Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model

Uninhibited bladder contractions are a problem in spinal cord injured patients. Accordingly, methods using electrical stimulation to inhibit the bladder were investigated in chronic spinal cord injured (C6-T1) male cats. In unanesthetized, restrained animals, spontaneous bladder contractions were observed after the bladder was filled above the micturition threshold. In 3 of the 5 cats studied, this bladder activity could be inhibited with stimulation of either sacral nerves or pudendal nerves. Pudendal nerve stimulation, however, was more selective than sacral nerve stimulation for inhibition with fewer side effects such as leg spasms. Tibial nerve stimulation was ineffective and caused leg spasms and increased bladder activity. Finally, high-frequency stimulation (1,000 Hz) of the sacral nerves was shown to block bladder contractions in 2 of 3 cats investigated. However, this method had adverse side effects such as leg flexion and secondary bladder contractions. We conclude that pudendal nerve/pelvic floor stimulation at low frequency is a relatively effective method in this model.     

Spasms in Spinal Cord Injury: A Study of 72 Subjects

Abstract

Seventy-two patients with spinal cord injury of at least two years duration were reviewed retrospectively to determine incidence and effects of spasms. The average time between the injury and the examination was ten years. Seventy patients experienced spasms. In 50 patients (72%) the spasms appeared within six months after the injury. Historically, the spasms reached their maximal severity within 12 months. No significant difference was found in intensity and frequency of spasms between patients with clinically complete or incomplete spinal cord injury. Extensor spasms were seen more frequently than flexor spasms in the long-term patients. Patients with incomplete myelopathies had more extensor spasms than those with complete SCI.     

False negative in spinal cord monitoring using spinal cord-evoked potentials following spinal cord stimulation during surgery for thoracic OPLL and OLF

Several electrophysiologic methods have been used for intraoperative monitoring of spinal cord functions. Recently, muscle responses following transcranial electric stimulation have also been widely used. However, in patients with severe myelopathy, only the spinal cord responses following spinal cord stimulation can be recorded. We report a false-negative case in monitoring using spinal cord responses following spinal cord stimulation. The patient presented with severe thoracic myelopathy due to ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum. Spinal cord responses following spinal cord stimulation were recorded during laminectomy and partial removal of the OPLL. Although the amplitude of those responses decreased transiently to within 50% of control data during decompression, it had recovered to the control level by the end of surgery. Just after surgery, the patient showed complete motor paralysis with preserved sensory function. Spinal cord responses following spinal cord stimulation can be recorded in patients with severe myelopathy. However, motor problems may occur when surgery is continued in the false belief that responses are accurate.     

Oxygenated fluorocarbon nutrient solution in the treatment of experimental spinal cord injury

We employed an extravascular perfusion system through the subarachnoid space of the traumatized spinal cord of the cat for the delivery of oxygen utilizing a fluorocarbon emulsion containing essential nutrients, termed the oxygenated fluorocarbon nutrient solution (OFNS). Animals perfused for 2 hours with saline after impact injury of the spinal cord had significantly less edema at 1 cm below this site of injury than injured, untreated animals. However, in injured animals perfused with OFNS there was significant protection from spinal cord edema at both 1 and 2 cm below the site of injury. OFNS perfusion reduced the magnitude of hemorrhagic necrosis in both the gray and the white matter and protected the anterior horn cells against lysis at the site of injury. Adenosine triphosphate (ATP) is decreased within 1 minute and remains suppressed for 1 hour in gray and white matter of unperfused, injured animals. The level of ATP in both gray and white matter was significantly higher in injured OFNS-perfused animals than in saline-treated animals at the site below the spinal cord injury. Our data show that OFNS perfusion of the injured spinal cord reduced necrosis and edema and tended to normalize the levels of high energy ATP and intact anterior horn cells. These results demonstrate the feasibility of treating ischemic hypoxia of the spinal cord after trauma through an extravascular perfusion route that utilizes a fluorocarbon emulsion as a vehicle for the delivery of oxygen and other cellular nutrients.     

