P22 Spinal Cord Normalization In Multiple Sclerosis

Saturday, June 1, 2013
Jiwon Oh, MD , Neurology, Johns Hopkins University, Baltimore, MD
Michaela Seigo, ScB , Neurology, Johns Hopkins University, Baltimore, MD
Shiv Saidha, MD , Neurology, Johns Hopkins University, Baltimore, MD
Elias S Sotirchos, MD , Neurology, Johns Hopkins University, Baltimore, MD
Kathleen M Zackowski, PhD, OT , Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD
Min Chen, BSc , Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD
Jerry Prince, PhD , Computer Science, Johns Hopkins University, Baltimore, MD
Marie Diener-West, PhD , Biostatistics, Johns Hopkins University, Baltimore, MD
Peter A Calabresi, MD, FAAN , Neurology, Johns Hopkins School of Medicine, Baltimore, MD
Daniel S Reich, MD, PhD , Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD

Background: Spinal cord(SC) pathology is common in multiple sclerosis(MS), and measures of SC atrophy, including SC volume(SCV), are increasingly being utilized. Normalization is an important procedure that can reduce biological variation of structural measurements unrelated to disease effects, but the optimal normalization factor for SCV remains unclear.

Objectives: Using a variety of normalization factors and clinical measures, we assessed the effect of SCV normalization on detecting group differences, and clarifying clinical-radiological correlations in MS.

Methods: 133 individuals with MS and 14 healthy control subjects (HCs) underwent cervical SC-MRI at 3T and clinical assessment, including the expanded disability status scale(EDSS), multiple sclerosis functional composite (MSFC), and quantitative tests of hip-flexion strength(HFS) and vibration sensation threshold (VST). SCV was measured between C3-C4. SCV was normalized by individual factors: height, spinal cord length (SCL - yielding an average measure of cross-sectional area), and intracranial volume(ICV).

Results: There were significant group differences between MS cases and HCs in raw SCV, and SCV normalized by height and SCL (p<0.05). SCV normalized to either height or SCL was greater in relapsing vs. progressive MS subtypes (p<0.05), while raw SCV was not (p=0.32). There were significant correlations between clinical measures and raw SCV(EDSS:ρ=-0.20; MSFC:ρ=0.16; HFS:ρ=0.35, VST:ρ=-0.19, all p<0.05 except MSFC=0.06). Observed clinical-radiological correlations consistently strengthened with normalization by SCL(EDSS:ρ=-0.43; MSFC:ρ=0.33; HFS:ρ=0.38, VST:ρ=-0.40, all p<0.001) and height(EDSS:ρ=-0.26; MSFC:ρ=0.28; HFS:ρ=0.22, VST:ρ=-0.29, all p<0.05), but generally diminished with normalization by ICV(EDSS:ρ=-0.23,p=0.01; MSFC:ρ=-0.10;p=0.24; HFS:ρ=0.23,p=0.01; VST:ρ=-0.35,p<0.01). In relapsing patients, normalization by SCL allowed the detection of clinical-radiological correlations that were not apparent with raw SCV.

Conclusions: SCV normalization by SCL consistently improves the ability to detect group differences, strengthens clinical-radiological correlations, and seems to be of particular relevance in settings of subtle disease-related SC atrophy in MS. Normalization by SCL should be performed to maximize the clinical utility of measures of SC atrophy.