Risk factors and long-term outcomes of oropharyngeal dysphagia in persons with multiple sclerosis: a systematic review protocol.

BACKGROUND: Oropharyngeal dysphagia (OPD) can be functionally debilitating in persons with multiple sclerosis (pwMS). OPD induces alterations in safety and efficiency of food and/or liquid ingestion and may incur negative sequalae such as aspiration pneumonia or malnutrition/dehydration. Early detection and timely management of OPD in pwMS could prevent such complications and reduce mortality rates. Identifying risk factors of OPD relative to its onset or repeat manifestation will enable the development of care pathways that target early assessment and sustained management. The aims of this systematic review are to compile, evaluate, and summarize the existing literature reporting potential risk factors and associated long-term outcomes (e.g., aspiration pneumonia, malnutrition, dehydration, and/or death) of OPD in pwMS. METHODS: We will undertake a systematic review to identify studies that describe patterns and complications of OPD in pwMS. Variables of interest include predictors of OPD along with long-term outcomes. We will search MEDLINE, Embase, CINAHL, AMED, the Cochrane Library, Web of Science, and Scopus. We will consider studies for inclusion if they involve at least 30 adult participants with MS and report risk factors for OPD and/or its long-term outcomes. Studies will be excluded if they refer to esophageal or oropharyngeal dysphagia induced by causes other than multiple sclerosis. Study selection and data extraction will be performed by two independent assessors for abstract and full article review. We will present study characteristics in tables and document research findings for dysphagia-related risk factors or its complications via a narrative format or meta-analysis if warranted (e.g., mean difference and/or risk ratio measurements). All included studies will undergo risk-of-bias assessment conducted independently by two authors with consensus on quality ratings. DISCUSSION: There is a lacune for systematic reviews involving risk factors and long-term outcomes of dysphagia in pwMS to date. Our systematic review will provide the means to develop accurate and efficient management protocols for careful monitoring and evaluation of dysphagia in pwMS. The results of this systematic review will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022340625.

A Self-Reported Study on Explanatory Variables of Stress in Multiple Sclerosis Patients: Exploring the Effect of Physical Conditions and Emotion Regulation Processes.

BACKGROUND: Multiple sclerosis (MS)-linked stress is frequent, multidetermined and facilitates the onset/exacerbation of MS. However, few explanatory models of stress analysed the joint explanatory effect of emotion regulation and clinical outcomes of MS in those patients. OBJECTIVE: This study explored whether self-reported MS-related conditions (number of relapses, fatigue and global disability) and specific emotion regulation processes (experiential avoidance and self-compassion) explain stress symptoms in MS patients. METHODS: The MS sample comprised 101 patients with MS diagnosis receiving treatment in hospitals and recruited through the Portuguese MS Society. The no-MS sample included 134 age-, sex- and years of education-matched adults without MS recruited from the general Portuguese population. Both samples did not report other neurological disorders. Data were collected using self-response measures. RESULTS: All potential explanatory variables differed significantly between samples, with higher scores found in MS patients. In MS clinical sample, those variables and years of education correlated with stress symptoms and predicted stress symptoms in simple linear regression models. These results allowed their selection as covariates in a multiple linear regression model. Years of education, the number of relapses, fatigue and experiential avoidance significantly predicted 51% of stress symptoms' total variance. CONCLUSIONS: This study provides preliminary evidence on the importance of clinicians and researchers considering the simultaneous contribution of years of education, the number of perceived relapses, fatigue and experiential avoidance as factors that can increase vulnerability to stress in MS patients. Psychological intervention programmes that tackle these factors and associated stress symptomatology should be implemented.

Study protocol: exercise training for treating major depressive disorder in multiple sclerosis.

BACKGROUND: Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period. METHODS: This study involves a parallel-group, assessor-blinded RCT that examines the effect of a 4-month home-based exercise training intervention on depression severity in a sample of persons with MS who have MDD based on the MINI International Neuropsychiatric Interview. The primary outcomes of depression severity are the Patient Health Questionnaire-9 and Hamilton Depression Rating Scale. Participants (N = 146) will be recruited from within 200 miles of the University of Illinois at Chicago and randomized (1:1) into either a home-based exercise training condition or control condition with concealed allocation. The exercise training and social-contact, attention control (i.e., stretching) conditions will be delivered remotely over a 4-month period and supported through eight, 1:1 Zoom-based behavioral coaching sessions guided by social-cognitive theory and conducted by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data at 0, 4 and 8 months using treatment-blinded assessors, and data analyses will involve intent-to-treat principles. DISCUSSION: If successful, the proposed study will provide the first Class I evidence supporting a home-based exercise training program for treating MDD in persons with MS. This is critical as exercise training would likely have positive secondary effects on symptoms, cognition, and quality of life, and provide a powerful, behavioral approach for managing the many negative outcomes of MDD in MS. The program in the proposed research is accessible and scalable for broad treatment of depression in MS, and provides the potential for integration in the clinical management of MS. TRIAL REGISTRATION: The trial was registered on September 10, 2021 at clinicaltrials.gov with the identifier NCT05051618. The registration occurred before we initiated recruitment on June 2, 2023.

[A case of COVID-associated encephalopathy in a patient with multiple sclerosis]. / Klinicheskii sluchai COVID-assotsiirovannoi entsefalopatii u patsienta s rasseyannym sklerozom.

A case of acute encephalopathy manifested with impaired consciousness, hemichorrhea, speech and cognitive impairment in a female patient with COVID-19 and multiple sclerosis is presented. In the literature, there are isolated reports of such a combination of diseases, and therefore difficulties arise in carrying out differential diagnosis and prescribing therapy. Given the limited knowledge about the long-term consequences of COVID-19, systematic analysis of such cases and follow-up of such patients is necessary.

Clinical variables influencing the perception of fatigue in people with multiple sclerosis: a cross-sectional study using FSIQ-RMS.

BACKGROUND: Physical fatigue is one of the most disabling symptoms in people with Multiple Sclerosis (PwMS). Several factors might influence the development of fatigue, such as gender, education, body mass index (BMI), Expanded Disability Status Scale (EDSS), disease duration, working status (Ws), physiotherapy (Ph), and disease-modifying therapies (DMTs). Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a patient-reported outcome (PRO) that allows one to define the impact of fatigue in PwMS clearly. This study aimed to assess fatigue impact on PwMS by using FSIQ-RMS. METHODS: The participants were enrolled from May to July 2021 in MS Centers of Sant'Andrea Hospital and Policlinico Umberto I Hospital in Rome. Fatigue was evaluated using the FSIQ-RMS, validated, and culturally adapted in Italian. Clinical and demographic data were collected at the same time. RESULTS: We enrolled 178 PwMS [Female 74.16%; RMS 82.58%, SPMS 17.52%]. FSIQ-RMS scores were significantly correlated with EDSS (p-value < 0.01). Analysis of variance between means showed a statistically significant difference between the BMI groups at the 24hours_FSIQ-RMS score and the 7days_FSIQ-RMS score (p < 0.01), with the lower BMI group having the highest scores. Furthermore, perceived fatigue significantly improved both in subjects performing Ph (p < 0.05) and in those who actively work (p < 0.01). CONCLUSIONS: The use of FSIQ-RMS in a real-world setting confirmed that underweight and high levels of disability are closely related to fatigue. In addition, Ph and active Ws are strongly correlated with fatigue in PwMS.

Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Objective: Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS), such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS), offers potential solutions. Among NIBS techniques, theta burst stimulation (TBS) is notable for its ability to modulate cortical activity. The objective of this systematic review is to assess the impact of TBS on MS symptoms.Data Sources: The study conducted rigorous systematic searches in PubMed, Google Scholar, and Scopus databases up to June 2023, using specific Medical Subject Headings terms related to NIBS and MS, such as TMS and TBS, in conjunction with terms like MS or demyelinating disease. Additionally, the bibliographic references of included studies, book chapters, and original articles were manually reviewed.Study Selection: The study selection process involved a 2-tiered screening mechanism, beginning with an evaluation of titles and abstracts, followed by a full-text review of selected articles. Inclusion criteria incorporated randomized controlled trials (RCTs) focusing on TBS with MS patients. Exclusion criteria included non-qualitative, non-MS, and non-TBS studies. Risk of bias assessment was conducted using the 2008 Cochrane Risk of Bias 2 Scale for RCTs.Data Extraction: Data extraction was conducted by thoroughly reviewing each research article and systematically recording the relevant information using a standardized data extraction form, ensuring consistency and accuracy throughout the process.Results: In a systematic review encompassing 5 randomized controlled trials involving 117 individuals with relapsing-remitting or secondary progressive MS across Italy, France, and Russia, various forms of TBS were applied. These interventions ranged from intermittent TBS (iTBS) to continuous intermittent TBS (c-iTBS) that demonstrated favorable outcomes. Notably, TBS interventions led to significant reductions in spasticity, fatigue, and pain, with c-iTBS combined with vestibular rehabilitation showing additional improvements in vestibular-ocular reflexes, gait, and balance. While specific protocols varied among the studies, collectively, the results suggest promise for TBS approaches in alleviating MS-related symptoms.Conclusions: The findings of this review suggest that TBS may hold promise in addressing specific MS symptoms, notably fatigue and spasticity. Future research should include a more diverse participant pool to explore TBS effects across different MS subtypes and aim for larger sample sizes to enhance statistical power and result reliability.Prim Care Companion CNS Disord 2024;26(2):23r03645. Author affiliations are listed at the end of this article.

Voiding Phase Dysfunction in Multiple Sclerosis: Contemporary Review of Terminology, Diagnosis, Management, and Future Directions.

Lower urinary tract symptoms (LUTS) are highly prevalent in individuals with multiple sclerosis (MS). However, assessment of these symptoms is often hindered by vague definitions or absence of screening in asymptomatic patients. It is crucial to exercise caution when applying the non-neurogenic definition of urinary retention in this population. For men with MS experiencing persistent and treatment-resistant LUTS, urodynamic studies should be used to identify the underlying causes of symptoms. Although numerous therapies are presently accessible for managing LUTS in MS, there is a need for further investigation into emerging treatments such as percutaneous tibial nerve, and noninvasive brain stimulation.

Associations between respiratory function, balance, postural control, and fatigue in persons with multiple sclerosis: an observational study.

Introduction: Fatigue, postural control impairments, and reduced respiratory capacities are common symptoms in persons diagnosed with Multiple Sclerosis (MS). However, there is a paucity of evidence establishing correlations among these factors. The aim of this study is to analyze respiratory function in persons with MS compared to the control group as well as to analyze the relationship between fatigue, respiratory function and postural control in persons with MS. Materials and methods: A total of 17 persons with MS and 17 healthy individuals were enrolled for this cross-sectional study. The evaluated parameters included fatigue assessed using the Visual Analog Scale-fatigue (VAS-F) and the Borg Dyspnea Scale, postural control assessed through the Mini Balance Evaluation System Test (Mini-BESTest), Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Trunk Impairment Scale (TIS); and respiratory capacities measured by Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), FEV1/FVC ratio, Diaphragmatic excursion and diaphragmatic thickness. Results: A very high correlation was observed between the Borg Dyspnoea Scale and the BBS (r = -0.768), TUG (0.867), and Mini-BESTest (r = -0.775). The VAS-F exhibited an almost perfect correlation solely with the TUG (0.927). However, none of the variables related to fatigue exhibited any correlation with the respiratory variables under study. Balance-related variables such as BBS and Mini-BESTest demonstrated a very high and high correlation. Respectively, with respiratory function variables MEP (r = 0.783; r = 0.686), FVC (r = 0.709; r = 0.596), FEV1 (r = 0.615; r = 0.518). BBS exhibited a high correlation with diaphragmatic excursion (r = 0.591). Statistically significant differences were noted between the persons with MS group and the control group in all respiratory and ultrasound parameters except for diaphragmatic thickness. Conclusion: The findings suggest that decreased postural control and balance are associated with both respiratory capacity impairments and the presence of fatigue in persons with MS. However, it is important to note that the alterations in respiratory capacities and fatigue are not mutually related, as indicated by the data obtained in this study. Discrepancies were identified in abdominal wall thickness, diaphragmatic excursion, and respiratory capacities between persons with MS and their healthy counterparts.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus.

