Michael Craggs

A Microchannel Neuroprosthesis for Bladder Control After Spinal Cord Injury in Rat

An electronic interface for recording and stimulating nerves that innervate the bladder helps to restore normal bladder function in rats with spinal cord injury. Getting to the Root of Bladder Control Injury to the spinal cord typically results in loss of conscious bladder emptying and the sensation of fullness. Currently, only limited treatment options are available, with most of the patients receiving catheterization. However, this is cumbersome and leads to urological complications including unsolicited episodes of bladder contraction, leading to inappropriate emptying. In a new study, Chew et al. design a “closed-loop” electronic device that can accurately record bladder filling from sensory nerves after spinal cord injury in rat. Using this information, bladder emptying can be artificially stimulated on demand by electrically modulating nerve firing. It is traditionally difficult to record robust neuronal activity from peripheral nerves in vivo. Typically, cuff electrodes are used to record from whole nerves, but produce poor signal quality and provide little indication of bladder filling. Through nerve microdissection, Chew et al. implanted fine-diameter nerves (“rootlets”) into insulated microchannels, recording action potential firing that accurately encoded bladder filling. The device had multiple microchannels for concurrent recording, greatly improving the resolution. Using this sensory information and by manipulating stimulation characteristics, the authors prevented the rat bladder from emptying inappropriately, and bladder contraction was initiated when desired. This work opens a new avenue for the design of a neuroprosthesis for bladder control after spinal cord injury. A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic.

Dynamic biochemical information recovery in spontaneous human seminal fluid reactions via 1H NMR kinetic statistical total correlation spectroscopy.

Human seminal fluid (HSF) is a complex mixture of reacting glandular metabolite and protein secretions that provides critical support functions in fertilization. We have employed 600-MHz (1)H NMR spectroscopy to compare and contrast the temporal biochemical and biophysical changes in HSF from infertile men with spinal cord injury compared to age-matched controls. We have developed new approaches to data analysis and visualization to facilitate the interpretation of the results, including the first application of the recently published K-STOCSY concept to a biofluid, enhancing the extraction of information on biochemically related metabolites and assignment of resonances from the major seminal protein, semenogelin. Principal components analysis was also applied to evaluate the extent to which macromolecules influence the overall variation in the metabolic data set. The K-STOCSY concept was utilized further to determine the relationships between reaction rates and metabolite levels, revealing that choline, N-acetylglucosamine, and uridine are associated with higher peptidase activity. The novel approach adopted here has the potential to capture dynamic information in any complex mixture of reacting chemicals including other biofluids or cell extracts.

Alpha-1 adrenoceptor blockade

PURPOSE: Patients with chronic anal fissures are known to have high resting anal pressures that return to normal after successful surgical treatment. Internal anal sphincter activity is increased by sympathetic excitatory innervationvia alpha adrenoceptors. The objective of this study was to determine the effect of alpha-1 adrenoceptor blockade on anal sphincter pressure in patients with and without chronic anal fissures. METHODS: The effect on the anal canal pressure profile of a single oral 20 mg dose of indoramin, an alpha-1 adrenoceptor antagonist, on seven patients with chronic anal fissure and six healthy patients without a fissure was investigated. RESULTS: Indoramin reduced anal resting pressures in those with anal fissure by a mean of 35.8 percent, from 106.9 ± 22.15 cm H2O to 68.6 ± 20.35 cm H2O, and in those without anal fissure by a mean of 39.9 percent, from 84.17 ± 27.46 cm H2O to 52.17 ± 24.78 cm H2O, after one hour. This pressure reduction persisted at three hours, and its magnitude is comparable to that obtained after internal sphincterotomy. The pressure reduction occurred over the whole length of the anal canal. CONCLUSION: It is proposed that alpha-1 adrenoceptor antagonists could be a suitable treatment for chronic anal fissure and other painful conditions where reduction in anal pressure is warranted.

Induction of central nervous system plasticity by repetitive transcranial magnetic stimulation to promote sensorimotor recovery in incomplete spinal cord injury

Cortical and spinal cord plasticity may be induced with non-invasive transcranial magnetic stimulation to encourage long term potentiation or depression of neuronal circuits. Such plasticity inducing stimulation provides an attractive approach to promote changes in sensorimotor circuits that have been degraded by spinal cord injury (SCI). If residual corticospinal circuits can be conditioned appropriately there should be the possibility that the changes are accompanied by functional recovery. This article reviews the attempts that have been made to restore sensorimotor function and to obtain functional benefits from the application of repetitive transcranial magnetic stimulation (rTMS) of the cortex following incomplete spinal cord injury. The confounding issues that arise with the application of rTMS, specifically in SCI, are enumerated. Finally, consideration is given to the potential for rTMS to be used in the restoration of bladder and bowel sphincter function and consequent functional recovery of the guarding reflex.

Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement

Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.

THE RELATIONSHIP BETWEEN BLADDER MANAGEMENT AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH SPINAL CORD INJURY

Study design: Cross-sectional study. Objectives: (1) To assess the relationship between bladder management methods and the healthrelated quality of life (HRQL) in patients with spinal cord injury (SCI). (2) To identify any correlation between the two questionnaires used to assess the quality of life (one validated for SCI and one validated for bladder symptoms). Setting: Spinal Cord Injury Centre, Royal National Orthopaedic Hospital, Middlesex, UK. Methods: This study is based on two questionnaires with results collected from 142 people with SCI. The two questionnaires were based on information from the Short-Form 36-Item Health Survey (SF-36) and the King’s Health Questionnaire and included demographic characteristics, bladder management methods and the frequency of incontinence. Results: There is a moderate correlation between the results of the SF-36 and the King’s Health Questionnaire. Only 21% SCI patients report normal voiding without any other form of bladder management. The type of bladder management may influence the HRQL in patients with SCI. Clean intermittent catheterization by attendant, indwelling transurethral catheterization and indwelling suprapubic catheterization are the three groups with the worst mental status. In addition, the frequency of incontinence is a strong influence on HRQL. Conclusions: The results of this study may provide a general baseline HRQL for patients with SCI. Our findings show the relationships between bladder management methods and quality of life in patients with SCI. In addition, the impact of incontinence on quality of life was also confirmed. Spinal Cord (2010) 48, 319–324; doi:10.1038/sc.2009.132; published online 20 October 2009

Minimizing Stimulus Current in a Wearable Pudendal Nerve Stimulator Using Computational Models

After spinal cord injury, functions of the lower urinary tract may be disrupted. A wearable device with surface electrodes which can effectively control the bladder functions would be highly beneficial to the patients. A trans-rectal pudendal nerve stimulator may provide such a solution. However, the major limiting factor in such a stimulator is the high level of current it requires to recruit the nerve fibers. Also, the variability of the trajectory of the nerve in different individuals should be considered. Using computational models and an approximate trajectory of the nerve derived from an MRI study, it is demonstrated in this paper that it may be possible to considerably reduce the required current levels for trans-rectal stimulation of the pudendal nerve compared to the values previously reported in the literature. This was corroborated by considering an ensemble of possible and probable variations of the trajectory. The outcome of this study suggests that trans-rectal stimulation of the pudendal nerve is a plausible long term solution for treating lower urinary tract dysfunctions after spinal cord injury.

Design of sEMG assembly to detect external anal sphincter activity: a proof of concept

OBJECTIVE Conditional trans-rectal stimulation of the pudendal nerve could provide a viable solution to treat hyperreflexive bladder in spinal cord injury. A set threshold of the amplitude estimate of the external anal sphincter surface electromyography (sEMG) may be used as the trigger signal. The efficacy of such a device should be tested in a large scale clinical trial. As such, a probe should remain in situ for several hours while patients attend to their daily routine; the recording electrodes should be designed to be large enough to maintain good contact while observing design constraints. The objective of this study was to arrive at a design for intra-anal sEMG recording electrodes for the subsequent clinical trials while deriving the possible recording and processing parameters. APPROACH Having in mind existing solutions and based on theoretical and anatomical considerations, a set of four multi-electrode probes were designed and developed. These were tested in a healthy subject and the measured sEMG traces were recorded and appropriately processed. MAIN RESULTS It was shown that while comparatively large electrodes record sEMG traces that are not sufficiently correlated with the external anal sphincter contractions, smaller electrodes may not maintain a stable electrode tissue contact. It was shown that 3 mm wide and 1 cm long electrodes with 5 mm inter-electrode spacing, in agreement with Nyquist sampling, placed 1 cm from the orifice may intra-anally record a sEMG trace sufficiently correlated with external anal sphincter activity. SIGNIFICANCE The outcome of this study can be used in any biofeedback, treatment or diagnostic application where the activity of the external anal sphincter sEMG should be detected for an extended period of time.