TY - JOUR
T1 - Cervical spinal cord atrophy
T2 - An earlymarker of progressiveMSonset
AU - Zeydan, Burcu
AU - Gu, Xinyi
AU - Atkinson, Elizabeth J.
AU - Keegan, B. Mark
AU - Weinshenker, Brian G.
AU - Tillema, Jan Mendelt
AU - Pelletier, Daniel
AU - Azevedo, Christina J.
AU - Lebrun-Frenay, Christine
AU - Siva, Aksel
AU - Okuda, Darin T.
AU - Kantarci, Kejal
AU - Kantarci, Orhun H.
N1 - Funding Information:
The Article Processing Charge was funded by the Mayo Clinic.
Funding Information:
B. Zeydan received support from the Turkish Neurological Society. X. Gu reports no disclosures. E.J. Atkison received research support from Biogen and NIA. B.M. Keegan serves on the editorial board of Multiple Sclerosis and Related Disorders; receives publishing royalties from Cambridge University Press; consulted for Novartis, Bristol-Myers Squibb, and Bioness; and receives research funding from Biogen Pharmaceuticals. B.G. Weinshenker served on the scientific advisory board of Novartis and Mitsubishi; served on the editorial board of Canadian Journal of Neurological Sciences,TurkishJournalofNeurology,andNeurology®; holds patent for and receives royalties from a NMO-IG for diagnosis of neuromyelitis optica; consulted for Caladrius and BrainStorm Cell Therapeutics; is an adjudication committee member of MedImmune pharmaceuticals and Alexion Pharmaceuticals; and received research support from the Guthy-Jackson Charitable Foundation. J.-M. Tillema receives research support from the NCATS/NIH. D. Pelletier consulted for Biogen, EMD Serono, Sanofi Genzyme, Novartis, Hoffman La Roche, and Actelion and received research support from the National Multiple Sclerosis Society. C.J. Azevedo served on the scientific advisory board of Genzyme, Guerbet, Genentech, and Biogen and received research support from the University of Southern California Clinical and Translational Science Institute and the Race to Erase MS Foundation. C. Lebrun-Frenay served on the scientific advisory board of Biogen, Novartis, Merck, Genzyme, TEVA, and Roche; received travel funding and/or speaker honoraria from Biogen, Merck, Genzyme, and Roche; served on the editorial board of Revue Neurologique; and received research support from the French MS Society (SFSEP) EDMUS (OFSEP Center) Foundation. A. Siva received travel funding from Merck Serono, Biogen Idec/Gen Pharma of Turkey, Novartis, Sanofi Genzyme, Roche, and TEVA; served on the editorial board of Journal of the Neurological Sciences, Journal of Headache and Pain, and Turkish Neurological Journal; consulted for Biogen IDEC, Novartis, Merck Serono, Bayer, TEVA, Sanofi Genzyme, and Roche; served on the speakers’ bureau of EXCEMED, Sanofi Genzyme, Merck Serono, Biogen Idec/ Gen Pharma of Turkey, and TEVA; and received research support from The Scientific and Technological Research Council of Turkey. D.T. Okuda received travel funding and speaker honoraria from Acorda Therapeutics, Genentech, Genzyme, and TEVA; holds patents for Methods, Apparatuses, and Systems for Creating 3-Dimensional Representations Exhibiting Geometric and Surface Characteristics of Brain Lesions, System and method for medical surveillance through personal communication device; consulted for Celgene, Bayer, EMD Serono, Genzyme, and Novartis; and served on the speakers’ bureau of Acorda Therapeutics, Genzyme, and TEVA. K. Kantarci served on the data safety monitoring board of Takeda Global Research & Development Center, Pfizer Inc., and Janssen Alzheimer Immunotherapy and received research support from the NIH and Minnesota Partnership for Biotechnology and Medical Genomics. O.H. Kantarci received speaker honoraria (paid to Mayo Clinic) from Novartis and Biogen; performed a grant review for The National Multiple Sclerosis Society; and received research support from Biogen, the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation. Go to Neurology.org/nn for full disclosure forms.
