Ventriculo-lumbar perfusion in acute ischemic stroke.

INTRODUCTION: Effective treatment for severe ischemic stroke continues to be largely an unmet medical need. Using a nonvascular (paravascular cerebrospinal fluid) pathway to provide oxygen and nutrients to ischemic tissues may be a means of treating this disease. The primary objective of this study was to evaluate the safety and technical feasibility of ventriculo-lumbar perfusion with the oxygenated fluorocarbon nutrient emulsion (OFNE) perfusion system in the treatment of patients with severe hemispheric cerebral ischemia. RESULTS: Four patients were enrolled in this pilot study. At admission, patients' National Institutes of Health Stroke Scale scores ranged from 16 to 24. The perfusion pathway was successfully established in all four patients. Maximum perfusion rates varied from 25 to 40 mL/minute; total volume perfused over the 24-hour period ranged from 30.6 to 45.8 L. ICP ranged from -3 to 16 mmHg during the perfusion. The 24-hour perfusion was successfully completed in all four patients with no serious adverse events during the perfusion. CONCLUSION: It is technically feasible and safe to establish a ventriculo-lumbar perfusion pathway using a specially designed lumbar drainage catheter and to control intracranial pressure while perfusing large volumes of OFNE.

The effect of the prone position on venous pressure and blood loss during lumbar laminectomy.

STUDY OBJECTIVE: To determine the effects of three different prone support systems (Andrews spinal surgery frame, Cloward surgical saddle, and longitudinal bolsters) on inferior vena cava (IVC) and superior vena cava (SVC) pressures; the validity of measuring central venous pressure (CVP) for the determination of ideal positioning of the patient; and the relationship among frame type, blood loss, and hemodynamic measurements. DESIGN: Prospective, randomized study of the hemodynamic effects of the prone position. SETTING: Inpatient surgery at a university hospital (regional spinal cord injury treatment center). PATIENTS: Eighteen patients free of significant coexisting disease (ASA physical status I and II) undergoing elective lumbar laminectomy. INTERVENTIONS: Patients were assigned to one of three support frames and measurement of SVC pressure, IVC pressure, and mean arterial pressures (MAP) were obtained supine, prone, and after repositioning. These pressures and measured blood loss were obtained every 15 minutes during the surgical laminectomy portion of the procedure. MEASUREMENTS AND MAIN RESULTS: Patients positioned on the Andrews frame had decreased mean SVC and IVC pressures from 8.7 mmHg and 8.4 mmHg in the supine position to 3.3 mmHg and 1.8 mmHg in the prone position, respectively (p less than 0.001). Prone position CVP also was significantly lower in the Andrews group compared with that in the other two groups (p less than 0.001). Repositioning efforts did not significantly decrease CVP. Blood loss was higher in the Cloward group (1,150 +/- 989 ml) than in the Andrews (245 +/- 283 ml) and bolsters (262 +/- 188 ml) groups (p less than 0.02). CONCLUSIONS: Increased blood loss was not associated with increased SVC or IVC pressure, nor was there any significant correlation between any demographic or hemodynamic variable and blood loss. There was no evidence that CVP is useful in determining the ideal prone position in patients undergoing lumbar laminectomy.

Prognostic significance of magnetic resonance imaging in the acute phase of cervical spine injury.

Fifty-seven patients with acute cervical spine injuries and associated major neurological deficit were examined within 2 weeks of injury by magnetic resonance (MR) imaging. All patients had abnormal scans, indicating intramedullary lesions. This study was undertaken to determine if the early MR imaging pattern had a prognostic relationship to the eventual neurological outcome. Three different MR imaging patterns were observed in these patients: 21 patients had patterns characteristic of intramedullary hematoma (Group 1); 17 had intramedullary edema over more than one spinal segment, but no hemorrhage (Group 2); and 19 had restricted zones of intramedullary edema involving one spinal segment or less (Group 3). The neurological state was determined using standard motor index scores at admission and at follow-up examination. Characteristically, the patients in Group 1 had admission motor scores significantly lower than the other two groups. At follow-up examination, the median percent motor recovery was 9% for Group 1, 41% for Group 2, and 72% for Group 3. These studies suggest that the MR imaging pattern observed in the acutely injured human spinal cord has a prognostic significance in the final outcome of the motor system. It is only when an accurate prognosis can be given at the outset that useful treatment data might be collected for homogeneous injury groups, and accurately based long-term planning made for the best patient care.

