in order to validate the described methodology. The results constitute a starting point for further studies in order to support the clinical reliability of the proposed methodology and advocate for their implementation in the presurgical evaluation of patients with intractable non-lesional epilepsy.</p

Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson’s Patients

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’s Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs

Relation of Brain Perfusion Patterns to Sudden Unexpected Death Risk Stratification: A Study in Drug Resistant Focal Epilepsy

To explore the role of the interictal and ictal SPECT to identity functional neuroimaging biomarkers for SUDEP risk stratification in patients with drug-resistant focal epilepsy (DRFE). Twenty-nine interictal-ictal Single photon emission computed tomography (SPECT) scans were obtained from nine DRFE patients. A methodology for the relative quantification of cerebral blood flow of 74 cortical and sub-cortical structures was employed. The optimal number of clusters (K) was estimated using a modified v-fold cross-validation for the use of K means algorithm. The two regions of interest (ROIs) that represent the hypoperfused and hyperperfused areas were identified. To select the structures related to the SUDEP-7 inventory score, a data mining method that computes an automatic feature selection was used. During the interictal and ictal state, the hyperperfused ROIs in the largest part of patients were the bilateral rectus gyrus, putamen as well as globus pallidus ipsilateral to the seizure onset zone. The hypoperfused ROIs included the red nucleus, substantia nigra, medulla, and entorhinal area. The findings indicated that the nearly invariability in the perfusion pattern during the interictal to ictal transition observed in the ipsi-lateral putamen F = 12.60, p = 0.03, entorhinal area F = 25.80, p = 0.01, and temporal middle gyrus F = 12.60, p = 0.03 is a potential biomarker of SUDEP risk. The results presented in this paper allowed identifying hypo- and hyperperfused brain regions during the ictal and interictal state potentially related to SUDEP risk stratification

Harmonized-Multinational qEEG norms (HarMNqEEG)

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding