Longitudinal changes in magnetisation transfer ratio in secondary progressive
multiple sclerosis: data from a randomised placebo controlled trial of
lamotrigine.
Author(s): Hayton T, Furby J, Smith KJ, Altmann DR, Brenner R, Chataway J, Hunter K, Tozer
DJ, Miller DH, Kapoor R.
Affiliation(s): Department of Neuroinflammation, UCL Institute of Neurology, Queen Square,
London, WC1N 3BG, UK. t.hayton@ion.ucl.ac.uk
Publication date & source: 2012, J Neurol. , 259(3):505-14
Sodium blockade with lamotrigine is neuroprotective in animal models of central
nervous system demyelination. This study evaluated the effect of lamotrigine on
magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure
of intact brain tissue, in a group of subjects with secondary progressive
multiple sclerosis (MS). In addition, the utility of MTR measures for detecting
change in clinically relevant pathology was evaluated. One hundred seventeen
people attending the National Hospital for Neurology and Neurosurgery or the
Royal Free Hospital, London, UK, were recruited into a double-blind,
parallel-group trial. Subjects were randomly assigned by minimisation to receive
lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating and
assessing physicians and patients were masked to treatment allocation. Results of
the primary endpoint, central cerebral volume, have been published elsewhere.
Significant differences between the verum and placebo arms were seen in only two
measures [normal appearing grey matter (NAGM) p = 0.036 and lesion peak height
(PH) p = 0.004], and in both cases there was a greater reduction in MTR in the
verum arm. Significant correlations were found of change in MS functional
composite with all MTR measures except lesion and normal appearing white matter
(NAWM) PH. However, the change in MTR measures over 2 years were small, with only
NAGM mean (p = 0.001), lesion peak location (p = 0.11) and mean (p < 0.0001)
changing significantly from baseline. These data did not show that lamotrigine
was neuroprotective. The clinical correlation of MTR measures was consistent, but
the responsiveness to change was limited.
|