Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

AIMS: To investigate pudendal-to-bladder spinal reflexes in chronic spinal cord injured (SCI) cats induced by electrical stimulation of the pudendal nerve. METHODS: Bladder inhibition or voiding induced by pudendal nerve stimulation at different frequencies (3 or 20 Hz) was studied in three female, chronic SCI cats under alpha-chloralose anesthesia. RESULTS: Voiding induced by a slow infusion (2-4 ml/min) of saline into the bladder was very inefficient (voiding efficiency=7.3%+/-0.9%). Pudendal nerve stimulation at 3 Hz applied during the slow infusion inhibited reflex bladder activity, and significantly increased bladder capacity to 147.2+/-6.1% of its control capacity. When the 3-Hz stimulation was terminated, voiding rapidly occurred and the voiding efficiency was increased to 25.4+/-6.1%, but residual bladder volume was not reduced. Pudendal nerve stimulation at 20 Hz induced large bladder contractions, but failed to induce voiding during the stimulation due to the direct activation of the motor pathway to the external urethral sphincter. However, intermittent pudendal nerve stimulation at 20 Hz induced post-stimulus voiding with 78.3+/-12.1% voiding efficiency. The voiding pressures (39.3+/-6.2 cmH2O) induced by the intermittent pudendal nerve stimulation were higher than the voiding pressures (23.1+/-1.7 cmH2O) induced by bladder distension. The flow rate during post-stimulus voiding induced by the intermittent pudendal nerve stimulation was significantly higher (0.93+/-0.04 ml/sec) than during voiding induced by bladder distension (0.23+/-0.07 ml/sec). CONCLUSIONS: This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.     

Urinary bladder control by electrical stimulation: Review of electrical stimulation techniques in spinal cord injury

Evacuation of urine in paraplegics without the need for catheters would be possible when voiding could be induced by eliciting a bladder contraction. A challenging option to obtain detrusor contraction is electrical stimulation of the detrusor muscle or its motor nerves. This article reviews the 4 possible stimulation sites where stimulation would result in a detrusor contraction: the bladder wall, the pelvic nerves, the sacral roots, and the spinal cord. With respect to electrode application, sacral root stimulation is most attractive. However, in general, sacral root stimulation results in simultaneous activation of both the detrusor muscle and the urethral sphincter, leading to little or no voiding. Several methods are available to overcome the stimulation-induced detrusor-sphincter dyssynergia and allow urine evacuation. These methods, including poststimulus voiding, fatiguing of the sphincter, blocking pudendal nerve transmission, and selective stimulation techniques that allow selective detrusor activation by sacral root stimulation, are reviewed in this paper.     

The effect of intravesical electrical stimulation on bladder function and synaptic neurotransmission in the rat spinal cord after spinal cord injury

OBJECTIVE

To investigate the effects of intravesical electrical stimulation (IVES) on bladder function and synaptic neurotransmission in the lumbosacral spinal cord in the spinalized rat, as the clinical benefits of IVES in patients with increased residual urine or reduced bladder capacity have been reported but studies on the mechanism of IVES have mainly focused on bladder Aδ afferents in central nervous system‐intact rats.

MATERIALS AND METHODS

In all, 30 female Sprague‐Dawley rats were divided equally into three groups: normal control rats, sham‐stimulated spinalized rats and IVES‐treated spinalized rats. IVES was started 5 weeks after spinal cord injury (SCI) and was performed 20 min a day for 5 consecutive days. At 7 days after IVES, conscious filling cystometry was performed. Sections from the L6 and S1 spinal cord segments were examined for n ‐methyl‐d ‐aspartic acid receptor 1 (NMDAR1) subunit and γ‐aminobutyric acid (GABA) immunoactivity.

RESULTS

In IVES‐treated spinalized rats, the number and maximal pressure of nonvoiding detrusor contractions were significantly less than in sham‐stimulated spinalized rats. The mean maximal voiding pressure was also lower in IVES‐treated than in sham‐stimulated spinalized rats. IVES significantly reduced the interval between voiding contractions compared with the untreated spinalized rats. There was an overall increase in NMDAR1 immunoactivity after SCI, which was significantly lower in IVES‐treated spinalized rats. Immunoactivity of GABA after SCI was significantly lower than in the control group and was significantly higher in IVES‐treated spinalized rats.

