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Abstract
Multiple sclerosis is a chronic disease of the central nervous system characterized by multicentral inflammation and myelin destruction. Recent pathology studies have stressed the importance of axonal pathology in MS, in addition to demyelination.
Magnetic resonance imaging (MRI) is now widely used for diagnosing MS & detecting clinically silent lesions in clinical trials on MS treatment. However correlations found between conventional techniques, such as T2 – weighted lesion load and disability are weak or absent. Therefore neither the magnetic resonance techniques used so far nor clinical measurements are gold standard to assess disease or disability.
In vivo, this reflect the inability of conventional MRI to accurately depicit the pathology of MS as regards to histopathologic heterogeneity of MS lesions. This limitations may account for the weak correlation between disability & MRI findings in patients with MS.
Magnetic resonance spectroscopy (MRS) is a technique that has the potential to detect axonal loss non – invasively. It proved a non – invasive insight into the regional and global biochemical alterations that are concomitants of the dynamic process that underlie evolution of fundamental pathologic changes in MS.
These include new – well recognized alterations of neuronal biochemical markers that accompany tissue destruction readily visualized by MRI but also dynamic changes in several metabolite that preceed pathological process that preceed MRI defined lesions or completely escape current high resolution images.
Our study represent one of the studies used to evaluate the role of MRS as a prognostic tool in MS patient & used to differentiate between relapsing – remitting group & the secondary progressive group.
We prospectively included 34 patients with clinically definite MS according to McDonald criteria who were admitted to Ain shams University Specialized Hospital during a relapse. They were 19 patients with relapsing – remitting MS and 15 patients with secondary – progressive MS that were matched with 14 healthy control subjects.
All the patients were subjected to full clinical evaluation using history taking, full clinical examination. Also Neuroradilogical evaluation was done including conventional MRI techniques to define the site and number of lesions. MRS was done to all patients and the following ratios were calculated: NAA/Cr., NAA/Chol., Chol./Cr. and Mi./ Cr. ratio.
Patients neurological state and disability was assessed using Expanded Disability status (EDSS) which was done at the start of the study and was repeated after 6 months after receiving treatment in the form of pulsed steroids. The degree of improvements is measured in MS patients in this study by comparing the EDSS at the start of the study and comparing it with the EDSS after 6 months during the research period and were classified either with : stationary course (No improvement), slight improvement (One degree change in EDSS), moderate improvement (Two degree change in EDSS).
(Ebers et al.,2005).
And the results were as follows:
This study included 34 patients, 17 males (50 %) & 17 females (50 %) with definite multiple sclerosis and 14 healthy controls, 8 males (57.1 %) and 6 females (42.7 %). The patient group was further subdivided into patients with relapsing remitting MS ( n = 19, 55.9 %) and patients with secondary progressive MS ( n = 15, 44.1 %).
The mean age of the patients with multiple sclerosis ranged from 18 to 50 years with a mean of 32.29 +/- 8.77 years and was matched to that of the healthy control subjects (ranged from 20 to 40 years with a mean of 31.28 +/- 5.92 years).
The mean duration of illness among patients with multiple sclerosis in the study ranged from 1 year to 14 years with a mean 5.04 ± 3.4 years. The number of relapses among patients with multiple sclerosis ranged from 1 to 6 with a mean of 3.67 ± 1.7.
The mean EDSS at the beginning of the study for multiple sclerosis patients ranged from 1 to 8 with a mean of 4.1 ± 2.01. The mean EDSS after 6 months of the study for all patients ranged from 1 to 8with a mean of 3.68 +/- 2.01.
Regarding the spectroscopic differences between patients and control group; NAA was significantly lower in patients compared to controls (P = 0.02). Also statistically higher MI was found in patients with multiple sclerosis compared to controls (P = 0.002). The Chol. As well as Cr. was higher in patients with multiple sclerosis (P = 0.003, P = 0.002 respectively) compared to the controls. The MI / Cr. Ratio was significantly higher in patients compared to controls (P = 0.005).
Relapsing – remitting MS patient have significantly higher Chol./Cr. ratio (P = 0.03) as well as NAA / Cr. ratio (P = 0.04) compared to secondary progressive MS.
The patients who presented with slight improvement according to EDSS score had significantly higher NAA/Chol. Ratio compared to patients with moderate improvement (P = 0.04). A statistically higher MI/Cr. Ratio was found in patients with moderate improvement (P = 0.01) as compared to those patients with mild improvement or stationary course according to the EDSS scores.
The duration of illness & number of relapses in patients with moderate or severe disability (EDSS > 3) were significantly more than that of patients with mild disability (EDSS < 3) (P = 0.000) & (P = 0.01) respectively but no significant spectroscopic differences was found between those with EDSS < 3 or EDSS > 3.
SPMS patients had a significantly greater number of patients with abnormal V.E.P. (No. = 11, 84.6%) (P = 0.05) compared to RRMS patients.
Also SPMS patients had a greater number of patients with abnormal B.A.E.P. (N0. = 11, 84.6%) (P = 0.01) compared to RRMS patients.
Patients with abnormal V.E.P. have significantly higher E.D.S.S. score compared to patients with normal V.E.P. (P = 0.004). However no statistical significance was found between patients & B.A.E.P. results.
Patients with abnormal V.E.P. have significantly lower NAA, NAA/Cr ratio compared to patients with normalV.E.P. (P = 0.03, 0.02 respectively).
Patients with abnormal B.A.E.P. have significantly lower NAA/Cr ratio compared to patients with normal B.A.E.P. (P = 0.05). NAA was lower in patients with abnormal B.A.E.P. compared to patients with normal B.A.E.P. but don’t reach statistical significance.
Patients with active lesions have significantly higher NAA/Chol ratio (P = 0.001), as well as higher Chol/Cr. ratio (P = 0.001) compared to patients with inactive lesions.
Comparing the active lesions in both RRMS and SPMS revealed comparable values regarding different spectroscopic metabolic ratios which didn’t reach statistical significance. Comparing the inactive lesions in both RRMS and SPMS revealed comparable values regarding different spectroscopic metabolic ratios which didn’t reach statistical significance.