The somatosensory representation of the human clitoris: an fMRI study.

We studied the central representation of pudendal afferents arising from the clitoral nerves in 15 healthy adult female subjects using electrical dorsal clitoral nerve stimulation and fMRI. As a control body region, we electrically stimulated the right hallux in eight subjects. In a block design experiment, we applied bilateral clitoral stimulation and unilateral (right) hallux stimulation. Activation maps were calculated for the contrasts 'electrical dorsal clitoral nerve stimulation versus rest' and 'electrical hallux stimulation versus rest'. A random-effect group analysis for the clitoral stimulation showed significant activations bilateral in the superior and inferior frontal gyri, insulae and putamen and in the postcentral, precentral and inferior parietal gyri (including the primary and secondary somatosensory cortices). No activation was found on the mesial surface of the postcentral gyrus. For the hallux, activations occurred in a similar neuronal network but the activation in the primary somatosensory cortex was localized in the inter-hemispheric fissure. The results of this study demonstrate that the central representation of pudendal afferents arising from the clitoral nerves and sensory inputs from the hallux can be studied and distinguished from each other by fMRI. From the somatotopic order described in the somatosensory homunculus one would expect for electrical clitoral nerve stimulation activation of the mesial wall of the postcentral gyrus. In contrast, we found activations on the lateral surface of the postcentral gyrus.

The facilitatory effect of duloxetine combined with pelvic floor muscle training on the excitability of urethral sphincter motor neurons.

INTRODUCTION AND HYPOTHESIS: Aim of this study was to investigate the excitability of sphincter motor neurons under the influence of pelvic floor muscle training (PFMT) and duloxetine. Due to their mechanisms of action, there might be a synergistic effect of duloxetine and PFMT in regard to the facilitation of spinal reflexes controlling urethral sphincter contractions and hence continence. METHODS: In ten healthy female subjects, clitoral electric stimulation (CES) and transcranial magnetic stimulation (TMS) were used to determine individual motor thresholds for external urethral sphincter (EUS) contractions before and after PFMT, duloxetine, and PFMT + duloxetine. RESULTS: PFMT and duloxetine alone significantly decreased the motor thresholds for EUS contractions during CES and TMS. However, the combined treatment reduced the motor threshold for EUS contractions significantly stronger compared to PFMT or duloxetine alone. CONCLUSIONS: The results are suggestive for a synergistic facilitatory effect of PFMT and duloxetine on sphincter motor neuron activation.

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging.

OBJECTIVES: Although botulinum neurotoxin type A (BoNT/A) intradetrusor injections are a recommended therapy for neurogenic detrusor overactivity (NDO), refractory to antimuscarinic drugs, a standardisation of injection technique is missing. Furthermore, some basic questions are still unanswered, as where the toxin solution exactly spreads after injection. Therefore, we investigated the distribution of the toxin solution after injection into the bladder wall, using magnet resonance imaging (MRI). METHODS: Six patients with NDO were recruited. Three of six patients received 300 U of BoNT/A + contrast agent distributed over 30 injection sites (group 1). The other three patients received 300 U of BoNT/A + contrast agent distributed over 10 injection sites (group 2). Immediately after injection, MRI of the pelvis was performed. The volume of the detrusor and the total volume of contrast medium inside and outside the bladder wall were calculated. RESULTS: In all patients, a small volume (mean 17.6%) was found at the lateral aspects of the bladder dome in the extraperitoneal fat tissue, whereas 82.4% of the injected volume reached the target area (detrusor). In both groups there was a similar distribution of the contrast medium in the target area. A mean of 33.3 and 25.3% of the total detrusor volume was covered in group 1 and 2, respectively. Six weeks after injection, five of six patients were continent and showed no detrusor overactivity in the urodynamic follow-up. No systemic side effects were observed. CONCLUSIONS: Our results provide morphological arguments that the currently used injection techniques are appropriate and safe.

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve--an fMRI study in healthy women.

AIMS: Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS: After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS: A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION: Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.

The effects of tolterodine on bladder-filling sensations and perception thresholds to intravesical electrical stimulation: method and initial results.

OBJECTIVES: To study the effects of the antimuscarinic agent tolterodine on the perception thresholds to intravesical electrical stimulation (IES) and the effects of the drug on subjective bladder sensation during normal filling cystometry in healthy female volunteers. SUBJECTS AND METHODS: In seven healthy women IES was applied at 2.5 Hz (pulse width 10 ms, protocol 1), 2.5 Hz (pulse width 0.2 ms, protocol 2), and 250 Hz (pulse width 0.2 ms, protocol 3). Sensory perception thresholds were obtained using electric currents in 0.5 mA steps. Afterwards the bladder was filled and the first bladder-filling sensation, first desire to void, strong desire to void and urge to void were recorded. The bladder was then emptied, the volume measured and subjects were checked for residual urine by ultrasonography. The subjects then received 4 mg of tolterodine and the entire protocol was repeated 2 h afterward. The perception thresholds for IES and bladder sensation levels obtained at baseline were compared statistically with the corresponding values after tolterodine. RESULTS: Tolterodine significantly increased perception thresholds to IES for all three protocols (P = 0.027, 0.018 and 0.018, respectively). The drug had no effect on the filling levels for the corresponding bladder sensation. CONCLUSION: Oral tolterodine significantly increased the perception threshold to IES in healthy women; there was no effect on subjective bladder sensations during cystometry.

Persistence of therapeutic effect after repeated injections of botulinum toxin type A to treat incontinence due to neurogenic detrusor overactivity.