Foot salvage and improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation

Epidural spinal cord electrical stimulation has been suggested as an alternative treatment in patients with limb-threatening ischemia in whom vascular reconstructive surgery is not possible anymore. We studied the effects of epidural spinal cord electrical stimulation on microcirculatory blood flow in 20 patients with ischemic rest pain and ulcers. Angiography showed occluded crural arteries technically unsuitable for reconstructive surgery. Intravital capillary microscopy was used to assess capillary density and diameter and red blood cell velocity before and after a 1-minute period of arterial occlusion. After epidural spinal cord electrical stimulation 18 patients claimed immediate pain relief, which was confirmed by intravital capillary microscopy. Capillary density increased from 10 to 19/mm2 (p less than 0.001), red blood cell velocity increased from 0.088 to 0.496 mm/sec (p less than 0.001), and peak red blood cell velocity after arterial occlusion increased from 0.092 to 0.548 mm/sec (p less than 0.001). Two patients had no immediate pain relief; they did not show improvement of microcirculatory perfusion, and amputation was necessary. During the follow-up period (3 months to 3 years, mean 27 months), six other patients had recurrent ischemic pain, and amputation was necessary. In 12 patients pain relief continued, and ischemic ulcers healed; capillary microscopy confirmed improved microcirculatory blood flow. Microcirculatory parameters were significantly higher in respondents than in nonrespondents (p less than 0.001). Life-table analysis revealed a cumulative foot salvage of 80% and 56% after 1 and 2 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anaesthesia for chronic spinal cord lesions

Increasing numbers of patients with spinal cord injury present for surgery or obstetric care. Spinal cord injury causes unique pathophysiological changes. The most important peri-operative dangers are autonomic dysreflexia, bradycardia, hypotension, respiratory inadequacy and muscle spasms. Autonomic dysreflexia is suggested by headache, sweating, bradycardia and severe hypertension and may be precipitated by surgery, especially bladder distension. Patients with low, complete lesions, undergoing surgery below the level of injury, may safely do so without anaesthesia provided there is no history of autonomic dysreflexia or troublesome spasms. An anaesthetist should be present to monitor the patient in this situation. General anaesthesia of sufficient depth is effective at controlling spasms and autonomic dysreflexia but hypotension and respiratory dysfunction are risks. There is a growing consensus that spinal anaesthesia is safe, effective and technically simple to perform in this group of patients. We present a survey of 515 consecutive anaesthetics in cord-injured patients and a review of the current literature on anaesthesia for patients with chronic spinal cord lesions.     

The effect of anesthetic agents on descending spinal cord evoked potential and the compound muscle action potentials elicited by stimulation at the cerebral motor cortex and the spinal cord]

Recently, intraoperative monitoring of the motor tract by descending spinal cord motor evoked potentials (MEP) and compound muscle action potentials (CMAP) has been applied in clinical testing. Since several reports have mentioned the vulnerability of these potentials to anesthetic agents, experimental studies were carried out on the relationship between these potentials and anesthesia using 41 adult cats. The effects of anesthesia on changes in amplitude of the direct wave (D wave) and indirect wave (I wave) of the MEP and CMAPs were investigated. These potentials were generated by stimulation of the spinal cord and the motor cortex, respectively. Enflurane (2%), halothane (1%) and isoflurane (1.5%) with pure oxygen decreased the amplitude of the I wave to less than 50% of the control level. The CMAP after stimulation of the spinal cord was degraded to less than 30%, and the CMAP after cortical stimulation vanished completely. Only the D wave was stable against inhalational anesthetic agents. Sixty-seven percent nitrous oxide with the above concentrations of these inhalational anesthetic agents decreased the amplitude of the I wave to less than 30% and the CMAP evoked by spinal cord stimulation vanished. The effect of modified NLA (diazepam and pentazocine) on these potentials was weaker than that of the inhalational anesthetic agents.     

Creatinine clearance prediction in spinal cord injury patients: comparison of 6 prediction equations

The renal function of spinal cord injury patients frequently is overestimated by 3 commonly used equations to predict creatinine clearance. Overestimation of creatinine clearance may result in aminoglycoside overdosage and resultant nephrotoxicity. Three newer prediction equations have been developed from creatinine clearances measured in neurologically abnormal patients. These 6 equations were tested in 77 male and 9 female spinal cord injury patients (48 quadriplegics and 38 paraplegics, including 38 with acute and 48 with chronic injuries). The equation developed by Sawyer and Hutchins was superior to 2 other equations developed in spinal cord injury patients and 3 equations developed in neurologically normal patients. However, creatinine clearances predicted by this equation were within 30 ml. per minute of measured creatinine clearances in only two-thirds of the spinal cord injury patients. Errors ranged from overestimation by 95 ml. per minute (151 per cent) to underestimation by 106 ml. per minute (45 per cent). The potential for large errors in creatinine clearance prediction necessitates measurement of creatinine clearance as soon as possible when renal excreted and toxic pharmaceuticals are administered to spinal cord injury patients.     

Thromboprophylaxis in elective spinal surgery and spinal cord injury

The risk of deep vein thrombosis (DVT) after spinal cord injury is very high. Without prophylaxis the incidence of DVT using venography is 81% and the risk of symptomatic DVT is between 12 and 23%. The risk is much lower in elective spine surgery. After discectomy or laminectomy on less than two spine levels, the risk of DVT is less than 1%. After spinal fusion or extended laminectomy, the risk can be estimated between 0.3 and 2.2%. A prophylaxis is recommended for all patients after spinal cord injury (grade A). The association of a mechanical method and heparin is recommended (grade B). The duration of prophylaxis is 3 months in patients with a motor deficit (grade C). No prophylaxis is recommended after discectomy or limited laminectomy in patients without additional risk factors. Mechanical methods are recommended after spinal fusion or extended laminectomy. For patients with additional risk factors a low molecular weight heparin is recommended.     

Monitoring for spinal cord ischemia by use of the evoked spinal cord potentials during aortic aneurysm surgery

Purpose: This clinical study was to evaluate changes of evoked spinal cord potentials (ESCPs) elicited by direct spinal cord stimulation and to determine their relation to spinal cord ischemia during aortic aneurysm surgery.Methods: We monitored descending ESCPs from the thoracic spinal cord and lumbar enlargement after cervical spinal cord stimulation (thoracic descending ESCP and lumbar descending ESCP), and segmental ESCP at lumbar enlargement elicited by bilateral tibial nerve stimulation in 22 aortic aneurysm surgical operations.Results: ESCP changes were classified into three types: (1) decrease of amplitude in lumbar descending ESCP and segmental ESCP; (2) decrease of amplitude in segmental ESCP alone; (3) decrease of amplitude in all ESCPs. The late negative waves of both lumbar descending ESCP and segmental ESCP were more sensitive than other components of ESCPs. Postoperative paraplegia occurred in the two cases that showed persistent diminution of amplitude in the late negative waves. Segmental ESCP was less reliable than lumbar descending ESCP, because it depended entirely on the adequate perfusion of the lower extremities.Conclusions: Lumbar descending ESCP was the best method for the spinal cord ischemia during aortic aneurysm surgery. Spinal cord ischemia could be detected by diminution in the amplitude of the late negative wave of lumbar descending ESCP. The recovery amplitude of the late negative wave after declamping correlated with the neurologic outcome. (J VASC SURG 1994;20:826-33.)     

