title: Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome.
abstract: OBJECTIVE
  The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).
  
  
  METHODS
  A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing-remitting MS) and were also compared to two other population- and clinic-based PPMS cohorts.
  
  
  RESULTS
  Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow-up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6-5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow-up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow-up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS.
  
  
  CONCLUSIONS
  Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age-dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
authors.affiliation: Hôpital Pasteur, Service de Neurologie, Nice, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lebrun
authors.affiliation: Department of Neurology, Cerrahpasa School of Medicine, University of Istanbul, Istanbul, Turkey.
authors.forename: Aksel
authors.initials: A
authors.lastname: Siva
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Keegan
authors.affiliation: Department of Neurology, Multiple Sclerosis Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Azevedo
authors.affiliation: Mt. Sinai School of Medicine, New York, NY.
authors.forename: Matilde
authors.initials: M
authors.lastname: Inglese
authors.affiliation: MS Center of Catalunya Cemcat, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Tintoré
authors.affiliation: Department of Neurology & Neurotherapeutics, Clinical Center for Multiple Sclerosis, Multiple Sclerosis and NeuroImmunology Imaging ProgramUniversity of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Braeden D
authors.initials: BD
authors.lastname: Newton
authors.affiliation: Service de Neurologie, Hôpital Neurologique, Bron, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Durand-Dubief
authors.affiliation: Department of Neurology, University of Florence, Florence, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.affiliation: Department of Neurology, Neurosurgery and Behavioral Sciences, University of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.affiliation: Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Department of Neurology, Multiple Sclerosis Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.affiliation: Department of Neurology & Neurotherapeutics, Clinical Center for Multiple Sclerosis, Multiple Sclerosis and NeuroImmunology Imaging ProgramUniversity of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Darin T
authors.initials: DT
authors.lastname: Okuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D012737:Sex Factors; D055815:Young Adult