International spinal cord injury musculoskeletal basic data set.

OBJECTIVES: To develop an International Spinal Cord Injury (SCI) Musculoskeletal Basic Data Set as part of the International SCI Data Sets to facilitate consistent collection and reporting of basic musculoskeletal findings in the SCI population. SETTING: International. METHODS: A first draft of an SCI Musculoskeletal Basic Data Set was developed by an international working group. This was reviewed by many different organizations, societies and individuals over 9 months. Revised versions were created successively. RESULTS: The final version of the International SCI Musculoskeletal Basic Data Set contains questions on neuro-musculoskeletal history before spinal cord lesion; presence of spasticity/spasms; treatment for spasticity within the last 4 weeks; fracture(s) since the spinal cord lesion; heterotopic ossification; contracture; the location of degenerative neuromuscular and skeletal changes due to overuse after SCI; SCI-related neuromuscular scoliosis; the method(s) used to determine the presence of neuromuscular scoliosis; surgical treatment of the scoliosis; other musculoskeletal problems; if any of the musculoskeletal challenges above interfere with activities of daily living. Instructions for data collection and the data collection form are freely available on the International Spinal Cord Society (ISCoS) website (www.iscos.org.uk). CONCLUSION: The International SCI Musculoskeletal Basic Data Set will facilitate consistent collection and reporting of basic musculoskeletal findings in the SCI population.

Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury.

STUDY DESIGN: Randomized, double-blind, placebo-controlled, two-period crossover. OBJECTIVES: To evaluate the efficacy and safety of arbaclofen placarbil (AP) in patients with spasticity secondary to spinal cord injury (SCI). SETTING: United States and Canada. METHODS: Patients received extended-release AP tablets 10, 20 or 30 mg every 12 h in one of two AP/placebo sequences, with 26 days of each treatment. The primary analysis compared Ashworth scale assessments of muscle tone between AP and placebo for the muscle group with maximum baseline Ashworth score. Secondary endpoints included a patient-rated Severity of Spasticity Scale. RESULTS: In the primary analysis, AP significantly improved Ashworth scores compared with placebo over the dosing interval: least-squares mean reduction versus placebo was 0.60 for AP 20 mg (P=0.0059) and 0.88 for AP 30 mg (P=0.0007). The difference was significant for the pre-morning dose time point, 12 h after the prior evening dose, indicating that efficacy was maintained throughout the dosing interval. Treatment differences for AP 10 mg versus placebo were not significant. Severity of Spasticity ratings were significantly reduced for the combined 20/30-mg group versus placebo (P=0.018). No statistically significant differences between AP and placebo were observed for muscle strength. AP-related AEs were generally mild to moderate in intensity, and none led to early withdrawal or were serious. CONCLUSION: AP was well tolerated at all investigated dosages and, when administered at doses of 20 or 30 mg twice daily, was efficacious in reducing spasticity due to SCI.

Intrathecal drug therapy using the Codman Model 3000 Constant Flow Implantable Infusion Pumps: experience with 17 cases.

OBJECTIVES: The objective of this study was to evaluate the accuracy, reliability, safety, and efficacy of the Codman Model 3000 Constant Flow Implantable Infusion Pump for intrathecal baclofen delivery as a therapeutic option for the treatment of severe spasticity. The distinctive features of this pump include a raised, easily palpable septum, a safety valve protecting the bolus pathway, no programmer needed, and no battery to fail. DESIGN: A total of 17 patients with spinal cord injury, multiple sclerosis, or cerebral palsy were implanted with this pump. The accuracy of the pump and drug treatment efficacy was determined at each visit and adjustments to the dosages were made as required. All the intrathecal drug delivery system complications were reviewed. RESULTS: The expected efficacy was achieved. The accuracy of the implanted pumps ranged from 90-97% (average 94%). There were no complications due to primary pump problems. The complications reported are similar to other implantable infusion devices and include dehiscence of the suture line, pressure ulcer development, formation of seroma, inversion of the pump, baclofen overdose, and catheter failures. CONCLUSION: The Codman Model 3000 Constant Flow Implantable Infusion Pump is an accurate, reliable, and convenient option for patients needing intrathecal baclofen therapy, with complications similar to other available pumps.

