Pirko, Istvan

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.

Multiple sclerosis (MS), a chronic inflammatory-degenerative illness of the central nervous system (CNS), remains at the moment a treatable but incurable disease. Currently available disease-modifying agents (DMA-s), the majority of which are being injected, mainly relieve the inflammatory phase of MS with little beneficial effect, if any, in halting neurodegeneration. Cladribine is an immunosuppressive agent that can be administered orally and by cycles of short-course dosing as opposed to continuous administration. Cladribine has been shown to be effective in reducing inflammatory activity of MS but much remains unknown regarding its potential beyond the control of CNS inflammation. In addition, knowledge on the safety profile of cladribine in MS is limited. Data from on going clinical studies and registries on its safety profile will shed more light on the actual benefit/risk ratio of cladribine.

ABSTRACT The human monoclonal antibody rHIgM22 enhances remyelination following spinal cord demyelination in a virus‐induced murine model of multiple sclerosis. Using three‐dimensional T2‐weighted in vivo spinal cord magnetic resonance imaging (MRI), we have therefore assessed the extent of spinal cord demyelination, before and after 5 weeks of treatment with rHIgM22, to determine whether antibody enhanced remyelination can be detected by MRI. A significant decrease was seen in T2 high signal lesion volume following antibody treatment. Histologic examination of the spinal cord tissue reveals that this decrease in lesion volume correlates with antibody promoted remyelination. To show that rHIgM22 enters the spinal cord and colocalizes with demyelinating lesions, we used ultrasmall superparamagnetic iron oxide particle (USPIO)‐labeled antibodies. This may be considered as additional evidence to the hypothesis that rHIgM22 promotes remyelination by local effects in the lesions, likely by binding to CNS cells. The reduction in high signal T2‐weighted lesion volume may be an important outcome measure in future clinical trials in humans.