Maria Steenhof1, Egon Stenager2, Nete Munk Nielsen3, Kirsten Kyvik4, Sören Möller4, Jens Michael Hertz5. 1. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark; Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark; Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark. Electronic address: maria.steenhof@rsyd.dk. 2. Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark; Department of Regional Health Research, University of Southern Denmark, Denmark; MS Clinics of Southern Jutland (Sønderborg, Esbjerg, Kolding), Hospital of Southern Jutland, Sønderborg, Denmark. 3. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. 4. Department of Clinical Research, University of Southern Denmark, Denmark; Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark. 5. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Denmark.
Abstract
BACKGROUND: The diagnosis of multiple sclerosis (MS) is still complicated despite improvement in diagnostic guidelines. This means that time from first symptom to diagnosis in some cases is prolonged. Many aspects of MS aetiology are unknown, but the involvement of a genetic component is well established. This is also highlighted by the occurrence of familial MS cases, which represent 10-20% of all MS cases. We hypothesize that subsequent family members in a MS family, have a shorter time from onset of disease to diagnosis compared to sporadic MS cases. To investigate this, we have conducted a register study comparing time from onset to diagnosis in familial and sporadic MS cases. METHODS: This is a nationwide register study based on information from the Danish Multiple Sclerosis Registry and the Danish Civil Registration System. We included familial (first-degree relatives) and sporadic MS cases and calculated time lag between onset and diagnosis of MS for sporadic MS cases and for1st, 2nd and 3rd family members within the MS families. Median test and Cox regression were the statistical methods used to compare the familial and sporadic groups. RESULTS: We found that 2nd and 3rd affected family member had a significant shorter time from first symptom to diagnosis compared to sporadic MS cases (2nd family member: Hazard Ratio (HR): 1.12, CI: 1.03-1.21, p = 0.007 adjusted: HR: 0.95 p = 0.22, CI 0.89-1-03 and 3rd family member HR: 1.64 CI: 1.22-2.20, p = 0.001 adjusted model: HR: 1.70, p-value: 0.000, CI: 1.32-2.18). The same difference was not seen between 1st family members and sporadic cases (HR: 1.05, CI: 0.98-1.13, p = 0.15, adjusted: 0.98, p-value: 0.53, CI: 0.91-1.05). Estimated marginal mean delay in the four groups were 4.60 years (95% CI: 4.11-5.01) in1st family members, 4.23 years (3.71-4.75) in 2nd family members, 2.11 years (0.95-3.26) in 3rd family members and 4.99 years (4.99-4.99) in sporadic MS cases. CONCLUSION: The 2nd and 3rd family members in MS families tend do get diagnosed faster than sporadic cases. This has implications in the diagnostic process of familial MS cases.
BACKGROUND: The diagnosis of multiple sclerosis (MS) is still complicated despite improvement in diagnostic guidelines. This means that time from first symptom to diagnosis in some cases is prolonged. Many aspects of MS aetiology are unknown, but the involvement of a genetic component is well established. This is also highlighted by the occurrence of familial MS cases, which represent 10-20% of all MS cases. We hypothesize that subsequent family members in a MS family, have a shorter time from onset of disease to diagnosis compared to sporadic MS cases. To investigate this, we have conducted a register study comparing time from onset to diagnosis in familial and sporadic MS cases. METHODS: This is a nationwide register study based on information from the Danish Multiple Sclerosis Registry and the Danish Civil Registration System. We included familial (first-degree relatives) and sporadic MS cases and calculated time lag between onset and diagnosis of MS for sporadic MS cases and for1st, 2nd and 3rd family members within the MS families. Median test and Cox regression were the statistical methods used to compare the familial and sporadic groups. RESULTS: We found that 2nd and 3rd affected family member had a significant shorter time from first symptom to diagnosis compared to sporadic MS cases (2nd family member: Hazard Ratio (HR): 1.12, CI: 1.03-1.21, p = 0.007 adjusted: HR: 0.95 p = 0.22, CI 0.89-1-03 and 3rd family member HR: 1.64 CI: 1.22-2.20, p = 0.001 adjusted model: HR: 1.70, p-value: 0.000, CI: 1.32-2.18). The same difference was not seen between 1st family members and sporadic cases (HR: 1.05, CI: 0.98-1.13, p = 0.15, adjusted: 0.98, p-value: 0.53, CI: 0.91-1.05). Estimated marginal mean delay in the four groups were 4.60 years (95% CI: 4.11-5.01) in1st family members, 4.23 years (3.71-4.75) in 2nd family members, 2.11 years (0.95-3.26) in 3rd family members and 4.99 years (4.99-4.99) in sporadic MS cases. CONCLUSION: The 2nd and 3rd family members in MS families tend do get diagnosed faster than sporadic cases. This has implications in the diagnostic process of familial MS cases.