Alpha adrenergic and serotonergic agents in the treatment of spastic hypertonia.

In the treatment of patients with problematic spasticity, it is important to consider the following steps: 1. Establish the functional impact of the spasticity. 2. Identify the functional goal to be achieved by treatment. 3. Eliminate any remediable spasticity aggravating factors. 4. Evaluate the effects of previous antispasticity treatments. 5. Consider nonpharmacologic and pharmacologic treatments. 6. Initiate therapy with a low dosage, and titrate judiciously. 7. Stop the titration when functional goal is achieved. 8. If goal is not achieved or if side effects are intolerable, consider a second medication.

Surgical treatment of pressure ulcers: 20-year experience.

OBJECTIVE: To review the outcomes of surgical management of spinal cord injury (SCI) patients with severe pressure ulcers and to examine likely risk factors for recurrence of pressure ulcers. DESIGN: A retrospective medical record review. SETTING: An SCI unit in a tertiary care facility. PATIENTS: All admissions to the SCI unit for grade 4 pressure ulcers from 1976 to 1996. INTERVENTION: Surgical repair of pressure ulcers. MAIN OUTCOME MEASURE: Complication and recurrence rates of pressure ulcers. RESULTS: Of 598 pressure ulcers, 468 were pelvic area ulcers, of which 431 (92%) were treated surgically. Fifty-three had split-thickness skin grafting, and 380 were treated with 421 surgical procedures (253 fasciocutaneous or cutaneous flaps, 93 muscle or musculocutaneous flaps, 75 primary closures). One hundred eight (26%) of these procedures required some bone work. Suture line dehiscence occurred in 130 (31%), with 45 (11%) requiring reconstruction and 8 (2%) requiring skin grafting to heal. At discharge, 38 (9%) of these pelvic ulcers had not healed. Recurrent admissions occurred in 90 (54%) of the patients. Recurrence of ulcers at the same site occurred in 31% of the total number of ulcers and at a different site in 21%. At the time of the 415 admissions, 336 (81%) of the patients were unemployed; 159 (38%) had grade 8 or lower level of education; and 226 (55%) lived alone or with family but were independent in self-care. Of the 168 patients studied, 45 (27%) were aboriginal (Canadian native), and 59 (35%) had a history of drug or alcohol abuse. CONCLUSIONS: The vast majority of severe pressure ulcers were surgically treated. Complication and recurrence rates are similar to previous reports. Psychosocial problems (unemployment, low level of education, drug or alcohol abuse, poverty in the native communities) appear to increase the risk for pressure ulcer development.

BOLD MRI of the human cervical spinal cord at 3 tesla.

The feasibility of functional MRI of the spinal cord was investigated by carrying out blood oxygen-level dependent (BOLD) imaging of the human cervical spinal cord at a field of 3 T. BOLD imaging of the cervical spinal cord showed an average intensity increase of 7.0% during repeated exercise with the dominant hand with a return to baseline during rest periods. The areas of activation were predominantly on the same side of the spinal cord as the hand performing the exercise, between the levels of the sixth cervical and first thoracic spinal cord segments. The direct correspondence between these areas and those involved with the transmission of motor impulses to the hand, and reception of sensory information from the hand, demonstrates that spinal functional magnetic resonance imaging is feasible. Magn Reson Med 42:571-576, 1999.

Analgesics. Opioids, adjuvants, and others.

The purpose of this article is to summarize the main categories of pain-relieving medications. The authors review a number of analgesic preparations and treatments, with special emphasis on advantages, precautions, limitations, and various routes of administration.

Antispasticity medications.

The article illustrates a practical approach to the challenging management of problematic, generalized spasticity. Use of dose titration to achieve symptomatic relief is described. Currently approved pharmaceuticals used as antispasticity agents and muscle relaxants and other medications with antispasticity effects are reviewed.

Urinary and gastrointestinal systems medications.

This article reviews the medical management of the neurogenic bladder and bowel. The drugs discussed specifically affect detrusor instability, detrusor weakness, high urethral pressure, low urethral closure pressure, inflammatory cystitis, and chronic constipation.

Intravenous pamidronate attenuates bone density loss after acute spinal cord injury.