Tonicity of resuscitative fluids influences outcome after spinal cord injury

OBJECTIVE: This investigation was designed to test the hypothesis that the tonicity of resuscitative fluids administered after spinal cord injury influences the magnitude of secondary injury and, therefore, outcome. METHODS: Rat spinal cords were compressed with 50 g of weight for 5 minutes to produce injury. After spinal cord injury, the animals were randomized into three experimental groups. Group 1 (n = 10) received no fluid resuscitation after spinal cord injury. Group 2 (n = 6) received 5 ml/kg of intravenously administered Ringer's lactate 1 minute after the removal of compression. Group 3 (n = 7) was treated with 5 ml/kg of intravenously administered 7.5% hypertonic saline 1 minute after the removal of compression. Neurological outcome was assessed daily for 10 days using the Basso, Beattie, and Bresnahan locomotor rating scale. Histological evaluations of the spinal cord were obtained on Day 10. RESULTS: The average number of recovery days before the rats were able to spontaneously void their bladders was significantly less (P < 0.05) in the hypertonic saline-treated group. Spontaneous hindlimb movement also occurred sooner in the hypertonic saline-treated animals. The average neurological score was significantly higher (P < 0.05) in the hypertonic saline-treated group during each of the 10 days of recovery. Histological evaluation supported the finding of attenuation of injury in the hypertonic saline-treated animals. CONCLUSION: The results of this investigation with a chronic model of spinal cord injury support the contention that hypertonic saline treatment may provide protection to the spinal cord after mechanical injury.     

The use of spinal cord stimulation for severe limb-threatening ischemia: a preliminary report

Spinal cord stimulation has been shown to control ischemic pain. We have applied spinal cord stimulation to nine patients with rest pain, non-healing ulceration, or digital gangrene to evaluate its effect on limb salvage. The patients had a mean age of 69 years. Six were diabetic, and all had previous major complications of their atherosclerotic disease. Stimulation was obtained by placing an electrode on the spinal cord under local anesthesia. Seven patients experienced marked reduction in their ischemic pain immediately after stimulation. These patients also had improved healing of ulcers documented by direct measurement. No significant change in ankle/brachial Doppler indices could be measured in any patient. One patient became suddenly worse and required amputation after one year of good pain relief and ulcer improvement. Two patients were not helped and went on to amputation within one month of stimulation. We conclude from these preliminary data that spinal cord stimulation effectively relieves ischemic pain and is associated with improved ulcer healing.     

Spinal cord stimulation for amelioration of spasticity: experimental results

Fourteen cats underwent 500-g/cm dorsal impact injuries to the spinal cord and the placement of stimulating electrodes above and below the level of injury at T8. After recovery from the surgical procedure and the development of spasticity, each animal participated in several trials of spinal cord stimulation (SCS). Cord stimulation was provided above or below the level of injury using currents of less than 0.75 mA at 100 Hz. Electromyogram changes in hamstring and quadricep muscles (during spasms induced by dorsiflexion of the paw) were monitored. All animals showed complete paraplegia and, at 3 weeks, severe spasms. Spasticity was aggravated by SCS delivered above the level of injury. Spasms were markedly suppressed by monopolar stimulation delivered below the level of the lesion. Effects were maximal with the negative electrode applied to the cord and were slightly less with reversal of polarity. Muscle excitation was seen before diminution of spasms when bipolar currents were used. All effects lasted only as long as currents were delivered. These animal trials suggest that the effects of SCS are directly related to the current and its type. Beneficial effects were seen only when currents were delivered below the level of injury; this suggests that SCS activates local inhibitory processes or depolarizes local excitatory pathways. The poor results with bipolar stimulation do not support action on a multisynaptic cord system in short term stimulation.     

Successful improvement of blood pressure, cardiac output, and spinal cord blood flow after experimental spinal cord injury

Thirty-seven rats were anesthetized and ventilated and had continuous monitoring of mean systemic arterial pressure (MSAP) and central venous pressure (CVP). The animals underwent a 60-g clip compression injury at T-1 for 1 minute. Fifteen minutes after injury, microspheres were used to measure cardiac output (CO) and spinal cord blood flow (SCBF). Each animal was then randomized into one of five groups. Four groups received intravenous infusions for 1 hour each of 5% albumin, autologous packed cells, low molecular weight dextran, or autologous whole blood to maintain the MSAP. The fifth group served as a control group and received an infusion of normal saline. Seventy-five minutes after injury, CO and SCBF were measured. The posttraumatic reduction in CO was significantly improved by all four treatment infusions. However, only autologous whole blood and dextran successfully reversed the posttraumatic hypotension. Dextran significantly elevated the CVP (P less than 0.01) and reduced the hematocrit (P less than 0.01). Whole blood improved SCBF in all segments of the spinal cord by nearly 100% (P less than 0.05), and dextran increased SCBF by 200% (P less than 0.01). Thus, the most marked improvements in MSAP, CO, and SCBF were produced by hypervolemia and hemodilution associated with dextran infusion. The therapeutic implications of this reversal of local and systemic changes in acute spinal cord injury are discussed.     

