Impact of multiple sclerosis comorbidities on quality of life and job activity.

BACKGROUND: Multiple sclerosis (MS) is frequently accompanied by comorbid conditions. OBJECTIVES: This study aimed to determine the prevalence of key comorbid conditions in people with multiple sclerosis (pwMS) and assess their impact on quality of life and work-related activities. METHODS: A cross-sectional study involving 755 pwMS from two third-level Italian MS centers was conducted. Comorbidities were identified from medical records, and quality of life was assessed using the EQ-5D-3L questionnaire. Work-related challenges were evaluated using the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job). RESULTS: 53.8% of pwMS had at least one comorbidity. Hypertension, depression, and anxiety were the most prevalent. Comorbidity presence was associated with reduced quality of life scores in almost all EQ-5D-3L domains and greater job difficulties in all but one MSQ-Job domain. CONCLUSION: Comorbidities in pwMS are prevalent and have a profound influence on quality of life and work-related activities. This comprehensive study offers new insights into the role of comorbidities in MS within the Italian context, emphasizing the need for a multidisciplinary approach in MS management. Further research is crucial to deepen our understanding of these findings in the broader Italian MS community.

The economic impact of comorbidity in multiple sclerosis.

BACKGROUND: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment. OBJECTIVE: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach. METHODS: A retrospective study was carried out in two northern Italian areas. The socio-demographic and clinical information, including comorbidities data, were collected through ad hoc anonymous self-assessment questionnaire while disease costs (direct and indirect costs of disease and loss of productivity) were estimated using a bottom-up approach. Costs were compared between pwMS with and without comorbidity. Adjusted incremental costs associated with comorbidity were reported using generalized linear models with log-link and gamma distributions or two-part models. RESULTS: 51.0% of pwMS had at least one comorbid condition. Hypertension (21.0%), depression (15.7%), and anxiety (11.7%) were the most prevalent. PwMS with comorbidity were more likely to use healthcare resources, such as hospitalizations (OR = 1.21, p < 0.001), tests (OR = 1.59, p < 0.001), and symptomatic drugs and supplements (OR = 1.89, p = 0.012), and to incur non-healthcare costs related to investment (OR = 1.32, p < 0.001), transportation (OR = 1.33, p < 0.001), services (OR = 1.33, p < 0.001), and informal care (OR = 1.43, p = 0.16). Finally, they experienced greater productivity losses (OR = 1.34, p < 0.001) than pwMS without comorbidity. The adjusted incremental annual cost per patient due to comorbidity was €3,106.9 (13% of the overall costs) with MS disability found to exponentially affect annual costs. CONCLUSION: Comorbidity has health, social, and economic consequences for pwMS.

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients.

BACKGROUND: Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for the screening of dysphagia in ALS is validated, and the approach is heterogeneous across the Italian centres. OBJECTIVE: To validate the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire, adapting the DYMUS (dysphagia in multiple sclerosis) questionnaire, for the assessment of dysphagia in ALS patients, in order to uniform the evaluations across the Italian ALS network. METHODS: We included 197 patients diagnosed with ALS following the El Escorial criteria, in sixteen Italian ALS centres between 1st December 2019 and 1st July 2020. For each patient, we collected clinical and demographic data and obtained ALSFRS-r score, ALSAQ-5 score, DYMUS score, and EAT-10 score. RESULTS: Across the 197 patients, the ratio M/F was 113/84, and the median age was 64 years (IQR 56-72.5). Bulbar patients were 20%, and spinal patients 80%. The median ALSFRSr total score of patients was 35 (IQR 28-39). DYALS score was statistically higher in bulbar ALS than in spinal ALS (median = 6, IQR 4.5-9 vs median = 1, IQR 0-5, z = 6.253, p < 0.0001). DYALS questionnaire showed a high internal consistency (Cronbach's alpha = 0.88). There was a statistically significant correlation between DYALS and EAT-10 (rho = 0.90, p < 0.0001). CONCLUSIONS: DYALS scale is reliable, manageable, and easily usable for the screening of dysphagia in ALS. It can be shared with all the Italian ALS centres in order to collect uniform data for therapeutic strategies and clinical trials.

