Ethics, health care and spinal cord injury: research, practice and finance.

Dating back to ancient times, mankind has been absorbed with 'doing the right thing', that is, behaving in ways approved by the society and the culture during the era in which they lived. This has been and still is especially true for the medical and related health-care professions. Laws and professional codes have evolved over the years that provide guidelines as to how physicians should treat patients, beginning with the one authored by Hippocrates. Only more recently, however, have laws and codes been created to cover health-care research and the advances in health-care practice that have been brought to light by that research. Although these discoveries have clearly impacted the quality of life and duration of life for people with spinal cord injury and other maladies, they have also raised questions that go beyond the science. Questions such as when, why, how and for how long should such treatments be applied often relate more to what a society and its culture will condone and the answers can differ and have differed among societies depending on the prevailing ethics and morals. Modern codes and laws have been created so that the trust people have traditionally placed in their healers will not be violated or misused as happened during wars past, especially in Nazi Germany. This paper will trace the evolution of the rules that medical researchers, practitioners and payers for treatment must now follow and explain why guiding all their efforts that honesty must prevail.

Pilot trial of bacterial interference for preventing urinary tract infection.

OBJECTIVES: To examine the safety and efficacy of bacterial interference in preventing symptomatic urinary tract infection (UTI). METHODS: A prospective, nonrandomized, pilot clinical trial was conducted in patients with spinal cord injury who had neurogenic bladder and had frequent episodes of symptomatic UTI. The bladder of patients was inoculated with a nonpathogenic prototype of Escherichia coli 83972. The rate of symptomatic UTI in successfully colonized patients while colonized with E. coli 83972 was compared with (a) their own baseline prestudy rate and (b) the rate of symptomatic UTI in patients who were not successfully colonized. RESULTS: Of 44 inoculated patients, 30 (68%) became colonized with E. coli 83972 for 1 month or longer. Only two episodes of symptomatic UTI occurred in the group of 30 patients while colonized with E. coli 83972 (a total of 34 patient-years), and none was attributed to E. coli 83972. The group of 30 patients experienced a 63-fold reduction in the rate of symptomatic UTI while colonized with E. coli 83972 versus their baseline prestudy period (mean 0.06 versus 3.77 episodes of symptomatic UTI/patient-year, P <0.001). The rate of symptomatic UTI was also 33-fold lower in this group of 30 patients while colonized with E. coli 83972 than in the well-matched group of 14 patients who were not successfully colonized (mean 0.06 versus 1.80 episodes of symptomatic UTI/patient-year, P <0.001). CONCLUSIONS: The results of this pilot study indicate that bacterial interference using E. coli 83972 may be safe and effective in preventing UTI.

Intravenous infusion of 4-AP in chronic spinal cord injured subjects.

STUDY DESIGN: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). OBJECTIVE: To determine the efficacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. SETTING: The post anesthesia care unit (PACU) of a tertiary care acute hospital. METHODS: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal fluid (CSF) were also analyzed at similar intervals. RESULTS: Despite penetration of 4-AP into the CSF, no significant differences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. CONCLUSION: The intravenous route may not be the best way to administer this drug as no short term benefits were observed.

Intrathecal administration of 4-aminopyridine in chronic spinal injured patients.

STUDY DESIGN: Intrathecal administration of 4-aminopyridine (4-AP) in chronic spinal cord injured (SCI) patients. OBJECTIVE: To determine the safety and effects of intrathecal administration of 4-AP in a small population of chronic SCI patients. SETTING: The post anesthesia care unit of a tertiary care hospital. METHODS: Following animal mode studies to establish dosing safety, six subjects with chronic SCI were examined. In each subject, an intrathecal catheter was placed with the tip as close to the lesion level as possible. 4-AP was infused at 5 microg/h for a period of 4-5 h. Vital signs were recorded and sensory-motor physical examinations and pain questionnaires were administered for 24 h. In two patients, samples of cerebrospinal fluid for analysis were drawn from a second intrathecal catheter. RESULTS: No adverse systemic side effects were noted. One patient showed transient improvement in sensory function; two showed transient increases in spasticity; three showed transient increases in cutaneomuscular reflexes and two showed an apparent small increase in volitional motor control. The concentration of 4-aminopyridine in the cerebrospinal fluid reached a peak of 163 ng/ml at 4 h in one subject and 122 ng/ml at 5 h in the other subject examined. CONCLUSION: Intrathecal administration of 4-aminopyridine at a rate of 5 microg/h does not appear to cause adverse effects and may modify spinal cord function. This route of administration allows local cerebrospinal fluid concentrations equivalent to those produced by maximum tolerable systemic doses, which require 1000 times more drug substance to be delivered to the subject as a whole. Intrathecal administration offers the potential to focus therapeutic effects to the lesion site while minimizing systemic side effects.

Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems.

OBJECTIVE: To present data on neurologic recovery gathered by the Model Spinal Cord Injury (SCI) Systems over a 10-year period. DESIGN: Case series. SETTING: Twenty-one Model SCI Systems. PATIENTS: A total of 3,585 individuals with traumatic SCI admitted between January 1, 1988 and December 31, 1997. MAIN OUTCOME MEASURES: Neurologic impairment category; Frankel grade; American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade; motor score. RESULTS: SCI caused by violence is more likely than SCI from nonviolent etiologies to result in a complete injury. Changes in severity of injury were similar using the older Frankel scale and the newer ASIA Impairment Scale. Individuals who were motor-complete with extended zones of sensory preservation but without sacral sparing were less likely to convert to motor-incomplete status than those with sacral sparing (13.3% vs 53.6%; p < .001). Motor score improvements at 1 year were related to severity of injury, with greater increases for better AIS grades except grade D, because of ceiling effects. Individuals with AIS grade B injuries have a mixed prognosis. CONCLUSION: Neurologic recovery after SCI is influenced by etiology and severity of injury. Multicenter studies on prognostic features such as preserved pin sensation in grade B injuries may identify subgroups with similar recovery patterns. Identification of such groups would facilitate clinical trials for neurologic recovery in acute SCI.

Virulence properties of Escherichia coli 83972, a prototype strain associated with asymptomatic bacteriuria.

Little is known about bacteria associated with asymptomatic bacteriuria (ABU) with regard to urinary tract colonization mechanisms. In this study, virulence properties of Escherichia coli 83972, a strain that was isolated from a clinical ABU episode, were examined. The genetic potential for expression of P and type 1 pili was demonstrated, and DNA sequences related to type 1C and G (UCA) pilus genes were also detected. However, E. coli 83972 did not express D-mannose-resistant or D-mannose-sensitive hemagglutination after growth under standard conditions in vitro or upon isolation from the urine of colonized test subjects. Limited uroepithelial cell adherence was observed in vivo, and weak D-mannose-sensitive hemagglutination was detected after extended growth in urine in vitro.

A test of the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury.

This study was designed to test the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury. One hundred and six professionals in the field of spinal cord injury attending an instructional course at the 1994 ASIA Meeting participated in the test. Participants completed a pretest and posttest in which they classified two patients who had a spinal cord injury (one with complete tetraplegia and one with incomplete paraplegia) by sensory and motor levels, zone of partial preservation (ZPP), ASIA Impairment Scale and completeness of injury. Between tests, three members of the ASIA Standards Executive Committee gave presentations on the neurological assessment, scoring, scaling and classification of spinal cord injury and a video of the actual examinations of the two cases was viewed. Percent 'correct' (as defined by the ASIA Standards Committee) was calculated for sensory and motor levels, ZPP, ASIA Impairment and completeness. Overall, the analyses showed that participants had very little difficulty in correctly classifying the patient with complete tetraplegia. Pretests scores ranged from 72% (left motor level) to 96% (complete injury), posttest scores from 73% (left motor level) to 100% correct (complete injury). For the patient with incomplete paraplegia (Case 2), scores were considerably lower. Pretest scores ranged from 16% (right motor level) to 95% correct (incomplete injury); posttest scores from 21% (right motor level) to 97% correct (incomplete injury). The results showed that further revisions of the 1992 Standards and more training is needed to ensure accurate classification of spinal cord injury.

Virulence factors of Escherichia coli isolates from patients with symptomatic and asymptomatic bacteriuria and neuropathic bladders due to spinal cord and brain injuries.

Chronic bacteriuria is a common occurrence among spinal-cord injury patients and others with neuropathic bladders. If bacteria are present in the urinary tract, the patient may develop symptoms of infection or remain asymptomatic. We have compared virulence properties of 28 Escherichia coli isolates from patients with symptomatic urinary tract infections (UTI) and 29 E. coli isolates from patients with asymptomatic bacteriuria (ABU). Bacteria from patients with symptomatic UTI were more likely to be hemolytic than isolates from patients with ABU (P = 0.05) or fecal isolates obtained from healthy volunteers (P < 0.001). Bacteria from patients with symptomatic UTI were also more likely than strains isolated from patients with ABU (P = 0.08) or fecal strains (P < 0.001) to exhibit D-mannose-resistant hemagglutination of human erythrocytes. The results suggest that E. coli isolates from nonimmunocompromised patients who require intermittent catheterization and who develop symptomatic UTI may be distinguished from bacteria recovered from patients who remain asymptomatic and possibly from normal fecal E. coli.

Neurological issues.

The case histories of two patients who had had a spinal cord injury (SCI) were selected by the senior author and sent to four experts in the field of SCI. Based on the 1992 American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) standards, the four participants plus the senior author recorded the motor and sensory scores, the ASIA impairment scale (AIS), the neurological level (NL) and the zone of partial preservation (ZPP). Several minor scoring errors occurred among the participants, especially with motor scores when key muscles could not be tested due to pain, or external immobilization devices. Difficulties with interpretation occurred with the motor levels and the ZPP for the patient with a complete injury. This exercise points to the need for all examiners of SCI patients to thoroughly familiarize themselves with the standards and to use the motor and sensory scores to arrive at a NL and ZPP. They also indicate a need to revise the standards to clarify the determination of sensory levels and how to score muscles whose strength is inhibited by pain.

Analysis of gram negative recolonization of the neuropathic bladder among patients with spinal cord injuries.

Over a 4 year period, 119 acute spinal cord injury (SCI) patients were enrolled in this study. The 101 males and 18 females had a mean age of 35.9 years (range 16-87). Sixty-two patients were tetraplegic and 57 were paraplegic. All patients had a urine specimen taken for culture, colony count and sensitivity once weekly while they were receiving intermittent catheterization. Of these, 22 patients (18.5%), none of whom had underlying genito-urinary (GU) pathology, developed recolonization by an organism of the same species and genus previously cultured. All 22 reached sterile-urine between colonizations after being treated with antibiotics for at least 7 days. The 16 males and six females had a mean age of 35.1 years (range 17-79). Sixteen were tetraplegic and six were paraplegic. Plasmid analysis (PA) was used to determine whether these recolonizations were from the same or from a different strain. In those instances where the bacteria harbored no plasmids or where the results of plasmid analysis were otherwise inconclusive, bacteria were also compared using restriction fragment length polymorphism (RFLP) analysis. Recolonization was caused primarily by E. coli and K. pneumoniae. While there was no significant difference between the two organisms with respect to the number of days when sterile urine occurred to the time when recolonization was observed, there were significant differences seen in both organisms with regard to the time lapse from one colonization to the next: the average number of days to recolonization with an identical organism was 10.3 days, whereas with a different strain it was 15.9 days (P < 0.04). When a different organism was cultured between the recolonizations, the mean recolonization interval was 17.9 days. When no intervening organism occurred, the interval was 9.5 days (P < 0.005). Both intervals measured the days from the first sterile urine after the first colonization to the next colonization. These data indicate the proclivity for two common Gram negative normal bowel inhabitants to recolonize the neuropathic bladder of spinal cord injured patients even after adequate treatment. PA and RFLP provide a means of discriminating between relapses by the same organism versus recurrences by a different organism of the same species and genus. Those with the same identity tend to recur sooner than those of different identities and may be suspected when relapse occurs within two weeks of cessation of 7 day course of antibiotics. While an intervening organism may delay the relapse (or recurrence), it does not prevent it and identical organisms can reappear even after adequate therapeutic regimens. Since none of the patients in this study had GU pathology, recolonization by an identical strain (relapse) does not necessarily warrant an extensive investigation for disease within the GU tract.

Omental transposition in chronic spinal cord injury.

