What clinical parameter strongly associates white matter tract alterations in a Multiple Sclerosis population with voiding dysfunction? A prospective exploratory study.

Purpose: To correlate clinical and urodynamics parameters in Multiple Sclerosis patients (MS) presenting Lower Urinary Tract Symptoms (LUTS) with both Expanded Disability Status Scale (EDSS) and changes in white matter integrity as seen on Diffusion Tensor Images (DTI). LUTS worsen throughout MS, as does lesion burden. We investigated which symptoms correlated best with structural changes in white matter structure. Materials and Methods: Ten adult women >18 years were recruited with stable MS for ≥3 months and voiding dysfunction defined as %PVR/BV > 20%. Patients participated in a clinical Urodynamic Study (UDS) and completed several questionnaires (i.e., HAM, AUASS, NBS-QoL). DTI images were acquired using a 7-Tesla Siemens MAGNETOM Terra MRI scanner. DTI maps were constructed, and individual patients were co-registered with the ICBM-DTI-81 white matter atlas to extract fractional anisotropy (FA) and mean diffusivity (MD). Pearson's correlation test was performed between each WMT and clinical parameters and between clinical parameters and the EDSS score as well. P-values < 0.05 were considered significant. Results: Of the clinical parameters, %PVR/BV obtained from the average of multiple un-instrumented uroflow assessments had significant correlations to the greatest number of WMTs. Furthermore, we observed that in all recorded clinical parameters, %PVR/BV was the only significant parameter correlated to the EDSS score. Conclusion: This study demonstrates that %PVR/BV can be used as an objective parameter to gauge WMT changes and disease progression in MS patients. Future studies are needed to refine this model.

Is the Brainstem Activation Different Between Healthy Young Male and Female Volunteers at Initiation of Voiding? A High Definition 7-Tesla Magnetic Resonance Imaging Study.

PURPOSE: Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. METHODS: Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as "initiation of voiding." BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. RESULTS: We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. CONCLUSION: Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

Disruption of specific white matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis.

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD. METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman's correlation test was performed between each the Fractional Anisotropy (FA) and mean diffusivity (MD) of each WMT and the clinical parameters. RESULTS: Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The right inferior cerebellar peduncle, left posterior limb of internal capsule, and left superior cerebellar peduncle displayed significant associations to the greatest number of clinical parameters. CONCLUSIONS: Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts.