Reinnervation of spinal cord by cholinergic neurons.
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1. Intracellular responses in neck and forelimb motoneurons to electrical stimulation of the vestibular nerve, the optic tectum, and the optic nerve were studied in frog. 2. Stimulation of the anterior branch of the vestibular nerve typically produced EPSPs, bilaterally, in neck, shoulder (DOR), and forelimb extensor (TRI, RAD) motoneurons, and bilateral IPSPs in forelimb adductor (PED) and flexor (ULN, COR) motoneurons. 3. Latencies of PSPs recorded in neck, shoulder, and proximal extensor motoneurons (TRI) were mostly in the disynaptic range, whereas many of those recorded in distal extensor (RAD) and in adductor and flexor motoneurons involved three synapses. 4. Lesion of the vestibulospinal fibers greatly reduced the vestibular nerve-evoked field potentials in the spinal cord and the occurrence of PSPs in forelimb motoneurons. These results as well as the latency measurements suggest that the pathway linking vestibular nerve and forelimb motoneurons mainly consists of vestibulospinal fibers, though involvement of other structures for production of later PSPs could not be completely ruled out. Hemisection of the brain stem at its most caudal level showed that the pathway to the contralateral motoneurons crosses at the level of brain stem as well as in the spinal cord. 5. Stimulation of the optic tectum produced EPSPs, IPSPs, and a mixture of EPSPs and IPSPs in neck, shoulder, and forelimb motoneurons, bilaterally. Most frequently, a combination of an excitation and inhibition was observed. The pathway from the optic tectum to neck and limb motoneurons is at least dysnaptic in nature. 6. Stimulation of the optic nerve produced IPSPs and a mixture of EPSPs and IPSPs in neck and forelimb motoneurons. Impulses originating from the optic nerve descend as far as to lumbar motoneurons producing EPSP-IPSP sequences bilaterally. 7. Interaction studies suggested that the vestibular and optic pathways to neck and forelimb motoneurons are separate from each other so that the site of integration of vestibular and visual input occurs at the level of motoneurons. 8. Evidence for electronic coupling among forelimb motoneurons and electrical synaptic transmission in th pathway linking vestibular nerve and forelimb motoneurons is presented.
In this study we investigated the receptive field properties, responses to mechanical and thermal stimuli, and sensitivity to systemic administration of pentobarbital sodium and morphine of single neurons recorded in the sacral spinal cords of pentobarbital-anesthetized rats. Fifty-three neurons responded to innocuous mechanical stimulation of the tail. Of 45 neurons that were additionally tested with noxious thermal stimulation, 62% responded and were classified as wide-dynamic-range or multireceptive neurons. Recording sites were located mainly in the middle layers of the S2-S4 dorsal horn. Mechanosensitive receptive fields on the tail varied widely in size (range 0.14-35 cm2, mean 10.33 cm2) and form, and were in nearly all cases bilateral. Most neurons responded with a high-frequency discharge followed by a more slowly adapting response to pressure stimuli delivered with von Frey hairs. Responses (maximal frequency and total number of impulses) increased in a graded manner to pressure stimuli ranging from 1.2 to 447 g. For neurons responsive to noxious heating of the tail, responses increased in a linear manner over the range of 38-54 degrees C and often leveled off at higher temperatures. Of nine neurons tested with both graded von Frey and noxious heat stimuli, mean responses (maximal frequency and total number of impulses) evoked by the strongest pressure stimuli were larger than those evoked by the most intense heat stimuli, but the difference was not statistically significant. Responses to repeated 48 degrees C stimuli were significantly attenuated within 8 min after systemic administration of morphine (1 or 2 mg/kg ip), reaching maximal suppression (to 37.3%; N = 13) after 18 min, with recovery following systemic naloxone. After morphine (1 and 2 mg/kg ip), the slope of the population stimulus-response function for noxious heat was reduced (51.8%), and the threshold was increased (by 4 degrees C). Responses to noxious heat were significantly depressed (to a mean of 54%; N = 10) by supplemental administration of pentobarbital (mean 17 mg/kg over 5 min). On the basis of similarities between the present data and previous behavioral measures of tail flick stimulus-response functions and their modulation, it is suggested that some of the present neurons might function as interneurons in the tail flick reflex arc.
OBJECTIVE: Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. METHODS: Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. RESULTS: In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. CONCLUSIONS: We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.
