Search Results (8)

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Together with the wide range of possible benefits for the rehabilitation/training of people with multiple sclerosis (pwMS) and other neurologic conditions, exposure to immersive virtual reality (VR) has often been associated with unpleasant symptoms, such as transient dizziness, headache, nausea, disorientation and impaired postural control (i.e., cybersickness). Since these symptoms can significantly impact the safety and tolerability of the treatment, it appears important to correctly estimate their presence and magnitude. Given the existing data scarcity, this study aims to assess the existence and severity of possible adverse effects associated with exposure to immersive VR in a cohort of pwMS using both objective measurements of postural control effectiveness and subjective evaluations of perceived symptoms. To this aim, postural sway under upright quiet posture (in the presence and absence of visual input) of 56 pwMS with an Expanded Disability Status Scale score (EDSS) in the range of 0–6.5 (mean EDSS 2.3) and 33 unaffected individuals was measured before and after a 10-min immersive VR session and at 10 min follow-up on the basis of center of pressure (COP) trajectories. The severity of cybersickness symptoms associated with VR exposure was also self-rated by the participants using the Italian version of the Simulator Sickness Questionnaire (SSQ). Temporary impairments of postural control in terms of significantly increased sway area were observed after the VR session only in pwMS with mild–moderate disability (i.e., EDSS in the range of 2.5–6.5) in the presence of visual input. No changes were observed in pwMS with low disability (EDSS 0–2) and unaffected individuals. In contrast, when the visual input was removed, there was a decrease in sway area (pwMS with mild–moderate disability) and COP path length relating to the use of VR (pwMS with mild–moderate disability and unaffected individuals), thus suggesting a sort of “balance training effect”. Even in this case, the baseline values were restored at follow-up. All participants, regardless of their status, experienced significant post-VR side effects, especially in terms of blurred vision and nausea. Taken together, the findings of the present study suggest that a short immersive VR session negatively (eyes open) and positively (eyes closed) impacts the postural control of pwMS and causes significant disorientation. However, such effects are of limited duration. While it is reasonable to state that immersive VR is sufficiently safe and tolerable to not be contraindicated in the rehabilitation/training of pwMS, in order to reduce possible negative effects and maximize the efficacy, safety and comfort of the treatment, it appears necessary to develop specific guidelines that consider important factors like individual susceptibility, maximum exposure time according to the specific features of the simulation, posture to adopt and protocols to assess objective and perceived effects on participants. Full article

Aiming to identify the potential challenges in the classification of musculoskeletal manifestations in patients with psoriasis (PsO), this study analyzed the outcomes of a cross-sectional rheumatologic assessment of 1057 PsO patients. In total, 209 had a previous diagnosis of psoriatic arthritis (PsA). Out of the remaining 848 subjects, 293 (35%) were classified as suspected PsA cases according to the rheumatologist’s judgment and/or Early PsA Screening Questionnaire score (EARP) ≥ 3. However, only 14% received a PsA diagnosis, 49% had a PsA-alternative diagnosis, and the remaining 37% had nonspecific arthralgias. Most of the newly diagnosed PsA patients had a symptoms duration ≥1 year (72%) and moderate disease activity (55%) with active oligoarthritis (85%), dactylitis, or enthesitis (35%) as the most frequent clinical pattern. The most frequent PsA-alternative diagnoses were osteoarthritis and fibromyalgia (44% and 41%). The only factors with significant (p < 0.05) utility in discriminating PsA from other diseases and nonspecific arthralgias were young age and EARP score with a history of morning stiffness, swollen joints, or dactylitis. These results demonstrated a high prevalence of suspected musculoskeletal symptoms in PsO patients, with, however, only a small proportion due to PsA. Close collaboration between the dermatologist and rheumatologist plays a crucial role in the differential diagnosis of PsA, as well as in monitoring nonspecific arthralgias for the potential transition to overt PsA. Full article

