Effects of Pudendal and Cortical Paired Associative Stimulation on Plasticity of Sphincter Responses after Incomplete Spinal Cord Injury: A Feasibility Study

Special Article – Spinal Cord Injury Rehabilitation

Phys Med Rehabil Int. 2017; 4(3): 1118.

Effects of Pudendal and Cortical Paired Associative Stimulation on Plasticity of Sphincter Responses after Incomplete Spinal Cord Injury: A Feasibility Study

Vásquez N¹*, Knight S¹, Susser J¹, Gall A¹, Craggs MD1,2 and Ellaway PH1,3

¹The London Spinal Cord Injury Centre, Royal National Orthopaedic Hospital, UK

²University College London, UK

³Imperial College, London, UK

*Corresponding author: Natalia Vásquez, London Spinal Cord Injury Centre, Royal National Orthopaedic Hospital, Stanmore, HA7 4LP, UK

Received: June 30, 2017; Accepted: July 24, 2017; Published: July 31, 2017

Abstract

Objectives: To assess whether paired associative stimulation of the dorsal penile nerve and the motor cortex produces change in anal sphincter muscle responses in incomplete spinal cord injury (iSCI).

Methods: This was a prospective experimental study. Eighteen male iSCI subjects with neuropathic bladder history were recruited. Incontinence was assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ). Electromyographic activity of the external anal sphincter was recorded. Pudendo-anal reflexes (PAR) were elicited by electrical stimulation of the dorsal penile nerve (DPN) and anal sphincter motor evoked potentials (MEP) by transcranial magnetic stimulation (TMS). Paired associative stimulation (PAS) (DPN and TMS, interval 40ms) was applied for 8 min at 0.25Hz using either real or sham TMS of the motor cortex. Pudendal somatosensory evoked potentials (pSSEPs) were recorded.

Results: A PAR could be recorded in all subjects and an MEP in 12 subjects. The PAR was facilitated by prior (30ms) conditioning TMS. Group mean amplitudes of the PAR, the conditioned PAR and MEP, and ICIQ scores showed no change after real or sham PAS. However, 13 subjects individually showed significant changes (increases or decreases) in one or more sphincter responses to real or sham PAS. Individual responses were not correlated with the presence or latency of pSSEPs.

Conclusions: Paired pudendal nerve and cortical stimulation altered the excitability of cortico-spinal and reflex circuitry controlling the anal sphincter in iSCI individuals. Future work should investigate whether such changes in individuals might lead to altered neural circuitry accompanied by functional restoration of continence.

Keywords: Pudendal anal reflex; Sphincter muscle; Motor evoked potential; Paired associative stimulation; Incontinence

Abbreviations

DPN: Dorsal Penile Nerve; ICIQ: International Consultation On Incontinence Modular Questionnaire; Isci: Incomplete Spinal Cord Injury; MEP: Motor Evoked Potential; PAS: Paired Associative Stimulation; PAR: Pudendo-Anal Reflex; Pssep: Pudendal Somatosensory Evoked Potentials; TMS: Transcranial Magnetic Stimulation

Introduction

Incomplete spinal cord injury (iSCI) frequently impacts on spino-bulbo-spinal pathways causing major disruption to the control of the pelvic organs and sphincter muscles. Restoration of bladder and bowel control are top priorities for those with iSCI, especially in cases of paraplegia [1]. The neural control involved in bladder and bowel function is complex involving pelvic reflexes, a pontine coordination centre and the sensorimotor cortex. Disruption of spinal pathways can cause neuropathic detrusor over-activity (NDO) leading to detrusor-sphincter dyssynergia. One aspect of NDO and dyssynergia is incontinence resulting from disruption of the guarding reflex and its voluntary control [2,3]. This study specifically addresses the possibility of augmenting the guarding reflex in iSCI individuals through plasticity of their residual neural control.

The pudendal anal reflex may be regarded as a surrogate marker for the bladder guarding reflex [4]. In iSCI subjects who retain the reflex, it may be facilitated by conditioning transcranial magnetic stimulation of the motor cortex [5], which is likely to promote continence. This study attempted to establish the feasibility of using repeated, combined stimulation of the pudendal afferent and corticospinal pathways to generate a lasting facilitation through plasticity in the circuits responsible for the guarding reflex.

Repetitive, paired associative stimulation (PAS) [6] involving TMS and peripheral nerve stimulation [7,8] can induce changes in human corticospinal excitability. When a peripheral nerve stimulus was delivered in advance of a cortical TMS pulse with an interval such that the afferent nerve volley arrived at the sensorimotor cortex approximately synchronously with application of the TMS pulse, it produced a topographically specific increase in the amplitude of motor-evoked potentials (MEPs) that was long lasting [6].

If a PAS protocol based on paired pudendal nerve and cortical stimulation can be shown to induce plasticity in the cortico-spinal circuits controlling a sphincter muscle [9], a long-term aim would be to investigate whether development of the technique might lead to changes in neural circuitry accompanied by functional restoration of continence.

Methods

Subjects

Eighteen males with incomplete, chronic (>1y post injury) and grade C or D neurologically-graded supra-sacral spinal cord injuries (American Spinal Injuries Association (ASIA) Impairment Scale (AIS) were recruited following appropriate informed consent (Table 1). All subjects were required to have a history of neuropathic bladder, be able to elicit a weak residual voluntary anal contraction and show a pudendal anal reflex (PAR) in response to electrical stimulation of the dorsal penile nerve (DPN). Some subjects (Table 1) were receiving medical treatment appropriate for their bladder and urethral sphincter dysfunction. Exclusion criteria included lack of tolerance to TMS, contra-indications to TMS (e.g. cranial implants) and concomitant clinical interventions unrelated to the study. Ethics approval for the study was obtained through the UK National Research Ethics Service.