PAPER

Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon ß-1a (Rebif) treatment trial

X Lin, C R Tench, B Turner, L D Blumhardt and C S Constantinescu

Division of Clinical Neurology, Faculty of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham, UK

Correspondence to:
Correspondence to:
Dr C S Constantinescu, Division of Clinical Neurology, Faculty of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK;
cris.constantinescu{at}nottingham.ac.uk

Background: Pathology in the cervical spinal cord is considered an important cause of disability in multiple sclerosis. However, the majority of serial studies have failed to find a correlation between spinal cord atrophy and disability.

Objectives: To use a highly reproducible and accurate method to quantify spinal cord area change on three dimensional magnetic resonance imaging and relate this to disability change in patients with multiple sclerosis.

Methods: 38 patients with multiple sclerosis (20 with the relapsing–remitting (RRMS) form and 18 with the secondary progressive (SPMS) form) were imaged at baseline and at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly interferon ß-1a (IFNß, Rebif). Thirty one healthy subjects were also imaged at baseline. Upper cervical cord area (UCCA) was measured using Sobel edge detection.

Results: The intraobserver coefficient of variation of the method was 0.42%. A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INFß (p = 0.03). The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS), and 4.5% for those on IFNß throughout the study (p = 0.35). The change in UCCA was significantly correlated with change in the expanded disability status scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort.

Conclusions: Despite the small number of patients studied and the possible confounding effects of interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in spinal cord area, and that this change is related to changes in clinical disability. This suggests a role for measurement of spinal cord atrophy in monitoring disease progression and possible treatment effects in clinical trails.

Keywords: multiple sclerosis; magnetic resonance imaging; spinal cord atrophy; disability

Abbreviations: EDSS, expanded disability status scale; MICA, mean maximum intracranial area; PPMS, primary progressive multiple sclerosis; RRMS, relapsing remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; TD, time of delay; TE, time of echo; TI, time of inversion; TR, time of repetition; UCCA, upper cervical cord area

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