Neuromyelitis optica (NMO) is a rare inflammatory disease primarily targeting the optic nerves and spinal cord, with limited brain volvement. Its clinical features and relapsing course resemble that of relapsing-remitting multiple sclerosis (MS), although the underlying pathological mechanisms differ. In particular, there is no progressive phase in NMO, and current evidence suggests that neurodegeneration is absent between attacks. In a previous investigation, no evidence of ongoing diffuse cerebral damage was found using MRI relaxometry and atrophy measures¹. In the current study, we extended these evaluations to the cervical spinal cord, using multi-component relaxometry to evaluate changes in atrophy and quantitative parameters of tissue damage at baseline and one year in NMO patients versus MS patients and controls.13 anti-aquaporin-4 antibody-positive NMO patients (median age 45 (range 27-76)), 13 relapsing-remitting MS patients (38 (22-62)), and 17 age-matched healthy controls (54 (19-76)) were scanned at baseline. Patient groups had equivalent disease durations (NMO: median 60 months (12-186); MS: 54 (24-156)). A subset of 8 NMO, 11 MS patients and 14 controls was scanned again after one year. All but one NMO and one MS patient in the follow-up group had a history of transverse myelitis. A multi-component driven equilibrium single pulse observation of T₁/T₂ (mcDESPOT) protocol was acquired on a Siemens Verio 3T scanner over the whole cervical cord with 0.9x0.9x1.8 mm voxels². Images were registered with FSL-FLIRT, segmented using the Spinal Cord Toolbox³, and analysed voxelwise with a three-pool model⁴ to calculate the myelin water fraction (f_M) and T₁ (related to total water content). Median f_M and T₁ were obtained along the cervical cord from C1 to C7. Cord volume (CV), normalized by length and including lesioned areas, was measured on a T₁-weighted spoiled gradient echo image from the mcDESPOT protocol. Non-parametric statistics were used to compare groups at baseline, and change in metrics over time; mean percentage difference between groups or percentage change ± standard deviation are reported.

BASELINE (Fig. 1): Compared to controls, NMO patients had lower CV (-12.4±12.4%, p=.002), lower f_M (-11.3±9.2%, p=.004) and higher T₁ (+11.0±12.7%, p=.002); the MS group had lower f_M (-14.0±13.0%, p=.001) and higher T₁ (+8.2±11.0%, p=.01). There were no significant differences between patient groups.

LONGITUDINAL (Fig. 2): At one-year follow-up, controls were stable in all measures (all p≥.2). MS patients showed a loss of cord volume (-1.4±3.2%, p=.2), reduction in f_M (-2.1±11.8%, p=.2) and increase in T₁ (+4.4±10.3%, p=.3) (all non-significant). The NMO group showed a significant decrease in CV (-5.1±4.6%, p=.02), an increase in f_M (+6.6±8.3%, p=.04) and a decrease in T₁ (-2.4±2.5%, p=.04).

Cross-sectional analysis showed, as expected, lower volume & f_M and elevated T₁ in both patient groups compared to controls (see Fig. 3 for example maps). Over the one-year observation period, cord atrophy was seen in the NMO group, but not detected in the MS group. Given that focal cord pathology is known to be more severe in NMO, we hypothesize that the volume decrease is the result of continuing atrophy following transverse myelitis. The NMO group also displayed significant longitudinal changes in f_M and T₁, which were in the opposite direction to the (non-significant) changes in the MS group. Decrease in T₁ is likely due to the loss of tissue volume; where cystic lesions shrink, the amount of necrotic tissue diminishes, leaving a greater relative amount of healthy tissue and producing a lower median T₁ value over the cord, which may also explain the observed increase in f_M. Alternatively, the increase in f_M could result from a drop in total water content (f_M being a ratio of myelin to total water). Finally, though less likely given the time frame for follow-up, the increase in f_M could reflect ongoing repair, which would be consistent with the hypothesis that progression is absent in NMO.The observed changes are consistent with what is known about the pathology of NMO. The decrease in cord volume can be attributed to residual damage from lesions. Changes in T₁ and f_M are linked with the volume loss, most likely at lesion sites. Thus, shrinkage of lesioned tissue leads to changes in median values calculated over the whole cervical cord. While evidence of disease progression has been previously demonstrated in the MS cord, these results suggest this is not the case in NMO and lend evidence to the current theory that subclinical progression is not a feature of the disease. Further work will look at segmenting lesioned from healthy tissue in order to separate the effects of lesion evolution from changes in normal-appearing tissue.