Health status of petrochemical workers: a narrative review.

SUMMARY: Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.

Increased prevalence of multiple sclerosis and clusters of different disease risk in Northern Italy.

BACKGROUND: The increasing multiple sclerosis (MS) prevalence is varying across the macroscopic regional areas. Only few studies have explored the microscopic geographic variation of MS prevalence, which could highlight MS spatial clusters. OBJECTIVE: In this ecological study, we aimed to estimate 2016 MS prevalence in the province of Pavia (Northern Italy) and to describe MS risk geographical variation across small area units, compared to the year 2000. METHODS: Bayesian models were fit to estimate area-specific MS relative risks. The mean of the posterior marginal distribution of relative risks differences for each area were used to describe the risk variation. RESULTS: The 2016 overall prevalence was 169.4 per 100,000 inhabitants (95% CI 158.8-180.6). The Bayesian mapping of MS showed some clusters of higher and lower disease prevalence. Furthermore, several municipalities located in the north part of the province were more at risk with respect to the year 2000. CONCLUSIONS: The current MS prevalence sets the province of Pavia among high-risk areas and, compared with the previous prevalence estimate (86 per 100,000 in year 2000), indicates an increased MS risk. The Bayesian mapping highlighted area with a significantly higher/lower MS risk where to investigate etiologic hypotheses based on environmental and genetic exposures.

[Epidemiological analysis on the hospitalization from neurological diseases in the Province of Pavia (Lombardy Region, Northern Italy)]. / Analisi epidemiologica dei ricoveri per patologie neurologiche in Provincia di Pavia.

OBJECTIVES: to evaluate time and spatial distribution of hospitalization due to neurological diseases in the province of Pavia (Lombardy Region, Northern Italy). DESIGN: ecological study. SETTING AND PARTICIPANTS: the study was performed on aggregate data of people residing in the province of Pavia in the period 2005-2014. MAIN OUTCOME MEASURES: hospital discharge records of neurological diseases and raw and standardized hospitalization rates. RESULTS: hospitalization due to neurological diseases in the Province of Pavia showed a slight decreasing trend in time. For the year 2014, the spatial analysis of hospitalizations highlights excesses of risk in the Lomellina district, both in males and in females. CONCLUSION: spatial analysis confirms previous results on specific neurological diseases and suggests more detailed analysis on hospitalization excesses in Lomellina area.

Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI.

BACKGROUND: Some environmental factors have been already associated to increased risk of multiple sclerosis (MS), but it is plausible that additional factors might play a role. OBJECTIVE: To investigate in MS patients the relationship between inflammatory activity, detected by brain magnetic resonance imaging (MRI) with gadolinium (Gd), and air pollution, namely, particulate matters with diameter less than 10 µm (PM10). METHODS: We analyzed from 52 remitting MS patients 226 brain MRIs, 34% with (Gd+MRI) and 66% without (Gd-MRI) T1-Gd-enhancing lesions. Daily recording of PM10 in the 30 days before MRI examination was obtained by monitors depending on the residence of subjects. RESULTS: PM10 levels in the 5, 10, 15, 20, and 25 days before brain MRIs were higher (plus 16%, 21%, 24%, 25%, and 21%, respectively) with reference to Gd+MRI versus Gd-MRI. There was a significant association between Gd+MRI and PM10 levels ( p = 0.013), independent of immune therapies, smoker status, and season. In patients who had two repeated MRIs with opposite outcomes (Gd-MRI and Gd+MRI), PM10 levels were strongly higher in concurrence with Gd+MRI ( p < 0.0001). CONCLUSION: Our findings suggest that air pollution may be a risk factor for MS favoring inflammatory exacerbations.

Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.

