Effects of dexamethasone and of local hypothermia on early and late tissue electrolyte changes in experimental spinal cord injury.

The current experiment reexamines this laboratory's frequently cited previous experimental conclusion that a mechanism underlying the beneficial effects of glucocorticoids in the treatment of spinal cord injury may be the enhanced preservation of spinal cord tissue potassium. For the first time, similar methodology also has been applied to study the effects of hypothermia. Canine spinal cords were injured at T13 by use of an epidural balloon and then were treated with local hypothermia or intramuscular dexamethasone or both. Motor recovery was assessed using a modified Tarlov scale. At either 6 days or 7 weeks, spinal cords T8 through L4 were removed and divided into 10 ordered blocks, which were analyzed for wet and dry weight, potassium concentration, and sodium concentration. Correlations between clinical motor and chemical results were evaluated. The conclusions drawn are as follows: 1) The canine severe rapid compressive injury model, unlike the previously published less severe feline impact injury model, is not associated with widespread early loss of spinal cord tissue potassium content (dry weight). 2) The dog compressive model, unlike the cat impact model, does not provide evidence that one fundamental mechanism of the confirmed beneficial action of steroids entails enhanced early preservation of tissue potassium content. 3) At 6 days, decrease in the percentage of dry weight and increase in sodium concentration, representing edema, occurred at and adjacent to the direct compression site in all lesioned dog groups except those treated with dexamethasone, demonstrating an antiedema effect of dexamethasone that was nullified by concurrent local hypothermia. 4) This antiedema effect of dexamethasone was associated with superior early motor improvement but did not lead to superior long-term function, in comparison with hypothermia. 5) At 7 weeks, decrease in the percentage of dry weight and potassium concentration, and increase in sodium concentration, all restricted to the directly compressed segment, signify necrosis. 6) This new chemical index of necrosis was highly correlated with clinical motor performance.

Optimization of the determination of 4-aminopyridine in human serum and urine by column liquid chromatography.

Two convenient reversed-phase column liquid chromatographic procedures are described for the determination of 4-aminopyridine in human serum and urine. A 0.5-ml aliquot of serum after the addition of a 0.5-ml solution of 4-(aminomethyl)pyridine in 0.1 M Na2HPO4 as the internal standard is passed through a 1-ml BondElut C18 silica extraction column. The column is selectively washed to remove acidic, neutral and weakly basic compounds. The desired compounds are eluted with a 0.3-ml aliquot of 35% perchloric acid-methanol (1:100, v/v). A 10-microliters aliquot of the eluate is injected onto a 150 x 4.6 mm I.D. column packed with 5-microns C18 silica particles that is eluted at ambient temperature with a mobile phase containing octanesulfonic acid as the ion-pairing agent. The peaks are monitored at 263 nm. A. 0.25-ml aliquot of urine or 0.5 ml of serum is mixed with N-propionylprocainamide as the internal standard and subjected to benzoylation by Schotten Baumann reaction. The reaction mixture is adjusted to pH 5.5-6 and extracted with a BondElut C18 extraction column. An aliquot of the eluate is chromatographed at ambient temperature with a mobile phase containing tetramethylammonium perchlorate. The peaks are monitored at 278 nm.

4-Aminopyridine in chronic spinal cord injury: a controlled, double-blind, crossover study in eight patients.

The potassium channel blocking drug 4-aminopyridine (4-AP) was administered to eight patients with chronic spinal cord injury, in a therapeutic trial based on the ability of the drug to restore conduction of impulses in demyelinated nerve fibers. The study was performed using a randomized, double-blind, crossover design, so that each patient received the drug and a vehicle placebo on different occasions, separated by 2 weeks. Drug and placebo were delivered by infusion over 2 h. An escalating total dose from 18.0 to 33.5 mg was used over the course of the study. Subjects were evaluated neurologically before and after the infusion. Two subjects returned for a second trial after 4 months and were examined daily for 3 to 4 days following drug infusion. Side effects were consistent with previous reports. Administration of the drug was associated with significant temporary neurologic improvement in five of six patients with incomplete spinal cord injury. No effect was detected in two cases of complete paraplegia and one of two severe incomplete cases (Frankel class B). Improvements in neurologic status following drug administration included increased motor control and sensory ability below the injury, and reduction in chronic pain and spasticity. The effects persisted up to 48 h after infusion of the drug, and patients largely returned to preinfusion status by 3 days. Compared with the more rapid elimination of the drug, these prolonged neurologic effects appear to involve a secondary response and are probably not a direct expression of potassium channel blockade.