OBJECTIVES: To study the effect of repeated botulinum toxin type A injections into the detrusor in patients with neurogenic detrusor overactivity and incontinence to determine the safety of repeated injections, the persistence of the clinical and urodynamic treatment efficacy, and potential changes in bladder compliance. METHODS: Seventeen patients with neurogenic detrusor overactivity who had received three or more botulinum toxin type A injections into the detrusor were studied. The clinical and urodynamic data were analyzed at baseline (before the first injection), after the first injection, and after the last repeated injection. RESULTS: No systemic side effects were observed for the total of 91 injections. The mean number of injections per patient was 5.4 (range 3 to 9). The mean number of incontinence episodes per day decreased from 2.6 at baseline to 0 after the first injection, and remained at 0 after the last injection. The maximal cystometric bladder capacity and reflex volume increased significantly after the first and last injection compared with at baseline. The maximal detrusor pressure decreased significantly after the first and last injection compared with at baseline. No difference in compliance was found from baseline to the first or last injection. CONCLUSIONS: Repeated injections of botulinum toxin A into the detrusor muscle are a safe and valuable treatment option for neurogenic detrusor overactivity. After repeated injections, the effect on the clinical and urodynamic parameters remained constant. Also, repeated injections did not decrease bladder compliance.

Facilitatory neuromodulative effect of duloxetine on pudendal motor neurons controlling the urethral pressure: a functional urodynamic study in healthy women.

OBJECTIVE: The aim of this functional urodynamic experiment in healthy women was to study the effect of duloxetine, which is a combined serotonin and norepinephrine (5-HT/NE) reuptake inhibitor, on urethral resting pressure, excitability of pudendal motor neurons, and urethral sphincter contractility. METHODS: In 11 healthy female subjects three baseline urethral pressure profiles (UPPs) were obtained to study resting pressure. Afterward the individual motor threshold (MT) for external urethral sphincter (EUS) contraction in response to transcranial magnetic stimulation (TMS) was determined to study the excitability of pudendal motor neurons. Another three UPPs were recorded while sacral root magnetic stimulation (SMS) was performed to evoke reproducible urethral contractions to study urethral sphincter contractility. Then the women received 40 mg duloxetine and the protocol was repeated 4 h after drug administration. The resting pressure values, MT values following TMS, and the EUS pressure amplitudes in response to SMS obtained at baseline were statistically compared to the corresponding values at follow-up after duloxetine. RESULTS: Oral administration of duloxetine significantly lowered MT for EUS contraction in response to TMS (p=0.013). In addition, duloxetine significantly increased EUS pressure amplitudes in response to SMS (p=0.0007, 5 of 11 subjects evaluated) but did not change urethral resting pressures. CONCLUSIONS: This is the first functional, urodynamic controlled study to show that the combined 5-HT/NE reuptake inhibitor duloxetine has a significant effect on the excitability of pudendal motor neurons and on urethral sphincter contractility in healthy women in vivo but no significant effect on urethral resting tone. Our data confirm a facilitatory neuromodulative effect of duloxetine on sphincter motor neurons in humans.

Understanding detrusor sphincter dyssynergia--significance of chronology.

OBJECTIVES: To evaluate in patients with spinal cord injury (SCI) and detrusor sphincter dyssynergia (DSD) whether the onset of external urethral sphincter (EUS) contractions precedes or follows the onset of bladder contractions and to address the issue of potential therapeutic approaches based on the understanding of DSD chronology. METHODS: A retrospective review of video-urodynamic recordings of patients with SCI that demonstrated both untreated neurogenic overactive bladder and DSD, from January 2002 to December 2003, was performed. Delay A was defined as the period between the onset of an EUS pressure increase and the onset of a bladder pressure increase and delay B as the period between the onset of a urethral sphincter pressure increase and the moment at which the bladder pressure increase reached 10 cm H2O greater than the baseline value. RESULTS: Twenty patients with traumatic SCI matched all inclusion criteria. Delay A was positive (EUS contracted first) in 16 (80%) of 20 patients. The mean time for delay A was 2.2 seconds. A positive association was found among a positive delay A, the completeness of the spinal lesion, and continuous DSD type. Delay B was positive in all 20 patients (100%). The mean time for delay B was 7.6 seconds. CONCLUSIONS: In most patients with SCI and DSD, the EUS contraction started before the onset of the bladder contraction. Additionally, in all patients with SCI, the EUS contraction started before the critical part of the bladder contraction. A pathophysiologic hypothesis for such chronology is discussed. A potential therapeutic application would be to use urethral sphincter activity to trigger inhibition of bladder contractions (conditional neuromodulation) and treat the neurogenic overactive bladder.

A case of undiagnosed tethered cord syndrome aggravated by transurethral prostate resection.

BACKGROUND: A 68-year-old man presented with a history of significant urinary urge incontinence, pollakiuria, and weak bladder sensation. He also reported mild fecal incontinence and a hypotrophic and slightly weaker left leg. At 63 years of age he had presented to a urologist for treatment of irritative lower urinary tract symptoms and incontinence. A transurethral resection of the prostate had been performed. After the operation, the symptoms had persisted and the incontinence seriously worsened. INVESTIGATIONS: Clinical neurologic examination, videourodynamic examination, neurophysiologic examination, and MRI of the spinal cord. DIAGNOSIS: Neurogenic bladder dysfunction caused by adult tethered cord syndrome with myelon up to S2 level, spina bifida occulta, and lipoma infiltrating the conus medullaris. MANAGEMENT: Conservative anticholinergic treatment failed, and injection of botulinum-A toxin is planned.