BACKGROUND: Few studies, and with conflicting results, have evaluated the potential effects of iodinated contrast media on children's thyroid function. OBJECTIVE: To investigate the effects of iodinated contrast medium on thyroid function in neonates, infants and young children with congenital heart disease undergoing cardiac computed tomography (CT). MATERIALS AND METHODS: We retrospectively evaluated 10 neonates (group 1) and 23 infants and young children (group 2) without thyroid or renal disease for serum levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine before contrast-enhanced cardiac CT, 48 h after CT and at discharge from the hospital. Cardiac CT was performed with intravenous administration of 1.14±0.17 mL/kg of body weight of iopromide (containing 370 mg of iodine/mL). RESULTS: Group 1 had a reduction of thyroid-stimulating hormone from baseline to 48 h post injection (P=0.002). Group 2 had a reduction of thyroid-stimulating hormone median levels from baseline to 48 h post injection and an increase from 48 h to discharge (P=0.0005 and P=0.0001, respectively). CONCLUSION: Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.

Falling asleep at the wheel and distracted driving. The High-Risk Professional Drivers study.

BACKGROUND: Sleepiness at the wheel and driving while engaged in other activities are well known risk factors for traffic accidents. This article estimates the prevalence of these factors among Italian Professional Drivers (PDs) and their impact on reported driving mistakes. METHODS: A cross-sectional study was conducted using anonymous questionnaires. PDs (n=497) were divided into two groups: high-risk PDs (HiRis_PDs) (those who self-reported more than one incident during the last 3 years and/or more than one mistake during the past year) and non-HiRis_PDs (subjects who did not meet the above-mentioned inclusion criteria). Logistic regression analyses were performed to assess the association of self-reported sleepiness and/or risky driving behaviour with the condition of being a high-risk driver. RESULTS: 161 (32.4%) subjects were defined as HiRis_PDs. Forty-one percent of the interviewees experienced at least one episode per month of sudden-onset sleep at the wheel. Twenty-eight point two percent reported a regular use of a hand-held cell phone. Predictive factors for being HiRis_PDs were: at least one self-reported episode per month of falling asleep at the wheel [odds ratio (OR) 5, 95% confidence interval (CI) 3.21-7.80, P<0.001], driving while regularly engaged in other activities (mainly hand-held cell phone use) (OR 6.11, 95% CI 2.90-12.84, P<0.001), and young age (OR 0.96, OR 1 year of age increase, 95% CI 0.94-0.98, P=0.001). CONCLUSIONS: Focusing prevention efforts on recognizing sleepiness at the wheel and on avoiding other distracting activities while driving can reduce the possibility of driving errors on the road by about 5-6 times.

Incidence of apparent life-threatening events and post-neonatal risk factors.

AIM: Even though a standard clinical definition for an apparent life-threatening event (ALTE) was established more than two decades ago, the specific International Classification of Disease (ICD) code was firstly included only in 2012. This study estimated the incidence of ALTEs in Northern Italy, together with features and risk factors. METHODS: We used the Lombardy Region Hospital Discharge Records (HDR) database to estimate the cumulative incidence for ALTE during 2002-2006 and drew up a risk profile by comparing cases with and without ALTE who were followed in infancy. RESULTS: There were 246 infants registered in the HDR with ALTE putative diagnostic codes, suggesting a cumulative incidence of 4.1 per 1000 live births in the study area. Of the 148 cases with clinical co-morbidities, 31% had gastroesophageal reflux and 7% had acute respiratory infections. We analysed follow-up data from 15 ALTE cases and 1619 healthy infants and found that the significant risk factors were gastroesophageal reflux and a family history of sudden death. CONCLUSION: We established the regional incidence of ALTE and found risk factors in infants considered healthy in the first week of life and without pathological perinatal conditions. The systematic use of the specific ALTE ICD code (R68.13, ICD-10-CM) and common knowledge about ALTE diagnostic guidelines are clearly needed.

Area-Level Deprivation and Adverse Consequences in People With Substance Use Disorders: Findings From the Psychiatric and Addictive Dual Disorder in Italy (PADDI) Study.