OBJECTIVES: To explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. METHODS: Sixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. RESULTS: PwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26-0.39, p = 0.01-0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). CONCLUSIONS: Structural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Assessing multimodal emotion recognition in multiple sclerosis with a clinically accessible measure.

BACKGROUND: Multiple sclerosis (MS) negatively impacts cognition and has been associated with deficits in social cognition, including emotion recognition. There is a lack of research examining emotion recognition from multiple modalities in MS. The present study aimed to employ a clinically available measure to assess multimodal emotion recognition abilities among individuals with MS. METHOD: Thirty-one people with MS and 21 control participants completed the Advanced Clinical Solutions Social Perceptions Subtest (ACS-SP), BICAMS, and measures of premorbid functioning, mood, and fatigue. ANCOVAs examined group differences in all outcomes while controlling for education. Correlational analyses examined potential correlates of emotion recognition in both groups. RESULTS: The MS group performed significantly worse on the ACS-SP than the control group, F(1, 49) = 5.32, p = .025. Significant relationships between emotion recognition and cognitive functions were found only in the MS group, namely for information processing speed (r = 0.59, p < .001), verbal learning (r = 0.52, p = .003) and memory (r = 0.65, p < 0.001), and visuospatial learning (r = 0.62, p < 0.001) and memory (r = 0.52, p = .003). Emotion recognition did not correlate with premorbid functioning, mood, or fatigue in either group. CONCLUSIONS: This study was the first to employ the ACS-SP to assess emotion recognition in MS. The results suggest that emotion recognition is impacted in MS and is related to other cognitive processes, such as information processing speed. The results provide information for clinicians amidst calls to include social cognition measures in standard MS assessments.

Prevalence of primary headaches in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system. It is characterized by symptoms such as visual disturbances, paresis with spasticity, paresthesia, numbness, and fatigue. However, several studies have shown a high prevalence of headaches in individuals with MS. Migraine and tension-type headaches are the most frequent types of headaches experienced by those with MS. Additionally, the role of MS disease-modifying agents must be considered. These agents have different modes of action and side effect profiles, and their use may sometimes trigger headaches in patients with MS. OBJECTIVES: This study aimed to explore the prevalence and clinical characteristics of primary headaches in MS patients. The relationship between headache and clinical features of MS (Course of MS, duration, EDSS, brain imaging and DMD) are also investigated. SUBJECTS AND METHODS: Two hundred and eighty-one MS patients diagnosed according to according to the 2017 revisions to the McDonald Criteria were included in the study. Data was collected from the MS unit medical records and from the interview with the patients. Patients with reported headaches are asked to recall their headache characteristics and patterns using an interviewer administered Arabic language-structured validated questionnaire. RESULTS: The median age of patients was 33 years old, with a range of 22-55. Tension-type headache (TTH) was more common in males, patients with more severe disability (EDSS ≥ 3), and those with SPMS and PPMS phenotypes. Additionally, patients on rituximab or cyclophosphamide therapy were more likely to have TTH. On the other hand, females, patients with milder disability (EDSS < 3), and those with RRMS phenotype were more likely to have migraine. This was also true for patients with MRI lesions involving the periaqueductal gray, and those receiving INF or fingolimod (P < 0.05). Periaqueductal gray matter lesions were found in the MRI of 48 patients (40 %) who experienced headaches on more than 10 days per month. Sensorimotor lesions in the brain were found in 55 patients (53.4 %) with severe headaches (p-value < 0.001). Interferons were associated with an increased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 2.84, 3.72; relative risk: 1.63, 2.04; p-value = 0.03, < 0.001, respectively). On the other hand, rituximab was associated with a decreased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 0.04, 0.09; relative risk: 0.11, 0.18; p-value = < 0.001, < 0.001, respectively). CONCLUSION: Primary headaches are a common occurrence in patients with MS. Migraines and tension-type headaches (TTH) are among the most prevalent types. It has been observed that interferon can exacerbate preexisting headaches and even cause new ones. Additionally, the location of MS plaques may play a role in the frequency and severity of headaches.

