Sclerosis

Cognitive impairment is one of the most significant burdens among the many neurological complaints in multiple sclerosis patients. Cognitive deficits negatively impact these patients’ quality of life, leading to partial or total loss of several mental functions, such as learning, memory, perception, or problem-solving. While the precise mechanisms involved in the onset and evolution of cognitive decline remain unknown, several risk factors have been associated with intellectual disability. With increasing data on this topic in recent years, the main aim of this review is to summarize the most relevant risk factors correlated with cognitive impairment in multiple sclerosis patients. Firstly, the authors demonstrate the importance of mental disability based on epidemiological data from multiple sclerosis patient cohorts. Subsequently, the intensely debated major risk factors for cognitive decline are discussed, with brief insights into the pathophysiology and possible underlying mechanisms. Finally, the authors describe the impact of medication on cognitive impairment in multiple sclerosis patients, highlighting the main research directions for future studies. Full article

Background: People with Multiple Sclerosis (PwMS) have reported a higher unemployment rate compared to the general population. The complexity of environmental-contextual factors, such as structural and functional social support, may influence employment status (ES). Objectives: to study the relationship between perceived social support and ES, assess the effects of potential mediators, and analyze how these predictors influence components of ES, including absenteeism, work harassment, negative work events, and the use of accommodations. Material and Method: 90 PwMS were recruited. A single-visit assessment included: the Medical Outcomes Study Social Support Survey (MOS-SSS), the Buffalo Vocational Monitoring Survey, the Symbol Digit Modalities Test (SDMT), patient-reported outcomes measuring depression (Beck Depression Inventory-II (BDI-II) and fatigue (Fatigue Severity Scale), and the EDSS. Results: Sixty-three (70%) of PwMS were employed. Mediation analysis revealed the involvement of BDI-II and SDMT in the relationship between social support and ES. The functional social support of friends had a significant effect on absenteeism and NWEs. Total functional support was related to harassment, while family support had a significant effect on accommodations. Conclusion: These results show that structural and functional social support, in relation to the clinical variables of the disease, increase the probability of employment and a better quality of work. Full article

Fatigue is a common symptom in Multiple Sclerosis (MS), and its assessment depends entirely on patient reports. Importantly, managing MS symptoms is increasingly supported by Digital Health Technology (DHT), which includes Mobile Health Technology (mHT). Considering the growing interest, we aimed to synthesise evidence about smartphone applications for the assessment and management of fatigue in MS, as well as to investigate their usability, feasibility, and reliability. We performed a literature search in PubMed, Science Direct, and Embase using a scoping review approach. We included 16 articles and, although many lacked crucial methodological details, DHT was evaluated in all MS clinical subtypes and with disease durations up to more than 20 years. Despite the marked heterogeneity in terms of the employed methods, all documented a high degree of usability, assessed both as feedback from participants and completed tasks. Moreover, the feasibility assessment also showed good results, as apps were able to discriminate between patients with and without fatigue. Importantly, most also showed excellent results in terms of reliability, and some patients reported a reduction in fatigue thanks to mHT. Despite limitations, mHT has been positively evaluated by patients, suggesting a promising role of DHT in the self-management of MS. Full article

Multiple sclerosis is an autoimmune disease that affects the central nervous system. In Brazil, there are currently several therapeutic options for the treatment of this condition, with some being distributed free of charge, while others are not included in the list of free medications. The objective of this article is to provide a pharmacoepidemiological analysis of the available medications in the country, covering their mechanisms of action, the historical context of approval and free distribution within the healthcare system, and their geographical distribution of application. Additionally, we discuss the impact of the inclusion of these medications on hospitalization and mortality rates in the country. We hope that this work serves as a resource for healthcare professionals to better understand pharmacoepidemiology and for health policymakers seeking data for the planning of public policies aimed at the treatment of multiple sclerosis. Full article

