Multiple Sclerosis Population Research Articles

Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population.

BackgroundEvidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (<55 and ≥55 years), DMD exposure and health service use in the MS population.MethodsWe conducted a population-based observational study using linked administrative health data from British Columbia, Canada. We selected all persons with MS and followed from the most recent of their first MS or demyelinating event, 18th birthday or 01-January-1996 (index date) until the earliest of emigration, death or 31-December-2017 (study end). We assessed DMD exposure status over time, initially as any versus no DMD, then by generation (first or second) and finally by each individual DMD. Age-specific analyses were conducted with all-cause hospitalizations and number of physician visits assessed using proportional means model and negative binomial regression with generalized estimating equations.ResultsWe included 19,360 persons with MS (72% were women); 10,741/19,360 (56%) had ever reached their 55th birthday. Person-years of follow-up whilst aged <55 was 132,283, and 93,594 whilst aged ≥55. Any DMD, versus no DMD in the <55-year-olds was associated with a 23% lower hazard of hospitalization (adjusted hazard ratio, aHR0.77; 95%CI 0.72-0.82), but not in the ≥55-year-olds (aHR0.95; 95%CI 0.87-1.04). Similar patterns were observed for the first and second generation DMDs. Exposure to any (versus no) DMD was not associated with rates of physician visits in either age group (<55 years: adjusted rate ratio, aRR1.02; 95%CI 1.00-1.04 and ≥55 years: aRR1.00; 95%CI 0.96-1.03), but variation in aRR was observed across the individual DMDs.ConclusionOur study showed beneficial effects of the DMDs used to treat MS on hospitalizations for those aged <55 at the time of exposure. In contrast, for individuals ≥55 years of age exposed to a DMD, the hazard of hospitalization was not significantly lowered. Our study contributes to the broader understanding of the potential benefits and risks of DMD use in the ageing MS population.

Multilocus evaluation of genetic predictors of multiple sclerosis.

Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals. Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation. In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models. We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR=2.16, CI:1.85-2.74, P=2.53x10-13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T+STAT3 rs744166*T combination (OR=11.87), in men - by C6orf10 rs3129934*T+EOMES rs11129295*C+RPS6KB1 rs180515*C combination (OR=3.25). We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia.

NIRS Studies Show Reduced Interhemispheric Functional Connectivity in Individuals with Multiple Sclerosis That Exhibit Cortical Hypoxia.

Many with multiple sclerosis (MS) have low cortical microvascular oxygen levels (hypoxia), which have been previously proposed to exacerbate inflammation in MS. We do not know if hypoxia impacts or relates to brain function. We hypothesise that within the MS population, those who have hypoxia may show reduced brain functional connectivity (FC). We recruited 20 MS participants and grouped them into normoxic and hypoxic groups (n=10 in each group) using frequency-domain near-infrared spectroscopy (fdNIRS). Functional coherence of the haemodynamic signal, quantified with functional near-infrared spectroscopy (fNIRS) was used as a marker of brain function and was carried out during resting-state, finger-tapping, and while completing two neurocognitive tasks. Reduced FC was detected in the hypoxic MS group. fNIRS measures of haemodynamic coherence in MS could be a biomarker of functional impairment and/or disease progression.

POSA44 The Societal Impact of Multiple Sclerosis in France: Results from the Petals Study

Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by chronic inflammation, demyelination, and neuronal loss. MS places a considerable financial burden on society. However, data quantifying the total societal burden including extra costs, forgone income and production losses endured by MS patients, their caregivers and employers in France is lacking. The present study, PETALS, was undertaken to address the existing gap and estimate the financial burden (direct and indirect) imposed by MS in the French population. Between October and November 2020, 208 French adults with a confirmed diagnosis of MS were recruited via MSCopilot®, a MS self-assessment digital tool, and several MS patients’ networks. A patient-based questionnaire consisting of 142 questions was used to retrieve patients' insights. Indirect costs were estimated using a combination of top-down and bottom-up approaches. Data on direct costs were retrieved from Assurance Maladie. Out-of-pocket expenses (OOPE) incurred by MS patients were also reported. All costs were expressed in €2020. Data from the survey were extrapolated to the overall French MS population. The societal cost of MS was estimated to be €2.7 Billion (Bn) a year in France. Direct costs amount to €1.4 Bn a year. Indirect costs amount to €1.3 Bn a year. Loss of income/costs due to reduction in work time contributed over half of the indirect cost (53.3%), followed by health-related aids/benefits (42.5%). Furthermore, OOPEs incurred by MS patients contributed to a notable proportion of the total annual costs (over €90 million). The results from the current study showed that MS not only affected the productivity and income of individuals but also the working time of caregivers. Understanding the magnitude of the socioeconomic burden posed by MS may provide valuable insights for optimizing resource allocation and devising effective disease management strategies that can reduce its impact.

