BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.
BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS:Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.
Authors: O H Kantarci; D D Hebrink; S J Achenbach; S J Pittock; A Altintas; J L Schaefer-Klein; E J Atkinson; M De Andrade; C T McMurray; M Rodriguez; B G Weinshenker Journal: Neurology Date: 2004-03-09 Impact factor: 9.910
Authors: S J Pittock; W T Mayr; R L McClelland; N W Jorgensen; S D Weigand; J H Noseworthy; B G Weinshenker; M Rodriguez Journal: Neurology Date: 2004-01-13 Impact factor: 9.910
Authors: A J Thompson; A G Kermode; D Wicks; D G MacManus; B E Kendall; D P Kingsley; W I McDonald Journal: Ann Neurol Date: 1991-01 Impact factor: 10.422
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Authors: M Mateo Paz Soldán; Martina Novotna; Nuhad Abou Zeid; Nilufer Kale; Melih Tutuncu; Daniel J Crusan; Elizabeth J Atkinson; Aksel Siva; B Mark Keegan; Istvan Pirko; Sean J Pittock; Claudia F Lucchinetti; Brian G Weinshenker; Moses Rodriguez; Orhun H Kantarci Journal: Neurology Date: 2014-11-14 Impact factor: 9.910
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Authors: Kristen M Krysko; Roland G Henry; Bruce A C Cree; Jue Lin; Stacy Caillier; Adam Santaniello; Chao Zhao; Refujia Gomez; Carolyn Bevan; Dana L Smith; William Stern; Gina Kirkish; Stephen L Hauser; Jorge R Oksenberg; Jennifer S Graves Journal: Ann Neurol Date: 2019-10-02 Impact factor: 10.422
Authors: Martina Novotna; M Mateo Paz Soldán; Nuhad Abou Zeid; Nilufer Kale; Melih Tutuncu; Daniel J Crusan; Elizabeth J Atkinson; Aksel Siva; B Mark Keegan; Istvan Pirko; Sean J Pittock; Claudia F Lucchinetti; John H Noseworthy; Brian G Weinshenker; Moses Rodriguez; Orhun H Kantarci Journal: Neurology Date: 2015-07-24 Impact factor: 9.910
Authors: Josa M Frischer; Stephen D Weigand; Yong Guo; Nilufer Kale; Joseph E Parisi; Istvan Pirko; Jay Mandrekar; Stephan Bramow; Imke Metz; Wolfgang Brück; Hans Lassmann; Claudia F Lucchinetti Journal: Ann Neurol Date: 2015-08-24 Impact factor: 10.422
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