Pathogenesis of spinal cord injury and newer treatments. A review.

Many victims of traumatic spinal cord injury (SCI) suffer immediate paralysis as well as a subsequent progressive worsening of the cord pathology. Certain sensorimotor functions that might otherwise have returned are irreversibly lost because of this delayed response. An understanding of the pathophysiology behind this progressive, self-destructive sequence is yet to be acquired; however, numerous proposals have been set forth involving processes such as edema formation, vascular changes, an inflammatory reaction, and destruction of the neuronal plasma membranes. In this review, the authors outline many of the chemical, anatomic, and functional changes associated with SCI as well as a number of treatment regimens that have been found to improve recovery from SCI (including parenteral glucocorticoid therapy, localized cord cooling, calcium channel blockers, and opiate antagonism). From this, a number of mechanisms accounting for the mediation and/or prevention of the secondary destructive response are synthesized.

Monitoring spinal cord blood flow using hydrogen polarography.

Spinal cord blood flow (SCBF) is an important physiological variable that may undergo changes following cord injury. We measured SCBF in healthy dogs whose cord had been cooled, a technique that is useful for treating spinal cord injured patients. A microcomputerized system developed for efficient recording of SCBF on-line is described in this paper.

The effects of local cooling on canine spinal cord blood flow.

The internal spinal cord blood flow was measured in dogs at the site of local cooling using hydrogen polarography. Blood flow decreased to 50% of the normothermic values during cooling of the cord to a central temperature of 16 degrees Celsius. Upon cessation of cooling internal blood flow rapidly returned to normal values. Implications of this finding for the treatment of spinal cord injury are discussed.

Current status of spinal cord cooling in the treatment of acute spinal cord injury.

In order to determine any beneficial effects of parenteral steroid administration and local cord cooling following complete cord injury, ten patients in the present series were treated by a combination of these modalities within 8 1/2 hours after injury. There was a better than expected rate of recovery of motor function and sensation and the mortality rate was reduced compared with more traditional forms of therapy. A literature review showed that local cord cooling had been applied to 52 patients with complete cord injuries in various centers. The rate of neurologic improvement was 48%, the ambulation rate was 17% and the 1-year mortality rate was reduced to 17%. These figures appear considerably better than the comparable expected rate for traditional treatment of such injuries. The results are encouraging enough to suggest further trials of treatment using localized cord cooling where such treatment can be instituted within 4 hours following injury.

Oxygenated fluorocarbon perfusion as treatment of acute spinal cord compression injury in dogs.

Experiments were conducted to determine the therapeutic value of subarachnoid perfusion of the traumatized dog spinal cord with the fluorocarbon, Fluosol-DA (20%). Control dogs without lesions, but which had durotomy, subarachnoid catheter placement, and saline irrigation for 4 hours, did not have any residual neurological deficit. A series of 41 dogs underwent an acute spinal cord compression using an epidural balloon inflated to a pressure of 160 mm Hg and maintained for 1 hour. Treatment included durotomy only (11 dogs), durotomy with saline perfusion at room temperature (15 dogs), and durotomy with oxygenated Fluosol-DA perfusion at room temperature (15 dogs). The dogs underwent daily grading of neurological status for a 60-day period. Dogs undergoing perfusion of the spinal cord with either saline or oxygenated Fluosol-DA had significantly improved motor recovery (p less than 0.004) compared with dogs undergoing durotomy only. Perfusion with oxygenated Fluosol-DA resulted in significantly better motor recovery (p less than 0.05) than did perfusion with normal saline. Microscopic examination of the traumatized spinal cords failed to reveal a substantial difference between the three groups. However, dogs with better functional results tended to have less destruction of the white matter. Hemorrhagic necrosis of the central gray matter was consistently observed in all traumatized spinal cords.

Use of hypertension and electroencephalographic monitoring during carotid endarterectomy.

