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Multiple Sclerosis is a chronic autoimmune disorder characterized by the degradation of the myelin sheath in the central nervous system, leading to neurological impairments. In this work, we analyze a reaction-diffusion model derived from kinetic theory to study the formation of demyelinating lesions. We perform a Turing instability analysis and a weakly nonlinear analysis to investigate different spatial patterns that may emerge. Our study examines how key parameters, including the squeezing probability of immune cells and the chemotactic response, impact pattern formation. Numerical simulations confirm the analytical results, revealing the emergence of distinct spatial structures.

Multiple Sclerosis (MS) is a chronic autoimmune disease that can significantly reduce the quality of life of a patient. Existing treatment options can only help slow down the progression of the disease. Therefore, early detection and precise monitoring of disease progression are important. Deep learning offers state-of-the-art models for detecting and segmenting MS lesions in brain MRI scans. However, most of these models are evaluated using the Dice score, without accounting for lesion-wise detection and segmentation performance or other metrics that quantify model performance in cases that are complex or confusing for human annotators, or in cases that are essential for disease detection and progression monitoring. In this paper, we highlight the need to rethink the evaluation of MS lesion segmentation models. In this context, we first present problem fingerprinting in detail to highlight what neurologists look for in brain MRI scans for MS detection and progression monitoring, and which metrics are required to properly quantify model performance in these contexts. Additionally, we present an analysis of state-of-the-art models on two open-source datasets using these metrics to h

We establish an existence result for weak solutions to an aggregation-diffusion-reaction equation with a constraint, arising in the modelling of multiple sclerosis. The model is derived from a general chemotaxis-type framework and describes the time evolution of the density of activated macrophages, which is subject to attraction by oligodendrocytes. The latter are governed by a constraint equation. The proof relies on a variational splitting scheme that isolates the transport (aggregation-diffusion) and reaction contributions. The structure of the constraint makes it possible to recover the oligodendrocyte density as the limit of a sequence of characteristic functions.

Background: Gait and balance impairment can profoundly impact people with multiple sclerosis (PwMS). Objectives: To evaluate the analytical and clinical validity of the U-Turn Test (UTT), a smartphone-based assessment of dynamic balance in PwMS. Methods: The GaitLab study (ISRCTN15993728) enrolled adult PwMS (EDSS 0.0-6.5). PwMS performed the UTT in a gait laboratory (supervised) using 6 smartphones at different wear locations and daily during a two-week remote period (unsupervised) using one smartphone (belt front). Median turn speed was computed per UTT. In the supervised setting, turn detection accuracy of smartphones was compared to motion capture (mocap) via F1 scores. Agreement between smartphone- and mocap-derived turn speed was assessed by Bland-Altman and ICC(3,1). In the unsupervised setting, test-retest reliability (ICC[2,1]) and correlations with Timed 25-Foot Walk (T25FW), EDSS, Ambulation Score, 12-item Multiple Sclerosis Walking Scale (MSWS-12), and Activities-specific Balance Confidence scale (ABC) were evaluated. Results: Ninety-six PwMS were included. Turn speed was comparable across supervised (1.44 rad/s) and unsupervised settings (1.47 rad/s). In the supervised

This report summarizes the outcomes of the ICPR 2024 Competition on Multiple Sclerosis Lesion Segmentation (MSLesSeg). The competition aimed to develop methods capable of automatically segmenting multiple sclerosis lesions in MRI scans. Participants were provided with a novel annotated dataset comprising a heterogeneous cohort of MS patients, featuring both baseline and follow-up MRI scans acquired at different hospitals. MSLesSeg focuses on developing algorithms that can independently segment multiple sclerosis lesions of an unexamined cohort of patients. This segmentation approach aims to overcome current benchmarks by eliminating user interaction and ensuring robust lesion detection at different timepoints, encouraging innovation and promoting methodological advances.

In this paper, a class of reaction-diffusion equations for Multiple Sclerosis is presented. These models are derived by means of a diffusive limit starting from a proper kinetic description, taking account of the underlying microscopic interactions among cells. At the macroscopic level, we discuss the necessary conditions for Turing instability phenomena and the formation of two-dimensional patterns, whose shape and stability are investigated by means of a weakly nonlinear analysis. Some numerical simulations, confirming and extending theoretical results, are proposed for a specific scenario.