A novel treatment for ischemic intracranial hypertension in cats.

There is no accepted efficacious treatment for ischemic cerebral edema. We show in a cat model of focal cerebral ischemia that infarct volume can be reduced (p less than 0.05) by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion (bis-perfluorobutylethylene). An accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure. At 18 hours following the start of the perfusion, there was a significant (p less than 0.05) difference in intracranial pressure between nonperfused controls (mean 11.4 [range 2.3-23.0] torr, n = 6) and cats perfused with an oxygenated nutrient solution not containing fluorochemical (mean 11.3 [range 3.0-29.0] torr, n = 8) or animals perfused with the oxygenated fluorochemical emulsion (mean 2.21 [range 0-3.5] torr, n = 7). Perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure.

Spinal cord injury: a ten-year report.

In the past 10 years, the RSCICDV has had a unique opportunity to serve and expand the bounds of knowledge regarding this most devastating injury. The RSCICDV has collaborated with other model SCI systems in research regarding the incidence of respiratory complications, the value of removing bullet fragments lodged within the spinal canal, the survival/cause of death following spinal cord injury, the cost of spinal cord injury care, and the recovery of motor strength after quadriplegia. Key on-site research efforts have focused on preventing deep vein thrombosis and in documenting the course of motor recovery after spinal cord injury. The identification of electrical stimulation plus low dose heparin as a prophylaxis has been a major breakthrough in the prevention of deep vein thrombosis. The documentation of motor recovery after injury has led to the designation of Thomas Jefferson University as a federally-funded National Rehabilitation Research and Training Center in Neural Recovery and Functional Enhancement (1988-1993). It cannot be stressed enough, however, that the accomplishments of the Regional Spinal Cord Injury Center of Delaware Valley would have been quite impossible without the cooperation and support of the many physicians who have referred their patients to this regional center program. Continuing and expanding this cooperative effort should result in even greater achievements for persons with spinal cord injury in the years to come.

Local cerebral glucose metabolism after global ischemia: treatment by ventriculocisternal perfusion with a fluorocarbon emulsion.

The local cerebral metabolic rate for glucose (LCMRg) was measured in cats subjected to global cerebral ischemia (GCI). Control (nonperfused) cats showed decreased LCMRg (P less than 0.01) in the frontal, temporal, parietal, and occipital cortex 9.5 hours after a 10-minute exposure to GCI. Cats perfused ventriculocisternally with oxygenated nutrient solution (ONS) for 8 hours showed significant increases in the LCMRg (p less than 0.05) at 9.5 hours postischemia in the parietal and occipital areas over the levels found in untreated ischemic cats. Supplementing the ONS perfusion medium with fluorocarbon (OFNS) increased the LCMRg (P less than 0.05) in the frontal, as well as the parietal and occipital areas, over that seen in untreated ischemic brains. The increase of LCMRg in three (rather than only two) cortical areas may be a result of the ability of the fluorocarbon in OFNS to deliver greater quantities of oxygen to the brain than ONS without fluorocarbon. Perfusion with OFNS without glucose, or with low (50 mg%) glucose, was more effective than OFNS with high (200 mg%) glucose in restoring LCMRg to normal in all four cortical areas affected by GCI. In five brain areas not affected by GCI, perfusion with OFNS having no glucose significantly increased LCMRg as compared to normal animals. This study demonstrates that OFNS perfused by the ventriculocisternal route can restore toward normal the LCMRg following GCI and that different concentrations of glucose in the perfusing fluid will have variable effects on LCMRg in certain brain areas.

