Page 45 - Bladder Dysfunction in the Context of the Bladder-Brain Connection - Ilse Groenendijk.pdf

A systematic review and meta-analysis of the central innervation of the lower urinary tract 43
a patient population instead of healthy controls. One micturition related study included patients with MS15 and one PFMC related study included patients with SUI.28 Both ALE analyses (PFMC and micturition) were repeated without inclusion of the patient data to assess the influence on the outcome. Only the amount of clusters changed (the ones with the lowest ALE values disappeared), however, most probably due to the lower number of included subjects in the ALE analysis which is critical for the validity of such analysis and hampers a reasonable interpretation of these differences from a statisti- cal point of view. As visible in the raw data in the supplements, both studies including patient data do not show remarkable outliers, or other distinguishing results compared to the studies including healthy volunteers.
Studying differences in activation patterns between healthy controls and patients is important for future clinical implications of neuroimaging and the search towards find- ing the pathophysiology of diseases within functional urology. The SMA, cingulate gyrus and prefrontal cortex have been independently described as areas of interest when evaluating differences between patients and healthy controls, full or empty bladder and effect of therapies.10,15,28,45-47
ALE analysis highlights consistently involved brain areas during the execution of both tasks, however, not every included study found the same main core areas. This poor reliability or reproducibility might be the cause of the limited clinical translat- ability of functional neuroimaging findings. Recently, two studies investigated the reliability of functional neuroimaging of the LUT.48,49 Both studies investigated the reliability with bladder-filling protocols, rather than the motor control addressed here, and detected a moderate reliability with maximum inter-class correlation coefficients of 0.4448 and 0.55.49 Several reasons for this poor reliability can be sug- gested like inhomogeneous patient groups, small patient groups, inconsistent task execution or habituation to tasks. In addition, the strong involvement of psychological factors in performing LUT motor tasks may considerably contribute to the variabil- ity of results, not only between subjects but also within a given subject over time. Hence, reliability requires improvement. Two aspects appear relevant for this endeavor: a) validation of task and recording parameters to better understand and control for mea- surement related bias and b) correlation of neuroimaging findings to clinical outcomes to better understand the relation between supraspinal activity patterns and dysfunction or symptoms. To better compare between or pool studies, harmonization of protocols and terminology would be of great advantage.50
Limitations
The current systematic review and ALE analysis makes all raw data available and creates a clear overview of fMRI and PET imaging of the supraspinal control of the LUT. Our liberal search strategy additionally allowed a very comprehensive review. Nevertheless, there
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