Higher Neural Correlates in Patients with Multiple Sclerosis and Neurogenic Overactive Bladder Following Treatment with Intradetrusor Injection of OnabotulinumtoxinA

Abstract

Purpose: OnabotulinumtoxinA is a well described treatment of neurogenic overactive bladder. While motor effects on the detrusor muscle have been extensively studied, the sensory effects have not. The aim of this study was to evaluate the impact of intradetrusor onabotulinumtoxinA injection on brain activity in female patients with multiple sclerosis and neurogenic overactive bladder.

Materials and methods: We prospectively studied 12 women with stable multiple sclerosis and neurogenic overactive bladder using concurrent functional magnetic resonance imaging and urodynamic studies prior to and 6 to 10 weeks following onabotulinumtoxinA injection. Individual functional magnetic resonance imaging activation maps at the time of strong urgency were averaged before and after onabotulinumtoxinA injection where areas of significant activation were identified.

Results: After onabotulinumtoxinA injection functional magnetic resonance imaging activation increased in the right cingulate body (p = 0.0012), the left posterior cingulate (p = 0.02), the left anterior cingulate (p = 0.0015), the right prefrontal cortex (p = 0.0015), the insula (p = 0.0138) and the pons micturition center (p = 0.05). Sparse areas showed decreased activity, including the left cerebellum (p = 0.001), the left fusiform gyrus (p = 0.065) and the bilateral lentiform nucleus (p = 0.026).

Conclusions: Intradetrusor injection of onabotulinumtoxinA appeared to increase the activity of most brain regions known to be involved in the sensation and process of urinary urgency in female patients with multiple sclerosis and neurogenic overactive bladder. To our knowledge this is the first study of its kind to evaluate the possible effects of onabotulinumtoxinA at the human brain level where sensory awareness is located. This activation pattern may be used to further phenotype patients to optimize therapy or determine the sensory effects of onabotulinumtoxinA beyond the bladder.

Figures

Figure 1.

The subtraction BOLD activation maps at the time of strong desire to void (Full Urge) of post-pre OnabotA for the ROIs. The green crosshair indicated the ROI in each panel. 1) Right Cingulate 2) Pons 3) Insula 4) Right Prefrontal Cortex

Figure 2.

Demonstrates Amygdala/parahippocampal gyrus at the time of strong desire to void (Full Urge) at baseline(a) with elevated blood flow and following OnabotA treatment (b) with decreased blood flow.

Figure 3.

The subtraction of BOLD activation maps at the time of strong desire to void (Full Urge) of MS patients from Healthy Controls prior (top row) and following (middle row) OnabotA injection. The bottom row depicts the subtraction of BOLD activation maps of MS patients post OnabotA from pre OnabotA at the time of Full Urge.