Multiple sclerosis is a chronic autoimmune disease that affects the central nervous system. Understanding multiple sclerosis progression and identifying the implicated brain structures is crucial for personalized treatment decisions. Deformation-based morphometry utilizes anatomical magnetic resonance imaging to quantitatively assess volumetric brain changes at the voxel level, providing insight into how each brain region contributes to clinical progression with regards to neurodegeneration. Utilizing such voxel-level data from a relapsing multiple sclerosis clinical trial, we extend a model-agnostic feature importance metric to identify a robust and predictive feature set that corresponds to clinical progression. These features correspond to brain regions that are clinically meaningful in MS disease research, demonstrating their scientific relevance. When used to predict progression using classical survival models and 3D convolutional neural networks, the identified regions led to the best-performing models, demonstrating their prognostic strength. We also find that these features generalize well to other definitions of clinical progression and can compensate for the omission of h

We introduce conversion to the stochastic process known as chase-escape in an effort to model aspects of inflammatory damage from multiple sclerosis. We prove monotonicity results for aggregate damage for the model on the positive integers, trees, stars, and the complete graph. Additionally, we establish the existence and asymptotic order of a phase transition on bounded degree graphs with a non-trivial site percolation threshold.

Quantitative susceptibility maps from magnetic resonance images can provide both prognostic and diagnostic information in multiple sclerosis, a neurodegenerative disease characterized by the formation of lesions in white matter brain tissue. In particular, susceptibility maps provide adequate contrast to distinguish between "rim" lesions, surrounded by deposited paramagnetic iron, and "non-rim" lesion types. These paramagnetic rim lesions (PRLs) are an emerging biomarker in multiple sclerosis. Much effort has been devoted to both detection and segmentation of such lesions to monitor longitudinal change. As paramagnetic rim lesions are rare, addressing this problem requires confronting the class imbalance between rim and non-rim lesions. We produce synthetic quantitative susceptibility maps of paramagnetic rim lesions and show that inclusion of such synthetic data improves classifier performance and provide a multi-channel extension to generate accompanying contrasts and probabilistic segmentation maps. We exploit the projection capability of our trained generative network to demonstrate a novel denoising approach that allows us to train on ambiguous rim cases and substantially incr

Amyotrophic lateral sclerosis (ALS) is a severe disease with a typical survival of 3-5 years after symptom onset. Current treatments offer only limited life extension, and the variability in patient responses highlights the need for personalized care. However, research is hindered by small, heterogeneous cohorts, sparse longitudinal data, and the lack of a clear definition for clinically meaningful patient clusters. Existing clustering methods remain limited in both scope and number. To address this, we propose a clustering approach that groups sequences using a disease progression declarative score. Our approach integrates medical expertise through multiple descriptive variables, investigating several distance measures combining such variables, both by reusing off-the-shelf distances and employing a weak-supervised learning method. We pair these distances with clustering methods and benchmark them against state-of-the-art techniques. The evaluation of our approach on a dataset of 353 ALS patients from the University Hospital of Tours, shows that our method outperforms state-of-the-art methods in survival analysis while achieving comparable silhouette scores. In addition, the learn

Quantifying the complex/multifractal organization of the brain signals is crucial to fully understanding the brain processes and structure. In this contribution, we performed the multifractal analysis of the electroencephalographic (EEG) data obtained from a controlled multiple sclerosis (MS) study, focusing on the correlation between the degree of multifractality, disease duration, and disability level. Our results reveal a significant correspondence between the complexity of the time series and multiple sclerosis development, quantified respectively by scaling exponents and the Expanded Disability Status Scale (EDSS). Namely, for some brain regions, a well-developed multifractality and little persistence of the time series were identified in patients with a high level of disability, whereas the control group and patients with low EDSS were characterised by persistence and monofractality of the signals. The analysis of the cross-correlations between EEG signals supported these results, with the most significant differences identified for patients with EDSS $> 1$ and the combined group of patients with EDSS $\leq 1$ and controls. No association between the multifractality and di

Automatic prediction of amyotrophic lateral sclerosis (ALS) disease progression provides a more efficient and objective alternative than manual approaches. We propose ALS longitudinal speech transformer (ALST), a neural network-based automatic predictor of ALS disease progression from longitudinal speech recordings of ALS patients. By taking advantage of high-quality pretrained speech features and longitudinal information in the recordings, our best model achieves 91.0\% AUC, improving upon the previous best model by 5.6\% relative on the ALS TDI dataset. Careful analysis reveals that ALST is capable of fine-grained and interpretable predictions of ALS progression, especially for distinguishing between rarer and more severe cases. Code is publicly available.

Multiple sclerosis is a disease that affects the brain and spinal cord, it can lead to severe disability and has no known cure. The majority of prior work in machine learning for multiple sclerosis has been centered around using Magnetic Resonance Imaging scans or laboratory tests; these modalities are both expensive to acquire and can be unreliable. In a recent paper it was shown that disease progression can be predicted effectively using performance outcome measures and demographic data. In our work we build on this to investigate the modeling side, using continuous time models to predict progression. We benchmark four continuous time models using a publicly available multiple sclerosis dataset. We find that the best continuous model is often able to outperform the best benchmarked discrete time model. We also carry out an extensive ablation to discover the sources of performance gains, we find that standardizing existing features leads to a larger performance increase than interpolating missing features.

