scholarly journals Higher EBV response is associated with more severe gray matter and lesion pathology in relapsing multiple sclerosis patients: A case-controlled magnetization transfer ratio study

2019 ◽  
Vol 26 (3) ◽  
pp. 322-332 ◽  
Author(s):  
Dejan Jakimovski ◽  
Murali Ramanathan ◽  
Bianca Weinstock-Guttman ◽  
Niels Bergsland ◽  
Deepa P Ramasamay ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Magnetization Transfer ◽  
Humoral Response ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Transfer Ratio ◽  
Multiple Sclerosis Patients

Background: Epstein–Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS). Objective: To evaluate associations between EBV-specific humoral response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs). Methods: The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini–Hochberg–adjusted p-values < 0.05 were considered significant. Results: MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR ( r = –0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR ( r = –0.524, p = 0.001) and NAGM MTR ( r = –0.308, p = 0.043). These associations were not present in HCs or SPMS patients. Conclusion: Greater EBV humoral response is associated with lower GM MTR changes and focal destructive lesion pathology in RRMS patients.

Emergence of thalamic magnetization transfer ratio abnormality in early relapsing—remitting multiple sclerosis

2005 ◽  
Vol 11 (3) ◽  
pp. 276-281 ◽  
Author(s):  
G R Davies ◽  
D R Altmann ◽  
W Rashid ◽  
D T Chard ◽  
C M Griffin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetization Transfer ◽  
Inverse Correlation ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Transfer Ratio ◽  
Imaging Sequence ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

While there is now evidence for thalamic abnormality in established secondary progressive and relapsing—remitting multiple sclerosis (MS), it remains unclear when such abnormality begins. This study investigated the emergence of thalamic abnormality in relapsing—remitting MS by assessing the thalamic magnetization transfer ratio (MTR) in a cohort with clinically early disease. Twenty-three patients with early relapsing—remitting MS (mean age 37; mean disease duration 1.9 years; Expanded Disability Status Scale (EDSS) range 0-3) and 19 healthy controls (mean age 34) were imaged yearly with a magnetization transfer imaging sequence. Twenty-two MS patients and 14 controls completed two-year follow-up. Regions of interest were placed in both thalami and mean thalamic MTR calculated. At baseline, significant differences between patient and control thalamic MTR were not observed. However, at years one and two, the thalamic MTR in patients was significantly lower than control MTR. Although baseline lesion volume did not correlate with baseline thalamic MTR, at year one, an association between baseline lesion volume and year one thalamic MTR emerged. There was also a significant inverse correlation between EDSS and thalamic MTR (r= −0.47, P=0.02). The study suggests that thalamic involvement occurs within the first five years of MS onset, when most patients are still minimally disabled.

Cortical functional reorganization and its relationship with brain structural damage in patients with benign multiple sclerosis

2010 ◽  
Vol 16 (11) ◽  
pp. 1326-1334 ◽  
Author(s):  
Antonio Giorgio ◽  
Emilio Portaccio ◽  
Maria Laura Stromillo ◽  
Silvia Marino ◽  
Valentina Zipoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Tissue Damage ◽  
Brain Volume ◽  
Magnetization Transfer ◽  
Cortical Reorganization ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Transfer Ratio ◽  
Relapsing Remitting ◽  
Normal Controls

Background: Patients with multiple sclerosis (MS) who have a favourable clinical status several years after disease onset are classified as ‘benign’. In many cases brain tissue damage does not differ between benign MS and the ‘classical’ MS forms. Objective: To assess whether the favourable clinical course in benign MS could be explained by the presence of an efficient functional cortical reorganization. Method: Twenty-five right-handed patients with benign MS (defined as having Expanded Disability Status Scale ≤ 3 and disease duration >15 years) underwent functional MRI during a simple motor task (right-hand tapping) to assess movement-associated brain activation. This was compared with that of 10 patients with relapsing—remitting MS and 10 normal controls. Benign MS patients also underwent conventional brain MRI and magnetization transfer imaging, which was compared with an identical examination obtained 1 year before. Quantitative structural magnetic resonance measures were baseline and changes over time in T2-lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing brain and total brain volume. Results: Movement-related activation was greater in patients with benign MS than in those with relapsing—remitting MS or normal controls, extensively involving bilateral regions of the sensorimotor network as well as basal ganglia, insula and cerebellum. Greater activation correlated with lower T2-lesion magnetization transfer ratio, and with decreasing brain volume and increasing T2 lesion volume. Conclusions: The results suggest that bilateral brain networks, beyond those normally engaged in motor tasks, are recruited during a simple hand movement in patients with benign MS. This increased activation is probably the expression of an extensive, compensatory and tissue-damage related functional cortical reorganization. This can explain, at least in part, the favourable clinical expression of patients with benign MS.

Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease

2007 ◽  
Vol 13 (6) ◽  
pp. 708-716 ◽  
Author(s):  
H. Vrenken ◽  
P.J.W. Pouwels ◽  
S. Ropele ◽  
D.L. Knol ◽  
J.J.G. Geurts ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetization Transfer ◽  
Cerebral Atrophy ◽  
Peak Position ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Multilevel Method ◽  
Ratio Measurement ◽  
Transfer Ratio ◽  
Post Hoc

We investigated the magnetization transfer ratio (MTR) of normal-appearing white (NAWM) and grey matter (NAGM) in a relatively large group of multiple sclerosis (MS) patients, and the relations of MTR changes with clinical disability. MTR was measured in 66 MS patients (12 PP, 35 RR, 19 SP) and 23 healthy controls, using a whole-brain 3D-FLASH technique corrected post-hoc for B1-induced variation. Histogram parameters of conservatively selected NAWM and cortical NAGM were analysed using Bonferroni-corrected ANOVA with age as covariate. Additionally, manually outlined regions of interest were analysed using a multilevel method. Lesions had low MTR (mean 22.7±6.9%), but NAWM exhibited limited changes: MTR histogram peak position was 32.8±1.0% in controls and 32.4±0.9% in MS patients, with a significant decrease compared to controls only in SPMS patients (31.9±1.1%, p=0.045). Cortical NAGM histograms did not differ significantly between patients and controls. In SPMS, regional mean MTR was significantly decreased in corpus callosum and hippocampus. MTR histogram parameters of NAGM and NAWM were correlated with EDSS and MSFC scores, with lesion volume and with normalized brain volume. We conclude that disease-induced MTR changes were small in MS NAWM and NAGM, but did correlate with clinical decline, lesion volume and overall cerebral atrophy. Multiple Sclerosis 2007; 13: 708-716. http://msj.sagepub.com

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

2006 ◽  
Vol 12 (5) ◽  
pp. 662-665 ◽  
Author(s):  
A Charil ◽  
D Caputo ◽  
R Cavarretta ◽  
M P Sormani ◽  
P Ferrante ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Magnetization Transfer ◽  
Small Sample ◽  
Cervical Cord ◽  
Magnetization Transfer Ratio ◽  
Short Term ◽  
Disease Evolution ◽  
Transfer Ratio ◽  
Relapsing Remitting

Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

Brain atrophy and magnetization transfer ratio following methylprednisolone in multiple sclerosis: short-term changes and long-term implications

2005 ◽  
Vol 11 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Robert J Fox ◽  
Elizabeth Fisher ◽  
Jean Tkach ◽  
Jar-Chi Lee ◽  
Jeffrey A Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Short Term ◽  
Whole Brain ◽  
Transfer Ratio ◽  
Short Term Change ◽  
Term Change ◽  
The Impact

Background: The short-term effect of corticosteroids on MRI measures of multiple sclerosis (MS) is not well understood and may have a significant impact when using these quantitative measures to evaluate disease activity and changes following other therapeutic interventions. Objective: To determine the impact of a course of intravenous methylprednisolone (IVMP) on quantitative measures of disease activity and tissue injury in MS patients. Methods: We prospectively measured brain parenchymal fraction (BPF), magnetization transfer ratio (MTR, lesional and whole brain), and lesion volumes on nine weekly brain MRI studies in ten MS patients receiving a course of IVMP. A group of nine MS patients not receiving IVMP served as controls. Results: In comparison to untreated controls, BPF declined over the eight weeks following IVMP treatment (P<0.02). BPF decline was most prominent in patients with secondary progressive MS (SPMS, P<0.03), and was not seen in relapsing-remitting (RR) MS patients. Short-term change in BPF correlated with baseline BPF (r=0.62, P=0.05) and short-term change in lesional MTR (r=-0.55, P=0.03), but not with change in enhancing lesion volume. Short-term change in lesional MTR inversely correlated with baseline lesional and whole brain MTR (r=-0.79, P=0.04 for both). There was no significant difference between treated and control patients in measures of MTR or T2, T1 or enhancing lesion volumes. Conclusions: Patients with SPMS showed a greater decline in BPF following IVMP than RRMS patients. A correlation between changes in BPF and MTR suggest that these changes are secondary to altered water content within MS lesions. Differential response to a standardized therapeutic intervention in RRMS and SPMS suggests that responses to therapy may differ due to a fundamental pathologic difference between early and late stage MS.

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