Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases

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Resumé

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.

OriginalsprogEngelsk
TidsskriftMultiple Sclerosis and Related Disorders
Vol/bind32
Sider (fra-til)97-102
ISSN2211-0348
DOI
StatusUdgivet - 1. jul. 2019

Fingeraftryk

Proportional Hazards Models
Registries
Regression Analysis
Guidelines

Citer dette

@article{0bae2a0bbde445c293d691e4e585baf9,
title = "Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases",
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.",
keywords = "Delay in diagnosis, Disease onset, Familial multiple sclerosis, Multiple sclerosis",
author = "Maria Steenhof and Egon Stenager and Nielsen, {Nete Munk} and Kirsten Kyvik and S{\"o}ren M{\"o}ller and Hertz, {Jens Michael}",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.msard.2019.04.012",
language = "English",
volume = "32",
pages = "97--102",
journal = "Multiple Sclerosis and Related Disorders",
issn = "2211-0348",
publisher = "Elsevier",

}

TY - JOUR

T1 - Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases

AU - Steenhof, Maria

AU - Stenager, Egon

AU - Nielsen, Nete Munk

AU - Kyvik, Kirsten

AU - Möller, Sören

AU - Hertz, Jens Michael

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - Delay in diagnosis

KW - Disease onset

KW - Familial multiple sclerosis

KW - Multiple sclerosis

U2 - 10.1016/j.msard.2019.04.012

DO - 10.1016/j.msard.2019.04.012

M3 - Journal article

VL - 32

SP - 97

EP - 102

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

ER -