The Economic and Humanistic Burden of Pediatric-Onset Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Pediatric-onset MS (POMS), defined as onset of MS before 18 years of age, is estimated to account for 2% to 5% of the MS population worldwide. Objectives: To conduct a literature review focused on the healthcare resource utilization and cost as well as quality-of-life (QOL) outcomes among patients with POMS. Methods: We conducted a systematic literature review of English-language studies published after September 2010 in MEDLINE and Embase to describe the global economic healthcare resource utilization and costs and humanistic (QOL) burden in patients with POMS. Results: We found 11 studies that reported on healthcare resource utilization, cost, or insurance coverage and 36 studies that reported on QOL outcomes in patients with POMS. Patients with POMS had higher rates of primary care visits (1.41 [1.29-1.54]), hospital visits (10.74 [8.95-12.90]), and admissions (rate ratio, 4.27 [2.92-6.25];OR, 15.2 [12.0-19.1]) compared with healthy controls. Mean per-patient costs in the United States were $5907 across all settings per year of follow-up between 2002 and 2012; mean costs per hospital stay were $38 543 (in 2015 USD) between 2004 and 2013. Three studies reported psychosocial scores between 71.59 and 79.7, and 8 studies reported physical health scores between 74.62 to 82.75 using the Pediatric Quality of Life Measurement Model (PedsQLTM). Twelve studies used the PedsQL™ Multidimensional Fatigue Scale. Mean scores on the self-reported general fatigue scale ranged from 63.15 to 78.5. Quality-of-life scores were lower than those of healthy controls. Discussion: Our review presents a uniquely broad and recent overview of the global economic and humanistic burden of patients with POMS. Additional research on healthcare resource utilization and cost would provide a more robust understanding of the economic burden in this population. Conclusions: Healthcare resource utilization and costs are high in this population, and patients report reduced QOL and significant fatigue compared with healthy children and adolescents.

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment.

Pediatric-onset multiple sclerosis (POMS) is a rare neuroinflammatory and neurodegenerative disease that has a significant impact on long-term physical and cognitive patient outcomes. A small percentage of multiple sclerosis (MS) diagnoses occur before the age of 18 years. Before treatment initiation, a careful differential diagnosis and exclusion of other similar acquired demyelinating syndromes such as anti-aquaporin-4-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody spectrum disorder (MOGSD) is warranted. The recent 2017 changes to the McDonald criteria can successfully predict up to 71% of MS diagnoses and have good specificity of 95% and sensitivity of 71%. Additional measures such as the presence of T1-weighted hypointense lesions and/or contrast-enhancing lesions significantly increase the accuracy of diagnosis. In adults, early use of disease-modifying therapies (DMTs) is instrumental to a better long-term prognosis, including lower rates of relapse and disability worsening, and numerous FDA-approved therapies for adult-onset MS are available. However, unlike their adult counterparts, the development, testing, and regulatory approval of POMS treatments have been significantly slower and hindered by logistic and/or ethical considerations. Currently, only two MS DMTs (fingolimod and teriflunomide) have been tested in large phase III trials and approved by regulatory agencies for use in POMS. First-line therapies not approved by the FDA for use in children (interferon-β and glatiramer acetate) are also commonly used and result in a significant reduction in inflammatory activity when compared with non-treated POMS patients. An increasing number of POMS patients are now treated with moderate efficacy therapies such as dimethyl fumarate and high-efficacy therapies such as natalizumab, anti-CD20 monoclonal antibodies, anti-CD52 monoclonal antibodies, and/or autologous hematopoietic stem cell transplantation. These high-efficacy DMTs generally provide additional reduction in inflammatory activity when compared with the first-line medications (up to 62% of relapse-rate reduction). Therefore, a number of phase II and III trials are currently investigating their efficacy and safety in POMS patients. In this review, we discuss potential changes in the regulatory approval process for POMS patients that are recommended for DMTs already approved for the adult MS population, including smaller sample size for pharmacokinetic/pharmacodynamic studies, MRI-centered primary outcomes, and/or inclusion of teenagers in the adult trials.

