Orthostatic hypotension with brainstem tumors.

Three patients with brainstem tumors had orthostatic hypotension as the major presenting manifestation. Two patients had primary tumors that involved the dorsal medulla, pons, and rostral spinal cord; one was a malignant astrocytoma and the other a hemangioblastoma. The third patient had an oat cell carcinoma of the lung with subependymal spread to the medulla, pons, hypothalamus, and thalamus. Evaluation of baroreceptor function in the patient with the malignant astrocytoma showed a defect in the efferent sympathetic limb of the baroreceptor reflex arc.

Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury.

We measured levels of thromboxane B2 and 6-keto-PGF1 alpha in rabbit spinal cord and cat CSF after impact injury to spinal cord. Rabbit tissue thromboxane B2 levels increased more than 6-keto-PGF1 alpha. In cat, CSF thromboxane B2 was higher the first hour postinjury; CSF 6-keto-PGF1 alpha also increased, but less so. These results imply activation of arachidonic acid metabolism. The relatively greater increase of thromboxane B2 suggests that thromboxane-prostacyclin imbalance may contribute to post-traumatic ischemia.

Protective effect of methylprednisolone on vascular injury in rat spinal cord injury.

High-dose methylprednisolone (MP) given to patients within 8 h of traumatic spinal cord improved neural function at 6 and 12 months, suggesting a probable secondary injury process that may be amenable to therapeutic intervention. Vascular injury plays an important role in the secondary injury process of CNS trauma. We have examined the effect of MP on vascular changes, including tissue edema, vascular permeability, and polymorphonuclear (PMN) cell infiltration in a rat model of spinal cord impact injury. MP significantly reduced extravasation of fluorescein isothiocyanate dextran (FITC-D), a macromolecular tracer, by 64.3% and 50.7% with trauma forces of 20 and 40 g-cm, respectively, when MP was administered IV immediately after trauma at a bolus of 165 mg/kg, with a subsequent continuous MP infusion at 31.5 mg/kg/h for 23 h. MP reduced the water content in the 40 g-cm traumatic cord lesion to 73.0% compared to the traumatic control (74.3%, p < 0.001) at the same schedule of large dose 24-h infusion. The same doses of MP showed a trend to decrease the extent of neutrophil infiltration as determined by myeloperoxidase (MPO) activity, but the change was not significant. MP had little effect in decreasing FITC-D extravasation and cord edema when given at a lower dose (bolus of 30 mg/kg with continued infusion of 1.3 mg/kg/h for 23 h). MP did not reduce extravasation of FITC-D and edema when administered IV as one bolus injection at high (165 mg/kg) or low (30 mg/kg) doses.(ABSTRACT TRUNCATED AT 250 WORDS)

A sensitive fluorometric method for measurement of vascular permeability in spinal cord injury.

A sensitive fluorometric method was modified for the evaluation of drug action upon vascular permeability in rat spinal cord injury. Fluorescein isothiocyanate-conjugated dextran (FITC-D MW 71,200), used as a macromolecular tracer, was injected iv 2 hours before sacrifice. The optimal pH for FITC-D fluorescence was 8.2. The recovery in spinal cord was 101.4 +/- 4.0% (mean +/- SD). The extent of FITC-D extravasation, expressed as the vascular injury index (VII), was increased in proportion to the trauma force. The peak of VII after trauma was at 2 hours. This fluorometric method is sensitive, simple, and reliable for evaluation of drug effects upon vascular permeability in CNS trauma.

MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study.