CONCLUSION

Our results suggest that IVES might affect voiding contractions in addition to inhibiting C‐fibre activity and that IVES seems to have a more complex effect on the bladder control pathway. For synaptic neurotransmission in the spinal cord, IVES could possibly shift the balance between excitation and inhibition towards inhibition.     

Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury

AIMS: Although electrical stimulation of the pudendal nerve has been shown to evoke reflex micturition-like bladder contractions in both intact and spinalized cats, there is little evidence to suggest that an analogous excitatory reflex exists in humans, particularly those with spinal cord injury (SCI). We present two cases where electrical activation of pudendal nerve afferents was used to evoke excitatory bladder responses. SUBJECTS AND METHODS: A percutaneously placed catheter electrode was used to electrically stimulate the pudendal nerve trunk in two males with SCI. The response was quantified with recorded changes in detrusor pressure and EMG activity of the external anal sphincter. RESULTS: In both individuals, frequency specific (f = 20-50 Hz) activation of the pudendal nerve trunk evoked excitatory bladder contractions that also depended on the stimulus amplitude and bladder volume. CONCLUSION: The results suggest that selective activation of the perineal branches of the pudendal nerve may further augment the excitatory reflex evoked by electrical stimulation.     

Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview

Structural discontinuity in the spinal cord after injury results in a disruption in the impulse conduction resulting in loss of various bodily functions depending upon the level of injury. This article presents a summary of the scientific research employing electrical stimulation as a means for anatomical or functional recovery for patients suffering from spinal cord injury. Electrical stimulation in the form of functional electrical stimulation (FES) can help facilitate and improve upper/lower limb mobility along with other body functions lost due to injury e.g. respiratory, sexual, bladder or bowel functions by applying a controlled electrical stimulus to generate contractions and functional movement in the paralysed muscles. The available rehabilitative techniques based on FES technology and various Food and Drug Administration, USA approved neuroprosthetic devices that are in use are discussed. The second part of the article summarises the experimental work done in the past 2 decades to study the effects of weakly applied direct current fields in promoting regeneration of neurites towards the cathode and the new emerging technique of oscillating field stimulation which has shown to promote bidirectional regeneration in the injured nerve fibres. The present article is not intended to be an exhaustive review but rather a summary aiming to highlight these two applications of electrical stimulation and the degree of anatomical/functional recovery associated with these in the field of spinal cord injury research.     

Detrusor-myoplasty,innervated rectus muscle transposition study,and functional effect on the spinal cord injury rat model

The purpose of this investigation was to determine the feasibility of striated muscular augmentation of the urinary bladder (detrusor-myoplasty, DMP). Initial studies, transposition, and bladder wrap using several distinct muscle groups was attempted in laboratory rats, goats, and fresh human cadavers. The rectus abdominus muscle was found to be best suited to completely encompass the bladder with an intact neural and vascular supply. The technique was then applied in a rat model of spinal cord injury (SCI). Modified Tarlov ratings were employed to assess neurologic function 30 days after SCI. The median final neurological score of SCI rats with and without DMP was 4 and 5, respectively. Sham-operated SCI (control) rats, with and without DMP, both had normal final Tarlov scores of 12 (P < 0.05). Muscle blood flow values for the flap and the contralateral undissected rectus muscles were not significantly different (97 ± 34 and 105 ± 40 ml/100 g tissue/min, respectively, P = 0.47). Postoperatively, no bowel or abdominal wall functional deficits were apparent. The rotated muscular flap remained innervated and vascularized. Analysis of 24 hr micturition patterns demonstrated no differences in oral fluid intake/24hr. voided volume/24hr, and ratio of number of micturitions during the night vs. day among the four groups: (1) control (neither SCI nor DMP), (2) DMP only, (3) SCI only, and (4) SCI with DMP. Spinal cord injured rats with and without detrusor-myoplasty demonstrated a significant decrease in the number of micturitions/24hr, an increased volume per micturition, and greater largest and smallest micturition volumes (P < 0.05) when compared to controls. The micturition patterns among SCI rats with and without DMP were similar, as were non-SCI animals with and without DMP. This is the first report of the principle and technique of detrusor-myoplasty. Dissection of rats, goats, and human cadavers revealed that a vascularized and innervated rectus muscle flap can be rotated into the pelvis and wrapped around the bladder without tension. Significant loss of bladder capacity did not occur with skeletal muscle adaptation. Detrusor-myoplasty may be applicable for patients with an areflexic detrusor and non-intact sacral motor roots who are not candidates for sacral anterior root neurostimulation. © 1994 Wiley-Liss, Inc.     

A clinically meaningful training effect in walking speed using functional electrical stimulation for motor-incomplete spinal cord injury

Context/Objective: The study aimed to investigate the presence of a training effect for rehabilitation of walking function in motor-incomplete spinal cord injury (SCI) through daily use of functional electrical stimulation (FES).

Setting: A specialist FES outpatient centre.

Participants: Thirty-five participants (mean age 53, SD 15, range 18-80; mean years since diagnosis 9, range 5 months - 39 years) with drop foot and motor-incomplete SCI (T12 or higher, ASIA Impairment Scale C and D) able to ambulate 10 metres with the use of a walking stick or frame.

Interventions: FES of the peroneal nerve, glutei and hamstrings as clinically indicated over six months in the community.

Outcome Measures: The data was analysed for a training effect (difference between unassisted ten metre walking speed at baseline and after six months) and orthotic effects (difference between walking speed with and without FES) initially on day one and after six months. The data was further analysed for a minimum clinically important difference (MCID) (>0.06 m/s).

Results: A clinically meaningful, significant change was observed for initial orthotic effect (0.13m/s, CI: 0.04-0.17, P?=?0.013), total orthotic effect (0.11m/s, CI: 0.04-0.18, P?=?0.017) and training effect (0.09m/s, CI: 0.02-0.16, P?=?0.025).

Conclusion: The results suggest that daily independent use of FES may produce clinically meaningful changes in walking speed which are significant for motor-incomplete SCI. Further research exploring the mechanism for the presence of a training effect may be beneficial in targeting therapies for future rehabilitation.     

Bladder cancer in patients with spinal cord injuries

OBJECTIVE: To evaluate the age-standardized incidence rate of bladder cancer in patients with spinal cord injury (SCI) and the overall risk for this population. PATIENTS AND METHODS: We reviewed 1334 patients with SCI whose dates of SCI, or first attendance at our centre, were between 1940 and 1998. The length of follow-up was calculated for each patient and age-specific incidence rates of bladder cancer calculated using 5-year age bands. This was used to calculate the overall incidence rate, using direct standardization with the European standard population. The cancers were analysed histochemically to characterize the phenotype. RESULTS: The 1324 patients contributed a total of 12 444 person-years of follow-up. There were four cases of bladder cancer, giving an age-standardized incidence rate of 30.7 per 100 000 person-years. Histochemistry showed areas were positive for cytokeratin 14, which was also positive in the undifferentiated areas. Immunohistochemical staining was positive for cytokeratin 14 and consistently negative for cytokeratin 20, suggesting a pure squamous phenotype. CONCLUSIONS: The age-standardized incidence of invasive bladder cancer in patients in our SCI unit is not statistically different from that of the general population. However, the incidence of invasive bladder cancer in the present study appears to be lower than that reported in other series. Histochemical analysis confirmed a squamous cell phenotype in these tumours.     

Comparison of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) for spasticity in spinal cord injury - A pilot randomized cross-over trial

Objective: Spasticity following spinal cord injury (SCI) can impair function and affect quality of life. This study compared the effects of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) on lower limb spasticity in patients with SCI.

Design: Double blind randomized crossover design.

Setting: Neuro-rehabilitation unit, Manipal University, India.

Participants: Ten participants (age: 39 ± 13.6 years, C1–T11, 1–26 months post SCI) with lower limb spasticity were enrolled in this study.

Interventions: Participants were administered electrical stimulation with TENS and FES (duration - 30 minutes) in a cross over manner separated by 24 hours.