BACKGROUND: Environmental factors may operate with individual ones to influence the risk of substance use. Research has focused on severe adverse consequences influenced by contextual variables. However, the literature on community level factors influencing substance use behaviors is relatively limited across Europe so far. OBJECTIVE: We capitalized on data from a National survey, exploring individual and contextual characteristics, to study adverse consequences among people with substance use disorders. METHODS: The impact of area-level deprivation on nonfatal overdose, hepatitis C or B infections, and major involvement with the criminal justice system, was explored. Logistic regression models with cluster-robust errors, modeling subject-level and area-level effects, were used. RESULTS: Living in deprived and intermediate areas, as compared with affluent ones, was associated with greater likelihood of both nonfatal overdose and jail sentences longer than 6 months, though not of active viral hepatitis. CONCLUSIONS: Area-level deprivation may play an important role in determining adverse consequences in people with substance use disorders, also after controlling for individual-level characteristics. More research is needed to understand the aspects of social and physical environments that matter for drug outcomes before effective policy and research interventions can be developed.

The Music Therapy Session Assessment Scale (MT-SAS): Validation of a new tool for music therapy process evaluation.

BACKGROUND: Music therapy (MT) interventions are aimed at creating and developing a relationship between patient and therapist. However, there is a lack of validated observational instruments to consistently evaluate the MT process. AIM: The purpose of this study was the validation of Music Therapy Session Assessment Scale (MT-SAS), designed to assess the relationship between therapist and patient during active MT sessions. METHODS: Videotapes of a single 30-min session per patient were considered. A pilot study on the videotapes of 10 patients was carried out to help refine the items, define the scoring system and improve inter-rater reliability among the five raters. Then, a validation study on 100 patients with different clinical conditions was carried out. The Italian MT-SAS was used throughout the process, although we also provide an English translation. RESULTS: The final scale consisted of 7 binary items accounting for eye contact, countenance, and nonverbal and sound-music communication. In the pilot study, raters were found to share an acceptable level of agreement in their assessments. Explorative factorial analysis disclosed a single homogeneous factor including 6 items (thus supporting an ordinal total score), with only the item about eye contact being unrelated to the others. Moreover, the existence of 2 different archetypal profiles of attuned and disattuned behaviours was highlighted through multiple correspondence analysis. CONCLUSIONS: As suggested by the consistent results of 2 different analyses, MT-SAS is a reliable tool that globally evaluates sonorous-musical and nonverbal behaviours related to emotional attunement and empathetic relationship between patient and therapist during active MT sessions.

Validation of the Besta Neurological Institute rating scale for myasthenia gravis.

INTRODUCTION: We validated the scale for myasthenia gravis (MG) developed at the Neurological Institute Foundation of Milan (INCB-MG scale). METHODS: A total of 174 patients were evaluated with the INCB-MG and compared with the MG Composite (MGC) as the gold standard. Dimensionality, reliability, and validity of the INCB-MG scale were studied by principal component factor analysis, Cronbach alpha, and Pearson correlation coefficients; interobserver reliability was calculated by the weighted Cohen K coefficient. RESULTS: Generalized and bulbar INCB-MG subscales were unidimensional with excellent consistency; the INCB-MG and MGC scales were strongly correlated. Fatigability assessment was correlated with the INCB-MG generalized, bulbar, and respiratory subscales. CONCLUSIONS: The INCB-MG scale is a reliable tool to assess MG and is strongly correlated with the MGC. The INCB-MG scale is a valid tool for every day practice and should be further investigated for its application in clinical trials.

Patient-reported outcomes measure for children born preterm: validation of the SOLE VLBWI Questionnaire, a new quality of life self-assessment tool.

