Lifetime exposure to smoking and substance abuse may be associated with late-onset multiple sclerosis: a population-based case-control study.

BACKGROUND: Late-onset multiple sclerosis (LOMS), defined as the development of MS after the age of 50, has shown a substantial surge in incidence rates and is associated with more rapid progression of disability. Besides, studies have linked tobacco smoking to a higher chance of MS progression. However, the role of smoking on the risk of developing LOMS remains unclear. This study aims to evaluate the possible association between lifetime exposure to cigarette and waterpipe smoking, drug abuse, and alcohol consumption and the risk of LOMS. METHODS: This population-based case-control study involved LOMS cases and healthy sex and age-matched controls from the general population in Tehran, Iran. The primary data for confirmed LOMS cases were obtained from the nationwide MS registry of Iran (NMSRI), while supplementary data were collected through telephone and on-site interviews. Predesigned questionnaire for multinational case-control studies of MS environmental risk factors was used to evaluate the LOMS risk factors. The study employed Likelihood ratio chi-square test to compare qualitative variables between the two groups and utilized two independent sample t-test to compare quantitative data. Adjusted odds ratio (AOR) for age along with 95% confidence intervals (CI) were calculated using matched logistic regression analysis in SPSS 23. RESULTS: Totally, 83 LOMS cases and 207 controls were included in the analysis. The female to male ratio in the cases was 1.5: 1. The mean ± SD age of 83 cases and 207 controls was 61.14 ± 5.38) and 61.51 ± 7.67 years, respectively. The mean ± SD expanded disability status scale (EDSS) score was 3.68 ± 2.1. Although the results of waterpipe exposure had no significant effect on LOMS development (P-value: 0.066), ever cigarette-smoked participants had a significantly higher risk of developing LOMS than those who never smoked (AOR: 2.57, 95% CI: 1.44-4.60). Furthermore, people with a history of smoking for more than 20 years had 3.45 times the odds of developing MS than non-smokers. Drug and alcohol abuse were both associated with LOMS in our study; of which opioids (AOR: 5.67, 95% CI: 2.05-15.7), wine (AOR: 3.30, 95% CI: 1.41-7.71), and beer (AOR: 3.12, 95% CI: 1.45-6.69) were found to pose the greatest risk of LOMS, respectively. CONCLUSION: For the first time, we identified smoking, drug, and alcohol use as potential risk factors for LOMS development. According to the global increase in cigarette smoking and alcohol use, these findings highlight the importance of conducting interventional approaches for prevention.

Radiological features of late-onset multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Late-onset multiple sclerosis (LOMS) is most commonly defined as the onset of the disease's presentations at age 50 or older. There is still much to discover about the radiological features of LOMS. The current study aims to assess the imaging features of LOMS, as well as the correlation between these findings and the clinical characteristics of these patients. METHOD: This study was conducted following the PRISMA statement. A systematic search was conducted through PubMed, Scopus, and EMBASE databases to identify the studies that have applied magnetic-resonance imaging (MRI) or other imaging methods to investigate the radiological findings, as well as the relationship between them and clinical findings of LOMS patients. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklists. Meta-analysis was conducted using the third version of the compressive meta-analysis software (CMA3). RESULTS: Our search identified 753 unique titles. Among them, 15 studies, including seven case-control, five case-series, and three cross-sectional studies, met the eligibility criteria. According to the quantitative synthesis, brain lesions were detected among 72.2% of LOMS patients (4 studies; 95% CI: 67.0% - 93.1%). In the context of spinal lesions, overall spinal cord involvement was 64.0% (8 studies; 95% CI: 42.5% - 81.1%). Based on the available evidence, supratentorial involvement was found in 82.7% of cases (3 studies; 95% CI: 17.4% - 99.1%), juxtacortical involvement in 34.1% (3 studies; 95% CI: 26.4% - 42.7%), infratentorial involvement in 51.3% (4 studies; 95% CI: 32.1% - 70.1%), and cerebellar involvement in 18.5% (3 studies; 95% CI: 13.9% - 24.1%). CONCLUSION: Based on the neuroimaging findings, we found that, given the heterogeneity of MS, LOMS patients have a high rate of spinal cord lesions and supratentorial involvement. The limited available evidence suggests that Barkhof criteria are the best compromise for the diagnosis of LOMS. There is still a need for future studies.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Cognition and disease characteristics in adult onset versus late onset multiple sclerosis.