Automating Multiple Sclerosis (MS) lesion segmentation would be of great benefit in initial diagnosis as well as monitoring disease progression. Deep learning based segmentation models perform well in many domains, but the state-of-the-art in MS lesion segmentation is still suboptimal. Complementary to previous MS lesion segmentation challenges which focused on optimizing the performance on a single evaluation dataset, this study aims to develop models that generalize across diverse evaluation datasets, mirroring real-world clinical scenarios that involve varied scanners, settings, and patient cohorts. To this end, we used all high-quality publicly-available MS lesion segmentation datasets on which we systematically trained a state-of-the-art UNet++ architecture. The resulting models demonstrate consistent performance across the remaining test datasets (are generalizable), with larger and more heterogeneous datasets leading to better models. To the best of our knowledge, this represents the most comprehensive cross-dataset evaluation of MS lesion segmentation models to date using publicly available datasets. Additionally, explicitly enhancing dataset size by merging datasets improv

Magnetic resonance imaging is a fundamental tool to reach a diagnosis of multiple sclerosis and monitoring its progression. Although several attempts have been made to segment multiple sclerosis lesions using artificial intelligence, fully automated analysis is not yet available. State-of-the-art methods rely on slight variations in segmentation architectures (e.g. U-Net, etc.). However, recent research has demonstrated how exploiting temporal-aware features and attention mechanisms can provide a significant boost to traditional architectures. This paper proposes a framework that exploits an augmented U-Net architecture with a convolutional long short-term memory layer and attention mechanism which is able to segment and quantify multiple sclerosis lesions detected in magnetic resonance images. Quantitative and qualitative evaluation on challenging examples demonstrated how the method outperforms previous state-of-the-art approaches, reporting an overall Dice score of 89% and also demonstrating robustness and generalization ability on never seen new test samples of a new dedicated under construction dataset.

Multiple Sclerosis (MS) is a chronic autoimmune and inflammatory neurological disorder characterised by episodes of symptom exacerbation, known as relapses. In this study, we investigate the role of environmental factors in relapse occurrence among MS patients, using data from the H2020 BRAINTEASER project. We employed predictive models, including Random Forest (RF) and Logistic Regression (LR), with varying sets of input features to predict the occurrence of relapses based on clinical and pollutant data collected over a week. The RF yielded the best result, with an AUC-ROC score of 0.713. Environmental variables, such as precipitation, NO2, PM2.5, humidity, and temperature, were found to be relevant to the prediction.

We present a mathematical study for the development of multiple sclerosis based on a reaction-diffusion system. The model describes interactions among different populations of human cells, motion of immune cells stimulated by cytokines, consumption of myelin sheath due to anomalously activated lymphocytes and its restoration by oligodendrocytes. Successively, we introduce a therapy term representing injection of low-dose IL-2 interleukine. A natural step is then to study the system, investigating the formation of spatial patterns by means of a Turing instability analysis of the problem. In particular, we get spatial patterns oscillating in time that may reproduce brain lesions characteristic of the early stage of the pathology, in both non-treatment and treatment scenarios.

Predicting survival in Amyotrophic Lateral Sclerosis (ALS) is a challenging task. Magnetic resonance imaging (MRI) data provide in vivo insight into brain health, but the low prevalence of the condition and resultant data scarcity limit training set sizes for prediction models. Survival models are further hindered by the subtle and often highly localised profile of ALS-related neurodegeneration. Normative models present a solution as they increase statistical power by leveraging large healthy cohorts. Separately, diffusion models excel in capturing the semantics embedded within images including subtle signs of accelerated brain ageing, which may help predict survival in ALS. Here, we combine the benefits of generative and normative modelling by introducing the normative diffusion autoencoder framework. To our knowledge, this is the first use of normative modelling within a diffusion autoencoder, as well as the first application of normative modelling to ALS. Our approach outperforms generative and non-generative normative modelling benchmarks in ALS prognostication, demonstrating enhanced predictive accuracy in the context of ALS survival prediction and normative modelling in gener

Multiple Sclerosis (MS) is a chronic disease developed in human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale (EDSS), composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) creates opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to the data insufficiency or model simplicity. In this paper, we proposed an idea of using patients' multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity at the hospital visit. This work has two important contributions. First, we describe a pilot effort to leverage structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict