Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity A. Conte a,* , A. Giannantoni b,* , S. Proietti b , S. Giovannozzi b , G. Fabbrini a , A. Rossi c , M. Porena b and A. Berardelli a a Department of Neurology and Psychiatry, ÔSapienzaÕ, University of Rome, Viale dell’Universita ´ 30, Rome, and IRCCS Neuromed, Rome; b Department of Urology and Andrology, Ospedale S. Maria della Misericordia, S. Andrea delle Fratte, University of Perugia, Perugia; and c Department of Neurology, Ospedale S. Maria della Misericordia, S.Andrea delle Fratte, University of Perugia, Perugia Keywords: bladder afferents, botu- linum toxin A, Parkin- sonÕs disease, spinal cord injury Received 13 September 2011 Accepted 4 November 2011 Background: Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overac- tivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity. Methods: To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with ParkinsonÕs disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls. Results: Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A signifi- cantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition. Conclusions: These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity. Introduction Intravesical botulinum toxin type A (BoNT/A) injec- tion has been proposed as a treatment option for neu- rogenic and non-neurogenic overactive bladder refractory to conventional oral antimuscarinic therapy [1], and BoNT/A improves overactive bladder symp- toms in patients with ParkinsonÕs disease (PD) [2–4]. Whereas ample evidence shows how BoNT/A acts at the neuromuscular junction [5], less is known about its effects when injected in the bladder wall [6,7]. Studies on biopsy specimens from bladder tissue and urine from patients who received an intradetrusor BoNT/A injec- tion suggested that BoNT/A may act by reducing afferent nervous transmission [7,8]. In this study, we investigated whether BoNT/A in- jected into the detrusor muscle in humans improves detrusor overactivity by modulating bladder afferent activity. In healthy subjects, afferent information from the bladder (C- and Ad fibers) modulates spinal moto- neuron excitability as tested with the soleus Hoffmann reflex (H reflex) [9–11]. We, therefore, tested the H re- flex from soleus muscle during bladder filling before and after a single BoNT/A injection in patients with PD and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conven- tional anticholinergic therapy. All patients underwent clinical, urodynamic, and neurophysiological assess- ments before and one and 6 months after BoNT/A injection. To investigate possible abnormal H reflex modulation in the two groups of patients studied (PD and SCI), we compared the possible changes in H reflex size during bladder filling before BoNT/A injection Correspondence: A. Berardelli, Department of Neurology and Psychiatry, ÔSapienzaÕ, University of Rome, Viale dellÕUniversita` , 30, 00185 Rome, Italy (tel.: +39 06 49914700; fax: +39 06 49914700; e-mail: alfredo.berardelli@uniroma1.it). *These authors contributed equally to this work. Ó 2011 The Author(s) European Journal of Neurology Ó 2011 EFNS 1 European Journal of Neurology 2011 doi:10.1111/j.1468-1331.2011.03618.x