This case report describes a 38-year-old female patient with a 3-year history of multiple sclerosis who developed rituximab-induced pancolitis, possibly representing a new onset of inflammatory bowel disease. The patient presented with bloody diarrhea, epigastric pain, fever, and general malaise. Laboratory testing revealed elevated acute inflammation markers, and endoscopy showed deep ulcerations and severe perianal disease. The patient was treated effectively with corticosteroids. Monthly doses of ustekinumab have been administered during follow-up due to perianal disease that has remitted. Rituximab was discontinued and ozanimod was initiated with clinical and analytical stability to date. Full article

While previous studies have described the time course of the dissipation of motor sleep inertia (around 70 min after wake-up time) and motor wake inertia (around 20 min after bedtime) in healthy controls (HCs), the corresponding knowledge for persons with early relapsing–remitting multiple sclerosis (RRMS) is lacking. To fill in this knowledge gap, we carried out a secondary analysis of previously collected data in 35 persons (24 females; mean age = 31.51 ± 7.74 years) with early relapsing–remitting multiple sclerosis (RRMS) and 35 (24 females; mean age = 31.29 ± 8.02) healthy controls (HCs). Each participant wore an actigraphic Micro Motionlogger Watch (Ambulatory Monitoring, Ardlsey, NY, USA) for seven consecutive days. The Functional Linear Modeling statistical framework was adopted to compare the dissipation of motor sleep inertia as well as motor wake inertia between RRMS and HC. As regards motor sleep inertia, no significant differences in motor activity were observed in the first 70 min after the wake-up time; however, with reference to motor wake inertia, the motor activity of RRMS persons was significantly higher than HCs in approximately the first 30 min after bedtime. Despite the small sample size, this pattern of results suggests that the dissipation of motor wake inertia is only slower in persons with RRMS as opposed to HCs. Full article

The aim of this study was to investigate signal patterns and parameters of digital biomarkers in the assessment of mobility in individuals with multiple sclerosis, captured through motion sensors. This is an integrative literature review based on the PRISMA recommendations, which included studies that used wearable technology, such as accelerometers, wearable sensors or inertial sensors, and analyzed mobility/gait-related parameters, such as speed, step count, rhythm, balance, duration and intensity of activity. A total of 1602 studies were identified, of which only 21 were included in the final qualitative synthesis. The main digital biomarkers identified presented signal patterns and parameters captured through different wearable devices, including triaxial accelerometers, inertial sensors, smartphones or smartwatches. The studies employed different objective biomarker reference measures, such as walking speed and step count, and subjective biomarker reference measures, such as fatigue and quality of life assessment scales, for a comprehensive assessment of the participants’ health and mobility. It was found that digital biomarkers play a fundamental role in any individual’s health assessment and protocols. However, it is essential to understand these signals and standardize the choice of the best method to capture signals of high quantity and quality, especially for individuals affected by some neurological pathology. Full article

Lower urinary tract dysfunction is frequently observed in individuals with multiple sclerosis (MS), significantly impacting their quality of life and increasing the risk of upper urinary tract (UUT) damage. Magnetic resonance imaging (MRI) serves as the gold standard imaging technique for identifying demyelinating lesions and aiding in the clinical diagnosis of MS. However, despite its diagnostic utility, the precise relationship between MRI lesions and bladder dysfunction remains poorly established. We aimed to examine the correlation between MRI lesion localizations and both urodynamic parameters and risk factors for UUT damage. In this retrospective study, we conducted a comprehensive review of 201 patients diagnosed with MS who were referred for primary neurourological evaluation, including a videourodynamic study (VUDS). To explore potential significant relationships between the independent variable of MRI lesion localization and the dependent outcome variables, we conducted a multivariate analysis of variance (MANOVA) regression. A significant correlation was observed between the presence of a brainstem lesion and specific urodynamic parameters, including lower maximum cystometric bladder capacity and higher bladder compliance. Similarly, an increased number of diverse MRI lesion localizations demonstrated a significant correlation with these urodynamic parameters. In conclusion, MRI findings did not exhibit a significant association with urodynamic risk factors for UUT damage, thereby limiting their utility in stratifying MS patients for subsequent neurourological assessment and treatment. Full article