Population-based incidence and clinico-radiological characteristics of tumefactive demyelination in Olmsted County, Minnesota, United States.

Tumefactive demyelination (TD) presents with large inflammatory lesions mimicking tumors or other space-occupying lesions. Limited epidemiological, clinical and radiological data exist for TD. We aimed to report the incidence rate, and clinical and radiological features of TD in Olmsted County, Minnesota. We retrospectively reviewed patients with central nervous system inflammatory demyelination-related diagnostic codes (January 1, 1998 to December 31, 2018) in the Rochester Epidemiology Project database, and adjusted incidence rates by age and sex to the 2010 US total population. We used the Expanded Disability Status Scale (EDSS) to assess outcomes (index attack and last follow-up). Of 792 multiple sclerosis (MS) patients, 15 (eight males, seven females) had tumefactive MS, representing 1.9% of the MS population. The median (range) age at attack onset was 34.2(2-61) years. Tumefactive lesion was the first clinical MS attack in 8/16 patients. Cerebrospinal fluid oligoclonal bands (OCBs) were present in 8/12 patients and 11/16 patients met the Barkhof criteria for dissemination in space. Most patients remained fully ambulatory (EDSS score ≤4 in 13/16 patients [81%]) after a median (range) follow-up duration of 10.5(1-20.5) years. Age-adjusted annual incidence rates were 0.46/100,000 (95% confidence interval [CI] 0.12-0.81) for female patients, 0.66/100,000 (95% CI 0.23-1.02) for male patients, and 0.56/100,000 [95% CI 0.28-0.83] overall. When age- and sex-adjusted to the 2010 US total population, the overall annual incidence rate was 0.57 (95% CI 0.28-0.84). Despite aggressive clinical presentation at disease onset, most patients remained fully ambulatory (EDSS score ≤4 in 13/16 patients) with a relapsing-remitting course. Although incidence is rare, TD should be suspected in patients presenting with subacutely progressive neurological deficits associated with magnetic resonance imaging findings of ring enhancement, apparent diffusion coefficient restriction, and OCB on spinal fluid analysis.

Validation of algorithms for identifying outpatient infections in MS patients using electronic medical records

Background Our multiple sclerosis (MS) stakeholder groups expressed concerns about whether MS disease-modifying therapies (DMTs) increase the risk of specific outpatient infections. Validated methods for identifying the risk of these selected outpatient infections in the general population either do not exist, exclude the clinically important possibility of recurrent infections, or are inaccurate, largely because existing studies relied primarily on International Classification of Diseases (ICD) codes to identify infectious outcomes. Additionally, no studies have validated methods among the MS population, where some MS symptoms can be mistaken for infections (e.g., urinary tract infections (UTIs)).Objective To utilize multiple data elements in the electronic health record (EHR) to improve accurate identification of selected outpatient infections in an MS cohort and general population controls.Methods We searched Kaiser Permanente Southern California's EHR based on ICD-9/10 codes for specified outpatient infections from 1/1/2008-12/31/2018 among our MS cohort (n=6000) and 5:1 general population controls matched on age, sex, and race/ethnicity (n=30,010). Random sample chart abstractions from each group were used to identify common coding errors for outpatient pneumonia, upper and lower respiratory tract infection, UTIs, herpetic infections (herpes zoster (HZ), herpes simplex virus (HSV)), fungal infections, otitis media, cellulitis, and influenza. This information was used to define discrete infectious episodes and to identify the algorithm with the highest positive predictive value (PPV) after supplementing the ICD-coded episodes with radiology, laboratory and/or pharmacy data.Results PPVs relying on ICD codes alone were inaccurate, particularly for identifying recurrent herpetic infections (HZ (42%) and HSV (60%)), UTIs (42%) and outpatient pneumonia (20%) in MS patients. Defining and validating episodes improved the PPVs for all the selected infections. The final algorithms’ PPVs were 80-100% in MS and 75-100% in the general population, after including dispensed treatments (UTI, herpetic infections and yeast vaginitis), timing of dispensed treatments (UTI, herpetic infections and yeast vaginitis), removal of prophylactic antiviral use (herpetic infections), and inclusion of selected laboratory (UTIs) and imaging results (pneumonia). The only exception was outpatient pneumonia, where PPVs improved but remained ≤70%. There were no significant differences in the PPVs for the final algorithms between the MS and general population.Conclusions Provided herein are accurate and validated algorithms that can be used to improve our understanding of how the risk of recurrent outpatient infections are influenced by MS treatments, MS-related disability, and co-morbidities. Findings from such studies will be important in helping patients and clinicians engage in shared decision-making and in developing strategies to mitigate risks of recurrent infections.

