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A Potential Surrogate Marker for Progression in Early Primary Progressive Multiple Sclerosis

Zhaleh Khaleeli, MRCP; Daniel R. Altmann, DPhil; Mara Cercignani, PhD; Olga Ciccarelli, PhD; David H. Miller, FRCP; Alan J. Thompson, FRCP

Arch Neurol. 2008;65(11):1454-1459.

Background  Magnetization transfer imaging has the potential to provide a surrogate marker for progression in primary progressive multiple sclerosis (PPMS).

Objectives  To investigate whether brain magnetization transfer imaging, T2 lesion load, and atrophy changes over 3 years reflect concurrent clinical changes, and which baseline imaging measure best predicts progression over 3 years in early PPMS.

Design  Prospective study.

Setting  National Hospital for Neurology and Neurosurgery and the Institute of Neurology, London, England.

Patients  Forty-seven patients with PPMS (of whom 43 completed the study) and 18 control subjects.

Interventions  Brain magnetization transfer imaging (including T2-weighted images) and volume sequences every 6 months for 3 years.

Main Outcome Measures  Changes in Expanded Disability Status Scale (EDSS) score and associations with rate of change in imaging variables.

Results  More rapid decline in gray matter mean and peak location magnetization transfer ratio and T2 lesion load increase were associated with greater rates of progression on the EDSS. Baseline gray matter peak height magnetization transfer ratio best predicted progression over 3 years.

Conclusion  Gray matter magnetization transfer ratio meets many of the criteria for a surrogate marker of progression in early PPMS.

Author Affiliations: Departments of Brain Repair and Rehabilitation (Drs Khaleeli, Ciccarelli, and Thompson) and Neuroinflammation (Drs Altmann, Cercignani, and Miller), Nuclear Magnetic Resonance Unit, Institute of Neurology, University College London; and Medical Statistics Unit, London School of Hygiene and Tropical Medicine (Dr Altmann), London, England.

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