title: Phase white matter signal abnormalities in patients with clinically isolated syndrome and other neurologic disorders.
abstract: OBJECTIVE
  Identifying MRI biomarkers that can differentiate multiple sclerosis patients from other neurological disorders is a subject of intense research. Our aim was to investigate phase WM signal abnormalities for their presence, prevalence, location, and diagnostic value among patients with clinically isolated syndrome and other neurologic disorders and age-, sex-, and group-matched healthy controls.
  
  
  METHODS
  Forty-eight patients with clinically isolated syndrome and 30 patients with other neurologic diseases and a healthy control group (n = 47) were included in the study. Subjects were scanned at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities ≥3 mm being classified.
  
  
  RESULTS
  Patients with clinically isolated syndrome had significantly more phase and T2 WM signal abnormalities than healthy controls (P < .001). Phase WM signal abnormalities were more prevalent among patients with clinically isolated syndrome compared with patients with other neurologic disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity for differentiating patients with clinically isolated syndrome and healthy controls, patients with other neurologic disorders, and patients with other neurologic disorders of other autoimmune origin (specificity, 70%-76.7%). Combining the presence of ≥2 phase lesions with the McDonald 2005 and 2010 criteria for dissemination in space improved the specificity (90%), but not the accuracy, in differentiating patients with clinically isolated syndrome from those with other neurologic disorders. In subanalyses among patients with clinically isolated syndrome who converted to clinically definite multiple sclerosis versus those who did not within a 3-year follow-up period, converters had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities.
  
  
  CONCLUSIONS
  Phase WM signal abnormalities are prevalent among patients with clinically isolated syndrome. The presence of (multiple) phase WM signal abnormalities tended to be more predictive of conversion to clinically definite multiple sclerosis and was specific in differentiating patients with clinically isolated syndrome and other neurologic disorders, compared with T2 WM signal abnormalities; however, the accuracy remains similar to that of the current McDonald criteria.
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.).
authors.forename: J
authors.initials: J
authors.lastname: Hagemeier
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.).
authors.forename: M
authors.initials: M
authors.lastname: Heininen-Brown
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.) Department of Neurology (T. Gabelic), Referral Centre for Demyelinating Disease of the Central Nervous System, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Gabelic
authors.affiliation: Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York.
authors.forename: T
authors.initials: T
authors.lastname: Guttuso
authors.affiliation: Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York.
authors.forename: N
authors.initials: N
authors.lastname: Silvestri
authors.affiliation: Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York.
authors.forename: D
authors.initials: D
authors.lastname: Lichter
authors.affiliation: Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York.
authors.forename: L E
authors.initials: LE
authors.lastname: Fugoso
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.) Istituto Di Ricovero e Cura a Carattere Scientifico (N.B.), Don Gnocchi Foundation, Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.).
authors.forename: E
authors.initials: E
authors.lastname: Carl
authors.affiliation: Department of Anatomy and Neurosciences (J.J.G.G.), Section of Clinical Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: J J G
authors.initials: JJ
authors.lastname: Geurts
authors.affiliation: Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York.
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (J.H., M.H.-B., T. Gabelic, N.B., E.C., R.Z.) Baird MS Center (T. Guttuso, N.S., D.L., L.E.F., B.W.-G., R.Z.), Department of Neurology, University at Buffalo, Buffalo, New York rzivadinov@bnac.net.
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000328:Adult; D000368:Aged; D003711:Demyelinating Diseases / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D049292:Leukoaraiosis / Q000175:diagnosis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis; D015995:Prevalence; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology*