title: Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS).
  
  
  METHODS
  We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test).
  
  
  RESULTS
  In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse.
  
  
  CONCLUSIONS
  Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Martina
authors.initials: M
authors.lastname: Novotna
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: M Mateo
authors.initials: MM
authors.lastname: Paz Soldán
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Nuhad
authors.initials: N
authors.lastname: Abou Zeid
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Kale
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Melih
authors.initials: M
authors.lastname: Tutuncu
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Crusan
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Aksel
authors.initials: A
authors.lastname: Siva
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: B Mark
authors.initials: BM
authors.lastname: Keegan
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Istvan
authors.initials: I
authors.lastname: Pirko
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: John H
authors.initials: JH
authors.lastname: Noseworthy
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey.
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: From the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology (M.N., M.M.P.S., B.M.K., I.P., S.J.P., C.F.L., J.H.N., B.G.W., M.R., O.H.K.), Department of Neurology, and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Neurology (N.A.Z.), Wake Forest Medical Center, Winston-Salem, NC; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul, Turkey; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey. kantarci.orhun@mayo.edu.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
mesh_terms: D000328:Adult; D017668:Age of Onset; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000503:physiopathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000503:physiopathology; D012008:Recurrence; D012075:Remission, Spontaneous; D013997:Time Factors