Analysis of T2 Intensity by Magnetic Resonance Imaging of Deep Gray Matter Nuclei in Multiple Sclerosis Patients

Effect of Immunomodulatory Therapies

Siddharama Pawate, Lily Wang, Yanna Song, Subramaniam Sriram

Research output: Contribution to journalArticle

9 Citations (Scopus)

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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalJournal of Neuroimaging
Volume22
Issue number2
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Immunomodulation
Multiple Sclerosis
Red Nucleus
Magnetic Resonance Imaging
Cerebellar Nuclei
Globus Pallidus
Substantia Nigra
Interferon-beta
Linear Models
Mycophenolic Acid
Therapeutics
Gray Matter
Brain
Nonparametric Statistics
Immunotherapy
Atrophy
Natalizumab
Anti-Inflammatory Agents
Iron
Prospective Studies

Keywords

  • Black T2
  • Magnetic resonance imaging
  • T2 hypointensity

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology

Cite this

Analysis of T2 Intensity by Magnetic Resonance Imaging of Deep Gray Matter Nuclei in Multiple Sclerosis Patients : Effect of Immunomodulatory Therapies. / Pawate, Siddharama; Wang, Lily; Song, Yanna; Sriram, Subramaniam.

In: Journal of Neuroimaging, Vol. 22, No. 2, 01.04.2012, p. 137-144.

Research output: Contribution to journalArticle

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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). Conclusion: 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.",
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N2 - 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). Conclusion: 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.

AB - 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). Conclusion: 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.

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