Tunisian version of the brief international cognitive assessment for multiple sclerosis: Validation and normative values

BackgroundThe Brief International cognitive assessment for Multiple sclerosis (BICAMS) is a specific batterie used to identify cognitive impairment in Multiple Sclerosis (MS) in a reliable and easy way. To date, for the Arabic-speaking Tunisian MS patients, there is no consensus for the use of specific cognitive batteries in MS. ObjectiveThe aim of our work was to develop and validate the Tunisian version of the BICAMS (T-BICAMS) and to determine our own normative values. Material and methodsPatients diagnosed with MS and followed up in the department of Neurology of Razi Hospital were recruited and matched to healthy controls according to age, sex and educational level. T-BICAMS validity was established by comparing MS and healthy controls for symbol digit modalities test (SDMT), brief visual memory test (BVMT-R) and Tunisian verbal learning tests (TVLT) which was used instead of the California verbal learning test (CVLT-II). ResultsThe 104 MS patients and 104 healthy controls were comparable for age, sex and educational level. The MS group exhibited lower performances in all T-BICAMS domains compared to healthy controls: SDMT (x003Dp<10-3), BVMT-R (p = 0.002) and TVLT (p x003D<10-3). T-BICAMS Cronbach alpha value was 0.741. Normative values were identified for patients with MS: SDMT [39–40], BVMT-R [26–27] and TVLT [43–44]. Cognitive impairment was identified among 76 patients (73.1%). Males, lower educational levels and progressive MS were associated with a more severe cognitive impairment. ConclusionsThe current study has established the BICAMS as a valid and reliable tool for the identification of cognitive impairment in the Tunisian MS population.

COVID-19 Infection in Fingolimod- or Siponimod-Treated Patients: Case Series.

Background and ObjectivesA descriptive analysis of COVID-19 infection in patients with multiple sclerosis (MS) receiving fingolimod or siponimod.MethodsWe reviewed the cases of COVID-19 from postmarketing or ongoing clinical trials reported to Novartis through December 27, 2020.ResultsAs of December 27, 2020, 283 cases had been reported in fingolimod-treated patients. The mean age was 44 years (from n = 224; range 11–69 years), and 190 were women. Of 161 cases with available information, 138 were asymptomatic (6), mild (100), or moderate (32); 50 cases required hospitalization. At the last follow-up, 140 patients were reported as recovered/recovering, condition was unchanged in 22, and deteriorated in 3 patients; 4 patients had a fatal outcome. Information was not available for 114 patients. Of the 54 cases of COVID-19 reported in siponimod-treated patients, 45 were from the postmarketing setting and 9 from an ongoing open-label clinical trial. The mean age was 54 years (from n = 45; range 31–70), and 30 were women. Of 28 cases with available information, 24 were asymptomatic (2), mild (17), or moderate (5); 9 cases required hospitalization. At the last follow-up, 27 patients were reported as recovered/recovering, condition remained unchanged for 1, and 3 patients had a fatal outcome. Information was not available for 23 patients.DiscussionBased on a review of available information, the risk of more severe COVID-19 in patients receiving fingolimod or siponimod seems to be similar to that reported in the general population and the MS population with COVID-19. However, limitations of spontaneous reporting, especially missing data, should be considered in the interpretation of these observations.

