Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population

The exact pathogenesis of multiple sclerosis (MS) is incompletely understood. Although auto-immune responses have an important role in the development of hallmark focal demyelinating lesions, the underlying mechanism of axonal degeneration, the other key player in MS pathology and main determinant of long-term disability, remains unclear and corresponds poorly with inflammatory disease activity. Perfusion-weighted imaging studies have demonstrated that there is a widespread cerebral hypoperfusion in patients with MS, which is present from the early beginning to more advanced disease stages. This reduced cerebral blood flow (CBF) does not seems to be secondary to loss of axonal integrity with decreased metabolic demands but appears to be mediated by elevated levels of the potent vasospastic peptide endothelin-1 in the cerebral circulation. Evidence is evolving that cerebral hypoperfusion in MS is associated with chronic hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue. Restoring CBF may therefore emerge as a new therapeutic target in MS.

Background: Multiple sclerosis (MS) is a complex chronic inflammatory and degenerative disorder of the central nervous system. Accelerated brain volume loss, or also termed atrophy, is currently emerging as a popular imaging marker of neurodegeneration in affected patients, but, unfortunately, can only be reliably interpreted at the time when irreversible tissue damage likely has already occurred. Timing of treatment decisions based on brain atrophy may therefore be viewed as suboptimal.Main body: This Narrative Review focuses on alternative techniques with the potential of detecting neurodegenerative events in the brain of subjects with MS prior to the atrophic stage. First, metabolic and molecular imaging provide the opportunity to identify early subcellular changes associated with energy dysfunction, which is an assumed core mechanism of axonal degeneration in MS. Second, cerebral hypoperfusion has been observed throughout the entire clinical spectrum of the disorder but it remains an open question whether this serves as an alternative marker of reduced metabolic activity, or exists as an independent contributing process, mediated by endothelin-1 hyperexpression. Third, both metabolic and perfusion alterations may lead to repercussions at the level of network performance and structural connectivity, respectively assessable by functional and diffusion tensor imaging. Fourth and finally, elevated body fluid levels of neurofilaments are gaining interest as a biochemical mirror of axonal damage in a wide range of neurological conditions, with early rises in patients with MS appearing to be predictive of future brain atrophy.Conclusions: Recent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed. Although the overall level of evidence on the presented topic is still preliminary, this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the abovementioned measures, possibly leading to novel insights in early disease mechanisms and therapeutic intervention strategies.

Background: Telemedicine (TM) is currently flourishing in rural and emergency settings, but its implementation in the routine management of chronic neurological disorders has developed with more hesitation. Limited access to specialized care facilities and expanding patient populations, combined with unprecedented mobility restrictions imposed by the coronavirus disease pandemic, are currently stressing the need for remote solutions in this field. Studies in patients with multiple sclerosis (MS) have been heterogeneous in objectives and methodology but generally support the concept that TM interventions produce clinical benefits, cost-effectiveness, and user satisfaction. Nonetheless, data on live interaction between patients and health care providers for MS teleconsultation purposes remain scarce. Objective: The aim of this study is to demonstrate the feasibility of planned real time audiovisual teleconsultation over the internet for patients with MS. Methods: A total of 20 patients with MS presenting at a specialized MS center in Belgium were recruited for this study. One teleconsultation was scheduled for each participant. Patients were provided a unique hyperlink by mail in advance, leading them automatically and directly to the virtual waiting room, where they could accept or decline our incoming call. All teleconsultations were performed by a trained medical student with the intention to keep the conversation similar to what is usually discussed during a classic face-to-face MS consultation; no remote physical exams were performed. The approach was considered feasible if at least 80% of the planned TM visits could be successfully completed at the foreseen moment. Patient satisfaction (technical quality, convenience, and overall quality of care) was evaluated at the end of each teleconsultation by means of 5-point Likert scales containing the categories very unsatisfied, unsatisfied, neutral, satisfied, and highly satisfied. Results: Out of 20 consultations, 17 were successfully completed (85%). Failures were due to patients not responding (n=2) and technical issues (n=1). Out of the 17 consultations, 17 patients declared themselves satisfied or highly satisfied for technical quality, 15 patients for convenience, and 16 patients for overall quality of care. Conclusions: Planned real time audiovisual teleconsultation over the internet is feasible and highly appreciated in patients with MS. Incorporation of such services in routine clinical MS practice is expected to improve access to specialized care facilities for affected patients.

Inflammatory processes are involved in the pathophysiology of both Alzheimer’s disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.