Abstract
BACKGROUND: Spinal cord atrophy associates with motor disability in multiple sclerosis (MS). The influence of intracranial lesion burden (ILB) on spinal cord atrophy requires further investigation. Tumefactive MS (TMS) offers a model for studying the contribution of ILB on spinal cord atrophy. OBJECTIVES: Determine the relationship between upper cervical cord (UCC) area, ILB, and progressive TMS. METHODS: Individuals with tumefactive demyelinating disease (TDD) undergoing UCC area analysis (C1-C3) were stratified into three groups based on ILB: single-lesion (SL-TDD), multiple-lesion (ML-TDD), and tumefactive MS (TMS). Descriptive characteristics and UCC area were compared across radiological and clinical phenotypes. RESULTS: Of 109 individuals, six (6%) were SL-TDD, 28 (26%) ML-TDD, and 75 (69%) TMS. All seven (6%) with progressive MS met TMS criteria. TMS had more spinal cord (63% vs. 26%; p = 0.003), and lateral tract lesions (54% vs. 14%; p = 0.001), and a higher final EDSS [median 2.5 (IQR 1.5,3.0) vs. 2.0 (0.0,2.0); p = 0.01] than ML-TDD. After excluding individuals with UCC lesions, there was an inverse trend between median C2 area and ILB across groups: SL-TDD, 56.3 mm(2) (47.9,69.0); ML-TDD, 53.4 mm(2) (37.2,63.2), and TMS, 50.8 mm(2) (32.0,64.3); p = 0.08. CONCLUSIONS: During the course of TMS, early disability may be driven by a single tumefactive lesion while late disability is related to the accrual of intracranial lesions, spinal cord disease, and UCC atrophy. Across the TMS spectrum, there appears to be an inverse relationship between UCC area and ILB, partially independent of UCC lesions which trended towards statistical significance, warranting further investigation.