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.

Clinical characteristics and dynamics of disability progression in a cohort of patients with multiple sclerosis in Latvians.

There is wide variation in the time from the onset to secondary progressive multiple sclerosis (MS) and some controversy regarding the clinical characteristics of the courses (phenotypes) of MS. The present study aimed to characterize demographic and clinical factors that potentially influence long-term disability progression in the cohort of Latvian MS patients. A descriptive longitudinal incidence study was conducted using a cohort of 288 MS patients beginning in 2011 (disease duration from 1 to 51 years). Socio-demographic and clinical information from the first visit to 15/20 years was analysed in groups stratified by gender and visits at five-time points (the first visit; after a year or 2; after 5 ± 1 year; after 10 ± 2 years; after 15-20 years). Our study was dominated by patients from urban areas and non-smokers. The female/male ratio was 2.4:1; the distribution of clinical courses at the first visit was consistent with most European studies. The most common symptom at presentation in our study was optic manifestations, followed by sensory disturbances and motor deficits. In the Latvian study, gender was not a significant influencing factor on the rate of disease progression; however, patient age was statistically significantly associated with EDSS (Expanded Disability Status Scale) value at the first visit. Early clinical features of MS are important in predicting the disability accumulation of patients. Despite the small differences regarding the first MS symptoms, the disability outcomes in the cohort of Latvian patients are similar to other regions of the world.

A novel tool for characterising upper limb function in progressive multiple sclerosis through kinematic assessment.

INTRODUCTION: Current upper limb assessment methods in MS rely on measuring duration in tasks like the nine-hole peg test (9HPT). Kinematic techniques may provide a more useful measure of functional change in clinical and research practice. The aim of this study was to assess upper limb function prospectively in people with progressive MS using a kinematic 3D motion capture system and compare with current measures. METHODS: 42 people with progressive MS (PwPMS) and 15 healthy controls reached-and-grasped different objects whilst recorded by a kinematic assessment system. 9HPT, Expanded Disability Status Scale (EDSS), and patient reported outcome measures (PROs) were collected. All measures were taken at baseline for PwPMS and controls, and again at six months for PwPMS. RESULTS: Relative to controls, PwPMS had significantly longer reaction (0.11 s, p < 0.05) and reach (0.25 s, p < 0.05) times. PwPMS took longer to pick-up (0.34 s, p < 0.05), move (0.14 s, p < 0.05), and place (0.18 s, p < 0.05) objects. PwPMS had lower peak velocities when reaching (7.4 cm/s, p < 0.05) and moving (7.3 cm/s, p < 0.05) objects. Kinematic assessment demonstrated consistent differences between PwPMS with mild and severe upper limb dysfunction as defined by PROs, which were not captured by 9HPT or EDSS in this group. PwPMS demonstrated altered grip apertures profiles, as measured by their ability to complete individual parts of the reach and grasp task, between the baseline and follow-up timepoints. CONCLUSIONS: We have created and tested a novel upper limb function assessment tool which has detected changes and characteristics in hand function, not currently captured by the EDSS and 9HPT.

The multidimensional assessment of body representation and interoception in multiple sclerosis.

BACKGROUND: The mental representation of the body (or body representation, BR) derives from the processing of multiple sensory and motor inputs and plays a crucial role in guiding our actions and in how we perceive our body. Fundamental inputs for BR construction come also from the interoceptive systems which refer to the whole bidirectional processes between the brain and the body. People with Multiple sclerosis (MS) show an abnormal multisensory integration which may compromise BR and interoception integrity. However, no study has evaluated possible deficits on distinct and dissociable dimensions of body representation (i.e., action-oriented, aBR; and a nonaction-oriented body representation, NaBR) and interoception (i.e., interoceptive accuracy, interoceptive sensibility, and interoceptive awareness) in MS. OBJECTIVE: In the present study, we aimed to determine whether participants with MS present changes in BR and interoceptive dimensions. METHODS: We performed comparison analyses on tasks and questionnaires tapping all BR and interoceptive dimensions between 36 people with relapsing-remitting MS (RRMS) and 42 healthy controls, and between 23 people with progressive MS (PMS) and 33 healthy controls. RESULTS: Overall, patients with MS exhibited lower interoceptive accuracy than matched controls. The RRMS group also showed higher visceral interoceptive sensibility levels. No differences were found in BR accuracy measures, but the PMS reported longer response times when performing the aBR task. CONCLUSION: These findings open a new issue on the role of inner-signal monitoring in the body symptomatology of MS and highlight the need for an accurate BR and interoceptive assessment in a clinical setting.

Prevalence and Associated Clinical Characteristics of Walking-Related Motor, Cognitive, and Fatigability in Progressive Multiple Sclerosis: Baseline Results From the CogEx Study.