OBJECTIVES: During a screening trial to determine candidacy for sacral nerve stimulation (SNS), several patients were required to repeat the baseline dietary because of discrepancies in the 24-hour urine output before and after successful stimulation. This raised a question regarding the relationship between urine production and neuromodulation. A more complete diary analysis of patients affected by urgency/frequency and/or urge incontinence was therefore carried out to evaluate the possibility of a direct modulatory influence of SNS on urine production. METHODS: Voiding diaries of 40 patients (37 females and 3 males, average age 39.4 years) who underwent SNS were evaluated. Voiding diaries were obtained at baseline, during and after peripheral nerve evaluation (PNE) and after permanent implantation. RESULTS: There was an increase in the average volume/void during PNE in 39 patients. Twenty-four-hour urine volume during PNE was statistically greater than that at baseline. Volume/void and diurnal volume were also significantly greater in follow-up periods after permanent implantation. CONCLUSION: SNS appears to influence not only bladder function but also urine production. Increase in volume/void is paralleled by an increase in 24-hour urine output. The mechanism is unclear, but it is consistent with an altered release of antidiuretic hormone. This observation reflects the direct refractory involvement of the hypothalamus in micturition.
OBJECTIVES: To compare the effectiveness of sacral root neuromodulation with that of conservative management in ameliorating symptoms of refractory urinary urge incontinence and enhancing quality of life, to assess the objective response to neuromodulation as revealed by urodynamic testing, and to delineate the long-term outcomes of neuromodulation. METHODS: Forty-four patients with refractory urge incontinence were randomized to undergo neuromodulation with an implantable impulse generator (n = 21) or to continue their prior conservative management (n = 23). At 6 months the control group was eligible for crossover to implant. Patient evaluation included voiding diaries, quality of life questionnaires, urodynamic testing, and documentation of adverse events. Long-term follow-up evaluations were conducted at 6-month intervals up to 36 months. RESULTS: At 6 months mean leakage episodes, leakage severity and pad usage in the implant group were significantly lower by 88% (p < 0.0005), 24% (p = 0.047) and 90% (p < 0.0005), respectively, than the corresponding control group mean values. Improvements in leakage episodes and pad usage of >/=90% were attained by 75 and 85% of the implant group, respectively, but none of the control group. One third of implant patients, but none of the control patients, achieved >/=50% improvement in leakage severity. Over half of the implant patients (56%) were completely dry compared with 1 control patient (4%). Implant patients, but not control patients, exhibited significant improvement with respect to two quality of life measures. Neuromodulation resulted in increases of 220% (p < 0.0005) and 39% (p = 0.013), respectively, in urodynamically assessed bladder volume at first contraction and maximum fill. At 36 months the actuarial rate of treatment failure was 32.4% (95% CI, 17.0-56.0%). Adverse events most frequently involved pain at the implant site, and the incidence of serious complications was low. CONCLUSIONS: Neuromodulation is markedly more effective than conservative management in alleviating symptoms of refractory urge incontinence. Quality of life and urodynamic function are also improved by neuromodulation. The effects of neuromodulation are long-lasting, and associated morbidity is low.
Neuromodulation of the sacral nerves has been found to be an effective therapy for a variety of lower urinary tract dysfunctions. The reported success rate for the period of trial stimulation (peripheral nerve evaluation test) prior to permanent implantation of a sacral nerve stimulator is variable, but generally reported to be in the region of 30-50%. We present here the results of the peripheral nerve evaluation test in 38 patients with urinary retention. 34 of the 38 had been found to have an abnormality of their striated urethral sphincter on electromyography using a concentric needle electrode, i.e., they had the disorder which was described by Fowler and coworkers in 1988. The overall success rate in this group was 68%. We believe that our relatively high success rate is due to sacral neuromodulation working via a mechanism which involves the urethral sphincter, an abnormality which had been demonstrated in 89% of these patients. Twelve of the patients subsequently underwent permanent implantation of a sacral nerve stimulator, and all of them have experienced a return of voiding. However, in 2 patients, there is a persisting need for self-catheterization. There is, however, a high reoperation rate.
OBJECTIVE: In the standard operation procedure for sacral neuromodulation, the implantable pulse generator (IPG) is implanted in a subcutaneous pocket at the lower part of the anterior abdominal wall. This procedure requires a long operation time and three incisions. With the IPG in the abdominal wall, some patients complain of displacement or pain at the IPG site postoperatively. By modifying the technique of placement of the IPG, these disadvantages are overcome. METHODS: Between August 1999 and July 2000, 39 patients underwent a buttock implant of the IPG. In 2 of these patients the position of the IPG was changed from abdominal region to the buttock. During follow-up, complications concerning the operation and location of the IPG were compared to the published literature. RESULTS: Operation time is reduced in all patients by approximately 1 h. No repositioning of the patient is required during surgery. Only a short subcutaneous tunnel is required to connect the lead to the IPG. Pain at the level of the IPG was noted in 10% of the patients, which needed no further treatment. No infections were seen and the IPG did not displace postoperatively. CONCLUSION: Buttock placement of the IPG in sacral nerve stimulation leads to shorter operation time; only two incisions are needed instead of three and a shorter subcutaneous tunnel is needed. Using this technique there are less complications and a lower re-operation rate.
