Background

Background:

Multiple Sclerosis (MS) clearly results from complex interactions between genetic and environmental factors. Most MS cases are sporadic. However, familial cases were reported, ranging between 2% and 32.7% of patients with MS. Nowadays, it’s still unclear whether heredity affects the phenotype and severity of the disease.

Objectives

Our aim was to compare clinical and outcome characteristics of MS between familial from and sporadic form to evaluate the imapct of heredity in the disease phenotype and course

Methods

We conducted a retrospective study including MS patients followed in the Department of Neurology in Razi hospital (Tunis, Tunisia). We identified two groups: Familial MS (fMS) with history of first or second degree relative affected by MS and sporadic MS (sMS) with no family history of MS. Clinical characteristics were analyzed from a local MS database. Disability assessment was based on expanded disability status scale (EDSS). Multiple Sclerosis Severity Score (MSSS) was calculated using conversion table based on EDSS score and duration of disease in years.

Results

We included 55 fMS patients and 459 sporadic cases. MS patients with familial form had an older age at onset compared to sMS group (31.6 versus 29.9; p = 0.03). Relapsing form were predominant in the 2 groups (87.6% in group 1 and 78.3% in group 2; p= 0.131). First relapses were more often sensory (41% versus 34%, p= 0.3) and visual (34% versus 26%, p= 0.23) in the fMS. Annual relapse rate was comparable in the 2 groups (0.8 versus 0.86; p=0.5). Mean EDSS scores were lower in the familial MS group at first evaluation (p=0.1), at 3 years (p=0.34) and 5 years (p=0.25) after disease onset. Mean time to reach EDSS 3 and EDSS 6 was longer in the familial form compared to the sporadic form (respectively {9.3 versus 8.7; p= 0.85} {18.4 versus 10.8; p= 0.02}). MSSS scores were similar in the 2 groups (5.16 versus 5.25 ; p=0.83).

Conclusions

We found an older age at onset and a less aggressive disease outcome in fMS compared to sMS. Interestingly, these findings confirm the substantial differences between familial and sporadic forms also in this North African population. However, they are in contrast with previous Caucasians and Latin American studies.

Background

Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS.

Objectives

We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016).

Methods

Inclusion required adult-onset progressive MS; ≥ 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS ≤ 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if ≥ 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over ≥ 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS ≥ 7 (wheelchair required) was assessed (Kaplan-Meier).

Results

5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 ± 10.2, vs. 41.5 ± 10.7 [mean ± SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78–0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98–0.99); and higher in males (1.18; 1.12–1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71–0.87) but similar for PPMS-A (1.01; 0.93–1.10) and SPMS-N (0.94; 0.85–1.05). Sensitivity analyses corroborated these results. However, patients with SPMS-A reached EDSS ≥ 7 at younger ages (cumulative probability 30% by 57, vs. 64–66 for SPMS-N, PPMS-A, PPMS-N).

Conclusions

Progressive phase onset is later in SPMS than PPMS. Hazard of disability accrual during the progressive phase is lower in SPMS than PPMS. However, patients with SPMS-A reach wheelchair requirement younger than other progressive phenotypes, reflecting earlier progression onset versus SPMS-N, and greater disability at onset versus PPMS