BACKGROUND: Cognitive impairment is common sequelae of multiple sclerosis (MS); however, relatively little is known about cognitive impairment in late-onset multiple sclerosis (LOMS). OBJECTIVE: To investigate differences in disease characteristics and cognition in LOMS and adult-onset multiple sclerosis (AOMS) patients. METHODS: Archival medical records and neuropsychological evaluations from an MS specialty center were reviewed. Differences in disease characteristics between 53 LOMS and 124 AOMS were compared using chi-square or analysis of variance (ANOVA). To investigate differences in cognitive functioning, age-adjusted standardized scores were compared via analysis of covariance (ANCOVA), using cardiac risk factors and disease duration as covariates. RESULTS: Compared to AOMS, LOMS patients had significantly more cardiac risk factors, shorter disease duration, and shorter time to diagnosis. LOMS patients had similar Expanded Disability Status Scale scores as AOMS patients. LOMS patients demonstrated significantly more impairment on tasks of visual learning and memory, and working memory than AOMS patients. CONCLUSION: Despite a shorter disease duration, LOMS and AOMS patients had similar levels of physical impairment. However, even after accounting for differences in disease duration and cardiac risk, LOMS patients showed a greater burden of cognitive impairment than AOMS patients, suggesting MS diagnosed later in life may progress faster due to the interaction between MS neuropathology and aging.

Late onset multiple sclerosis - multiparametric MRI characteristics.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with heterogenic character. Typical age of onset is between 20 and 35 years. Clinically definite multiple sclerosis (CDMS) can occur also in patients older than 50 years. This type of MS is called Late Onset Multiple Sclerosis (LOMS). Until now, the differences in clinical course, type of first symptoms, and prognosis of LOMS have not been well established. Also the MRI characteristics of patients with LOMS have not been determined. Neither conventional nor nonconventional MRI features are known to be typical for LOMS. CLINICAL RATIONALE FOR THE STUDY: To investigate the MRI characteristics of LOMS patients based on conventional and non-conventional techniques. MATERIALS AND METHODS: Twenty patients with LOMS were included in the study and 17 patients with typical onset of MS (TOMS) served as a comparative group. The two groups were matched in terms of disease duration and EDSS score. Conventional (T1- and T2-weighted images) and non-conventional (magnetization transfer images, proton magnetic resonance spectroscopy) MRI techniques were performed in all participants. Parameters from both techniques were compared between LOMS and TOMS groups. RESULTS: Patients with late onset of MS had lower Brain Parenchyma Fraction (BPF) (p < 0.001) and Grey Matter Fraction (GMF) values (p = 0.008) than the TOMS group. There was no statistical differences in White Matter Fraction (WMF) values between the groups (p = 0.572). Patients with LOMS and TOMS statistically differed in the peak height (p = 0.018), peak location (p < 0.001), and MTR mean value (p < 0.001). Patients with LOMS manifested lower concentrations of NAA+NAAG and NAA+NAAG/Cr than patients with TOMS (p = 0.009 and p < 0.001 respectively). No statistical difference was found between the groups in terms of mean mIn (p = 0.346) and mean GPC+PCh (p = 0.563). We did not find a statistical difference in T1- and T2- lesion load (p = 0.1, p = 0.3 respectively) although T1/T2 lesion ratio was higher in the LOMS group. CONCLUSION AND CLINICAL IMPLICATIONS: MRI parameters in patients with LOMS differed significantly from those obtained from the TOMS group. Our results, which indicate that in LOMS patients brain tissue damage is more advanced than in TOMS patients, may contribute to a better understanding of the heterogeneity of MS.

Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

Horizontal Gaze Palsy and Ipsilateral Facial Nerve Palsy in Older Patient as Initial Manifestation of Very Late-Onset Multiple Sclerosis Successfully Treated with Oral Corticosteroids: A Case Report.

Introduction: Multiple sclerosis (MS) is a demyelinating condition of the central nervous system (CNS) that primarily affects young adults. Very late-onset multiple sclerosis (VLOMS) is an uncommon form of MS, accounting for only 0.5 percent of all MS patients. Eye movement impairments such as internuclear ophthalmoplegia are common in MS, while horizontal gaze palsy is an uncommon occurrence. Case Presentation: We report a case of a patient diagnosed with VLOMS who presented with left horizontal gaze palsy and ipsilateral facial nerve palsy. Brain magnetic resonance imaging showed Dawson's fingers in the left and right periventricular white matter; multiple small, round, hyperintense lesions in the left and right cortex and juxtacortical cerebellar hemisphere; and small hyperintense lesion in the left paramedian pontine reticular formation, suggesting the diagnosis of MS. Oral corticosteroids led to complete resolution of ocular movement and ipsilateral facial nerve palsy. Conclusion: We propose that neuroimaging should be performed in ophthalmoplegia with a pattern representing CNS lesion and oral corticosteroids may be an effective alternative to high-cost intravenous corticosteroids.

Comparative analysis of cognitive and physical characteristics in late-onset, adult-onset and early-onset multiple sclerosis patients.

BACKGROUND: Late-onset multiple sclerosis (LOMS or L; MS) and early-onset MS (EOMS or E) are less common, and their prognosis can be different. To characterize the demographic and clinical features, and clinical outcomes of LOMS and EOMS patients, comparing them to adult-onset MS (AOMS or A) patients. METHODS: The study was conducted as a secondary analysis of a prospective study. The participants were divided into three groups according to age of MS onset: early onset (<18 years of age), adult-onset (20-40 years of age), and late-onset (>55 years of age). Demographic variables, oligoclonal bands, IgG index, and Expanded Disability Status Scale (EDSS) score in admission, first year, second year and current EDSS were evaluated. The Timed 25-Foot Walk Test (T25FW), Timed Up and Go (TUG), Multiple Sclerosis Walking Scale-12, Single Leg Standing Test, Activity-Specific Balance Confidence Scale, Nine-Hole Peg Test, Epworth Sleepiness Scale and Restless Legs Syndrome Severity Scale were performed. Appropriate statistical analysis was made. RESULTS: A total of 658 pwMS was included in the study and divided into three groups: EOMS (n = 117), AOMS (n = 499), and LOMS (n = 42). Statistically significant differences were determined between groups in terms of age [L (mean:59.86±5.45 years-y-)> A (36.87±9.12 y)> E(26.56±8.85 y), p < 0.001], education level, current EDSS score (L > E, p < 0.001), EDSS score in first admission, EDSS score in the first year, EDSS score in the second year (L > A > E, p < 0.001), reached an EDSS score 6 (E > L p = 0.001, E > A p = 0.015), disease duration (E > A, E > L, mean E = 11.66±9.7 y, A = 7.99±7.4 y, L = 6.31±4.67 y) time switching second-line treatment to the third line (E > L p < 0.001, A > L p = 0.002, mean E = 171.73±83.29 months-m-, A = 136.13±65.75 m, L = 65.85±45.96 m), number of relapses (A > E > L, median E = 4.0, A = 3.0, L = 2.0), distribution of MS type and oligoclonal band types. Significant differences were found in T25FW and TUG. Post-hoc analysis showed that participants in the LOMS group have longer T25FW (mean L = 7.8 ± 6.11, A = 6.25±5.09, E = 5.72±3.13, p = 0.011) and TUG (mean L = 11.01±5.53, A = 9.57±8.04, E = 8.38±5.51, p = 0.007) times than the AOMS and EOMS groups. CONCLUSION: Our result revealed that individuals with LOMS face elevated disability levels and a heightened propensity to transition from first-line treatments to more advanced therapeutic interventions. LOMS have worse lower extremity functional status than AOMS and EOMS patient. Clinical evaluations and treatment choices require more attention in LOMS. However, according to the low number of LOMS in our cohort, these results were considered cautious, and more wide and multi-center studies must be designed.

Challenges in Diagnosis and Therapeutic Strategies in Late-Onset Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative demyelinating disease of the central nervous system of unknown etiology, which affects individuals in their early adulthood. However, nearly 5-10% of people with MS can be diagnosed at ages above 50 years old, referred to as late-onset multiple sclerosis (LOMS). Some studies have reported a distinctive presentation, clinical course, and prognosis for LOMS, implicating a different diagnostic and therapeutic approach for this population. Furthermore, similar manifestations between LOMS and other age-related conditions may lead to potential misdiagnosis and diagnostic delays, and a higher burden of multimorbidity associated with aging can further complicate the clinical picture. This review aims to explore the clinical characteristics, the disease course, and the differential diagnosis of LOMS and addresses therapeutic considerations for this population.

Management of multiple sclerosis in older adults: review of current evidence and future perspectives.

IMPORTANCE: The prevalence of multiple sclerosis (MS) and aging MS patients is increasing worldwide. There is a need to better understand this MS sub-population, which historically is underrepresented in the literature. This narrative review examines the evolving demographics, disease course, and treatments for older adults with MS (OAMS) to address current knowledge gaps and highlight areas critical for future research. OBSERVATIONS: OAMS populations require special consideration by clinicians. Older individuals have different care needs than individuals with adult onset MS who are mid-life or younger. Comorbidities, an aging immune system, increasing neurodegeneration, decreasing neurologic reserve, changing benefit/risk relationship for disease modifying therapies (DMTs), and wellness require special attention to provide holistic comprehensive care. Active areas of research include potential cessation of DMTs and novel disease targets. CONCLUSIONS AND RELEVANCE: This review highlights both the current knowledge and information gaps in the literature that are critical to understanding and properly managing OAMS. The aims are to inform MS clinicians in their current practice, as well as inspire future studies which are critical to providing quality and evidence-based care for OAMS.