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Vincent Navarro

Publications and source records attributed to Vincent Navarro.

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Graph-based analysis of inflammatory profiles in New Onset Refractory Status Epilepticus (NORSE)

Background and Objectives: Cryptogenic new-onset refractory status epilepticus (cNORSE) represents one of the most severe forms of status epilepticus, occurring in patients without prior neurological disease, and remaining of unknown aetiology despite extensive diagnostic evaluation. Emerging evidence supports a role for immune dysregulation in cNORSE; however, marked heterogeneity in inflammatory signatures has been reported, complicating the selection of targeted immunotherapies. Therefore, a critical need for tools facilitating the interpretation of cytokine panels exists. Methods: Building on the identification of distinct inflammatory groups of cNORSE patients using a graph clustering approach applied to a cohort of 62 patients with serum profiling of 96 cytokines, we tailored new models to quantify attribution probability to biologically validated clusters. Statistical assessment of the most informative model involved Monte-Carlo simulations and custom-developed parametric tests. Ultimately, we applied our framework to the implementation of a clinician-friendly interface for inflammatory profiling. Results: Our approach enables quick processing of several cytokine profiles, providing the most likely inflammatory cluster, associated attribution probability, and statistical confidence. For longitudinal assessments, the proposed method may also allow tracking the evolution of inflammatory trajectories over time. Conclusion: Systematic statistical characterization of the inflammatory heterogeneity in cNORSE requires the development of clinically actionable support tools. Our study offers a framework that may support personalized immunomodulatory strategies in cNORSE patients through clustering-based cytokine profiling.

q-bio.NC

Low-dimensional representation of brain networks for seizure risk forecasting

Identifying preictal states -- periods during which seizures are more likely to occur -- remains a central challenge in clinical computational neuroscience. In this study, we introduce a novel framework that embeds functional brain connectivity networks, derived from intracranial EEG (iEEG) recordings, into a low-dimensional Euclidean space. This compact representation captures essential topological features of brain dynamics and facilitates the detection of subtle connectivity changes preceding seizures. Using standard machine learning techniques, we define a dimensionless biomarker, $\mathcal{B}$, that discriminates between interictal (seizure-free) and preictal (within 24 hours of seizure) network states. Our method focuses on connectivity patterns among a subset of informative iEEG electrodes, identified through permutation-based testing, enabling robust classification of brain states across time. We validate our approach using a leave-one-out cross-validation scheme and a pseudo-prospective forecasting strategy, assessing performance with metrics such as F1-score and balanced accuracy. Results show that low-dimensional Euclidean embeddings of iEEG connectivity yield interpretable and predictive markers of preictal activity, offering promising implications for real-time seizure forecasting and individualized therapeutic interventions.

q-bio.NC

Geometric representations of brain networks can predict the surgery outcome in temporal lobe epilepsy

Epilepsy surgery, particularly for temporal lobe epilepsy (TLE), remains a vital treatment option for patients with drug-resistant seizures. However, accurately predicting surgical outcomes remains a significant challenge. This study introduces a novel biomarker derived from brain connectivity, analyzed using non-Euclidean network geometry, to predict the surgery outcome in TLE. Using structural and diffusion magnetic resonance imaging (MRI) data from 51 patients, we examined differences in structural connectivity networks associated to surgical outcomes. Our approach uniquely utilized hyperbolic embeddings of pre- and post-surgery brain networks, successfully distinguishing patients with favorable outcomes from those with poor outcomes. Notably, the method identified regions in the contralateral hemisphere relative to the epileptogenic zone, whose connectivity patterns emerged as a potential biomarker for favorable surgical outcomes. The prediction model achieves an area under the curve (AUC) of 0.87 and a balanced accuracy of 0.81. These results underscore the predictive capability of our model and its effectiveness in individual outcome forecasting based on structural network changes. Our findings highlight the value of non-Euclidean representation of brain networks in gaining deeper insights into connectivity alterations in epilepsy, and advancing personalized prediction of surgical outcomes in TLE.

q-bio.NC

Hyperbolic embedding of brain networks as a tool for epileptic seizures forecasting

The evidence indicates that intracranial EEG connectivity, as estimated from daily resting state recordings from epileptic patients, may be capable of identifying preictal states. In this study, we employed hyperbolic embedding of brain networks to capture non-trivial patterns that discriminate between connectivity networks from days with (preictal) and without (interictal) seizure. A statistical model was constructed by combining hyperbolic geometry and machine learning tools, which allowed for the estimation of the probability of an upcoming seizure. The results demonstrated that representing brain networks in a hyperbolic space enabled an accurate discrimination (85%) between interictal (no-seizure) and preictal (seizure within the next 24 hours) states. The proposed method also demonstrated excellent prediction performances, with an overall accuracy of 87% and an F1-score of 89% (mean Brier score and Brier skill score of 0.12 and 0.37, respectively). In conclusion, our findings indicate that representations of brain connectivity in a latent geometry space can reveal a daily and reliable signature of the upcoming seizure(s), thus providing a promising biomarker for seizure forecasting.

q-bio.NC

A self-supervised learning strategy for postoperative brain cavity segmentation simulating resections

Accurate segmentation of brain resection cavities (RCs) aids in postoperative analysis and determining follow-up treatment. Convolutional neural networks (CNNs) are the state-of-the-art image segmentation technique, but require large annotated datasets for training. Annotation of 3D medical images is time-consuming, requires highly-trained raters, and may suffer from high inter-rater variability. Self-supervised learning strategies can leverage unlabeled data for training. We developed an algorithm to simulate resections from preoperative magnetic resonance images (MRIs). We performed self-supervised training of a 3D CNN for RC segmentation using our simulation method. We curated EPISURG, a dataset comprising 430 postoperative and 268 preoperative MRIs from 430 refractory epilepsy patients who underwent resective neurosurgery. We fine-tuned our model on three small annotated datasets from different institutions and on the annotated images in EPISURG, comprising 20, 33, 19 and 133 subjects. The model trained on data with simulated resections obtained median (interquartile range) Dice score coefficients (DSCs) of 81.7 (16.4), 82.4 (36.4), 74.9 (24.2) and 80.5 (18.7) for each of the four datasets. After fine-tuning, DSCs were 89.2 (13.3), 84.1 (19.8), 80.2 (20.1) and 85.2 (10.8). For comparison, inter-rater agreement between human annotators from our previous study was 84.0 (9.9). We present a self-supervised learning strategy for 3D CNNs using simulated RCs to accurately segment real RCs on postoperative MRI. Our method generalizes well to data from different institutions, pathologies and modalities. Source code, segmentation models and the EPISURG dataset are available at https://github.com/fepegar/ressegijcars .

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