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Title: ¹H Magnetic resonance spectroscopy in the investigation of multiple sclerosis and other disorders of white matter
Author: Davie, Charles Anthony
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1997
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¹H magnetic resonance spectroscopy (MRS) is a technique that allows the in vivo and non-invasive quantification of metabolites from the human brain. MRS was used in the study of patients with multiple sclerosis (MS) to determine the metabolic profile of acute MS lesions and areas of normal apearing white matter (NAWM). Abnormally elevated metabolite peaks attributable to mobile lipids and cytosolic proteins indicative of myelin breakdown were found in all acute lesions studied. A study of chronic MS lesions and NAWM was performed in patients in the four clinical subgroups of MS - benign, relapsing/remitting, primary and secondary progressive disease to evaluate mechanisms of disability in MS. This study showed a correlation between reduction of NAA - a neuronal marker and disability in the different clinical subgroups of MS. To test the hypothesis that a reduction in NAA may occur as a consequence of axonal loss, a group of patients were studied with hereditary autosomal dominant cerebellar ataxia (ADCA) a condition in which axonal loss is known to be a striking pathological feature. This study supported the relationship between axonal loss and reduction of NAA by showing a significant reduction in the concentration of NAA from cerebellar white matter. To provide a more rigorous test of the hypothesis that axonal loss is an important determinant in the development of disability, an MRS study was performed in two groups of MS patients - a group with severe cerebellar deficit and a group with no clinical evidence of cerebellar involvement in these two conditions. Again, this study showed a strong correlation between the presence of persistent functional deficit and axonal loss as evidenced by a reduction of N acetyl aspartate only in the group of MS patients with severe cerebellar deficit. MRS was also performed in a group of patients with neuropsychiatric manifestations of systemic lupus erythematosus (SLE) to determine whether MRS is useful in differentiating this condition from MS. The pattern of abnormality did not allow differentiation of SLE lesions from the chronic plaques occurring in MS. Finally, MRS was carried out in a group of adult patients with phenylketonuria (PKU) who had abnormalities visible with magnetic resonance imaging (MRI) to show that MRS is able to differentiate between the pathological processes that produce MRI abnormalities in MS and those occurring in PKU. Patients with PKU showed a normal metabolite profile from MRI visible lesions and NAWM indicating axonal preservation from lesions which on conventional MRI resemble lesions seen in MS. These studies have shown that MRS is a useful non- invasive technique which can help, not only in understanding the pathophysiology of MS, but may also help in differential diagnosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available