The results of omental transposition in chronic spinal cord injury have been reported in 160 patients operated upon in the United States, Great Britain, China, Japan, India and Mexico, with detailed outcomes reported in few studies. Recovery of function to a greater degree than expected by natural history has been reported. In this series, 15 patients with chronic traumatic spinal cord injury (> 1.5 years from injury) underwent transposition of pedicled omentum to the area of the spinal cord injury. Of the first series of four patients who were operated upon in 1988, one died, one was lost to follow-up and two were followed with sequential neurological examinations and Magnetic Resonance Imaging (MRI) scans preoperatively, at 1 year post injury and 4 1/2 years post injury. Another 11 patients were operated in 1992 and underwent detailed neurological and neurophysiological examinations and had MRI scans preoperatively and every 4 months for at least 1 year after surgery. All patients completed a detailed self-report form. Of the total of 13 operated patients in both series followed for 1-4 1/2 years, six reported some enhanced function at 1 year and five of these felt the changes justified surgery primarily because of improved truncal control and decreased spasticity. MRI scans showed enlargement of the spinal cord as compared to preoperative scans in seven patients. Increased T2 signal intensity of the spinal cord was found by 1 year after surgery in eight of 13 operated patients. Neurophysiological examinations of 11 patients in the second series agreed with self-reports of increases or decreases in spasticity (r = 0.65, P < 0.03). Somatosensory evoked potentials and motor evoked potentials at 4 month intervals up to 1 year in these patients showed no change after surgery. Neurological testing, using the American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) international scoring standards, failed to show any significant changes when the 1-year post operative examination was compared to the first preoperative examination except for decreased sensory function after surgery which approached statistical significance. When the 11 patients in the second series were compared to eight non-operated matched patients, followed for a similar length of time, no significant differences were found. Complications encountered in the operated patients from both series included one postoperative death from a pulmonary embolus, one postoperative pneumonia, three chronic subcutaneous cerebrospinal fluid (CSF) fistulae requiring wound revision, and one patient who developed biceps and wrist extensor weakness bilaterally requiring graft removal. We conclude that the omental graft remains viable over time and this operation can induce anatomical changes in the spinal cord as judged by MRI. Some patients reported subjective improvement but this was not supported by objective testing. We, therefore, find no justification for further clinical trials of this procedure in patients who have complete or sensory incomplete lesions. Further testing in motor incomplete patients would seem appropriate only with compelling supportive data.

Operative and nonoperative management of spinal cord injury. A review.

Technological developments over the last two centuries have advanced the spinal surgeon's capability to service the needs of the spinal cord injured person. While the role that surgery can play in shortening hospitalization for tetraplegics has yet to be proven, it does play a much needed role in the correction of instability and prevention of deformity when the possibility of these conditions exist. Surgical intervention for purposes of neural decompression has yet to be proven as justifiable in view of the risks involved. All surgical procedures must be undertaken only after due consideration of the patients' general medical condition, including coexisting trauma, the potential for and actual instability and deformity of the spine, and the neurological level and degree of incompleteness of the patient. In general, the greater the remaining neurological function, the more there is to be gained by early mobilization. Yet, in the face of progressive improvement in neurological function, caution is advised since there will be much to lose if anything goes wrong with the operation.

Hyperbaric oxygen therapy: implications for spinal cord injury patients with intrathecal baclofen infusion pumps. Case report.

A patient with a cervical spinal cord injury receiving intrathecal baclofen for spasticity control underwent a 7 week course of hyperbaric oxygen therapy to induce healing of an ischial decubitus ulcer. After completion of this treatment and during a routine baclofen infusion pump refill, the actual pump reservoir volume exceeded computer measurements obtained with telemetry. Examination of the physiology of hyperbaric oxygen therapy in relation to infusion pump function revealed that the intraspinal pressures attained during hyperbaric oxygen therapy produced retrograde leakage of cerebrospinal fluid into the infusion pump reservoir.

Intrathecal baclofen: does tolerance occur?

Concern over the development of tolerance in patients on continuous intrathecal baclofen therapy has arisen as this new form of treatment for spasticity has gained wider use. We have studied time-dose relationships in 18 spinal cord injured patients who have undergone intrathecal baclofen infusion pump implantation since February 1988 in our facility. Our data show that there was a significant increase in baclofen dosage needed to control spasticity during the first 12 months post implantation. After 12 months, however, no significant changes in dosage requirement was detected. In addition, there was no significant difference between completely and incompletely spinal cord injured patients with regard to both the initial dose and the tolerance trend.

Neurological and skeletal outcomes in 113 patients with closed injuries to the cervical spinal cord.

Neurological and skeletal outcomes were evaluated in 113 patients for one year following closed lower cervical spinal cord injuries. The extent of neurological recovery did not depend on surgical versus nonsurgical management, or the degree of spinal angulation, vertebral displacement, spinal stenosis, or inferred mechanism of injury based on the initial plain cervical x-rays. Assessment of skeletal outcomes demonstrated significantly less vertebral angulation, more rapid stabilization, and less anterior callus formation among the patients in the surgical group. In addition, the surgical patients had marginally shorter lengths of hospitalization.

Effects of intrathecal baclofen on lumbosacral and cortical somatosensory evoked potentials.

We analyzed lumbosacral and cortical somatosensory evoked potentials in three spinal cord injury patients undergoing evaluation of intrathecal baclofen infusion for management of spasticity. The cauda equina propagating root wave (R wave) and conus medullaris postsynaptic responses (S and P waves) were analyzed before and during baclofen infusion. Baclofen abolished the concomitantly recorded H-reflex and markedly suppressed the P wave amplitude and area. The S wave amplitude and area were suppressed to a lesser degree. In contrast, there were no significant changes in cortical somatosensory evoked potentials.