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August 25, 2015; 85 (8) Article

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

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
First published July 24, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001856
Martina Novotna
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.
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M. Mateo Paz Soldán
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.
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Nuhad Abou Zeid
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.
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Nilufer Kale
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.
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Melih Tutuncu
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.
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Daniel J. Crusan
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.
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Elizabeth J. Atkinson
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.
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Aksel Siva
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.
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B. Mark Keegan
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.
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Istvan Pirko
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.
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Sean J. Pittock
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.
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Claudia F. Lucchinetti
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.
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John H. Noseworthy
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.
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Brian G. Weinshenker
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.
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Moses Rodriguez
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.
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Orhun H. Kantarci
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.
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Citation
Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis
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
Neurology Aug 2015, 85 (8) 722-729; DOI: 10.1212/WNL.0000000000001856

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This article has a correction. Please see:

  • Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis - October 13, 2015
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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.

GLOSSARY

DMD=
disease-modifying drug;
FSS=
Functional System Scores;
MS=
multiple sclerosis;
PPMS=
primary progressive MS;
RRMS=
relapsing-remitting MS;
SAPMS=
single-attack progressive MS;
SPMS=
secondary progressive MS

Footnotes

  • ↵† Deceased.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received November 17, 2014.
  • Accepted in final form May 5, 2015.
  • © 2015 American Academy of Neurology
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