Outcome Measures: Spasticity was measured using modified Ashworth scale (MAS) [for hip abductors, knee extensors and ankle plantar flexors] and spinal cord assessment tool for spastic reflexes (SCATS). Assessments were performed at baseline, immediately, 1 hour, 4 hours, and 24 hours post intervention.

Results: A between group analysis did not show statistically significant differences between FES and TENS (P > 0.05). In the within group analyses, TENS and FES significantly reduced spasticity up to 4 hours in hip adductors and knee extensors (P < 0.01). SCATS values showed significant reductions at 1 hour (P?=?0.01) following TENS and 4 hours following FES (P?=?0.01).

Conclusion: A single session of electrical stimulation with FES and TENS appears to have similar anti-spasticity effects that last for 4 hours. The findings of this preliminary study suggest that both TENS and FES have the potential to be used as therapeutic adjuncts to relieve spasticity in the clinic. In addition, FES may have better effects on patients presenting with spastic reflexes.     

Voiding reflex in chronic spinal cord injured cats induced by stimulating and blocking pudendal nerves

AIMS: To induce efficient voiding in chronic spinal cord injured (SCI) cats. METHODS: Voiding reflexes induced by bladder distension or by electrical stimulation and block of pudendal nerves were investigated in chronic SCI cats under alpha-chloralose anesthesia. RESULTS: The voiding efficiency in chronic SCI cats induced by bladder distension was very poor compared to that in spinal intact cats (7.3 +/- 0.9% vs. 93.6 +/- 2.0%, P < 0.05). In chronic SCI cats continuous stimulation of the pudendal nerve on one side at 20 Hz induced large amplitude bladder contractions, but failed to induce voiding. However, continuous pudendal nerve stimulation (20 Hz) combined with high-frequency (10 kHz) distal blockade of the ipsilateral pudendal nerve elicited efficient (73.2 +/- 10.7%) voiding. Blocking the pudendal nerves bilaterally produced voiding efficiency (82.5 +/- 4.8%) comparable to the efficiency during voidings induced by bladder distension in spinal intact cats, indicating that the external urethral sphincter (EUS) contraction was caused not only by direct activation of the pudendal efferent fibers, but also by spinal reflex activation of the EUS through the contralateral pudendal nerve. The maximal bladder pressure and average flow rate induced by stimulation and bilateral pudendal nerve block in chronic SCI cats were also comparable to those in spinal intact cats. CONCLUSIONS: This study shows that after the spinal cord is chronically isolated from the pontine micturition center, bladder distension evokes a transient, inefficient voiding reflex, whereas stimulation of somatic afferent fibers evokes a strong, long duration, spinal bladder reflex that elicits efficient voiding when combined with blockade of somatic efferent fibers in the pudendal nerves.     

Minimally-invasive electrical stimulation of the pudendal nerve: a pre-clinical study for neural control of the lower urinary tract

AIMS: Electrical stimulation of afferent pudendal nerve fibers can evoke sustained bladder contractions (SBC) in cats, yet evidence of therapeutic efficacy in human subjects is lacking. This pre-clinical study was undertaken to test the hypothesis that robust bladder contractions can be generated with a minimally-invasive needle electrode. MATERIALS AND METHODS: In seven adult cats, triggered electromyographic (EMG) signals from the external anal sphincter (EAS) were used to minimize the needle-to-nerve distance; while reflex bladder contractions were recorded as 20-sec trains of current pulses of varying amplitude (threshold to 10 mA) and frequency (1-100 Hz) were applied to the nerve. This stimulation paradigm was repeated at successively greater needle-to-nerve distances (0.5 cm intervals) and also at different electrode positions along the nerve. RESULTS: Electrophysiological access to the pudendal nerve was consistently achieved, as indicated by the average threshold for EAS activation (0.31+/-0.19 mA). Using different combinations of stimulus amplitude and frequency, robust SBCs were evoked in every experiment. More rostral electrode positions exhibited stimulation amplitudes and corresponding maximum bladder pressures (0.68+/-0.36 mA and 25.3+/-3.5 cmH2O, respectively) that were comparable to those of more invasive stimulation methods. CONCLUSIONS: The needle electrode provides a minimally-invasive approach that will enable the study of reflexes mediated by pudendal afferents in humans, and allow pre-operative testing before implanting a permanent device.     