BACKGROUND: People with progressive multiple sclerosis (PMS) present motor (eg, walking) and cognitive impairments, and report fatigue. Fatigue encompasses fatigability which is objectively measured by the capacity to sustain a motor or cognitive task. OBJECTIVE: To investigate the prevalence of walking and cognitive fatigability (CF) and the associated clinical characteristics in a large sample of PMS patients. METHODS: PMS patients (25-65 years old) were included from 11 sites (Europe and North America), having cognitive impairment (1.28 standard deviation below normative data for the symbol digit modality test [SDMT]). Walking fatigability (WF) was assessed using the distance walk index (DWI) and CF using the SDMT (scores from the last 30 seconds compared to the first 30 seconds). Additional measures were: cognitive assessment-Brief International Cognitive Assessment for multiple sclerosis (MS), cardiorespiratory fitness, 6-minute walk, physical activity, depressive symptoms, perceived fatigue-Modified Fatigue Impact Scale (MFIS), MS impact-MSIS-29, and walking ability. RESULTS: Of 298 participants, 153 (51%) presented WF (DWI = -28.9 ± 22.1%) and 196 (66%) presented CF (-29.7 ± 15%). Clinical characteristics (EDSS, disease duration, and use of assistive device) were worse in patients with versus without WF. They also presented worse scores on MSIS-29 physical, MFIS total and physical and reduced physical capacity. CF patients scored better in the MSIS-29 physical and MFIS psychosocial, compared to non-CF group. Magnitude of CF and WF were not related. CONCLUSIONS: Half of the cognitively-impaired PMS population presented WF which was associated with higher disability, physical functions, and fatigue. There was a high prevalence of CF but without strong associations with clinical, cognitive, and physical functions. TRIAL REGISTRATION NUMBER: The "CogEx-study," www.clinicaltrial.gov identifier number: NCT03679468.

Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). METHODS: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up). RESULTS: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025). DISCUSSION: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.

Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

INTRODUCTION: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS. METHODS: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored. RESULTS: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age. CONCLUSION: TS measured through our application is reliable and correlates with baseline disability scales.

Neurofilament Light Chain Serum Levels Mirror Age and Disability in Secondary Progressive Multiple Sclerosis: A Cross-Sectional Study.

OBJECTIVES: To assess neurofilament light chain serum (sNfL) levels in patients with secondary progressive multiple sclerosis (SP-MS). METHODS: Using a single molecule array, we analyzed sNfL levels in a cross-sectional cohort study of 153 patients with SP-MS hospitalized for rehabilitation in a clinic specialized in the care for patients with multiple sclerosis (MS). In addition, we investigated the correlation of disease activity with sNfL levels in 36 patients with relapsing-remitting MS (RR-MS). RESULTS: Mean sNfL levels in patients with SP-MS were consistently elevated when compared with age-matched controls and patients with RR-MS. In SP-MS, age dependency of sNfL levels was pronounced, whereas patients with RR-MS younger than 41 years without recent disease activity were not distinguishable from age-matched healthy controls. In a multivariate analysis, clinical disability was a risk factor for elevated sNfL levels in SP-MS, whereas no correlation with comorbidities, such as cardiovascular disease, diabetes mellitus, smoking status, or vitamin D serum levels, could be detected. DISCUSSION: These findings highlight that measurement of sNfL levels represents a useful tool to assess the extent of neuroaxonal damage as a surrogate for clinical progression in patients with SP-MS, when age and disease activity as major confounders are taken into account.

Evolution of retinal degeneration and prediction of disease activity in relapsing and progressive multiple sclerosis.

Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.

Evaluación clínica y por imágenes de la esclerosis múltiple progresiva / Clinical and radiological outcomes measures in progressive multiple sclerosis

Durante los últimos años, el desarrollo de medidas de evaluación de la acumulación de la discapacidad y la actividad inflamatoria en las formas progresivas de esclerosis múltiple (EM) ha sido un punto central de investigación de diversos grupos. Se han desarrollado y aplicado distintos instrumentos con el fin de identificar en forma precisa y precoz la actividad y la progresión en este fenotipo de EM. Muchas de esas herramientas, con mayor o menor sensibilidad, han sido utilizadas en ensayos clínicos, aunque su uso en la práctica asistencial no es del todo familiar para los profesionales involucrados en el cuidado de pacientes con EM. El objetivo de esta revisión es describir las medidas de evaluación clínica y por imágenes implementadas durante los últimos años para la identificación de la actividad y evolución de esta enfermedad en sus formas progresivas.

During recent years, the development of measures to assess the accumulation of disability and inflammatory activity in the progressive forms of multiple sclerosis (MS) has been a central point of research in various groups. Several instruments have been developed and implemented in order to accurately and early identify the activity and progression in this MS phenotype. Many of these tools, with greater or lesser sensitivity, have been used in clinical trials, although their use in healthcare practice is not entirely familiar to professionals involved in the care of patients with MS. The objective of this review is to describe the clinical and imaging evaluation measures implemented during the last years to identify the activity and the evolution of the disease in its progressive forms.