Predictive factors and screening strategy for obstructive sleep apnea in patients with advanced multiple sclerosis.

BACKGROUND: Obstructive sleep apnea (OSA) screening questionnaires have been evaluated in Multiple Sclerosis (MS) but not yet validated in patients with advanced disease. The aim of this study is to identify OSA predictive factors in advanced MS and to discuss screening strategies. METHODS: Oximetry data from 125 patients were retrospectively derived from polysomnographic reports. Univariate and multivariate analysis were used to determine predictive factors for OSA. A two-level screening model was assessed combining the oxygen desaturation index (ODI) and a method of visual analysis. RESULTS: multivariate analysis showed that among the clinical factors only age and snoring were associated with OSA. Usual predictive factors such as sleepiness, Body mass index (BMI) or sex were not significantly associated with increased Apnea Hypopnea Index (AHI). The ODI was highly predictive (p < 0.0001) and correctly identified 84.1 % of patients with moderate OSA and 93.8 % with severe OSA. The visual analysis model combined with the ODI did not outperform the properties of ODI used alone. CONCLUSION: As the usual clinical predictors are not associated with OSA in patients with advanced MS, questionnaires developed for the general population are not appropriate in these patients. Nocturnal oximetry seems a pertinent, ambulatory and accessible method for OSA screening in this population.

Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy.

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

Objectively assessed sleep quality parameters in Multiple Sclerosis at home: Association to disease, disease severity and physical activity.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune, neurodegenerative disease that affects regular mobility and leads predominantly to physical disability. Poor sleep quality, commonly reported in MS patients, impacts their physical activity (PA). Accelerometers monitor 24-h activity patterns, offering insights into disease progression in daily life. OBJECTIVE: To test if the sleep quality variables of MS patients, as assessed with wrist-worn accelerometers, differ from those of controls and are associated with PA and disease severity variables. METHODS: Seven-day raw accelerometer data collected from 40 MS patients and 24 controls was processed using an open-source GGIR package, from which variables of sleep quality (sleep efficiency, wake after sleep onset (WASO), sleep regularity index (SRI), intradaily variability (IV)) and PA (of different intensities: inactivity, light (LPA), moderate (MPA), vigorous (VPA)) were analyzed. The variables were compared between the two study groups and in MS patients, correlation tested associations among the variables of sleep quality, PA, and disease severity (assessed with the Expanded Disability Status Scale, EDSS). RESULTS: Sleep efficiency was the only variable that differed significantly between MS patients and controls (lower in MS, p = 0.01). Both SRI (positively) and IV (negatively) correlated with the time spent in LPA and MPA. WASO correlated negatively with inactivity. CONCLUSION: This is one of the few studies with a wrist-worn accelerometer that shows a difference in sleep efficiency between MS patients and controls and, in MS, an association of sleep quality variables with PA variables.

Headache in Multiple Sclerosis: A Narrative Review.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50-60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review.

BACKGROUND: Multiple sclerosis (MS) is a rare but serious condition associated with significant morbidity. OBJECTIVE: This review provides a focused assessment of MS for emergency clinicians, including the presentation, evaluation, and emergency department (ED) management based on current evidence. DISCUSSION: MS is an autoimmune disorder targeting the central nervous system (CNS), characterized by clinical relapses and radiological lesions disseminated in time and location. Patients with MS most commonly present with long tract signs (e.g., myelopathy, asymmetric spastic paraplegia, urinary dysfunction, Lhermitte's sign), optic neuritis, or brainstem syndromes (bilateral internuclear ophthalmoplegia). Cortical syndromes or multifocal presentations are less common. Radiologically isolated syndrome and clinically isolated syndrome (CIS) may or may not progress to chronic forms of MS, including relapsing remitting MS, primary progressive MS, and secondary progressive MS. The foundation of outpatient management involves disease-modifying therapy, which is typically initiated with the first signs of disease onset. Management of CIS and acute flares of MS in the ED includes corticosteroid therapy, ideally after diagnostic testing with imaging and lumbar puncture for cerebrospinal fluid analysis. Emergency clinicians should evaluate whether patients with MS are presenting with new-onset debilitating neurological symptoms to avoid unnecessary testing and admissions, but failure to appropriately diagnose CIS or MS flare is associated with increased morbidity. CONCLUSIONS: An understanding of MS can assist emergency clinicians in better diagnosing and managing this neurologically devastating disease.

