Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine

• Published in: Journal of neurology Vol. 259; no. 3; pp. 505 - 514
• Main Authors: Hayton, T., Furby, J., Smith, K. J., Altmann, D. R., Brenner, R., Chataway, J., Hunter, K., Tozer, D. J., Miller, D. H., Kapoor, R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.03.2012; Springer; Springer Nature B.V
• Subjects: Adult; Animal models; Biological and medical sciences; Brain; Calcium Channel Blockers - therapeutic use; Central nervous system; Clinical trials; Data processing; Demyelination; Disability Evaluation; Double-Blind Method; Drug dosages; Female; Hospitals; Humans; lamotrigine; Longitudinal Studies; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple sclerosis; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Chronic Progressive - drug therapy; Neurology; Neuroprotection; Neuroradiology; Neurosciences; Neurosurgery; Original Communication; Pathology; Reproducibility of Results; Severity of Illness Index; Sodium; Substantia alba; Substantia grisea; Time Factors; Triazines - therapeutic use; United Kingdom > UK; England; London England; Multiple sclerosis; MTR; MRI; Secondary progressive; MSFC; Nervous system diseases; Central nervous system disease; Placebo; Nuclear magnetic resonance imaging; Inflammatory disease; Lamotrigine
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-011-6212-9

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.