Multiple sclerosis (MS) is an autoimmune, neurological, and demyelinating disease of unknown etiology. Neuroinflammation caused by the disease has been associated with air pollution as well as bioclimatic conditions. The aim of this study was to investigate the impacts of air pollution and human thermal discomfort on hospitalizations for multiple sclerosis in Sao Paulo, Brazil, from 2008 to 2015. Generalized Additive Model for Location Scale and Shape (GAMLSS) with Zero Inflated Poisson was used to relate multiple sclerosis hospitalizations in three age groups (less than 30 years old, between 30 and 50 years old, and more than 50 years old) and gender (female and male) with atmospheric pollutants PM₁₀, SO₂, NO₂, NO, and NO_x and thermal discomfort. The results showed that the exposure to an increase of 1 µg/m³ in SO₂ concentration is highly associated with a 10% increase of the risk of MS hospitalization (95% CI: 2–21%) in female patients and a 7.5% (95% CI: 1.5–16%) increase in male patients. PM₁₀ and NO were associated with increased MS risk only for female patients, mainly aged between 30 and 50 years old (2% and 1% increase in hospitalizations, respectively). The cold discomfort was also associated with MS hospitalization, mainly in males (2% increase in hospitalizations; 95% IC: 1–3%). These results are important, since there are few studies that relate air pollution and thermal discomfort with hospitalizations for multiple sclerosis in Brazil. Full article

Extracellular vesicles (EVs) are involved in the regulation of immune system functioning and central nervous system (CNS) homeostasis, suggesting a possible role in multiple sclerosis (MS). Indeed, by carrying several types of mediators, such as cytokines, enzymes, and RNAs, EVs can display both anti- and pro-inflammatory roles on the innate and adaptive immune system, and are involved in several CNS functions, including neuronal plasticity, trophic support, disposal of cellular components, axonal maintenance and neuroprotection. In this review, we provide an overview of the studies carried out to understand the role of EVs in the compromised immune system and CNS functioning typical of MS. Moreover, we also highlight the potential of EVs for the diagnosis of this disorder, thanks to their ability to cross the blood-brain barrier (BBB). In addition, we describe the advances in the use of EVs as therapeutic agents by describing their therapeutic potential. Full article

Multiple sclerosis (MS) is a chronic neurological disease with a global prevalence that has risen over the past decade. The literature suggests that in comparison with a healthy control (HC) group, people with MS experience lower levels of quality of life (QoL). The purpose of this study was (1) to investigate the differences in QoL and a set of psychosocial variables between MS patients and an HC group; (2) to examine the correlations between QoL and psychosocial, sociodemographic, and clinical variables; and (3) to assess the predictive value of a set of psychosocial, sociodemographic, and clinical variables for the QoL of patients with MS. Participants in the clinical group (n = 135) and the HC group (n = 170) filled in a sociodemographic questionnaire and self-report assessments measuring QoL, body appreciation, body acceptance by others, functionality appreciation, body responsiveness, meaning in life, and difficulties in emotion regulation. The results show that the MS group had lower general, physical, psychological, and social QoL than the HC group and that body appreciation, body acceptance by others, body functionality, meaning in life, and difficulties in emotion regulation are important predictors of QoL. Full article

