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

To analyze diffusion tensor imaging (DTI) derived metrics between patients with childhood onset multiple sclerosis (MS), monophasic demyelinating illnesses, and healthy controls.

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.

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.

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.

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.