Non-lesional white matter changes in pediatric multiple sclerosis and monophasic demyelinating disorders

Objective: To analyze diffusion tensor imaging (DTI) derived metrics between patients with childhood onset multiple sclerosis (MS), monophasic demyelinating illnesses, and healthy controls. Background: Monophasic demyelinating illnesses can be indistinguishable clinically and radiologically, utilizing standard MRI studies. DTI studies in adults implicate the involvement of normal-appearing white matter (NAWM) in MS. Methods: Subjects with DTI studies (15 directions, 1.5 Tesla (GE), 3x3x3 mm, interpolated to 1.5x1.5x3 mm) were retrospectively identified. We studied three groups: childhood onset MS (n=18), monophasic illness (eight with acute disseminated encephalomyelitis (ADEM), seven with clinically isolated syndrome (CIS)) and age-matched controls. DTI had been obtained within one month of symptom onset for patients with ADEM and within a median of 20 months for the MS group. DTI measures were determined using a semi-automated method from standardized regions of interest (ROI) containing central fibers of the corpus callosum genu and internal capsule. Results: The MS group had significantly lower fractional anisotropy (FA) values compared to controls (p<0.001), with increased radial diffusivity (RD) and decreased axial diffusivity (AD). In the monophasic group FA was smaller than the controls (p=0.01) with increased RD and no difference in AD. Conclusions: This retrospective analysis provides evidence that NAWM is affected in pediatric MS and monophasic demyelinating disease, with a potentially novel pattern demonstrating reduced AD in pediatric MS. Further larger scale confirmatory studies are needed to address whether the demonstrated DTI changes could be used as a biomarker in pediatric patients presenting with an initial demyelinating event.