Multiple sclerosis is an autoimmune, inflammatory, and chronic neurodegenerative disease caused by myelin loss in the central nervous system. One strategy that shows evidence of numerous benefits is therapeutic exercise, but these therapies, based on repetitive physical actions, can sometimes be unmotivating for patients. Our proposal suggests that an exergame programme with immersive virtual reality (IVR) is feasible for people with multiple sclerosis (pwMS) and will improve their physical function through more motivational sessions. We present a protocol for a single-blind randomised controlled trial to assess the feasibility and impact on functional capacities of an 8-week IVR programme (ExeRVIEM protocol) in pwMS. Balance, gait, risk of falling, functional mobility and lower limb strength, fatigue, handgrip strength, and reaction times will be evaluated. The control group will maintain the usual activities scheduled in the centre, and the experimental group will add the ExeRVIEM protocol (two sessions per week). Therapies based on the combination of exercise and IVR explored in this study may offer new treatment approaches and open new lines of research in this field by improving the functionality of pwMS, as well as motivating patients and encouraging their adherence to treatment. Full article

Isolated paraneoplastic myelopathy (IPM) is a rare neurological manifestation of systemic cancer and represents an intermediate-risk phenotype of disease according to the diagnostic criteria for Paraneoplastic Neurologic Syndromes (PNS). Here, we present the case of a 47-year-old woman who developed subacute cervical myelopathy and was then diagnosed with breast cancer. Through this lens, we provide a discussion of current literature on IPM. Over four months, our patient developed progressive tetraparesis, hypoesthesia with C3 level, and urinary retention. The first MRI was negative, but a four-month-control MRI showed a T2-hyperintense spinal lesion (C2–C7 and T2–T4). Cerebrospinal fluid (CSF) analysis was normal. Infective and autoimmune screening, including onconeural, anti-MOG, and aquaporin-4 antibodies, was unremarkable. The total-body CT scan was negative, but total-body PET-CT scan evidenced an enlarged axillary lymph node, with the detection of breast cancer cells at fine-needle aspiration. Despite negative mammography, a breast MRI confirmed a mammary nodule, which was removed, and a ductal infiltrating breast carcinoma diagnosis was made. Her neurological condition partially improved after steroid therapy. Our final diagnosis was probable IPM, according to PNS criteria. This rare condition affects most frequently middle-aged women and is often associated with breast and lung cancer, even if two-thirds of patients’ cancer diagnosis is subsequent to the onset of neurological deficits. Clinical presentation is often subtle, and CSF analysis, neuroimaging, and onconeural autoantibodies could be negative or non-specific. However, if the suspect of paraneoplastic disease is strong, cancer should be searched thoroughly since early diagnosis and treatment are associated with a better outcome. Full article

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are among the commonly considered differential diagnoses in patients with inflammatory central nervous system (CNS)-diseases. Formerly diagnosed competing autoimmune diseases might impair diagnostics and treatment. Here, we report on a 41-year-old woman admitted to our hospital with primary manifestation of NMOSD (paresthesia, paralysis of the lower extremities, and urinary incontinence) while undergoing treatment for a diagnosed systemic lupus erythematosus (SLE) with hydroxychloroquine. CNS manifestation of the disease was considered. Magnetic resonance imaging (MRI) of the cranium and spinal cord showed multiple supratentorial lesions of the white matter and massive intramedullary lesions with contrast enhancement. Cerebrospinal fluid (CSF) showed pleocytosis (20/µL), positive antinuclear antibodies (ANA), antiphospholipid antibodies, and SSA/Ro antibodies, while formerly positive dsDNA antibodies were negative. Further diagnostics revealed a 1:10,240 serum titer of Aquaporine-4 antibodies. The patient received intravenous methylprednisolone for three days (2 g per day), which led to an escalation to plasmapheresis and to an improved EDSS from 8.0 to 4.0. Because of the comorbidity, a combined relapse prophylaxis with satralizumab and mycophenolate mofetil was established. Rehabilitation and continued treatment improved EDSS to 1.0 with no impairment of mobilization. Although formerly diagnosed SLE could have explained the symptoms, it is important to reconsider competitive diseases in order to establish adequate immunotherapy. Full article

