TY - JOUR
T1 - Long-term clinical, MRI, and cognitive follow-up in a large cohort of pathologically confirmed, predominantly tumefactive multiple sclerosis
AU - Kalinowska-Lyszczarz, Alicja
AU - Tillema, Jan Mendelt
AU - Tobin, W. Oliver
AU - Guo, Yong
AU - Fitz-Gibbon, Patrick D.
AU - Weigand, Stephen D.
AU - Giraldo-Chica, Monica
AU - Port, John D.
AU - Lucchinetti, Claudia F.
N1 - Funding Information:
The authors recognize and acknowledge the major contribution of their colleague Dr. Istvan Pirko, who passed away during the course of this study; Dr. Istvan Pirko was instrumental in the design of the study. The authors wish to also acknowledge the Mayo Center for MS and Autoimmune Disease; the Eugene and Marcia Applebaum Professorship in support of C.F.L.; Patricia Ziemer for expert technical assistance with pathology; Linda Linbo, RN, Jessica Sagen, MS, and Mandie Maroney-Smith for managing the imaging protocol and scheduling research subjects; and Peter Kollasch for his guidance in helping to configure the sequences on our MRI scanners. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from Novartis (CFTY720DUS37; CFL), NIH (R01 NS 49577-6; CFL), National Multiple Sclerosis Society (RG3185-B-3; CFL), National Center for Advancing Translational Sciences (KL2TR000136; JMT), and Department of Defense (W81XWH-13-1-0098; JDP). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.K.-L. received grant funding from Novartis and received compensation for speaking and consulting services from Biogen, Bayer, Novartis, Roche, Merck, Teva, CSL Behring, Shire, and Sanofi-Genzyme. None of the consulting agreements are relevant to the submitted work. J.-M.T. received grant support from NIH and National MS Society during the course of the study. W.O.T. received grant support from Mallinckrodt Pharmaceuticals and from the Mayo Clinic Center for MS and Autoimmune Neurology. Y.G., M.G.-C., S.D.W., and P.D.F.-G. report no financial disclosures or potential conflicts of interest. J.D.P. received grant support from DOD during the study and is an imaging consultant for Bioclinica. The consulting agreement is not relevant to the submitted work. C.F.L. received grant funding from Mallinckrodt, Biogen, Novartis, and the National Multiple Sclerosis Society.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from Novartis (CFTY720DUS37; CFL), NIH (R01 NS 49577-6; CFL), National Multiple Sclerosis Society (RG3185-B-3; CFL), National Center for Advancing Translational Sciences (KL2TR000136; JMT), and Department of Defense (W81XWH-13-1-0098; JDP). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Publisher Copyright:
© The Author(s), 2021.
PY - 2022/3
Y1 - 2022/3
N2 - Background: Limited studies have described long-term outcomes in pathology confirmed multiple sclerosis (MS). Objectives: To describe long-term clinical–radiographic–cognitive outcomes in a prospectively followed cohort of patients with pathologically confirmed CNS demyelinating disease, consistent with MS. Methods: Subjects underwent clinical assessment, standardized 3T-MRI brain, and cognitive battery. Results: Seventy-five patients were included. Biopsied lesion size was ⩾ 2 cm in 62/75. At follow-up, median duration since biopsy was 11 years. Median EDSS was 3 and lesion burden was large (median 10 cm3). At follow-up, 57/75 met MS criteria, 17/75 had clinically isolated syndrome, and 1 radiographic changes only. Disability scores were comparable to a prevalence cohort in Olmsted County (p < 0.001, n = 218). Cognitive outcomes below age-normed standards included psychomotor, attention, working memory, and executive function domains. Total lesion volume and index lesion-related severity correlated with EDSS and cognitive performance. Volumetric cortical/subcortical GM correlated less than lesion metrics to cognitive outcomes. Conclusion: Despite early aggressive course in pathologically confirmed MS, its long-term course was comparable to typical MS in our study. Cognitive impairment in this group seemed to correlate strongest to index lesion severity and total lesion volume. It remains to be established how the aggressive nature of the lesion, biopsy, and treatment affect clinical/cognitive outcomes.
AB - Background: Limited studies have described long-term outcomes in pathology confirmed multiple sclerosis (MS). Objectives: To describe long-term clinical–radiographic–cognitive outcomes in a prospectively followed cohort of patients with pathologically confirmed CNS demyelinating disease, consistent with MS. Methods: Subjects underwent clinical assessment, standardized 3T-MRI brain, and cognitive battery. Results: Seventy-five patients were included. Biopsied lesion size was ⩾ 2 cm in 62/75. At follow-up, median duration since biopsy was 11 years. Median EDSS was 3 and lesion burden was large (median 10 cm3). At follow-up, 57/75 met MS criteria, 17/75 had clinically isolated syndrome, and 1 radiographic changes only. Disability scores were comparable to a prevalence cohort in Olmsted County (p < 0.001, n = 218). Cognitive outcomes below age-normed standards included psychomotor, attention, working memory, and executive function domains. Total lesion volume and index lesion-related severity correlated with EDSS and cognitive performance. Volumetric cortical/subcortical GM correlated less than lesion metrics to cognitive outcomes. Conclusion: Despite early aggressive course in pathologically confirmed MS, its long-term course was comparable to typical MS in our study. Cognitive impairment in this group seemed to correlate strongest to index lesion severity and total lesion volume. It remains to be established how the aggressive nature of the lesion, biopsy, and treatment affect clinical/cognitive outcomes.
KW - Multiple sclerosis (MS)
KW - biopsy-confirmed multiple sclerosis
KW - magnetic resonance imaging (MRI)
KW - neuropsychological assessment
KW - tumefactive demyelinating lesions
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U2 - 10.1177/13524585211024162
DO - 10.1177/13524585211024162
M3 - Article
C2 - 34212755
AN - SCOPUS:85109139931
SN - 1352-4585
VL - 28
SP - 441
EP - 452
JO - Multiple Sclerosis
JF - Multiple Sclerosis
IS - 3
ER -