Publisher Copyright:
Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Objective To assess whether cervical spinal cord atrophy heralds the onset of progressive MS. Methods We studied 34 individuals with radiologically isolated syndrome (RIS) and 31 patients with relapsing-remitting MS (RRMS) age matched to 25 patients within a year of onset of secondary progressive MS (SPMS). Two raters independently measured (twice per rater) the cervical spinal cord average segmental area (CASA) (mm2) of axial T2-weighted images between C2 and C7 landmarks. The midsagittal T2-weighted image from the end of C2 to the end of C7 vertebra was used to measure the cervical spine (c-spine) length (mm). Sex, age at cervical MRI, number and location of cervical spinal cord lesions, c-spine length, and diagnoses were analyzed against the outcome measures of CASA and C2 and C7 slice segmental areas. Results Intrarater and interrater agreement was excellent (intraclass correlation coefficient >0.97). The CASA area (p = 0.03) and C7 area (p = 0.002) were smaller in SPMS compared with RRMS. The C2 area (p = 0.027), CASA (p = 0.004), and C7 area (p = 0.003) were smaller in SPMS compared with RIS. The C2 area did not differ between SPMS and RRMS (p = 0.09). The C2 area (p = 0.349), CASA (p = 0.136), and C7 area (p = 0.228) did not differ between RIS and MS (SPMS and RRMS combined). In the multivariable model, ≥2 cervical spinal cord lesions were associated with the C2 area (p = 0.008), CASA (p = 0.009), and C7 area independent of disease course (p = 0.017). Progressive disease course was associated with the C7 area independent of the cervical spinal cord lesion number (p = 0.004). Conclusion Cervical spinal cord atrophy is evident at the onset of progressive MS and seems partially independent of the number of cervical spinal cord lesions. Classification of evidence This study provides Class III evidence that MRI cervical spinal cord atrophy distinguishes patients at the onset of progressive MS from those with RIS and RRMS.
AB - Objective To assess whether cervical spinal cord atrophy heralds the onset of progressive MS. Methods We studied 34 individuals with radiologically isolated syndrome (RIS) and 31 patients with relapsing-remitting MS (RRMS) age matched to 25 patients within a year of onset of secondary progressive MS (SPMS). Two raters independently measured (twice per rater) the cervical spinal cord average segmental area (CASA) (mm2) of axial T2-weighted images between C2 and C7 landmarks. The midsagittal T2-weighted image from the end of C2 to the end of C7 vertebra was used to measure the cervical spine (c-spine) length (mm). Sex, age at cervical MRI, number and location of cervical spinal cord lesions, c-spine length, and diagnoses were analyzed against the outcome measures of CASA and C2 and C7 slice segmental areas. Results Intrarater and interrater agreement was excellent (intraclass correlation coefficient >0.97). The CASA area (p = 0.03) and C7 area (p = 0.002) were smaller in SPMS compared with RRMS. The C2 area (p = 0.027), CASA (p = 0.004), and C7 area (p = 0.003) were smaller in SPMS compared with RIS. The C2 area did not differ between SPMS and RRMS (p = 0.09). The C2 area (p = 0.349), CASA (p = 0.136), and C7 area (p = 0.228) did not differ between RIS and MS (SPMS and RRMS combined). In the multivariable model, ≥2 cervical spinal cord lesions were associated with the C2 area (p = 0.008), CASA (p = 0.009), and C7 area independent of disease course (p = 0.017). Progressive disease course was associated with the C7 area independent of the cervical spinal cord lesion number (p = 0.004). Conclusion Cervical spinal cord atrophy is evident at the onset of progressive MS and seems partially independent of the number of cervical spinal cord lesions. Classification of evidence This study provides Class III evidence that MRI cervical spinal cord atrophy distinguishes patients at the onset of progressive MS from those with RIS and RRMS.
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U2 - 10.1212/NXI.0000000000000435
DO - 10.1212/NXI.0000000000000435
M3 - Article
C2 - 29435472
AN - SCOPUS:85044256849
SN - 2332-7812
VL - 5
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 2
M1 - e435
ER -