Follow-up CT myelography of severe cervical spinal cord injury

There are many reports describing gross anatomical and microscopical findings of severely injured cervical cords in autopsy of the acute and chronic state, but no morphological findings of a severe cervical spinal cord injury in a chronic state by follow-up CT myelography have been found in the literature so far. The sagittal and transverse diameters of the cervical spinal cord and subarachnoid space of 9 out of 14 severe cervical spinal cord injury patients were measured with CT myelography within 7.5 years after the trauma and their size compared with a control group which was made up of 29 patients with slight radiculopathy due to cervical spondylosis and whiplash injuries. Injured cord levels were C4 4 cases, C5 4 cases and C6 1 case. Remarkable spinal cord atrophy was recognized in the sagittal diameter from C1 to C7 and in the transverse diameter below C4 and narrowing of the cervical subarachnoid space in the sagittal diameter from C2 to C5. The significance level was set at 1-5%. From these findings, we have concluded that atrophy appeared not only in the injured segment but also the whole cervical cord after the trauma. There was less cord atrophy in a good functional prognosis than in a poor prognosis.     

The effect of acute spinal cord compression injury on thyroid function in the rat

The effect of acute spinal cord injury on thyroid function was studied in rats subjected to severe spinal cord compression at T1. Serum thyroxine (T4), effective thyroxine index (ETI), and thyroid stimulating hormone (TSH) were measured at 1 and 100 minutes and at one, three, and seven days after laminectomy and spinal cord injury. Control animals were subjected to laminectomy only. T4 was decreased at 1 minute after laminectomy with or without spinal cord injury, though the animals with cord injury had a much more profound reduction. The effects on TSH at 1 minute were dramatically different: laminectomy alone caused an elevation of TSH, while spinal cord injury produced a marked decline. At the later time intervals both groups showed gradual normalization of T4 and TSH levels, and at seven days there were no significant differences between the groups. Thus, acute spinal cord compression injury produced a major alteration in thyroid function during the acute phase.     

Role of endogenous norepinephrine and effects of alpha- and beta-blockers in experimental spinal cord compression injury

The changes in spinal cord micro-circulation were investigated after administering alpha- and beta-blockers to rabbits with acute spinal cord injury. Immediately after the 8th thoracic spinal cord was injured by applying pressure with a weight (50 g) for 1 minute, an alpha or beta-blocker was injected into the subarachnoid space of the injured region of the spinal cord. Spinal cord edema, blood flow, vascular permeability, and the mean arterial pressure were compared between the groups treated with each agent and the control group. One hour after the injury, the water content of the spinal cord was significantly lower in the phenoxybenzamine-treated group than in the control group. After 6 hours, however, no significant difference was observed between these two groups. The spinal cord blood flow was higher in the phenoxybenzamine-treated group than in the control group until 6 hours after the injury. These results suggest involvement of norepinephrine in the formation of edema at the early stage of spinal cord injury.     

Evoked potentials from direct cerebellar stimulation for monitoring of the rodent spinal cord.