Background: This pilot study explored the effectiveness and feasibility of an online version of a group acceptance and commitment therapy (ACT) resilience training intervention for people with multiple sclerosis (PwMS), called e-READY for Multiple Sclerosis (MS). Methods: Fifty-six PwMS were randomized to intervention (n = 31) or waitlist control (WLC) (n = 25). The primary outcome, resilience, and secondary outcomes (quality of life (QoL), distress, psychological flexibility) were assessed at pre- and post-intervention and 12-week follow-up. Results: Intervention participants reported greater pre- to post-intervention improvements in anxiety (d = 0.56) and stress (d = 0.62) than WLC. Gains were maintained at follow-up. Confidence intervals revealed a trend for the intervention group to report greater improvements than WLC across all outcomes. Reliable Change Index data showed that, compared to WLC, there were trends for more intervention participants to evidence clinically significant improvements in physical health QoL. Recruitment response was weak, intervention retention was good, adherence to program progression guidelines was satisfactory, program usability satisfaction was high, and study protocol attrition at post-intervention and follow-up was low and high, respectively. Most participants viewed the intervention as enjoyable, helpful, and resilience-building, and would recommend it to other PwMS. Qualitative feedback validated the usefulness of intervention tools and digital delivery mode and bolstered resilience through improved ACT-related skills. Conclusions: Effectiveness and feasibility results from this proof-of-concept study provide preliminary support for the e-READY for MS program. Full article

A 38-year-old Brazilian man presented with slowly progressive quadriparesis since age 11 years. He progressed over 15 years with symptoms restricted to the lower limbs, and since then, with a progressive compromise of the upper limbs. His deceased brother had a similar clinical presentation. Examination showed spastic dysarthria, global amyotrophy, brisk tendon reflexes in the lower limbs, symmetrical quadriparesis, and fasciculations in the four limbs. Neurophysiological studies disclosed acute and chronic signs of denervation and chronic reinnervation involving the cervical, thoracic, and lumbosacral myotomes, with normal sensory conduction study. Fibrillation potentials, fasciculations, and positive sharp waves involved mainly the upper limbs. A diagnosis of long-standing juvenile-onset motor neuronopathy was established. Genetic testing identified the possibly pathogenic variant c.3G>T (p.Met1?) in homozygosity in the COQ7 gene. This report highlights the importance of considering a potentially treatable metabolic dysfunction as the primary mechanism in cases of juvenile motor neuron disease. Full article

Salt intake is associated with multiple sclerosis; however, controversial findings that challenge this association rely primarily on methods that do not measure total sodium storage within the body, such as food surveys and urinary sodium excretion. In contrast, tissue sodium concentrations measured with sodium MRI confirm high sodium levels in multiple sclerosis, suggesting a role for sodium toxicity as a risk factor for the disease. Research on demyelination in the central nervous system has identified myelin phase transitions associated with increased salinity, which cause structural instabilities of myelin sheaths and add further evidence implicating sodium toxicity as a causative factor in multiple sclerosis. Inflammatory and immune responses in multiple sclerosis are also related to high sodium intake. In addition, salt is a potential mediating factor associating multiple sclerosis with comorbidities, including systemic lupus erythematosus, rheumatic arthritis, inflammatory bowel disease, and cardiovascular disease. Current confusion exists over classifying dietary sodium intake levels as low, normal, and high, and questions remain over levels of sodium restriction necessary for disease prevention. To reduce multiple sclerosis symptoms and prevent disease progression in patients, future research should investigate low-salt interventions with levels of sodium intake associated with ancestral hunter-gatherer tribes. Full article

Paraneoplastic neurological syndromes (PNS) occur in 1–3% of all cancer patients with several cancer-related neurologic diseases involving any part of the nervous system. Paraneoplastic cerebellar degeneration (PCD) is a specific type of PNS characterized by sub-acute cerebellar syndrome with trunk and limb ataxia, dysarthria, diplopia, and vertigo. We report herein the case of a 70-year-old female patient with cerebellar symptoms and transient anti-Yo antibody PCD positivity manifested three years after a breast cancer diagnosis who is currently neurologically stable after an extended follow-up. Full article