Magnetic resonance imaging of acute cervical spine trauma. Correlation with severity of neurologic injury.

Prior to the advent of computer-assisted imaging techniques, conventional radiographic studies did not accurately depict the severity of soft tissue injury (spinal cord and paravertebral tissue) attending severe spinal trauma. Computed tomography scanning is clearly superior to plain radiography in the demonstration of osseous fractures and impactions, but this modality does not clearly depict ligamentous or disc injuries and does not image the spinal cord directly. The authors' preliminary experience indicates that magnetic resonance imaging (MRI) more accurately defines the extent of soft tissue damage in the zone of injury. In this study, the authors correlate these objective imaging techniques with findings on neurologic exam. Seventy-eight patients with cervical spine injuries admitted to the Regional Spinal Cord Injury Center of the Delaware Valley between August 1987 and January 1989 were evaluated with surface-coil MRI on a 1.5-Tesla unit. Fifty-nine patients were studied within 7 days of injury. Image sequences consisting of T1-, proton density, and T2-weighted images were obtained in saggital views. Axial gradient recalled acquisitions in the steady state (GRASS) images were obtained from most patients. We learned that certain patterns of MRI signal were associated with severe neurologic deficit. These include: 1) intramedullary hematoma and 2) spinal cord contusion associated with edema encompassing more than one spinal segment. Magnetic resonance imaging findings also correlated with less severe injury and include 1) normal spinal cord signal and 2) small focal contusions associated with edema encompassing one spinal segment or less.

Enhancement of the Arthus reaction and suppression of delayed type hypersensitivity (DTH) by pluronic F-68, a detergent frequently used to prepare perfluorocarbon emulsions.

The effect of a 20% w/v RM101 (perfluorobutyltetrahydrofuran) emulsion containing 5% w/v of the detergent Pluronic F-68 or 5% w/v Pluronic F-68 given alone on the Arthus reaction and on delayed type hypersensitivity (DTH) were evaluated in female A/J mice. The test substances were administered i.v. at 1% body weight at 0,4,7,14 and 28 days prior to the i.p. immunization with 10(7) sheep red blood cells (SRBC). The increase in footpad swelling at 4 h (Arthus reaction) and at 24 h (DTH) after elicitation with the s.c. administration of 10(8) SRBC into the left footpad was used to assess immune competence. Pluronic F-68 given alone enhanced the Arthus reaction only when administered on day 0 of immunization. Pluronic F-68 given alone, as well as the perfluorocarbon emulsion containing Pluronic F-68, suppressed the 24 h DTH for as long as 4 days prior to immunization. Nonemulsified perfluorocarbon, on the other hand, had no effect on either the Arthus reaction or on DTH. The immunostimulatory agent, levamisole, administered (10 mg/kg i.p.) 1.5-2 h prior to immunization with SRBC counteracted both the Arthus reaction and the DTH response produced by Pluronic F-68. The present data clearly demonstrate that the changes in Arthus reaction and the DTH response are due to the Pluronic F-68 used to emulsify the RM101 perfluorocarbon; the changes induced by the detergent in these two immune parameters probably involve separate mechanisms.

Preservation of neuronal function during prolonged focal cerebral ischemia by ventriculocisternal perfusion with oxygenated fluorocarbon emulsion.