OBJECTIVE: To compare the effects of a 6-month treatment with intravenous pamidronate (30-mg infusion once per month) to conventional rehabilitation without pamidronate on bone density of the spine and leg bones and on the excretion rate of N-telopeptide, a urinary marker of bone catabolism, in acutely spinal cord injured patients. DESIGN: A nonrandomized control trial in which 24 spinal cord injured subjects entered the study within 6 weeks of their injury. Fourteen subjects received pamidronate; 10 did not. OUTCOME MEASURES: Bone density measurements by dual x-ray absorptiometry were performed before the initial treatment (within 6 weeks of the injury) and at 3, 6, and 12 months postinjury and was the primary efficacy parameter. Urine for N-telopeptide levels was the secondary efficacy parameter. RESULTS: After acute spinal cord injury, patients treated with intravenous pamidronate had significantly less bone density loss compared with those who did not receive pamidronate (parametric ANOVA, p<.02). Also, ambulatory subjects had significantly less bone density loss over the study period (p<.05) than nonambulatory subjects. In general, a high excretion level of the urinary bone-breakdown product N-telopeptide was found before intravenous pamidronate treatment, followed by a dramatic reduction in excretion after pamidronate treatment. Ambulatory subjects excreted significantly less N-telopeptide than motor-complete subjects at all time points. CONCLUSION: Intravenous pamidronate treatment and ambulatory ability in the first 6 months after an acute spinal cord injury prevents bone density loss.

Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.

BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS. OBJECTIVE: To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity. SETTING: Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial. RESULTS: Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration. CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.

Cyclical etidronate: its effect on bone density in patients with acute spinal cord injury.

OBJECTIVE: To compare the effects of a 30-week trial of cyclical etidronate therapy (starting within 6 weeks of spinal cord injury [SCI] and conventional rehabilitation without etidronate treatment on the bone density of the lumbar spine and lower extremities of SCI patients. DESIGN: Prospective, randomized control trial. SETTING: Tertiary care, inpatient rehabilitation center. PATIENTS: Acute SCI, within 6 weeks of injury. Thirteen SCI subjects were recruited; 6 were assigned randomly to receive etidronate and 7 to receive conventional treatment. INTERVENTION: Etidronate, 800 mg orally, once per day for 2 weeks of 15 weeks, repeated once. MAIN OUTCOME MEASURES: Dual X-ray absorptiometry of the spine, hip, distal femur, and proximal tibia measured at baseline, 6 months, and 12 months. RESULTS: A significant interaction between etidronate treatment and ambulatory status over time was observed in the bone density of the patients after SCI (p = .0003). The patients who became ambulatory and received etidronate treatment had a preservation of bone density as compared to all other patients who showed a loss of bone density over time. The loss of bone density occurred in the leg bones, not the spine. Cyclical etidronate treatment was tolerated well without adverse or side effects. CONCLUSION: Cyclical etidronate is a feasible treatment and may prevent osteoporosis associated with SCI in patients who eventually walk.

Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American Tizanidine Study Group.

Tizanidine, an imidazoline that acts as an agonist at alpha 2-adrenergic receptors, has been shown to be effective in reducing spasticity caused by MS. This multicenter study (14 sites) assessed the efficacy and safety of oral tizanidine in patients who had spinal cord injury of > 12 months' duration. Of the 124 patients admitted to the study, 78 completed it. Tizanidine was titrated to an optimized dosage in each patient to a maximum of 36 mg/d. Muscle tone, assessed by Ashworth score, was significantly reduced (p = 0.0001) by tizanidine treatment in comparison with placebo. Video motion analysis of the pendulum test showed improvement in the tizanidine-treated patients vs placebo (p = 0.04) and showed a significant correlation with the Ashworth score (p < 0.001). No significant alterations in muscle strength or vital signs were noted in either treatment group. The most common adverse events during tizanidine treatment were somnolence, xerostomia, and fatigue. It was concluded that, overall, tizanidine is effective in reducing spasticity in patients with spinal cord injury.

A comparison of clonidine, cyproheptadine and baclofen in spastic spinal cord injured patients.