A serial mediation model of gratitude on life satisfaction in people with multiple sclerosis: The intermediary role of perceived stress and mental health symptoms

Background: Although prior research has explored the role of gratitude in individuals with disabilities, there is relatively limited research examining the positive influence of gratitude in decreasing psychological distress, promoting mental health, and ultimately improving well-being in the multiple sclerosis (MS) population. The study aimed to examine the cumulative mediating effect of perceived stress and mental health between gratitude and life satisfaction among people with MS. Methods: This study was cross-sectional. Participants were 373 individuals with MS. Descriptive statistics, correlation analyses, and a serial mediation analysis were performed in this study. Results: Gratitude was negatively associated with perceived stress and mental health symptoms, and was positively associated with life satisfaction. Perceived stress was positively associated with mental health symptoms and negatively associated with life satisfaction. Mental health symptoms were negatively associated with life satisfaction. The findings demonstrated that the relationship between gratitude and life satisfaction was partially mediated by perceived stress and mental health symptoms in individuals with MS. Conclusions: Findings provided implications on integrating gratitude interventions when working with people with MS. By increasing gratitude levels in people with MS, this may in turn lead to reduced perceived stress and mental health symptoms, which in turn may enhance their life satisfaction.

Impact of Lockdown during COVID-19 Pandemic on Central Activation, Muscle Activity, Contractile Function, and Spasticity in People with Multiple Sclerosis.

Background People with multiple sclerosis (MS) suffer from symptoms related to neural control, such as reduced central activation, lower muscle activity, and accentuated spasticity. A forced 9-week home confinement related to COVID-19 in Spain may have worsened these symptoms. However, no study has demonstrated the impact of home confinement on neuromuscular mechanisms in the MS population. This study was aimed at analyzing the effects of a 9-week home confinement on central activation, muscle activity, contractile function, and spasticity in MS patients. Methods Eighteen participants were enrolled in the study. Left and right knee extensor maximum voluntary isometric contraction (MVIC), maximal neural drive via peak surface electromyography (EMG) of the vastus lateralis, central activation ratio (CAR), and muscle contractile function via electrical stimulation of the knee extensor muscles, as well as spasticity using the pendulum test, were measured immediately before and after home confinement. Results Seventeen participants completed the study. CAR significantly decreased after lockdown (ES = 1.271, p < 0.001). Regarding spasticity, there was a trend to decrease in the number of oscillations (ES = 0.511, p = 0.059) and a significant decrease in the duration of oscillations (ES = 0.568, p = 0.038). Furthermore, in the left leg, there was a significant decrease in the first swing excursion (ES = 0.612, p = 0.027) and in the relaxation index (ES = 0.992, p = 0.001). Muscle contractile properties, MVIC, and EMG variables were not modified after confinement. Conclusions The results suggest that a home confinement period of 9 weeks may lead to an increase in lower limb spasticity and a greater deficit in voluntary activation of the knee extensors.

Preliminary Evaluation of an Adaptive Robotic Training Program of the Wrist for Persons with Multiple Sclerosis

Robotics can be used to describe wrist kinematics and assess sensorimotor impairments, while the implementation of training algorithms can be aimed at improving neuromuscular control. The purpose of this study was to use a robotic device to develop an adaptive and individualized training program of the distal upper extremity for individuals with multiple sclerosis (MS). This approach included an online assessment of performance aimed at changing the level of assistance/resistance provided during the task. Participants (N = 7) completed a robotic training program that occurred 3 times weekly for 4 weeks. The training protocol consisted of tracking a target moving along a figure by grasping the end-effector of the robotic device and moving it along the trajectory. Outcome measures were assessed pre- and post-intervention. Improvements in performance were quantified by average tracking (p = 0.028) and figural error (p = 0.028), which was significantly reduced by 26% and 43%, respectively. Isometric wrist strength significantly improved post-intervention (flexion: p = 0.043, radial and ulnar deviation: p = 0.028). The results of this work demonstrate that 4-weeks of adaptive robotic training is a feasible rehabilitative program that has the potential to improve distal upper extremity motor accuracy and muscular strength in a MS population.

Prevalence of SARS-CoV-2 antibodies in multiple sclerosis: The hidden part of the iceberg