The left middle cerebral artery and both carotid arteries of 17 cats were occluded to evaluate the effects of oxygenated fluorocarbon emulsion on brain ischemia. Carotid and middle cerebral arteries were occluded concurrently for 2 hours, followed by occlusion of the middle cerebral artery only for another 24 hours. Six animals were treated with oxygenated fluorocarbon emulsion delivered by ventriculocisternal perfusion, 5 received ventriculocisternal perfusion with mock cerebrospinal fluid, and 6 were untreated. Perfusions were started 3 hours after the initial ischemic insult. Infarct size judged by tetrazolium staining and standard neuropathological stains was significantly smaller in the treated animals. The mechanism of protection is as yet unknown, but most likely reflects oxygen/nutrient diffusion into the ischemic middle cerebral artery zone from the ventricular fluorocarbon, or removal of harmful metabolites. The results imply that ventriculocisternal perfusion with fluorocarbon emulsion can preserve neuronal function during a major cerebral vessel occlusion. In the cat, therapy is effective if begun within 3 hours after ischemia starts.

Fluorocarbon emulsion as a potential contrast medium in the subarachnoid space and brain tissue. Experiments in cats.

Ventriculosubarachnoid perfusion with oxygenated fluorocarbon emulsion has been used in the treatment of severe cerebral ischemia in cats. The perfusion vehicle is prepared mimicking cerebrospinal fluid in terms of electrolyte content, osmolality, pH, glucose and amino acids. Fluorocarbon emulsion is prepared with the vehicle as the external phase and charged with high partial pressures of oxygen. This fluorocarbon emulsion has been well-tolerated by the central nervous system. In addition to delivering oxygen to the ischemic tissues via the ventriculosubarachnoid space, the fluorocarbon emulsion has an absorption coefficient higher than normal brain and cerebrospinal fluid. This property makes it easily detected on the CT scan. Determination of appearance, attenuation, distribution, and absorption of the fluorocarbon has been performed in cats after direct intraventricular injection of the substances and after perfusion of the emulsion. The results of these experiments stress the possibility of using a fluorocarbon emulsion as a potential contrast medium in the brain and subarachnoid space, particularly after brain anoxia.

Ganglioside-induced regeneration and reestablishment of axonal continuity in spinal cord-transected rats.

In this study we examined the effect of chronic GM-1 ganglioside treatment on the reestablishment of axonal continuity and functional recovery in spinal cord-transected rats. Previous studies have shown that chronic treatment with GM-1 ganglioside is effective in producing regeneration of lesioned mesostriatal dopaminergic neurons in the central nervous system [1, 2]. In addition, GM-1 ganglioside advances peripheral nerve regeneration following nerve crush injury [12]. Axonal continuity was determined by the ability of the spinal cord to transport horseradish peroxidase across the region of transection. Comparisons between ganglioside-treated and saline-treated controls showed that ganglioside treatment resulted in the reestablishment of axonal continuity between the spinal cord distal to the level of the transection and the brainstem. Saline-treated controls showed little evidence of axonal continuity between these two regions. Thus gangliosides induce reestablishment of axonal continuity and thereby could advance functional recovery in rats following spinal cord transection.

Management of lumbar translocation injuries: case reports.

Lumbar translocation (complete lumbar dislocation) injuries constitute a severe and highly unstable form of thoraco-lumbar spinal injury and are uncommon. Adequate management of such injuries includes removing the neural tissue compression and realigning and stabilizing the spine. Computerized axial tomographic scans of the spine are very dramatic in demonstrating encroachment on the spinal canal by bony fragments. We report two cases of lumbar translocation injuries with favorable outcomes. The patients were initially managed with halo-femoral traction, resulting in spinal reduction and eliminating the need for acute surgical intervention, and subsequently underwent posterior fusion for stability. Anterior decompression was done at a later date as computed tomography showed retropulsed intracanalicular bone fragments. The use of Harrington rod instrumentation and realignment of the spine did not free the canal of bony fragments and, hence, decompression was required.

The use of autografts for vertebral body replacement of the thoracic and lumbar spine.