Multiple sclerosis (MS), neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are inflammatory diseases of the central nervous system (CNS) with a multifactorial aetiology. Environmental factors are important for their development and microorganisms could play a determining role. They can directly damage the CNS, but their interaction with the immune system is even more important. The possible mechanisms involved include molecular mimicry, epitope spreading, bystander activation and the dual cell receptor theory. The role of Epstein–Barr virus (EBV) in MS has been definitely established, since being seropositive is a necessary condition for the onset of MS. EBV interacts with genetic and environmental factors, such as low levels of vitamin D and human endogenous retrovirus (HERV), another microorganism implicated in the disease. Many cases of onset or exacerbation of neuromyelitis optica spectrum disorder (NMOSD) have been described after infection with Mycobacterium tuberculosis, EBV and human immunodeficiency virus; however, no definite association with a virus has been found. A possible role has been suggested for Helicobacter pylori, in particular in individuals with aquaporin 4 antibodies. The onset of MOGAD could occur after an infection, mainly in the monophasic course of the disease. A role for the HERV in MOGAD has been hypothesized. In this review, we examined the current understanding of the involvement of infectious factors in MS, NMO and MOGAD. Our objective was to elucidate the roles of each microorganism in initiating the diseases and influencing their clinical progression. We aimed to discuss both the infectious factors that have a well-established role and those that have yielded conflicting results across various studies. Full article

Current treatment for Multiple Sclerosis (MS) consists of a multidisciplinary approach including disease-modifying therapies. The response to treatment is heterogeneous, representing a crucial challenge in the classification of patients. Metabolomics is an innovative tool that can identifies biomarkers/predictors of treatment response. We aimed to evaluate plasma metabolic changes in a group of naïve Relapsing-Remitting MS patients starting Fingolimod treatment, to find specific metabolomic features that predict the therapeutic response as well as the possible side effects. The study included 42 Relapsing-Remitting MS blood samples, of which 30 were classified as responders after two years of FINGO treatment, whereas 12 patients were Not-Responders. For fifteen patients, samples were collected at four time points: before starting the therapy; at six months after the initiation; at twelve months after; and at twenty-four months after initiation. The serum was analysed through Nuclear Magnetic Resonance and multivariate and univariate statistical analysis. Considering the single comparison between each time point, it was possible to identify a set of metabolites changing their concentrations based on the drug intake. FINGO influences aminoacidic and energy metabolisms and reduces oxidative stress and the activity of the immune system, both typical features of MS. Full article

Subtle alterations of gait patterns in people with Multiple Sclerosis (pwMS) with minimal or no disability often coexist with normal spatio-temporal parameters. Here, we retrospectively investigate the existence of possible anomalies in lower limb inter-joint coordination (i.e., the functional relationship between joint pairs) in pwMS with apparently physiologic gait features. Twenty-seven pwMS with Expanded Disability Status Scale scores ≤ 2, and 27 unaffected age-and-sex-matched individuals, were tested using 3D computerized gait analysis. Raw data were processed to extract the main spatio-temporal parameters and the kinematics in the sagittal plane at the hip, knee, and ankle joints. Angle-angle diagrams (cyclograms) were obtained by coupling the flexion-extension values for the hip-knee and knee-ankle joint pairs at each point of the gait cycle. Cyclogram area, perimeter, and dimensionless ratio were employed to quantify inter-joint coordination. The results demonstrate that cyclograms of pwMS are characterized by significantly reduced perimeters for both investigated joint pairs and reduced area at the hip–knee joint pair. In the latter pair, the differences between groups involved the entire swing phase. For the knee-ankle pair, the average cyclogram of pwMS departed from normality from the late stance until the mid-swing phase. Such findings suggest that inter-joint coordination is impaired even in minimally disabled pwMS who exhibit a normal gait pattern in terms of spatio-temporal parameters. The quantitative and qualitative study of cyclogram features may provide information that is useful for better understanding the underlying mechanisms of walking dysfunctions in MS. Full article

In people with multiple sclerosis (pwMS), fatigue, weakness and spasticity may reduce mobility and promote sedentary behavior. However, little is known about the existence of possible differences in the way MS modifies the propensity to perform physical activity (PA) in men and women. The present study aimed to partly close this gap by means of quantitative analysis carried out using wearable sensors. Forty-five pwMS (23 F, 22 M, mean age 50.3) and 41 unaffected age- and sex-matched individuals wore a tri-axial accelerometer 24 h/day for 7 consecutive days. Raw data were processed to calculate average number of daily steps, vector magnitude (VM) counts, and percentage of time spent in sedentary behavior and in PA of different intensities (i.e., light and moderate-to-vigorous, MVPA). Women with MS spent more time in sedentary behavior and exhibited a reduced amount of light intensity activity with respect to men, while MVPA was similar across sexes. However, in comparison with unaffected individuals, the overall PA patterns appear significantly modified mostly in women who, in presence of the disease, present increased sedentary behavior, reduced MVPA, number of daily steps and VM counts. The findings of the present study highlight the urgency of including sex as variable in all studies on PA in pwMS. Full article

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD. Full article