Peripheral nerve stimulation via lumbosacral route has shown to modulate cortical and subcortical brain areas which seem to control the complex process of micturion, i.e. sensation of bladder filling and  the timing of micturition. The present study was conducted to investigate the changes in brain activity during modulation of various brain areas   after transcutaneous posterior tibial nerve stimulation (TcPTNS) for lower urinary tract symptoms (LUTS) in pediatric patients.

We used 18 FDG PET CT to investigate the effects of PTNS on brain activity in pediatric patients with urodynamically proven   detrusor overactivity (DO) or underactive detrusor (UD). Exclusion criteria were neurogenic bladder,  lower urinary tract surgery, urinary tract infection and lower urinary symptoms secondary to anatomical anomalies such as posterior urethral valves, ureterocele or ectopic ureter. A voiding diary was maintained for 3 days as an assessment tool for all patients. The number of voids daily (NV), average voided volume (AVV) and maximum voided volume (MVV) before and after treatment were evaluated using voiding diary. Transcutaneous posterior tibial nerve stimulation (TcPTNS) was performed using TENS III stimulator. Two Self-adhesive surface electrodes were  used (13). All the patient underwent weekly session for 30 minutes for 12 weeks followed by 3 weekly maintenance therapy. PET CT brain was done before the start of TcPTNS and at the end of induction therapy i.e. 3 months.
The clinical outcome was assessed on the basis international children continence society (ICCS) definition along with improvement in the parameters in bladder diary, uroflowmetry and post void residual urine.

The study included 21 pediatric patients with a mean age of 5.6Yrs (range 4-16 yrs.). Of the 21 patients, 12 (57.15%) had overactive bladder with urodynamically proven DO and 9 (42.85%) had under active detrusor. In cases overactive bladder TcPTNS decreased the activity in the mid-cingulate gyrus, Hypothalamus, premotor cortex    [more on right side] and Lateral pons (Figures 1a, b, c and d).
 These findings were explored further as to correlate them with the neuroanatomical and physiological regions of the brain involved in the process of micturition. It is interesting to note that these are the areas which actually modulate in integrated manner during the process of bladder filling (8, 9, 11, 20, and 21).
On the contrary avid uptake was noted in lateral cingulate gyrus, mid pons and periaqueductal grey [PAG] in cases of underactive detrusor (Figures 2 a, b, c and d).  Again these findings were correlated   with the neuroanatomical and physiological regions of the brain it was noted that hyper metabolism in these areas has been recorded during strong urge or the act of micturition (7, 10, 11, and 14).
On assessment of clinical outcome, over all 12 (57.14%) patients reported improvement in their symptoms. In cases of overactive bladder 7 (58.3%) patients were improved, of these 3 (42.85%) were completely cured, while 3 (42.85%) improved and 1(14.3%) had partial improvement. Four (33.3%) patient failed to show any clinical benefit. Interesting to note that in spite showing desired changes in the brain physiology 33.3 % of the patient failed to show any clinical improvement.
In cases of underactive bladder 5 (55.6%) patients reported improvement, of these 2 (40%) were completely cure, while 2 (40%) improved and 1(20%) had partial improvement. Four (44.4%) of the patients were not benefited clinically.
Here again in spite showing desired changes in the brain physiology 44.4% of the patient failed to show any clinical improvement. This shows that brain activation may not always translate in to successful clinical outcome.

The study included 21 pediatric patients with a mean age of 5.6Yrs (range 4-16 yrs).
Of the 21 patients, 12 had overactive bladder with urodynamically proven DO and 9 had under active detrusor.
In cases overactive bladder TcPTNS decreased the activity in the cerebellum, midbrain and adjacent midline thalamus and limbic cortical areas, i.e. the cingulate gyrus, ventromedial orbitofrontal gyrus and prefrontal cortex. These are the areas   involved in the sense of bladder filling. While, FDG uptake was more avid in these areas before the start of TcPTNS.  On contrary the avid uptake was noted in hypothalamus and prefrontal area in cases of underactive detrusor. These are the areas involved sensorimotor learning and the initiation of voiding.

These findings suggest that after therapy by TcPTNS the focus of brain activation changes   according to the sense of bladder filling or voiding i.e. to overcome urge in cases of overactive bladder and to initiate  voiding in cases of underactive detrusor.

Patidar N, Mittal V, Kumar M, Sureka SK, Arora S, Ansari MS. Transcutaneous posterior tibial nerve stimulation in pediatric overactive bladder: A preliminary report. J Pediatr Urol. 2015 Dec;11(6):351
Das Gupta R1, Kavia RB, Fowler CJ. Cerebral mechanisms and voiding function. BJU Int. 2007;99(4):731-4.
Michael Shy, Steve Fung, Timothy B. Boone, Christof Karmonik, Sophie G. Fletcher, and Rose Khavari  Functional Magnetic Resonance Imaging during Urodynamic Testing Identifies Brain Structures Initiating Micturition. Urol. 2014 October ; 192(4): 1149–1154