1H-MRS in patients with multiple sclerosis undergoing
treatment with interferon
-1a: results of a preliminary study
a Neurologic
Clinic, University of Perugia, Via E dal Pozzo 06126, Perugia, Italy, b Department of Medical Physics, Perugia General
Hospital, Perugia, Italy, c Department of Neuroradiology, Perugia General
Hospital, Perugia, Italy
Correspondence to: Dr Paola Sarchielli, Neurologic Clinic, Policlinico Monteluce, Via E Dal Pozzo 06126, Perugia, Italy. Tel 0039 75 5783568; Fax 0039 75 5783583; email: Neurol{at}unipg.it
Received 2 January 1997 and in revised form 13 August 1997;
Accepted 22 August 1997
BACKGROUND
In vivo magnetic resonance
spectroscopy (MRS) has been widely used to assess biochemical changes
which occur in demyelinating lesions in white matter of patients with
multiple sclerosis. It has been suggested that metabolic variations
evidenced by MRS are sensitive indicators of the effects of
immunomodulatory treatments in this disease.
Given the recent finding of an increase in the disease
activity in patients with multiple sclerosis treated with interferon (IFN)
-1a in the first period of treatment,1H MRS was
used to investigate further the modification in brain metabolic
indices, particularly in the first phase of IFN
treatment.
METHODS
A 1H MRS study was
performed on five patients with relapsing-remitting multiple sclerosis
who were being treated with intramuscular IFN
-1a (6 million
units/week) for six months and on five untreated patients. The mean
age, duration of the disease, and expanded disability status scores
(EDSS) of the two groups were similar. Patients were evaluated at the
beginning of the study and in the first, third, and sixth months of treatment.
RESULTS
In the multiple sclerosis white
matter lesions, N-acetylaspartate (NAA), choline (Cho), inositol (Ins),
and creatine (Cr) peaks did not vary significantly over the entire
period of the study in the untreated group.
In the treated group there was a significant increase in the
Cho peak area at the first month compared with the pretreatment period,
and this increase continued in the third and sixth months (p<0.001). A
slight but not significant rise in the Cho peak was also found in
normal appearing white matter in the patient group undergoing treatment
with IFN
-1a. The increase in Cho and the lack of significant
changes in Cr and NAA peaks induced a significant rise in Cho/Cr and
Cho/NAA ratios over the entire period of treatment compared with those
at the beginning of the study (p<0.02 and p<0.005 respectively).
In the treated group there was a slight but significant
increase in the Ins peak in the first month (p<0.05) but in the third and sixth months of treatment the Ins values returned to the
pretreatment range.
CONCLUSIONS
IFN
-1a has an impact on
metabolite concentrations in multiple sclerosis lesions measured by
proton MRS. The increase in Cho, Cho/NAA, and Cho/Cr ratios in multiple
sclerosis lesions reinforces the view that they are an index of active
or recent demyelination and could support the clinical,
neuroradiological and immunological evidence showing an increase in
disease activity during the first period of treatment with IFN
-1a.
On the other hand, the increase in the Cho peak could be indicative of
a rise in membrane turnover in multiple sclerosis lesions or a
remodelling of plaques which is not necessarily due to a de novo immune
mediated demyelination.
-1a
© 1998 by Journal of Neurology, Neurosurgery, and Psychiatry
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