The Multicenter Animal Spinal Cord Injury Study (MASCIS) adopted a modified 21-point open field locomotor scale developed by Basso, Beattie, and Bresnahan (BBB) at Ohio State University (OSU) to measure motor recovery in spinal-injured rats. BBB scores categorize combinations of rat hindlimb movements, trunk position and stability, stepping, coordination, paw placement, toe clearance, and tail position, representing sequential recovery stages that rats attain after spinal cord injury. A total of 22 observers from 8 participating centers assessed 18 hindlimbs of 9 rats at 2-6 weeks after graded spinal cord injury. The observers were segregated into 10 teams. The teams were grouped into 3 cohorts (A, B, and C), consisting of one experienced team from OSU and two non-OSU teams. The cohorts evaluated the rats in three concurrent and sequential sessions. After viewing a rat for 4 min, individual observers first assigned scores without discussion. Members of each team then discussed and assigned a team score. Experience (OSU vs. non-OSU) and teamwork (individual vs. team) had no significant effect on mean scores although the mean scores of one cohort differed significantly from the others (p = 0.0002, ANOVA). However, experience and teamwork significantly influenced reliability of scoring. OSU team scores had a mean standard deviation or discordance of 0.59 points, significantly less than 1.31 points for non-OSU team scores (p = 0.003, ANOVA) and 1.30 points for non-OSU individual scores (p = 0.001, ANOVA). Discordances were greater at the upper and lower ends of the scale, exceeding 2.0 in the lower (< 5) and upper (> 15) ends of the scale but were < 1.0 for scores between 4 and 16. Comparisons of non-OSU and OSU team scores indicated a high reliability coefficient of 0.892 and a correlation index (r2) of 0.894. These results indicate that inexperienced observers can learn quickly to assign consistent BBB scores that approach those given by experienced teams, that the scores are most consistent between 4 and 16, and that experience improves consistency of team scores.

The neuroprotective effect of high-dose methylprednisolone in rat spinal cord hemisection.

Multiple studies support a neuroprotective effect for high-dose methylprednisolone (MP) in acute blunt spinal cord injury. We know of no study that addresses the role of MP in prophylaxis for surgical trauma to the spinal cord or for the treatment of non-missile penetrating injuries to the spinal cord. We examined the neuroprotective effect of MP as measured by the retrograde transport of the fluorescent tracer Fluoro-Gold in 20 rats undergoing C-2 hemisection. Mean cell counts of retrogradely labeled rubrospinal neurons were determined 1 week post-injury. The group receiving MP had a significantly higher (P < 0.0001) number of labeled cells (x = 594) compared to controls (x = 387). The highly significant increase in mean cell counts in rats receiving steroids suggests less secondary axonal injury in the MP group. These findings are the first report of a neuroprotective effect of MP in rat spinal cord hemisection. We suggest that MP may be beneficial as prophylaxis during planned or incidental surgical trauma to the spinal cord and after non-missile penetrating injuries to the spinal cord.

Rubrospinal neurons and retrograde transport of fluoro-gold in acute spinal cord injury--a dose-response curve.

Using the fluorescent tracer Fluoro-Gold, we studied the relationship between severity of spinal cord trauma and the number of retrogradely labeled rubrospinal neurons in the rat. We compared the mean cell counts of retrogradely labeled rubrospinal neurons in rats receiving 0, 20, 40, and 60 g/cm concussive spinal cord traumas. For each incremental increase in trauma a significant reduction in mean cell counts took place (P < 0.0001). We demonstrate a dose-response relationship between trauma severity and Fluoro-Gold retrogradely labeled rubrospinal neurons in acute spinal cord injury of the rat. This relationship may be helpful in quickly assessing the efficacy of therapeutic interventions in acute spinal cord injury. Previous studies with HRP failed to demonstrate such a dose-response curve. Fluoro-Gold may be a more sensitive indicator of neuronal survival than HRP in the traumatized rat spinal cord.

Spinal cord glucose utilization after experimental spinal cord injury.

Metabolic alterations after experimental contusion injury of the spinal cord were evaluated by determining qualitative spinal cord glucose utilization (SCGU), SCGU was determined by the 2-deoxy-D-[14C] glucose technique. An increase in SCGU occurred at the site of maximal impact in the white matter after an injury causing paraparesis and in near trauma regions after an injury causing either paraparesis or paraplegia. These findings are most likely due to anaerobic glycolysis resulting from a reduction in blood flow that still allows delivery of substrate to tissue. Although an initial increase was observed at the site of maximal impact after a paraplegia-causing injury, SCGU in the white matter demonstrated a progressive deterioration by 4 and 8 hours after injury. A failure of substrate delivery resulting from ischemia is the most likely cause for this reduction in SCGU. The somatosensory evoked potential was found to be a very sensitive indicator of the remaining functional axons at the injury site.