Thirty-seven patients with fractures of the thoracic or lumbar spine underwent anterior corpectomy (partial or complete) and vertebral body replacement for either destructive lesions from tumor or infection (13 patients) or trauma (24 patients). The vertebral bodies were replaced using either rib (12 patients) or tricortical iliac crest (25 patients) autografts. The Dunn device was utilized in conjunction with the autografts in 19 patients. Posterior stabilization was used in five patients; three prior to anterior stabilization and two after anterior stabilization. Within 2 weeks of the operative procedure, all patients began walking or sitting. Of the 37 patients, 21 with incomplete neurologic deficits improved, and 10 of those went onto complete recovery. Of the 27 patients who have been followed for a minimum of 1 year, 25 have obtained solid fusions, one developed a pseudarthrosis that required regrafting, and one had a delayed union prior to death from metastatic disease. There were two deaths in the immediate postoperative period and three deaths in the first six postoperative wounds due to metastatic disease. The purpose of this study is to present a consecutive series of patients who have undergone corpectomy and vertebral body replacement as well as to define the adequacy of stabilization.

Focal cerebral ischemia: reduction in size of infarcts by ventriculo-subarachnoid perfusion with fluorocarbon emulsion.

A new method for brain resuscitation following acute focal ischemic insult has been developed in this laboratory. The technique utilizes a surrogate route to supply cerebral metabolites and employs highly oxygenated fluorocarbons (OFNS), which are efficient gas transport and exchange agents, perfused through the ventriculo-subarachnoid spaces. We previously described a return of aerobic metabolism and EEG after severe global ischemia by oxygenated perfusions and now report treatment-induced reduction in the size of experienced cerebral infarction. Twenty-eight cats were anesthetized (choralose and urethane), tracheotomized and placed in a stereotactic frame. Physiologic adjustments assured arterial blood pCO2 28-35 Torr, pO2 100-150 Torr pH 7.4 and glucose less than 200 mg%. The left middle cerebral artery was exposed transorbitally and temporarily clipped along with both common carotids for 2 h. One hour later (3 h after ischemic onset) the treated group were perfused by the ventriculo-cisternal route either with OFNS [pO2 = 600 Torr; 3 ml/min 6 h, 2 ml/min 2 h, 1 ml/min 2 h, 0.5 ml/min 2 h at 10 mm Hg intracranial pressure (ICP)] or with the vehicle perfusate. Eighteen to twenty hours after the ischemic insult the animals were sacrificed. Sections of fresh brain of 0.5 mm thickness were incubated in 1% triphenyl tetrazolium chloride. The infarcted areas were confirmed with classic neuropathologic techniques. Areas of infarction (expressed in cm3 and as % of the brain) were measured using a planimeter. OFNS-treated brains contained 80% less infarcted tissue than the vehicle-perfused or untreated stroked animals. The infarcted areas were significantly treatment reduced (P less than 0.05 ANOVA and Bonferroni tests).(ABSTRACT TRUNCATED AT 250 WORDS)

A reproducible experimental model of focal cerebral ischemia in the cat.

In the past experimental methods used for producing focal cerebral ischemia have had considerable difficulty with regard to reproducibility of the size of the infarcted region. In this study we have developed an experimental model which enables us to consistently produce focal regions of cerebral ischemia (resulting in infarction) which vary little in size in a number of animals. Thirty-seven cats (3-4 kg b. wt.) anesthetized with chloralose and urethane were used. Physiologic monitoring and adjustments maintained arterial blood values as follows: pCO2 27-35 Torr, pO2 100-150 Torr, pH +/- 7.4, glucose 200 mg%, hematocrit greater than 25. The left middle cerebral artery was exposed via a transorbital approach and occluded for 1-2 h with and without left and/or both carotid artery occlusion. Sixteen hours following the ischemic episode, the animals were sacrificed and sections of fresh brain tissue were processed for vital staining using 1% tetrazolium solution. With this method normal brain areas appear dark red, ischemic regions (without infarction) appear gray and irreversibly infarcted areas appear pinkish-white. The volumetric dimensions of the lesioned area were measured using a planimeter. The same tissue was also evaluated histologically by means of standard histopathologic techniques on paraffin-embedded material. Infarcted areas as delineated macroscopically by the tetrazolium correlated well with the light microscopic findings. Ten animals subjected to a 2-h occlusion of the left middle cerebral artery (LMCA) and both carotid arteries resulted in a reproducible infarct which was 3.2 +/- 0.7 ml in volume. This represents 13.3 +/- 2.9% of the total volume of both cerebral hemispheres (above the level of the inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Reanalysis of central cervical cord injury management.