Do proprioceptive neuromuscular facilitation techniques improve respiratory parameters and swallowing in people with multiple sclerosis: A randomized-controlled study.

AIM: This study aims to investigate the effects of Proprioceptive Neuromuscular Facilitation (PNF) techniques on respiratory parameters, swallowing, functional capacity, fatigue, and quality of life in people with Multiple Sclerosis (PwMS). METHOD: Thirty-four PwMS were included and randomized into the PNF Group (mean age: 43.23±10.55/years) or Control Group (mean age:38.47±8.18/years). In the PNF group, head-neck, upper extremity, trunk, and breathing techniques were applied three days/eight weeks. The control group continued home-based breathing exercises. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), forced expiratory flow 25-75 % (%FEF 25-75), peak cough flow (PCF), maximal inspiratory (MIP) and expiratory pressures (MEP) were and two minutes walking test (2MWT) were measured. Dysphagia in Multiple Sclerosis (DYMUS), Eating Assessment Tool (EAT-10), Fatigue Severity Scale (FSS) and Multiple Sclerosis Quality of Life (MusiQoL) were questioned. RESULTS: After treatment, MIP, MEP,%FEV1/FVCpred,%PEFpred,%FEF 25-75pred, PCF, DYMUS, EAT-10, FSS, and MUSIQoL were improved in the PNF group while MIP, MEP, PCF, DYMUS, EAT-10, MUSIQoL, and 2 MWT were improved in the control group (p < 0.05 for all). In the between-group analysis of the mean differences, the%FEV1pred was significantly different in favor of the PNF Group (p = 0.011), and MIP was significantly different in favor of the Control Group (p = 0.013). DISCUSSION: The PNF techniques can improve respiratory muscle strength, respiratory functions, cough efficiency, swallowing functions, and quality of life in mild to moderate PwMS. However, these improvements were not superior except for%FEV1pred compared to home-based breathing exercises.

Characteristics and predictors of sexual dysfunction in men with multiple sclerosis.

PURPOSE: To validate and culturally adapt the Sexual Health Inventory for Men (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT), to compare the frequency and severity of erectile dysfunction (ED) and premature ejaculation (PE) in male individuals with MS (mwMS) in comparison with healthy controls (HC) and to investigate predictors of the severity of ED and PE in mwMS. METHODS: 216 consecutive mwMS and 37 HC completed IIEF-5 and PEDT. Additionally, 114 mwMS completed the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-2), Composite Autonomic System Score-31 (COMPASS-31), and the 5-level EQ-5D questionnaire. RESULTS: The test-retest reliability was satisfactory for both questionnaires, with acceptable reliability for both questionnaires. mwMS scored less on IIEF-5 compared to HC (23, IQR 18.25-25 vs 24, IQR 20.25-25, p = 0.028). ED was present in 39.4 % of mwMS and 27.8 % of HC (p = 0.198). Definite PE was present in 12.1 %, and possible PE in 7.8 % of mwMS; and 5.6 % and 11.1 % of HC respectively (p = 0.496). An increase in EDSS was a positive predictor (Exp(B) 1.455, 95 %CI 1.135-1.886, p = 0.003) and the presence of cremasteric reflex was a negative predictor (Exp(B) 0.381, 95 %CI 0.183-0.790, p = 0.010) for the presence of ED. For the PE, disease duration was the only positive predictor in a univariable logistic regression (Exp(B) 1.084, 95 %CI 1.019-1.153, p = 0.070). CONCLUSION: SD is frequent in mwMS with EDSS being a positive and the presence of cremasteric reflex a negative predictor of ED and disease duration a positive predictor of PE symptoms.

Intrathecal B cell activation and memory impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. METHODS: A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. RESULTS: κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. CONCLUSION: Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans.