Multiple sclerosis (MS) is a chronic and potentially highly-disabling disease of the central nervous system, which can lead to physical and cognitive impairment, including walking difficulties, fatigue, poor balance, bladder and bowel dysfunction, reduced visual acuity, mood changes, and impaired cognition, (1). Symptoms can present in the form of relapses, followed by a recovery period [relapsing-remitting MS (RRMS)], or as gradual progression of disability, either preceded by relapses [secondary progressive MS (SPMS)] or not [primary progressive MS (PPMS)] (2). The MS natural history has changed thanks to the use of disease modifying treatments (DMTs), which primarily target relapses, but also affect disability outcomes in the long term (3).

MS holds significant psychological, physical, financial and social burden on patients, their caregivers, and healthcare services (4–6). The heavy financial burden of MS is related to young age at onset (usually around 30 years of age), variety of chronic symptoms, and subsequently high unemployment rates (7). Indeed, about 50% of workers with MS suffer from reduced working abilities from disease onset (e.g., scaling down from full-time to part-time work), and will eventually lose (or quit) their job (8–11). Exclusion from the workplace is responsible for worsening social status and finances, thus affecting health outcomes in MS (12). The main factors potentially associated with unemployment are progressive disease course, motor disability, fatigue, mood changes, and cognitive impairments (9, 11, 13–17). Nevertheless, data on work ability and occupational difficulties related to MS are rather limited. Also, most studies compared demographic and clinical variables between employed and unemployed people with MS, with potential bias coming from largely different populations (e.g., disease duration, disability) (12). As such, in the present study, we specifically focused on workers with MS to evaluate differences in occupational history and early working impairments (e.g., ability, productivity and activity), when compared with healthy workers as controls, and to define clinical correlates of MS-related perceived working difficulties. Identifying determinants of early working impairments in employed people with MS can direct work retention strategies, ultimately reducing the long-term burden of this chronic disease.

We included 71 people with MS and 71 controls. Demographics and occupational history in subjects with MS and controls are reported in Table 1. MS workers had similar age, when compared with controls (p = 0.61), but were more frequently females (p < 0.01), less educated (p = 0.01), more working disabled (p < 0.01), less exposed to occupational risk factors (p < 0.01), and more limited in fitness to work (p = 0.01) (Table 1).

Working impairment (e.g., ability, productivity and activity) of people with MS and controls, and their associations with clinical features (e.g., quality of life, depression, quality of sleep) are reported in Table 2. People with MS had worse WAI (Coeff = −5.47; 95% CI = −7.41, −3.53; p < 0.01), EuroQoL (Coeff = −4.24; 95% CI = −17.85, −6.50; p < 0.01), BDI-II (Coeff = 3.99; 95% CI = 2.37, 7.01; p < 0.01), and PSQI (Coeff = 4.74; 95% CI = 3.13, 7.61; p < 0.01), compared with controls, while no difference in WPAI was found (Coeff = −1.62; 95% CI = −7.82, 4.57; p = 0.60). EuroQoL, BDI-II, and PSQI were associated with both WAI and WPAI (all p < 0.01); however, when evaluating differences between people with MS and controls in these associations using interaction terms, only the association between EuroQoL and WAI was less strong in people with MS, when compared with controls (p < 0.01) (Table 2).

Clinical features of workers with MS, and their associations with perceived work-related difficulties (MSQJob) are reported in Table 3. Worse MSQJob was associated with higher EDSS (Coeff = 5.22; 95% CI = 2.24, 7.95; p < 0.01), walking impairment (EDSS > 4.0) (Coeff = 5.59; 95% CI = 7.20, 23.97; p < 0.01), progressive disease subtype (Coeff = 14.62; 95% CI = 5.56, 23.69; p < 0.01), EuroQoL (Coeff = 4.63; 95% CI = 2.92, 6.35; p < 0.01), FSS (Coeff = 0.55; 95% CI = 0.38, 0.72; p < 0.01), CVLT (Coeff = −0.31; 95% CI = −0.52, −0.09; p < 0.01), and MS-related cerebral functional system involvement (Coeff = 4.42; 95% CI = 0.67, 8.22; p = 0.02) (Table 3).

In the present study, we showed that, working ability, productivity and activity impairment are associated with quality of life, depressive symptoms, and sleep quality in both MS and age-matched controls, though overall working ability is lower in people with MS. In particular, determinants of perceived work-related difficulties in MS are disability, walking impairment, progressive symptoms, lower quality of life, fatigue and cognitive dysfunction. Of note, we specifically focused on employed people with MS, rather than on unemployment, and, thus, our work aims at increasing awareness on determinants of early working impairments, and at considering medications, rehabilitation, and specific working adaptations to tackle employability in clinical practice (16). The baseline level of work productivity is associated with work productivity trajectories over time (11), and, thus, variables associated with working difficulties should be identified and targeted as soon as possible during the course of the disease.

We showed that employed people with MS have lower working ability, when compared with controls, but are able to keep up with requested working productivity and activity, possibly thanks to the acknowledgment of working disability and subsequent arrangements (e.g., reduced or modified exposure to selected occupational risk factors). In previous studies, there was poor awareness on the tools to assist people with MS in retaining employment (27), while this does not seem the case in our population. Over the disease course, there is a progressive reduction of occupational activities, with up to 50% patients with MS being unemployed within 10 years from disease onset (8, 9, 27–29). As such, the employability of workers with MS should be preserved by adaptation and prevention of working conditions (e.g., ergonomic and technical aspects of the workplace) based on the individual clinical manifestations of the disease (11). In a recent survey, Italian occupational physicians reported on difficulties in rating fitness to work in people with MS (30), and, thus, we hope that our study will raise awareness on the opportunity to design and implement special and reasonable accommodations for MS workers in order to meet their individual needs, according to their clinical features.

Among the novelties of our study, we included both people with MS and controls, and showed that quality of life, depressive symptoms and quality of sleep were worse in people with MS, when compared with controls, but were equally associated with working activity and capacity (productivity and ability). These results suggest that, though quantitatively different, people with MS and controls share qualitatively similar correlates of working impairment. As such, early identification and clinical management of worsening quality of life, depression and sleep, along with subsequent working adaptations, may contribute to improve productivity and to retain employment in individuals with MS, as well as in otherwise healthy workers (10, 11).

Looking at MS-specific factors, in our study, self-perceived difficulties in work-related tasks were associated with higher disability (especially walking impairment), progressive disease subtype, fatigue and cognitive dysfunction, especially in relation to verbal learning and memory. These results are in line with previous studies showing associations between unemployment and mood changes (11, 13), fatigue (8, 13, 28), motor disability (8, 13, 28, 31, 32), and cognitive dysfunction (32). Intriguingly, we specifically focused on workers with MS, and decided to evaluate determinants of perceived working difficulties, which were ultimately not different from actual correlates of unemployment. In keep with this, previous studies showed associations between work difficulties and mood changes (14, 33, 34), fatigue (11, 14, 34), motor disability (11, 14, 33), and cognitive dysfunction (11, 14, 35). In a previous study also using the BICAMS, attention and processing speed (SDMT) was associated with working ability (35), while we found an association for verbal learning and memory (CVLT). While we acknowledge that the SDMT is a marker of overall cognitive function in MS (36), in our study, we computed the cerebral FS score based on overall BICAMS results, which also reflects cognitive impairment (26), and was associated with working difficulties. Not least, working difficulties can be associated with a variety of cognitive deficits based on the actual tasks. We cannot exclude a similar association in controls as well, but unfortunately did not have availability of cognitive variables.

Our study is limited by the single-center design and the relatively small sample size, though sufficiently powered to show consistently significant associations. Controls were recruited based on the age range, which is a main determinant of employability; however, cases and controls were not balanced in sex and education, which were included as covariates in the statistical models. As such, notwithstanding statistical adjustments, we have to acknowledge the risk of bias coming from sex and education differences. Also, our cross-sectional design does not allow causal inference, nor the evaluation of longitudinal changes in working difficulties, also in relation to treatments (20). Generalizability of our results is definitely limited to countries with similar working retention policies and universal healthcare coverage (e.g., Europe, Canada) (17, 37).

In conclusion, our study encourages the early identification and management of clinical features potentially causing an impairment of working ability in people with MS, along with the implementation of individually targeted prevention and protection measures on the workplace. Based on our results, MS specialists should primarily consider disability, fatigue, depression, and cognitive impairment, and liaise with occupational physicians to identify the most suitable arrangements, counseling programs and strategies to support workers with MS. In the future, multidisciplinary patient/worker management teams, including MS specialists, occupational physicians and other healthcare professionals (38, 39), should be considered to protect the health and the employment of vulnerable people with MS.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Federico II University Ethics Committee. The patients/participants provided their written informed consent to participate in this study.

MM and LF contributed to data collection, data analysis and interpretation, manuscript preparation, and revision. VB and II contributed to data interpretation, manuscript revision, and coordination. RP and MT contributed to data analysis and interpretation and manuscript revision. FFa, FFi, MF, RL, and LR contributed to data collection, database preparation, and manuscript revision.