Background. We compared the prevalence of SARS-CoV-2 IgG/IgM in multiple sclerosis (MS), low-risk, and high-risk populations and explored possible clinical correlates. Methods. In this cross-sectional study, we recruited MS patients, low-risk (university staff from non-clinical departments), and high-risk individuals (healthcare staff from COVID-19 wards) from 11 May to 15 June 2020. We used lateral flow immunoassay to detect SARS-CoV-2 IgG and IgM. We used t-test, Fisher’s exact test, chi square test, or McNemar’s test, as appropriate, to evaluate between-group differences. Results. We recruited 310 MS patients (42.3 ± 12.4 years; females 67.1%), 862 low-risk individuals (42.9 ± 13.3 years; females 47.8%), and 235 high-risk individuals (39.4 ± 10.9 years; females 54.5%). The prevalence of SARS-CoV-2 IgG/IgM in MS patients (n = 9, 2.9%) was significantly lower than in the high-risk population (n = 25, 10.6%) (p < 0.001), and similar to the low-risk population (n = 11, 1.3%) (p = 0.057); these results were also confirmed after random matching by age and sex (1:1:1). No significant differences were found in demographic, clinical, treatment, and laboratory features. Among MS patients positive to SARS-CoV-2 IgG/IgM (n = 9), only two patients retrospectively reported mild and short-lasting COVID-19 symptoms. Conclusions. MS patients have similar risk of SARS-CoV-2 infection to the general population, and can be asymptomatic from COVID-19, also if using treatments with systemic immunosuppression.

Evaluation of the Unidimensional Fatigue Impact Scale (U-FIS) in Crohn's Disease: The Importance of Local Item Dependency.

The Unidimensional Fatigue Impact Scale (U-FIS) was developed for use in a multiple sclerosis population. The aim was to determine whether the U-FIS is a valid tool for measuring the impact of fatigue in Crohn's disease (CD). CD patients completed the U-FIS as part of a validation study of the Crohn's Life Impact Questionnaire (CLIQ). Data were analyzed according to Rasch measurement theory (RMT). Two hundred sixty-one completed U-FIS questionnaires were available for analysis. After rescoring the items to resolve disordered thresholds, all 22 items showed acceptable RMT fit. However, there was considerable local item dependency (LID). The U-FIS did not provide unidimensional measurement in a sample of CD patients due to high levels of LID. Combining the three FIS outcomes into a single measure was not justified.

Peripheral nervous system electrodiagnostic abnormalities in predominantly Hispanic Multiple Sclerosis patients

BackgroundPeripheral nervous system (PNS) abnormalities in Multiple Sclerosis (MS) have been reported in case reports and small case series over the past several decades. Little is known, however, about the prevalence of electrodiagnostic abnormalities in patients with MS, including not only demyelinating neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but also axonal peripheral neuropathy and sympathetic dysfunction. MethodsThis is an observational, cross-sectional study with the objective of identifying the prevalence of the electrodiagnostic abnormalities in predominantly Hispanic MS patients in Miami, Florida. Electrodiagnostic data including nerve conduction study (NCS), electromyography (EMG) and sympathetic skin response (SSR) information was prospectively collected in 18 patients (16 females; 43.7±15.2 years) with a diagnosis of MS compared to 18 healthy (16 females; 39.9±11 years), age- and height-matched controls. The study was offered to all-comers in the MS Clinic over a period of 3 months, regardless of clinical suspicion for an underlying neuropathic process, in an effort to estimate the prevalence of abnormalities. Demographic data including age, sex, race/ethnicity was evaluated in addition to MS-specific characteristics including MS subtype, duration of disease, duration of therapy, clinical symptoms and laboratory data. ResultsThere were no significant differences in baseline characteristics of patients and controls for age (p=0.4) and height (164.0±6.4 vs 162.3±4.6 centimeters; p=0.3). The mean disease duration was 106±27 months (median 107 months; range 5-336 months). The mean Expanded Disability Status Scale (EDSS) was 2.4±1.87 (median: 2.5; range 1.0-6.5). The ethnicity of patients (15 Hispanic, 3 non-Hispanic) and controls (13 Hispanic, 5 non-Hispanic; p=0.56) was similar. The frequency of electrophysiological axonal polyneuropathy (PN) was 77.8% (14/18 patients), and 85.6% of these patients had clinical sensory symptoms. Interestingly, 1 patient had previously unrecognized CIDP. All 18 patients displayed prolonged SSR latencies consistent with autonomic dysfunction. Thirteen patients (72.2%) reported autonomic symptoms such as bladder abnormalities and blood pressure fluctuations. ConclusionThe prevalence of electrodiagnostic abnormalities, especially axonal polyneuropathy, in the MS population may be higher than traditionally considered. The relationship between axonal polyneuropathy and central axonopathy in the context of neurodegeneration in MS should be further explored. Analytic studies may identify common symptomatic and pathophysiologic etiologies to further understanding and potentially guide treatment of MS subtypes with PNS involvement.

Quality of Life of Children and Adolescents with Multiple Sclerosis-A Literature Review of the Quantitative Evidence.