多节段脊髓平面损伤后大鼠神经源性膀胱模型的制备

目的研制一种具有临床相似性、可调控性、可重复性的脊髓损伤后神经源性膀胱尿道功能障碍动物模型的制模方法。方法采用改良Allen法,将10g重的柯氏针从20cm高以自由落体落下,撞击在动物脊柱背侧的垫片上,造成一定程度的脊髓损伤。结果在脊髓休克期,骶上脊髓损伤(胸腰段)组和骶髓损伤组动物平均每次挤压膀胱排尿量差异无统计学意义(P>0.05),在脊髓休克期后,两组之间差异有统计学意义(P<0.001)。结论改良Allen法具有临床相似性等优点,能为脊髓损伤后神经源性膀胱尿道功能障碍的研究提供理想的动物模型。     

大鼠脊髓慢性压迫性损伤动物模型的建立

目的 建立一种大鼠脊髓慢性压迫性损伤模型。方法 应用平头不锈钢螺钉从大鼠C4椎体前侧钻入压迫脊髓腹侧，术后保留螺钉30d，并用联合行为评分(CBS)、神经电生理、光镜、电镜检查进行综合评判。结果 模型动物脊髓慢性压迫随着螺钉轻、中、重程度的不同，其术后行为学、运动诱发电位(MEP)及组织学观察符合脊髓慢性压迫症病理改变的特点。结论 建立了大鼠脊髓慢性压迫性损伤模型，此模型制作简便，可重复性强，脊髓损伤能表现出不同的压迫深度，为进一步研究脊髓慢性压迫损伤病理机制奠定了基础。     

Functional electrical stimulation therapy for grasping in traumatic incomplete spinal cord injury: randomized control trial

The purpose of this single-site randomized control trial was to assess the short-term and long-term efficacy of functional electrical stimulation (FES) therapy over conventional occupational therapy in improving voluntary hand function in incomplete C4-C7 spinal cord injury individuals. All 22 participants recruited in this randomized control trial received treatment for both the left and right upper extremities. Every participant, irrespective of group allocation, received one dose (60 min per day, 5 days per week for the duration of 8 weeks) of conventional occupational therapy for hand function. Of the 22 participants, 12 individuals received an additional dose of conventional occupational therapy, while the remaining 10 participants received a dose of FES hand therapy. The primary outcome measure was Functional Independence Measure (FIM) self-care subscore. The secondary outcome measures were Spinal Cord Independence Measure (SCIM) self-care subscore and Toronto Rehabilitation Institute Hand Function Test (TRI-HFT). The participants who received FES therapy showed significantly greater improvements in hand function at discharge, and were able to maintain their gains at long-term follow-up as assessed using FIM self-care subscore, SCIM self-care subscore, and TRI-HFT. The FES therapy effectively increased independence and thereby improved quality of life of individuals with tetraplegia when compared with conventional occupational therapy.     

磁刺激和碱性成纤维细胞生长因子对脊髓损伤早期的保护作用

目的探讨脊髓损伤后,应用磁刺激和外源性碱性成纤维细胞生长因子(bFGF)对损伤脊髓组织早期的保护作用。方法实验利用Allen WD(weight drop)技术,以致伤力(砝码质量10g,下落高度2．5cm)制成wistar大鼠T8脊髓损伤模型,治疗组分别于术后即刻、1h、2h、4h、24h分别予0．5HZ、70％输出强度的磁刺激,同时经蛛网膜下腔导管注入20ul bFGF,对照组不做处理。术后2h、6h、24h取治疗组、对照组动物损伤区脊髓组织作以下检测：用干湿法测水含量;用原子吸收光谱法测钙、镁离子含量;伤后5d取损伤脊髓组织,电镜观察脊髓结构。结果损伤区脊髓组织水含量增多,钙离子水平升高,镁离子水平下降,白质内髓鞘结构紊乱,囊性变严重;而应用磁刺激和bFGF可改善上述变化。结论脊髓损伤后应用磁刺激和bFGF可减轻脊髓损伤后的离子失衡,从而对继发性脊髓损伤具有保护作用。