In twenty-five SCI subjects, antispasticity effects of three putative antispasticity agents [clonidine (an alpha-2 noradrenergic agonist), cyproheptadine (a 5-HT2 antagonist) and baclofen (a GABA-B agonist)] were tested in terms of changes in leg tone as graded by the Ashworth scale (AS), in terms of the vibratory inhibition of the H-reflex (VII) and in terms of the ability of the knee to swing passively in the pendulum test as quantified by video motion analysis. When compared to the no drug period, all three drug treatments showed an antispasticity effect on the AS, the VII and the amplitude of the first swing and the relaxation index of the pendulum test, p. < 0001. Surprisingly, cyproheptadine and baclofen produced a greater reduction in the VII than clonidine, p. < 01. The amplitude of the first swing in the pendulum test correlated well with the AS, r = .88, and the antispasticity effects of the drugs produced improvements in both measures, a reduced AS and increased amplitude of knee swing in the pendulum test. Therefore, video motion analysis of the pendulum test is as valid a measure of spasticity as the Ashworth scale and is not limited by subjectivity of the examiner.

Vascular effects of a modified cold pressor test in spinal cord injured and able-bodied men.

The vascular reflex responses of the hands of ten spinal cord injured (SCI) men (sensory and motor complete) to a modified cold pressor test were compared to ten age-matched, able-bodied men. The skin temperature of the left index finger was measured before, during, and after the immersion of the feet in ice water for 20 seconds. The heart rate and blood pressure were measured 5 minutes before and 15 minutes after the cold stimulus. The able-bodied subjects showed an immediate vasoconstriction and fall in finger temperature after cold stimulation of the feet, followed by vasodilation and an increase in finger temperature (p < .0001), whereas, the SCI subjects did not show any change in finger temperature during this test. Prior to application of the cold stimulus, the SCI subjects had a significantly low diastolic blood pressure compared with the diastolic blood pressure of able-bodied subjects, which "normalized" after the cold stimulus. These data support the concept that regulation of vascular tone occurs at both spinal and supraspinal levels.

Relief of spasticity in SCI men and women using rectal probe electrostimulation.

Although there are numerous approaches to the treatment of spasticity, many patients are still unable to find a satisfactory method of managing their spasms with acceptable side effects. In the course of our fertility studies using rectal probe electrostimulation (RPES) in SCI men to produce ejaculation, we observed that a majority of the men experienced significant relief of their spasticity for many hours. This report describes a prospective, single-blinded study of this phenomenon in six SCI men and three SCI women who underwent RPES a total of 71 times. The mean age of the subjects was 28.2 years (21-41), the mean time from injury was 6.0 years (0.5-15); there were three paraplegic and six quadriplegic persons: four were Frankel class A and five were class B. Although all subjects had moderate to severe spasticity, only four took antispasm medications; one had undergone surgery for implantation of an epidural stimulator. The effectiveness of RPES on spasticity was evaluated by each subject for frequency of spasms and interference of daily activities and by independent, blinded assessors for tone, frequency of spasms and DTRs; four patients underwent quantitative videotape analysis of the pendulum test and two underwent somatosensory evoked potentials (SSEPs) to evaluate electrical activity in the central nervous system. Treatment variables included varying probe sizes and number of stimulations. All subjects experienced good to excellent decrease in tone, frequency of spasms and interference with ADL from 3 to 24 hours depending on treatment variables used. Mean duration of relief was 8.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociated hip and spine demineralization: a specific finding in spinal cord injury.

Bone mineral density of the lumbar spine and right hip was measured with dual x-ray absorptiometry in 14 men with chronic spinal cord injury (SCI). The pattern of demineralization was compared to that observed in 46 men with a variety of endocrine disorders (chronic steroid use seven, chronic neuroleptic use 15, prolactinoma three, hypogonadism six, hyperthyroidism three, idiopathic osteoporosis 12). The SCI patients had significant hip demineralization but normal bone density in the lumbar spine (percent of age-matched normal 86.0 +/- 3.8 for the femoral neck, 101.8 +/- 4.3 for the lumbar spine; t = 3.88, p = 0.002). In contrast, the endocrine disorders were associated with disproportionate lumbar spine demineralization (percent of age-matched normal 97.5 +/- 1.9 for the femoral neck, 81.8 +/- 2.0 for the lumbar spine; t = 8.98, p < 0.000001). We conclude that hip demineralization is a common complication of SCI but that lumbar bone density is well preserved. This pattern of highly selective bone loss from the hip appears to be unique compared to other endocrine causes of osteoporosis.