Intraoperative hypertension and continuous electroencephalographic (eeg) monitoring were used during 42 carotid endarterectomies performed on 37 patients from 1970 to 1978. Computer spectral analysis of a majority of the electroencephalograms was also performed. Under supplemented nitrous oxide general anesthesia, elevation of the mean arterial blood pressure to 20% above the individual's preoperative mean blood pressure resulted in reversal to normal of an ischemic EEG pattern in 19% of the patients. The authors discuss the benefit of this technique. they present guidelines for patient selection and analyse the data to help the surgeon decide whether to use shunt during carotid endarterectomy.

Acrylic spinal fusion. A 20-year clinical series and technical note.

Methyl methacrylate (acrylic) was used in fusion techniques in 82 patients, most of whom had metastatic disease, between 1959 and 1979. In all cases the acrylic was used to supplement stabilization with Meurig-Williams stainless steel plates or with wire. In cases involving a decompressive laminectomy and excisional biopsy (radical resection of a tumor mass) that required posterior stabilization, acrylic helped to achieve rapid fusion with excellent results. The series included one anterior fusion with acrylic and nine atlantoaxial fusions in patients without tumors. Strict guidelines for selection of patients are outlined. The advantage of acrylic over bone fusion in selected patients is discussed. Careful follow-up studies including autopsy examinations are included. The technique of the use of acrylic is outlined. There was no case of late instability. There was one instance of infection in a patient who was immunodeficient and in whom a combination acrylic and bone fusion was performed. Tissue reaction to the acrylic in autopsy specimens is discussed.

Local hypothermia in experimental spinal cord trauma.

A series of controlled animal experiments comparing the effects of one, four, and 18 hours of local hypothermia at 6 degrees C begun four hours after compression lesions to the thoracic cord in dogs is reported. Four hours of local cooling delivered by a small silastic epidural heat exchanger, without durotomy or tissue perfusion, is shown to give greater functional benefit than cooling for one hour or 18 hours. Experimental design, pathophysiological implications, and clinical relevance are discussed.

Hospital-acquired bacterial meningitis in neurosurgical patients.

The authors review 23 cases of hospital-acquired meningitis occurring over a 15 year period in neurosurgical patients. Factors associated with the development of meningitis include recent craniotomy, cerebrospinal fluid leak, the presence of ventricular or lumbar drainage tubes, and skull fracture. Four cases were caused by Staphylococcus epidermidis; one of these patients died. In 19 cases, Gram-negative enteric bacteria were the etiologic agents, most commonly members of the Klebsiella-Enterobacter-Serratia group. Eleven of these patients died. The particular antibiotic or group of antibiotics used and the route of administration made no difference in the outcome of Gram-negative bacillary meningitis.

Combined steroid and hypothermia treatment of experimental spinal cord injury.

Canine spinal cords were compressed at T-13 by an epidural balloon maintained at 160 mm Hg for one hour. After seven weeks, mean motor ratings of dogs treated with either parenteral dexamenthasone or non-irrigative local hypothermia (on the dorsal dura mater at 6 degrees C for four hours) indicated ability to walk well, whereas untreated dogs could not walk. A third treatment group received both dexamethasone and delayed local hypothermia; this group performed poorly in early weeks, but eventually surpassed the other groups and became the only group to attain a final mean motor rating which was superior to that of controls at a significance level of p less than .01. Hypothermia was induced by means of a miniature epidural heat exchanger which eliminated tissue irrigation as a possible experimental variable. The possible mechanisms of action of hypothermia are reviewed.

Effects of local hypothermia and of steroids upon recovery from experimental spinal cord compression injury.

Canine spinal cords were compressed by a cylindrical balloon placed in the T-13 epidural space and maintained at 160 mm Hg for one hour. Fifteen minutes after deflation, either local hypothermia or parenteral dexamethasone therapy was initiated. Local hypothermia (dorsal dura mater at 6 degrees C for four hours) was achieved with a miniature epidural heat exchanger which kept cooling fluid isolated from tissue. At seven weeks, the treated groups achieved motor ratings which were significantly superior to those of the untreated group. The untreated group were unable to walk, while both treated groups were able to do so.