MAGNETIC RESONANCE SPECTROSCOPY OF NORMAL APPEARING WHITE MATTER IN EARLY RELAPSING-REMITTING MULTIPLE SCLEROSIS Enas

Content Provider	Semantic Scholar
Author	Ahmed, El Sayed Mohamed Zaiton, Mahmoud Ashraf Hassan, Hanan Abd ElAzim Wael Elsayed, M. Shawki, Khalid Mohamed
Copyright Year	2018
Abstract	Back ground: Multiple sclerosis (MS) is an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged .MS is a chronic disease of the central nervous system characterised by multicentral inflammation and myelin destruction . Magnetic resonance imaging (MRI) is now widely used for diagnosing MS and detecting clinically silent lesions. However, correlations found between conventional techniques, such as T2-weighted lesion load, and disability, are weak or absent and therefore, neither the magnetic resonance techniques nor clinical measurements are gold standard to assess disease or disability.Alteration of NAWM is of great importance because its true patho-physiological significance is not completely understood. Decrease in N-Acetyl Aspartate (NAA) has been used as an marker of axonal damage or loss that presumably appears secondary to inflammation or demyelination ,although primary axonal damage is not excluded . Objectives : Demonstrate the limitation of convenential magnetic resonance techniques. Observation the pathological processes in NAWM by MRS. Correlation between the results of MRS and the physical disability of the patients using EDSS . Subjects and methods: This study was carried out on 23 patients with clinically definite multiple sclerosis patients, who met the criteria of clinically definite MS according to McDonald criteria 2010, selected from Neurology Department, Zagazig University Hospitals ]10[. Results: We found that the mean value of NAA and the mean ratios of NAA/CR and NAA/ CHO were significant lower in the Cases but the mean values of MI and GLX are significant higher. . Also there was significant negative correlation between the mean value of NAA in MS plaque by MRS and EDSS score as a measure of disability. There was significant negative correlation between the mean value of NAA in NAWM and EDSS score . Discussion: We have clearly demonstrated a correlation between an MRS measure and EDSS. EDSS seems to reflect the existence of irreversible disability probably related to axonal degeneration. Key wards Multiple sclerosis; Magnetic resonance imaging;Normal appearing white mater;Proton magnetic resonance spectroscopy;Expanded Disability Status Scale Corresponding author: Enas El Sayed Mohamed Ahmed Mobile:01001200386 Email:dr_enasneuro@yahoo.com INTRODUCTION ultiple sclerosis (MS) is an immunemediated inflammatory disease that attacks myelinated axons in the central nervous system (CNS), destroying the myelin and the axon in variable degrees. In most cases, the disease follows a relapsing-remitting pattern, with short-term episodes of neurologic deficits that resolve completely or almost completely. A minority of patients experience steadily progressive neurologic deterioration ]1[. MS distribution It is recognised that MS is unevenly but nonrandomly distributed throughout the world and that environmental factors play a significant role in the onset of MS. Many epidemiology studies have been performed to investigate these phenomena. Several of these studies support the existence of a gradient of MS M Z.U.M.J.Vol. 24; No.3 May .;2018 Magnetic Resonance Spectroscopy of Normal.... Enas E.; et al.... -201prevalence, which increases with distance from the equator in both northern and southern hemispheres ]2 [. Etiology The cause of MS is unknown, but it is likely that multiple factors act in concert to trigger the disease. It has been hypothesized that MS results when an environmental agent or event acts in concert with a genetic predisposition to immune dysfunction ]3 [. . Axonal Damage in Multiple Sclerosis Historically, axonal damage has been recognized as a histopathological hallmark of MS since the very early descriptions of the disease by Charcot in the late 1800s ]4 [ . More recent clinical, histopathological, and neuroimaging evidence has shed new light on these early findings and supported the concept that the debilitating disease course and longterm disability in MS patients was consequent to axonal loss possibly consequent to demyelination ]5 [ .The features of axonal damage in MS, however, were similar to those detected in other neurological diseases lacking demyelination, such as amyotrophic lateral sclerosis (ALS), and suggested the possibility that axonal damage in MS might be concurrent to demyelination, but not necessarily consequent to myelin destruction ]6,7 [ . Clinical Rating Scales A patient may be rated according to several clinical disability scales, on the basis of findings on the history and physical examination. The most widely accepted of these is the 10-point Kurtzke Expanded Disability Status Scale (EDSS), which was developed originally in 1955 as the Disability Status Scale and has been revised over the