Although the assessment of spinal cord function by electrophysiological techniques has become important in both clinical and research environments, current monitoring methods do not completely evaluate all tracts in the spinal cord. Somatosensory and motor evoked potentials primarily reflect dorsal column and pyramidal tract integrity, respectively, but do not directly assess the status of the ventral funiculus. The present study was undertaken to evaluate the use of evoked potentials, elicited by direct cerebellar stimulation, in monitoring the ventral component of the rodent spinal cord. Twenty-nine rats underwent epidural anodal stimulation directly over the cerebellar cortex, with recording of evoked responses from the lower thoracic spinal cord, both sciatic nerves, and/or both gastrocnemius muscles. Stimulation parameters were varied to establish normative characteristics. The pathways conducting these "posterior fossa evoked potentials" were determined after creation of various lesions of the cervical spinal cord. The evoked potential recorded from the thoracic spinal cord consisted of five positive (P1 to P5) and five negative (N1 to N5) peaks. The average conduction velocity (+/- standard deviation) of the earliest wave (P1) was 53 +/- 4 m/sec, with a latency of 1.24 +/- 0.10 msec. The other components followed within 4 msec from stimulus onset. Unilateral cerebellar stimulation resulted in bilateral sciatic nerve and gastrocnemius muscle responses; there were no significant differences (p greater than 0.05) in the thresholds, amplitudes, or latencies of these responses elicited by right- versus left-sided stimulation. Recordings performed following creation of selective lesions of the cervical cord indicated that the thoracic response was carried primarily in the ventral funiculus while the sciatic and gastrocnemius responses were mediated through the dorsal half of the spinal cord. It is concluded that the posterior fossa evoked potential has research value as a method of monitoring pathways within the ventral spinal cord of the rat, and should be useful in the study of spinal cord injury.     

Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord

Direct current stimulation has been shown by others to enhance the regeneration of several types of tissues, including nervous tissue in some species. The purpose of the present experiment was to assess the value of direct current stimulation for enhancing the recovery of spinal cord function after clip compression injury of the rat spinal cord. Twenty Wistar rats underwent a 1-minute, 50-g clip compression injury at T-1, after which electrodes were placed epidurally with the anode proximal and the cathode distal to the injury site. These electrodes were attached to a stimulator implanted subcutaneously. Ten animals received stimulators that produced a constant current of 14 microA, and the remainder received stimulators with no electrical output and served as controls. Assignment of stimulators was random, and the treatment group was not identified until sacrifice. Neurological function was tested weekly for 15 weeks by the inclined plane technique, after which the animals were killed and the injured cords were examined for histological evidence of regeneration. The mean inclined plane result for the treatment group (39 +/- 5 degrees) was significantly better than that for the control group (31 +/- 6 degrees) (P less than 0.02), although there was no significant difference in histological findings between the two groups. Thus, direct current stimulation of the injured mammalian spinal cord produced improvement in neurological function and warrants further investigation.     

Application of 2 vibrators salvages ejaculatory failures to 1 vibrator during penile vibratory stimulation in men with spinal cord injuries

PURPOSE: Penile vibratory stimulation is the treatment of first choice for anejaculation in men with spinal cord injury. Nonresponders to penile vibratory stimulation are usually referred for electroejaculation or surgical sperm retrieval. Compared to penile vibratory stimulation these methods are invasive and usually yield lower total motile sperm, potentially limiting options for assisted reproductive technologies. To avoid these less than ideal options a simple method to salvage penile vibratory stimulation failures would be of benefit to spinal cord injured patients. We investigated the recovery rate when 2 vibrators were used to salvage ejaculatory failures to 1 vibrator in men with spinal cord injury. MATERIALS AND METHODS: A retrospective chart review was performed in 297 spinal cord injured men who underwent a total of 965 trials of penile vibratory stimulation at our center between 1991 and 2006. Only trials with high amplitude vibrators were examined. All men underwent 2 or more penile vibratory stimulation trials using 1 vibrator applied to the dorsum or frenulum of the glans penis. Men failing to ejaculate with 1 vibrator received 1 or more trials in which the glans penis was then sandwiched between 2 vibrators. RESULTS: Of all men 49% and 57% of those whose level of injury was T10 or above responded to penile vibratory stimulation with 1 vibrator. Of failures with 1 vibrator 22% responded to penile vibratory stimulation with 2 vibrators. CONCLUSIONS: Application of 2 vibrators salvaged ejaculatory failures to 1 vibrator during penile vibratory stimulation procedures in men with spinal cord injury. This simple penile vibratory stimulation sandwich method is recommended before referring patients for electroejaculation or surgical sperm retrieval.