Reflex changes induced by clonidine in spinal cord injured patients.

In a single blind study of 6 spinal cord injured (SCI) men, the effects of clonidine, a selective alpha-2 adrenergic agonist, on spasticity were compared to diazepam and placebo. Since a potential side-effect of clonidine is postural hypotension, a combination of clonidine and desipramine was also tested. Vibration of the leg will inhibit the H reflex in a normal subject; whereas, this inhibition is markedly reduced in SCI patients with spasticity. A vibratory inhibition index (VII) was derived for each treatment. The pre-treatment VII was 92.08 +/- 3.15%; for SCI subjects, compared to 46.5 +/- 7.7% for 6 normal subjects. Clonidine significantly reduced the mean index of SCI patients to 59.42 +/- 3.91% (p less than 0.001). The VII for placebo, diazepam and the clonidine-desipramine combination were not statistically different than the pre-treatment values in SCI patients. In conclusion, clonidine has an anti-spasticity effect in SCI patients, both subjectively, and objectively, in terms of vibratory inhibition of the H reflex.

Substance P-induced long-term blockade of spinal adrenergic analgesia: reversal by morphine and naloxone.

Alpha agonists [noradrenaline (NA) and ST-91] inhibit the release of substance P (SP) from the spinal cord and block the biting, licking, scratching syndrome produced by intrathecal SP suggesting that these agents produce analgesia by an interaction with SP systems. In this study we determined the effect of a desensitizing regimen of SP (15 micrograms X 2 at a 30-min interval) on analgesia produced by intrathecal NA in the rat tail-flick test. When NA was injected immediately after the regimen or after a 90-minute delay, NA analgesia was blocked. This blockade persisted up to 11 days after exposure to SP. Exposure to a single dose of SP (15 or 30 micrograms) also blocked NA acutely, but the long-term blockade did not last as long. An identical effect was observed with ST-91. SP (15 micrograms X 2) potentiated the analgesic action of morphine acutely, but no interaction was observed 4 to 7 days later. Pretreatment with morphine and naloxone prevented the long-term blockade by SP. The effect of naloxone was not reversed by naltrexone suggesting that occupation of opiate receptors rather than an apparent agonist effect of naloxone caused the protection. Pretreatment with clonidine had only a slight effect on long-term blockade, but yohimbine was without effect. The present study describes a new long-term interaction between SP and alpha-2 agonists in the spinal cord. The mechanism(s) of the observed blockade by SP remains to be elucidated. However, there appears to be a functionally significant interaction between opiate and alpha-2 receptors in the spinal cord.

Neuroendocrine and behavioral effects of intrathecal capsaicin in adult female rats.

Neural feedback from the gonads and the reproductive tract has an integral role in normal reproductive function in female rats. To further assess the role of sensory feedback in neuroendocrine control, the effects of an intrathecal injection of the neurotoxin, capsaicin (100-125 micrograms) into the lumbosacral region of the spinal cord on reproductive function was tested in female rats. In addition, the effects of capsaicin on the response to noxious heat and pressure were tested. Intrathecal capsaicin had no effect on estrous cycles, ovarian compensatory hypertrophy or female sexual behavior. However, capsaicin treated animals showed a dramatic reduction in fertility, relative to vehicle treated control rats and this was shown to be due to the reduced capacity of vaginal/cervical stimulation to produce pseudopregnancy. Consistent with a selective loss in the effectiveness of cervical stimulation, immobilization produced by vaginal probing was reduced in capsaicin treated rats, but this response slowly recovered across time in some animals. Similarly, the ability of vaginal probing to induce a lordotic response during estrogen treatment was reduced in the capsaicin treated animals. The capsaicin treated animals showed analgesia to noxious heat, as measured by the tail flick test, but showed a normal foot withdrawal in response to pressure. The analgesic effect of vaginal stimulation on noxious pressure was unaltered in the capsaicin treated rats. Finally, the neurotoxic effect of capsaicin was verified in terms of a quantitative reduction in substance P immunoreactivity in the dorsal horns of the lumbosacral region of the spinal cord of capsaicin treated rats, relative to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)