Do brain structural abnormalities differentiate separate forms of urgency urinary incontinence?

Abstract

Aims: Urgency urinary incontinence (UUI) is a major problem for seniors. The underlying mechanisms of disease and therapy are unknown. We sought structural brain abnormalities that might underlie the functional differences previously observed by functional Magnetic Resonance Imaging in UUI patients versus controls, or among UUI responders versus non-responders to therapy-and thereby reveal potential disease mechanisms and therapeutic targets.

Methods: Secondary study of a trial of biofeedback-assisted pelvic floor muscle training (BFB) in 60 women (>60 yrs) with UUI, plus 11 age-matched continent controls. Brain structural abnormalities were investigated using: (1) white-matter hyperintensities (WMH); (2) diffusion tensor imaging (DTI) to reveal white-matter pathways with impaired integrity; and (3) voxel-based morphometry (VBM) to show regions of atrophy or hypertrophy.

Results: WMH burden was greater in UUI patients than controls (globally and in superior longitudinal fasciculus and cingulum), suggesting a possible causal connection. WMH burden was unexpectedly greater in responders than non-responders to BFB, and appeared to increase in non-responders but not in responders. DTI revealed even worse integrity of the cingulum than was apparent by WMH. VBM showed parahippocampal atrophy in UUI.

Conclusions: Many women with UUI have white-matter damage that interferes with pathways critical to bladder control; they can be taught by techniques like BFB to exert stronger control over the bladder. For others, in whom abnormalities of key brain areas are less marked, UUI's cause may reside elsewhere, and therapy targeting these brain centers may be less effective than therapy targeting the bladder or other brain centers.

Keywords: diffusion tensor imaging; magnetic resonance imaging; voxel-based morphometry; white matter hyperintensities.

Fig. 1.

Working model, showing 3 putative neural circuits that control the voiding reflex by inhibiting the periaqueductal gray (PAG). PMC = pontine micturition center, Sa = sacral parasympathetic region, ON = nucleus of Onuf, th = thalamus, lPFC and mPFC = lateral and medial prefrontal cortex, respectively, dACC/SMA = dorsal anterior cingulate cortex and supplementary motor area.

Fig. 2.

Results of tract-based spatial statistics (TBSS), applied to diffusion tensor imaging (DTI) in continent and urgency-incontinent women. The figure shows a sagittal section at × = −7. Green coloring shows skeletonized white-matter tracts for whole group of women with UUI. Red color shows where mean fractional anisotropy (FA) is significantly smaller in UUI than in continent controls (P < 0.05 at cluster level, uncorrected for multiple comparisons). The red tract is in the cingulum. An earlier provisional analysis²⁶ identified the adjacent fornix instead, an inconsistency that presumably reflected low statistical power.

Fig. 3.A

(left). Results of VBM analyses at baseline. Regions where tissue volume was smaller in UUI than in normal controls (atrophy). Blue: significant at P<0.05 at cluster level. Crosshairs are at MNI coordinates [−29,−16,−28]. Note that removing those on anticholinergic medications from the analysis did not make any difference to these results.

Fig. 3. B

(right) Results of VBM analyses at baseline. Regions where tissue volume was larger in responders than in non-responders (relative hypertrophy). Red/yellow: significant at P<0.05 at cluster level. Crosshairs are at [1, 4, 40]. Note that removing those on anticholinergic medications from the analysis did not make any difference to these results.