AIM: This study was conducted to develop and validate a new self-report questionnaire for measuring quality of life (QoL), at school age, in children with a very low birthweight (VLBW). METHOD: Through a focus group approach, children were involved directly in defining the questionnaire items, which were presented as illustrations rather than written questions. This preliminary validation of the questionnaire was conducted in 152 participants with VLBW (aged 7-11y) randomly selected from the five participating Italian centres. The questionnaire was completed by children and parents separately; data on children's demographic and medical history, and intellectual, adaptive, and behavioural functioning were collected using standardized scales. All the children also completed the Paediatric Quality of Life Inventory (PedsQL), another Italian-language measure of QoL in children. RESULTS: Our questionnaire was readily accepted and understood, and quick to complete. The Cronbach's alpha value showed it to be a reliable instrument. The child-compiled version correlated well with the PedsQL, whereas no correlations emerged with the other scales used, IQ, or degree of impairment. Conversely, these variables correlated significantly with the parent-compiled version. Children's and parents' answers were divergent on practically all the items. INTERPRETATION: The results confirm the validity of the new instrument and highlight a poor overlap between parents' and children's perspectives.

Correlates of dependence and treatment for substance use among people with comorbid severe mental and substance use disorders: findings from the "Psychiatric and Addictive Dual Disorder in Italy (PADDI)" Study.

OBJECTIVE: People with severe mental illness (SMI) have often comorbid alcohol and other substance disorders but substantial barriers to addiction care remain. The study is aimed at describing correlates associated with dependence and with treatment for substance use among people with SMI and comorbid substance disorders cared in community mental health teams (CMHTs). METHODS: This study capitalized on data from a national survey on comorbid severe mental and substance use disorders, among 2235 subjects in 42 CMHTs nationwide. RESULTS: 26% of people with SMI and comorbid misuse suffered from dependence on alcohol and 21% on any other substance. Use of opioids, liver diseases, involvement with criminal justice system, but also area of residence, all were associated with dependence in people with SMI. As regards treatment for substance use, only 50% of comorbid people with SMI were treated by specialist services in the past 12 months. This was associated with opioids and cocaine use, as well as with liver diseases, and involvement with criminal justice. People with schizophrenia and those living in Central and Southern Italy, had the lowest chances to be treated for their comorbid substance use disorder. CONCLUSIONS: There are extensive unmet treatment needs among comorbid individuals with SMI. Better integration of substance abuse and mental health care systems, and more effective reciprocal referral procedures, are needed.

Detection of clinical relapses in multiple sclerosis cohorts: construction and validation of a model based on administrative data.

Multiple sclerosis (MS) is the main cause of chronic disability in young people during their most productive years of life and therefore carries a high social and economic burden. The present study aimed to: (1) verify the capacity of an administrative data source to furnish data for constructing a model able to detect the occurrence of clinical relapses in MS patients and (2) validate the constructed theoretical model on a set of real-world data. Two MS experts identified some administrative variables as proxies of clinical relapses. Thereafter, the two MS experts analysed 889 events in 100 MS patients, considering only the administrative data relating to these patients, while a third neurologist independently analysed the real-world data (documented medical history) of the same patients in the same period. Absolute concordance between the theoretical model and the real-world data was found in 86 % of the events. The model we propose is easily and rapidly applicable, requiring the collection of just a few variables that are already present in local health authority administrative databases in Italy. It can be used to estimate, with a good level of reliability, the occurrence of relapses in various settings. Moreover, the model is also exportable to different and larger MS cohorts and could be useful for healthcare planning and for evaluating the efficacy of drugs in the real-world, thus favouring better resource allocation and management.

Assessing executive function with the D-KEFS sorting test: normative data for a sample of the Italian adult population.

One of the major problems in clinical neuropsychology is to apply ecological, easily administrable and sensitive tests that can help in the diagnosis of executive functions. In the present paper we present normative values for the D-KEFS sorting test (ST), exploring the ability of reasoning, categorization abilities, problem solving, flexibility of thinking and abstraction. We collected normative data in a group of 181 normal Italian subjects aged between 20 and 69 years old, matched for educational level. Multiple regression analysis was performed to evaluate the potential effects of age, sex and education. Age and education had a significant effect on ST performance. Our study provided normative data for the D-KEFS ST for the adult Italian population, corrections of raw scores for relevant demographic factors, and percentile grids for both baseline data and on re-testing after 9 months of follow-up. These normative Italian values support the use of the D-KEFS ST as a valid instrument for initial neuropsychological evaluation and longitudinal analysis of executive functions in clinical practice and for research purposes.

Early prediction of unfavorable evolution after a first clinical episode suggestive of multiple sclerosis: the EUMUS score.

BACKGROUND: Predicting disease progression in patients with the first clinical episode suggestive of multiple sclerosis (MS) is crucial for personalized therapeutic approaches. This study aimed to develop the EUMUS score for accurately estimating the risk of early evidence of disease activity and progression (EDA). METHODS: Retrospective analysis was conducted on data from 221 patients with a first clinical MS episode collected from four Italian MS centers. Various variables including socio-demographics, clinical features, cerebrospinal fluid analysis, evoked potentials, and brain MRI were considered. A prognostic multivariate regression model was identified to develop the EUMUS score. The optimal cutoff for predicting the transition from no evidence of disease activity (NEDA3) to EDA was determined. The accuracy of the prognostic model and score were tested in a separate UK MS cohort. RESULTS: After 12 months, 61.54% of patients experienced relapses and/or new MRI lesions. Younger age (OR 0.96, CI 0.93-0.99; p = 0.005), MRI infratentorial lesion(s) at baseline (OR 2.21, CI 1.27-3.87; p = 0.005), positive oligoclonal bands (OR 2.89, CI 1.47-5.69; p = 0.002), and abnormal lower limb somatosensory-evoked potentials (OR 2.77, CI 1.41-5.42; p = 0.003) were significantly associated with increased risk of EDA. The EUMUS score demonstrated good specificity (72%) and correctly classified 80% of patients with EDA in the independent UK cohort. CONCLUSIONS: The EUMUS score is a simple and useful tool for predicting MS evolution within 12 months of the first clinical episode. It has the potential to guide personalized therapeutic approaches and aid in clinical decision-making.

[Multiple sclerosis and occupational exposures: results of an explorative study]. / Sclerosi multipla e esposizioni occupazionali: risultati di uno studio preliminare.

OBJECTIVES: The aim of the study is to explore possible relationships between occupational exposures and Multiple Sclerosis (MS), whose etiology is not well defined yet. To date, only few literature data are available on this subject. METHODS: We carried out a case-control study, where cases were MS patients included in the MS Register of the Province of Pavia, Northern Italy, and controls, 1:4 matched by sex and age (5 years classes), were randomly selected from the National Health Service population files. The occupational histories were obtained from Italian Institute for Social Security (INPS) archives by automatic linkage using Italian Occupational Cancer Monitoring (OCCAM) method that estimates the risk of specific occupational cancers, by geographic area and industrial sector. OR adjusted for sex and age and corresponding 90% confidence intervals were used to estimate the association between exposure and disease. RESULTS: We included in the study 227 MS patients (130 (57.3%) female, 97 (42.7%) male) and 907 controls (514 (56.7%) female, 393 (43.3%) male). Our results suggest an increased risk for men in mechanical manufacturing industry (OR 1.71, 90% CI 1.03-2.85) and agriculture (OR 2.47, 90% CI 1.03-5.91). Women show an increased risk in mechanical manufacturing industry (OR 2.05, 90% CI 1.22-3.45), agriculture (OR 2.57, 90% CI 1.09-6.09) and leather/shoe industry (OR 2.34, 90% CI 1.06-5.20). CONCLUSIONS: Our preliminary findings indicate that solvent exposures could be related to the risk of MS, as both shoe/leather workers and mechanical manufacturing industry workers are exposed to organic solvents. Interestingly, a major risk of MS was also found among workers engaged in agriculture, suggesting a role of pesticides, whose neurotoxic effect is well known.