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system that also develops in patients under 18 years of age. The disease negatively affects the quality of life (QoL) of children and adolescents. We conducted a literature review. The aim of the review was to identify the QoL of pediatric patients with MS and assess the factors determining their QoL. Methods: We analyzed studies published between 2000 and 2020 in PubMed, Scopus, Science Direct, Web of Science, and EBSCO databases. Results: In all, 17 studies were included in the review. The most common tool in assessing QoL was the generic module PedsQL. The range of mean/median global score of QoL was 53.8–81.7. The worst QoL was dominantly reported in the school and emotional spheres, on the contrary, the disease’s least determined area of QoL was the social and physical dimension. In particular, disability and fatigue were important predictors of QoL. Conclusions: MS negatively affects the school and emotional spheres in particular, so it is important to pay greater attention to these spheres of life of MS patients. As the review studies pay insufficient attention to the analysis of positive factors and their impact on the QoL of MS patients, research should integrate these phenomena. The use of MS-targeted tools in future research in the pediatric MS population is also appropriate.

Demographic, clinical, and symptomatic correlates of subjective sleep quality in adults with multiple sclerosis

BackgroundThis study examined a comprehensive set of demographic, clinical, and symptomatic variables as correlates of subjective sleep quality in adults with multiple sclerosis (MS). MethodsParticipants with MS(N=485) completed the Pittsburgh Sleep Quality Index(PSQI), a demographics and clinical characteristics questionnaire, the Patient Determined Disease Steps Scale(PDDS), the Fatigue Severity Scale, and the Hospital Anxiety and Depression Scale. We conducted bivariate Spearman's rho (ρ) correlation analyses and multiple linear regression analysis for identifying variables associated with PSQI scores. ResultsParticipants had a mean (standard deviation) age of 55.4 (12.6) years and were mostly female (78%) with a median [interquartile range] PDDS of 2.0[3.0]. Higher levels of fatigue (ρ=0.32), more symptoms of anxiety (ρ=0.39) and depression (ρ=0.36), younger age (ρ=−0.12), lower income status (ρ=−0.13), shorter MS disease duration (ρ=−0.11), being in a minority group (ρ=0.09), and being unemployed (ρ=−0.10) were associated with worse sleep quality. There were no significant associations between gender, marital status, parental status, education level, disability status, or MS disease type and sleep quality. The overall regression model accounted for 26.3% of variance in sleep quality (F[8,229.8]=20.25) and there were significant coefficients for anxiety(β=0.25), fatigue(β=0.18), depression(β=0.16), and employment status(β=−0.12), but not disease duration, age, race, or income level. DiscussionParticipants with higher levels of anxiety, fatigue, and depression and who were unemployed reported worse sleep quality in our sample of adults with MS. These results may identify specific subgroups of the MS population that experience more sleep problems, and therefore are in greatest need for interventions designed to improve sleep impairment.

Prevalence and predictors of bowel dysfunction in a large multiple sclerosis outpatient population: an Italian multicenter study

IntroductionBowel dysfunction (BD) is reported as a common and disabling symptom in multiple sclerosis (MS) patients. To date, no studies have explored the prevalence of these symptoms in a large multicenter outpatient setting. The aims of the present study are to assess: (i) the prevalence of BD in a large multicenter Italian MS population, and (ii) the correlation between clinico-demographic variables and the severity of BD.MethodsEach of the nine participating center screened MS patients prospectively: 1100 subjects were enrolled. All patients underwent the Expanded Disability Status Scale (EDSS) and completed the Neurogenic Bowel Dysfunction score (NBDs). Multivariable linear and logistic regression models were used to assess the association between NBDs and several clinico-demographic variables.ResultsFourteen percent of MS patients showed a moderate/severe BD (NBDs > 10); this percentage increased in patients with high disability, ranging from 26 to 32%. Moderate/severe BD was more frequent in MS patients with: progressive phenotypes, higher disability, older age, and longer disease duration. NBDs severity was predicted by female sex, ambulation impairment and bladder symptoms.ConclusionThis study confirms the relatively high prevalence of moderate/severe BD in a large, multicenter, unselected, outpatient MS population. BD appears to be mainly associated to female sex and MS-related disability.

Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry

ObjectiveTo evaluate the impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany.DesignThis study employs real-world data captured in-time during clinical visits in 67 German neurology...