title: Analysis of T2 intensity by magnetic resonance imaging of deep gray matter nuclei in multiple sclerosis patients: effect of immunomodulatory therapies.
abstract: OBJECTIVE
  To investigate differences in T2 intensity of deep gray matter (dGM) structures by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients undergoing various immunomodulatory therapies.
  
  
  BACKGROUND
  In MS, dGM T2 hypointensities by MRI are hypothesized to represent iron deposition and are known to be associated with worse disease stage as assessed by brain atrophy, cognitive and physical disability. The relation between immunotherapies and T2 intensity, however, has been not been investigated in detail.
  
  
  METHODS
  A total of 255 MS patients were stratified into those on no treatment (NON, n= 45), and those on immunomodulatory treatments for ≥6 months (ie, interferon beta [IFNβ]n= 118, glatiramer acetate [GA]n= 41, natalizumab [NAT]n= 39, and mycophenolate mofetil [MMF]n= 12). T2 intensities of dentate nucleus (DN), substantia nigra (SN), red nucleus (RN), and globus pallidus (GP) were measured. Group differences in T2 intensities were assessed using a linear regression model with T2 intensities as outcome variable, treatment group as main independent variable, and clinical measures such as Expanded Disability Status Scale (EDSS) score, years of MS, and 25-feet walk time (T25-FW) as covariates. To compare T2 intensities before and after treatment in a subset of NAT-treated patients, we used the Wilcoxon signed-rank test.
  
  
  RESULTS
  When adjusted for EDSS, duration of disease and T25-FW, across all deep nuclei, NAT-treated patients had significantly higher T2 intensities than untreated patients (DN p= 1.65 × 10(-5) ; SN p= 2.37 × 10(-5) ; RN p= 3.90 × 10(-6) ; GP p= 1.05 × 10(-6) ), IFNβ-treated patients (DN p= 1.65 × 10(-5) ; SN p= 2.37 × 10(-5) ; RN p= 3.90 × 10(-6) ; GP p= 1.05 × 10(-6) ), and GA-treated patients (DN p= 1.65 × 10(-5) ; SN p= 2.37 × 10(-5) ; RN p= 3.90 × 10(-6) ; GP p= 1.05 × 10(-6) ). In a subset of MS patients receiving NAT, there was a significant increase in T2 intensities in all the dGM nuclei after 24 months of treatment (DN p= 0.00021; SN p= <0.0001; RN p= 0.00015; GP p= 0.00011).
  
  
  CONCLUSIONS
  Our preliminary observations suggest that long-term NAT therapy in MS patients may affect T2 intensity levels of dGM brain nuclei, hence suggesting a potential effect of NAT beyond anti-inflammatory effect. Prospective studies are warranted to provide more insights into our preliminary observations.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. siddharama.pawate@vanderbilt.edu
authors.forename: Siddharama
authors.initials: S
authors.lastname: Pawate
authors.forename: Lily
authors.initials: L
authors.lastname: Wang
authors.forename: Yanna
authors.initials: Y
authors.lastname: Song
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sriram
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D002529:Cerebellar Nuclei / Q000187:drug effects* / Q000473:pathology; D005260:Female; D000068717:Glatiramer Acetate; D005917:Globus Pallidus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000069442:Natalizumab; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D012012:Red Nucleus / Q000187:drug effects* / Q000473:pathology; D012189:Retrospective Studies; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D009173:Mycophenolic Acid