MP48-16: Comparative evaluation of white matter demyelination by magnetic resonance imaging and neurogenic voiding dysfunction in a viral murine model of multiple sclerosis

Li Lu, Alison Xie, Natalie Serkova, Anna Malykhina

Introduction: Lower urinary tract symptoms (LUTS) are present in 70–80% of patients with multiple sclerosis (MS), having a negative effect on the quality of the individual’s life. In 10–15% of patients, neurogenic LUTS are present at the onset of MS when there may be only few lesions identified in the CNS. In this study, we aimed to establish if early white matter demyelination could be detected by MRI, and whether it could be associated with the first signs of neurogenic LUTS.

Methods: Adult mice were inoculated with A59 strain of mouse hepatitis virus (coronavirus-induced encephalomyelitis model, CIE). The level of neurodegeneration was assessed by the Clinical Symptom Score (CSS). MRI experiments were performed on a 9.4 Tesla/ 20-cm BioSpec MRI scanner. Bladder function was evaluated in vivo by a filter paper assay, and in vitro by detrusor contractility studies.

Results: The spines from control and CIE mice (CSS=1-2, 10 wks) were subjected to a FLASH MRI ultra-high resolution sequence, and DTI-EPI protocols. The mean diffusivity (D) and fractional anisotropy (FA) parameters were used to assess the integrity and organization of the white matter. The representative T2 MRI and DTI images, and FA maps are included in Fig. 1. The D values were significantly reduced in CIE mice (5.36±0.21x10-4 mm2/s) in comparison to control (6.98±0.37x10-4 mm2/s, p=0.01). The FA parameters were also significantly lower in CIE mice (0.39±0.02 vs 0.56±0.02 in control, p=0.002). Micturition patterns in CIE mice were not significantly changed, but the differences were detected in the contractile responses of the detrusor to various stimuli.

Conclusions: The early changes in D and FA parameters reflect the ongoing changes in white matter structural integrity of the spinal cord. These early signs of demyelination are associated with modified detrusor contractile responses, which likely reflect the early stage of neurogenic LUTS development. Source of

Funding: The study was supported by the NIH/NIDDK grant DK121506 and Department of Surgery AEF grant.