Early investigators indicated that conservative management was superior to operative intervention in the treatment of central cord injuries. Their clinical data suggested that operative treatment, in fact, worsened the condition. Recent experience with this clinical entity, however, indicates that in selected patients operative intervention may be of value in improving the rate and degree of motor recovery. A retrospective study of all individuals admitted to our hospital (Delaware Valley Spinal Cord Injury Center) with central cervical spinal cord injury was done (28 patients). One-half had been treated with medical therapy alone (Group I); the others were treated both medically and surgically (Group II). Medical therapy consisted of intravenous mannitol, dexamethasone, and sodium bicarbonate given during the acute phase of the injury. Both groups were immobilized using either a halo or a Philadelphia collar. Criteria for entry into the surgical group were one or both of the following: (a) failure to improve progressively after an initial period of improvement, with persistent compression of neural tissue visualized on myelography and (b) unacceptable instability of the spinal bony elements. The patients were given neurological scores based on the motor power of the major muscle groups. The stability of the spine was scored using the Panjabi-White scale. The two groups were compared using Student's t-test and the two-factor analysis of variance. There was no significant difference in initial neurological scores between the groups. The surgical groups had a higher incidence of instability of the bony elements of the cervical spine, as judged by the Panjabi-White scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe cerebral ischemia treatment by ventriculosubarachnoid perfusion with an oxygenated fluorocarbon emulsion.

Global hemispheric ischemia was produced in cats by bilateral carotid ligation and bleeding to a mean arterial pressure of 30 +/- 2 (SE) mm Hg. Total electrocerebral silence, as determined by computer-based power analysis, was obtained and maintained for 15 minutes. After this severe cerebral ischemic episode, the heparinized blood was reinfused and the carotid clamps were removed. After the cerebral ischemia, the ventriculosubarachnoid space was perfused with an oxygenated fluorocarbon nutrient solution (OFNS) or modified Elliott's B solution (ES) (control perfusion). The OFNS perfusate contained 400 to 640 mm Hg pO2 (produced by means of a bubble oxygenator pump system) as well as electrolytes, glucose, and amino acids, all of which are known to be important in cerebral metabolism. Flow rates of the perfusion were maintained at either 3 or 6 ml/minute and intracranial pressures were never permitted to exceed 10 mm Hg. During passage through the ventriculosubarachnoid space, oxygen, carbon dioxide, and electrolytes were exchanged between the brain and the OFNS perfusate. In addition, the OFNS perfusate was capable of picking up pCO2, lactate, and pyruvate. This produced a significant return of electrocerebral activity (P less than 0.01) and oxidative metabolism (P less than 0.01), as evidenced by a decline in the lactate/pyruvate ratio in the OFNS-treated cats, but not in nonperfused animals or those perfused with ES. In this study the ventriculosubarachnoid system served as an alternate vascular tree and enabled the perfusate to accomplish many of the functions of blood. Substantial penetration of the perfusate products into the brain occurred, enabling oxidative metabolism, removal of waste products, and electrocerebral activity to be reestablished.

Arachnoiditis presenting as a cervical cord neoplasm: two case reports.

Neurological evaluation supplemented by myelography has been highly successful in diagnosing spinal cord tumors. Our experience shows that a widening of the cord on myelography is not always diagnostic of spinal cord tumors. Two patients who presented clinically with evidence of spinal cord tumor and had a widening of the cord on myelography were found to have severe cervical arachnoiditis without any evidence of intrinsic cord abnormality. Hence, cervical arachnoiditis should be considered in the differential diagnosis of spinal cord tumor on myelography.