The present work shows efficacy of the use of copaxone (glatiramer acetate) in treatment the patients with relapsing-remitting MS (RRMS), assessed by the ...
THE USE OF IN VIVO H – MAGNETIC RESONANCE SPECTROSCOPY FOR EVALUATING THE EFFICACY OF TREATMENT OF PATIENTS WITH RELAPSINGREMITTING MULTIPLE SCLEROSIS WITH COPAXONE (GLATIRAMER ACETATE) 1
Authors: Z. Rozhkova2, O. Myalovitska1, T. Kobys3, I. Lobanova1 Department of Neurology, National Medical University, T. Shevchenko Av., 13, Kyiv city, Ukraine 2 Department of Radiology, Medical Clinic «BORIS», Prosp. Bazhana12-A, Kyiv city, Ukraine 3 Department of Neurology, Kyiv City Clinical Hospital №4, Solomyanska Street, 17, Kyiv city, Ukraine 1
INTRODUCTION: • Brain proton magnetic resonance (MR) spectroscopy (1H-MR spectroscopy) is a useful technique for evaluation of neuronal/axonal damage and demyelization in multiple sclerosis (MS). • Multiple sclerosis is a central nervous system disease with a complex relapsing and remitting course, including inflammation, demyelination, remyelination, axonal loss and gliosis, alternating or present at the same time. • MR spectroscopy studies of patients with MS can evaluate specific metabolites which are used for establishing the course of disease. • The N-acetylaspartate peak in MR spectrum is interpreted to represent neuronal/axonal dysfunction or loss, and an elevated choline peak represents heightened cell-membrane turnover in patients with MS and is considered to reflect demyelination, remyelination, inflammation or gliosis. • The present work shows efficacy of the use of copaxone (glatiramer acetate) in treatment the patients with relapsing-remitting MS (RRMS), assessed by the method of in vivo 1Н- MR spectroscopy. • The mechanism of glatiramer acetate effect consists in development of specific in relation to myelin immune tolerance and reduction of autoimmune response in case of MS, that is provided due to synthesizing anti-inflammatory cytoxins IL-4,5,10 and factor TGF-b.
THE PURPOSE of the present research was to use
Н- MR spectroscopy to assess the modifications in the cerebral metabolite concentration in lesional areas of patients with multiple sclerosis treated with copaxone (glatiramer acetate) in the 36 months of treatment, comparing them with the same indices obtained in untreated (without treatment which can change the course of MS) patients with multiple sclerosis matched for age and disability. 1
METHODS: • The 1Н- MR spectroscopy analysis was performed on 42 patients (24 female and 18 male aged 23-46, the average age 33,5±0,4) with RRMS that had not previously had treatment specific for MS. • For both treated and untreated patients the inclusion criteria was definite multiple sclerosis for at least two years, a baseline expanded disability status score of 1.0 to 3.5 inclusive, at least two documented exacerbations of the disease in the two years before the study, but no exacerbation in the past three months. • At the beginning of the study, the untreated patients with multiple sclerosis (without treatment which can change the course of MS) were matched to the treated group with RRMS who were taking copaxone (glatiramer acetate) in the dose of 20mg per day for average age, duration of the disease, and EDSS (Table 1). • At the beginning of the study 1H MR spectroscopy was also performed on 20 (11 female and 9 male) healthy, age matched control subjects (average age 32.5±0.7years) with no systemic or neurological diseases. • MR spectroscopy of patients with RRMS was carried out before the beginning the treatment and 12, 24 and 36 months after the beginning of treatment. • All the patients had the assessment of disability degree with the use of Kurztke Expanded Disability Status Score (EDSS) scale before the beginning of the treatment and then every 6 months.
RESULTS: • The results of the analysis of the map of distribution of the main cerebral metabolites for the patients taking copaxone as well as for patients with RRMS without treatment which can change the course of MS are given in Table 2 and Figure 1, 2. • Рatients with RRMS who were taking copaxone, according to the results of MR spectroscopy, had the increase of tNAA (total N-acetylaspartate)/Cr (creatine) correlation from 1,95±0,07 (before treatment) to 2,25±0,06 (after 36 months), р0,05 (in comparison with indices before treatment) and in the contralateral hemisphere - 2,36±0,07 (before treatment) to 2,41±0,04 (after 36 months), р>0,05 (in comparison with indices before treatment).
TABLE 1. Baseline patient demographic and
TABLE 2. Metabolite indices of control subjects and patients with RRMS of different clinical groups
disease characteristics.
Treated patients
Untreated patients
EDSS
33,4 ± 0,3 22 10 (45%) 12 (55%) 2,5 ± 0,8
31,4 ± 0,7 20 8 (40%) 12 (60%) 2,8 ± 0,5
mean relapse rate of MS
0,7/year
0,7/year
Characteristic Age, years Sex, n (%) Male Female
before and after the treatment.
Localization of the area of study Before treatment Treated patients, in the focus of active demyelination After 36 months Before treatment Unreated patients, in the focus of active demyelination After 36 months Before treatment Treated patients, in the intact tissue of the affected hemisphere After 36 months Before treatment Untreated patients, in the intact tissue of the affected hemisphere After 36 months Before treatment Treated patients, in the contralateral hemisphere After 36 months Before treatment Untreated patients, in the contralateral hemisphere After 36 months
Control subjects
Total N-acetylaspartate/Cr (creatine) correlation 1,95 ± 0,07 ^ 2,25 ± 0,06 *• 1,92 ± 0,07 ^ 2,06 ± 0,08 2,08 ± 0,07 ^ 2,33 ± 0,04 *• 2,1 ± 0,06 ^ 2,2 ± 0,05 2,38 ± 0,08 ^ 2,43 ± 0,06 2,36 ± 0,07 ^ 2,41 ± 0,04 2,69 ± 0,11
^ – p