Dural plasmacytoma.

Dural plasmacytoma is an unusual form of myeloma. We describe a woman with plasmacytoma of the tentorium cerebelli that was managed successfully with surgical decompression and radiotherapy. Computed tomography, not previously reported in cases of dural plasmacytoma, was useful in her management. Another unique feature was the restoration of a normal immunoglobulin G content in the blood and cerebrospinal fluid after local treatment of the neoplasm. Two previously reported cases showed similar normalization of cerebrospinal fluid immunoglobulin G after local radiotherapy. Dural plasmacytoma presents a characteristic clinical syndrome. The typical patient is a woman (92% of the reported cases) in the 5th decade of life. Clinical findings reflect intracranial hypertension, often with focal neurological signs, consistent with the usual dural or tentorial origin of the tumor. Immunoglobulin abnormalities may be found in serum or cerebrospinal fluid. The prognosis is good after surgical decompression and local radiotherapy.

Pressor response resulting from experimental contusion injury to the spinal cord.

Experimental contusion paraplegic injury to the posterior spinal cord in cats results in a sudden increase of systemic blood pressure to between 200 and 250 mm Hg, and an increase in pulse pressure and a slowing of pulse rate. This initial hypertensive phase lasts approximately 3 to 4 minutes, and then is followed by a hypotensive phase. This pressor response is mediated by the alpha adrenergic receptor sites of the peripheral sympathetic nervous system and can be blocked by intravenous phenoxybenzamine, an alpha adrenergic blocking agent. The hypotensive phase is the result of an overall reduction in alpha adrenergic vascular tone and can be reversed by the infusion of metaraminol or intravenous fluids. The alterations in blood pressure that follow impact injury are most likely related to alterations of peripheral arteriolar resistance and venous return of blood to the heart.

Myelotomy for control of mass spasms in paraplegia.

A new myelotomy knife is described and a procedure, designed to sever certain reflex connections while preserving as many corticospinal connections as possible, is presented. Through intermittent dorsal midline incisions the gray matter lateral to the central canal is severed bilaterally under the microscope from L-1 to S-1. This procedure relieved mass spasms and hyperactive reflexes in 14 paraplegic or tetraplegic patients, but preserved postural reflexes and whatever voluntary motor power the patients had prior to myelotomy. Before myelotomy all patients were bedridden. Afterward nine patients were able to use a wheel chair and five were able to walk with the use of parallel bars or crutches.

Treatment of nontraumatic atlantoaxial dislocation and fibrous fusion. Case report.

The authors describe a case of nontraumatic atlantoaxial dislocation secondary to acute rheumatic fever, in which there appeared to be fibrous fusion between the axis and the atlas in the subluxed position. The dislocation was reduced by means of combined traction and steroid therapy. Fibrous fusion occurred in the realigned position after immobilization.

Adverse reactions to intrathecal saline injection for control of pain.

The authors report the results of a questionnaire regarding the use of hypertonic saline for the control of pain. Of 2105 patients so treated, nearly 11% had an adverse temporary symptom or sign, reported as an untoward reaction; slightly over 1% suffered a significant morbidity, of which paraplegia or quadriplegia was by far the most common, and two patients died (0.1%).

The histopathology of experimental spinal cord trauma. The effect of systemic blood pressure.

The early sequential histopathological alterations following a concussive paraplegic injury to the posterior thoracic spinal cord in cats were studied. The lack of significant progression of hemorrhages over a 4-hour period after injury indicates that most hemorrhages probably occur within the first hour. The marked enhancement or retardation of hemorrhages in the post-injury period, when the blood pressure was increased or decreased, respectively, demonstrates the loss of autoregulation of spinal cord vasculature at the trauma site after a concussive paraplegic injury. Progressive edema formation was evident over a 4-hour period following injury, and it could be enhanced or retarded by elevation or reduction of the systemic blood pressure.

Evaluation of acute nonpenetrating cervical spinal cord injuries with CT metrizamide myelography.

Computerized tomography metrizamide myelography was performed in 46 patients with acute, nonpenetrating cervical spinal cord injuries. By visualizing the spinal canal, spinal cord, and any compressive lesion, the study proved valuable in the decision as to whether surgical decompression was indicated and what approach should be used. Eleven patients were found to have significant spinal cord compression, 10 of whom were treated surgically. The technique, results, and complications resulting from the study are discussed.

Intracranial fibro-osseous lesion. Case report.

A rare tumor closely associated with the trigeminal ganglion produced a syndrome of atypical facial pain in a 44-year-old man. Two previous reports have designated similar tumors as "fibro-osseous lesions." The distinctive morphological appearance is illustrated and possible histogenesis discussed.

Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial.

OBJECT: A randomized double-blind clinical trial was conducted to compare neurological and functional recovery and morbidity and mortality rates 1 year after acute spinal cord injury in patients who had received a standard 24-hour methylprednisolone regimen (24MP) with those in whom an identical MP regimen had been delivered for 48 hours (48MP) or those who had received a 48-hour tirilazad mesylate (48TM) regimen. METHODS: Patients for whom treatment was initiated within 3 hours of injury showed equal neurological and functional recovery in all three treatment groups. Patients for whom treatment was delayed more than 3 hours experienced diminished motor function recovery in the 24MP group, but those in the 48MP group showed greater 1-year motor recovery (recovery scores of 13.7 and 19, respectively, p=0.053). A greater percentage of patients improving three or more neurological grades was also observed in the 48MP group (p=0.073). In general, patients treated with 48TM recovered equally when compared with those who received 24MP treatments. A corresponding recovery in self care and sphincter control was seen but was not statistically significant. Mortality and morbidity rates at 1 year were similar in all groups. CONCLUSIONS: For patients in whom MP therapy is initiated within 3 hours of injury, 24-hour maintenance is appropriate. Patients starting therapy 3 to 8 hours after injury should be maintained on the regimen for 48 hours unless there are complicating medical factors.

Experimental spinal cord trauma, I: Correlation of blood flow, tissue oxygen and neurologic status in the dog.

Spinal cord blood flow and tissue oxygen were measured concurrently in a series of paraplegic dogs subjected to experimental spinal cord trauma. Injury to the spinal cord sufficient to cause clinical paraplegia is associated with a significant (P less than 0.01) decrease in blood flow in the central spinal cord from 15.2 to 6.1 ml/min/100gms at two to three hours following injury. Also, at two and three hours post-injury, paraplegic dogs demonstrate a significant (P less than 0.01) decrease in tissue oxygen levels from 35-39 mm Hg to 17-24 mm Hg. No significant changes occurred in systemic blood pressure or carotid blood flow. A delay often precedes the significant onset of blood flow and tissue oxygen alterations, which suggests that therapeutic efforts could be directed during this critical interval.

Experimental spinal cord trauma, II: Blood flow, tissue oxygen, evoked potentials in both paretic and plegic monkeys.

Graded clinical motor deficits were produced in a series of Rhesus monkeys subjected to experimental spinal cord trauma from a variety of impact loads. An argon washout technique was used to measure spinal cord blood flow; tissue oxygen carbon dioxide, and somatosensory evoked potentials (SEPs) were also monitored. Each animal received a clinical grade and, after a week of study, the spinal cords were removed for histopathological grading. Blood flow in paraplegic animals was significantly decreased at two hours and seven days following injury (5 ml/min/100 gms tissue); paraparetic animals showed no significant difference from preinjury levels (14 ml/min/100 gms tissue). Animals which completely recovered demonstrated increased flow (27 ml/min/100 gms tissue). Composite tissue oxygen was generally depressed in paraplegic animals (28 mm Hg/kg) but showed no clear pattern in other groups. Only 8% of monkeys rendered paraplegic preserved a somatosensory evoked potential (SEP) at five minutes after injury. Paraparetic animals were more likely (40%) to show initial preservation of the SEP and in normal animals, the SEP always returned by three hours. Histopathological grading tended to parallel clinical grading in 92% of the cases. Although the extremes of possible postinjury deficits (complete paraplegia or recovery) can be predicted from a combination of these measurements, incomplete lesions (whether judged clinically or pathologically) present a more variable picture.