Sensory input has an important influence on the integrity of neural circuitry. Central nervous system circuitry is programmed and reinforced by everyday experience. Even the simplest of behaviors participate in this process. A balance between inhibition and facilitation must be maintained for the CNS to function normally. For example, the bladder stores urine because of the inhibition from a closed sphincter, and relaxation of the sphincter disinhibits the bladder to permit voiding. This synergistic 'seesaw' in reflex neural activity preserves the functional and anatomical integrity of the lower urinary tract. Dysfunction and anatomical change results when an unnatural bias develops between inhibitory and facilitatory neural activity. Neurostimulation has an inherent conditioning effect on neural excitability and can restore the neural equilibrium. Voiding diaries are very useful in documenting these changes.
OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.
A 60-year-old woman was treated for severe interstitial cystitis pain using sacral nerve stimulation. Pain and accompanying bladder dysfunction were improved by temporary and permanent sacral nerve stimulation. Six months after implantation of a sacral neuromodulator the patient is pain free and significantly improved on bladder dysfunction. Interstitial cystitis may be an indication for functional electrostimulation.
OBJECTIVE: Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. METHODS: The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. RESULTS: The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. CONCLUSIONS: Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.
The effect of lanthanum (La) on kainate (KA) responses in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) was investigated using the nystatin-perforated patch-recording configuration under voltage-clamp conditions. The responses to KA were mediated by activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in SDCN neurons. La(3+) reversibly inhibited KA (100 microM) activated currents (I(KA)) in a concentration-dependent manner over the range from 30 microM to 30 mM, with IC(50) values of 0.64 +/- 0.06 mM at a holding potential (V(H)) of -40 mV. Our further study indicated that the effects of La(3+) on I(KA) were voltage independent. Moreover, the inhibition was not use dependent and was not overcome by increasing the concentration of agonist. These findings indicate that La(3+) is an efficacious inhibitor of AMPA receptor mediated responses which may contribute to its cytotoxic effect.
Faecal incontinence is a common problem. Conservative measures are effective in a significant proportion of patients. Failure of conservative management has until recently meant recourse to surgical intervention. Surgical treatment is often associated with disappointing results. Recently, sacral nerve stimulation (SNS) has been developed as a minimally invasive, effective technique for idiopathic and acquired faecal incontinence. The technique uses chronic low-level electrical stimulation of the sacral nerves, or neuromodulation, to produce a clinically beneficial effect on the distal colon and rectum, the pelvic floor and the anal sphincter complex. SNS is a 2-stage procedure: a diagnostic stage - temporary percutaneous nerve evaluation (PNE), and a therapeutic stage - permanent SNS. The predictive value of PNE is high, and the surgical trauma and morbidity of both procedures extremely low. The technique has been adapted from its original application in urinary dysfunction. It is almost impossible to produce level 1 evidence for this type of intervention; however, the results are superior to other interventions. Patient selection criteria are evolving, but there is a growing body of evidence that supports its use as first-line treatment for faecal incontinence in patients where conservative measures have failed.
Bladder outlet obstruction can negatively affect renal function in the kidney transplant population. Functional obstruction represents a clinical challenge as conventional treatments are either ineffective or not recommended. Sacral neuromodulation was successfully used in functional voiding dysfunction in a kidney transplant patient. This is the first case to be reported in the literature.
BACKGROUND: Publications concerning perineal infantile hemangiomas are scarce, and comprise no large series. OBJECTIVE: Studying clinical features of hemangiomas of the perineal area, complications and associated malformations. METHODS: Retrospective analysis of all hemangiomas localized in the perineal area, encountered at the Children's Hospital in Bordeaux from 1994. RESULTS: Of 49 perineal hemangiomas (34 girls, 15 boys), 5 patients had accompanying malformation, mainly lipomyelomeningocele with tethered cord. The superficial hemangiomas were more represented in males and presented sooner than the nodular counterpart. The average rate of ulceration was 73%, ulcerations developed earlier in the superficial forms than their nodular counterparts (2 vs. 4 months). CONCLUSION: Superficial perineal hemangiomas are more often complicated by ulceration, and are associated with developmental anomalies. As a counterpart for the PHACE syndrome in facial hemangioma, we propose the acronym SACRAL for perineal hemangiomas: Spinal dysraphism, Anogenital anomalies, Cutaneous anomalies, Renal and urologic anomalies, associated with Angioma of Lumbosacral localization.