years ]8 [ . The EDSS assigns a severity score to the patient's clinical status that ranges from 0-10 in increments of 0.5. The scores from grades 0-4 are determined using functional systems (FS) scales that evaluate dysfunction in the following 8 neurologic systems:  Pyramidal,Cerebellar ,Brainstem,Sensory,Bladder and bowel, Vision, Cerebral, Other Advantages of the EDSS are that it is widely used clinically, is easy to administer, and requires no special equipment. Proton magnetic resonance (MR) imaging plays an essential role in the management of patients with a wide range of neurological conditions. While conventional MR imaging provides important structural information, data on underlying brain function is often limited. The generation of a spectrum of brain metabolites by MR spectroscopy provides the clinician with information on the regional chemical environment ]9 [ . Proton MR Spectroscopy Over the years, scientists have obtained MR spectra using a variety of nuclei ] 10 [ .However, the high sensitivity of the hydrogen ( 1 H) nucleus, its abundance within certain neurometabolites and the fact that the technique can be performed using standard clinical MR imaging machines makes hydrogen the principal nucleus applicable to spectroscopic investigation associated with clinical imaging of the brain ]11 [ . The proton MR spectrum comprises a set of resonances (peaks) distributed along the x-axis, labelled in parts per million (ppm) . The amplitude of the resonances is measured on the y-axis typically using an arbitrary scale. Three prominent peaks are consistently seen: N-acetyl aspartate (NAA) at 2.02; Creatine (Cr) at 3.02; and Choline (Cho) at 3.2 .Although the positions of the resonances along the x-axis are constant, the relative heights of the resonances can differ depending on various MR imaging parameters ]12 [ . SUBJECTS AND METHODS This study was carried out on 23 patients with clinically definite multiple sclerosis patients, who met the criteria of clinically definite MS according to McDonald criteria 2010, selected from Neurology Department, Zagazig University Hospitals ]13 [ . Ten healthy volunteers with similar age and gender distribution as control group were included in this study. The study was approved by the Ethical Committee of our Faculty and Z.U.M.J.Vol. 24; No.3 May .;2018 Magnetic Resonance Spectroscopy of Normal.... Enas E.; et al.... -202informed written consent was obtained from patients and controls. Patients were classified according to clinical course as having recurrent relapse with partial remission and no progression between attacks (relapsing remitting course) The patients group: This group included 23 Patients with clinically definite relapsing remitting MS according to the Mc Donald criteria ]14 [ . Their ages ranged from 17 year to 45 year, with disease duration ranged from 1 to 12 years The control group: Ten apparently healthy unmedicated subjects, of matched age and gender served as a control group. All patients were subjected to the following: (1) History and examination:  Detailed history taking about age of onset, duration of disease, number of relapse and current treatment(disease modifying therapy).  The duration of the disease (measured in years). Patient’s age at first symptoms ..  Assessment of disease severity by the Expanded Disability Status Scale (EDSS) ] 15 [ . (2)Routine laboratory investigations: (3) Radiological evaluation was performed in Zagazig University Radiology MRI Unit: MR images were acquired using a 1.5T Philips using a standard quadrature head coil. Prior to H-MRS examination each patient's disability was measured using EDSS . The H-MRS was performed the same day as the neurological examination by the same radiologist at the same center using the same MRI scanner and following the same protocol. The radiologist was blinded to the neurological examination results and all the neurologists were blinded to the MRS results. At the beginning of the study MRI and H-MRS were also performed on 10 healthy, age matched control subjects with not known systemic or neurological disease by the same radiologist using the same MRI scanner and following the same protocol as well. These conventional MR images were used to position a spectroscopic volume of interest (VOI) in one or two areas with demyelinating lesions and one area of normal appearing white matter in MS patients and in one area of normal white matter in the healthy control group The number of peaks fitted included the chemical shift ranges: o N-acetylasparate (NAA) at 2.0 ppm. o Creatine/phosphocreatine (Cr) at 3.0 ppm. o Choline compounds (Cho) at 3.2 ppm. o Myo-inositol (mI) at 3.5 ppm. o Glutamine–glutamate–GABA complex (Glx) between 2.1 and 2.5 ppm Z.U.M.J.Vol. 24; No.3 May .;2018 Magnetic Resonance Spectroscopy of Normal.... Enas E.; et al.... -203RESULTS Table (1) : Comparison between the different metabolic values of MS plaques and that of NAWM of the patient group by MRS .
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