Search Results

You are looking at 1 - 10 of 20 items for

  • Author or Editor: Michael Fehlings x
  • By Author: Tator, Charles H. x
Clear All Modify Search
Full access

Charles H. Tator and Michael G. Fehlings

In this paper the authors review the clinical trials of neuroprotection that have been performed for the treatment of acute spinal cord injury (SCI). The biological rationale for the selection of each treatment modality is discussed with reference to current knowledge of the principles in the management of acute SCI as well as the primary and secondary injury mechanisms identified by experimental and clinical studies of the pathophysiology of acute SCI. The trials are evaluated with regard to the availability and use of accurate clinical outcome measures, and the methodologies of the trials are critically evaluated with an emphasis on prospective randomized controlled studies. A detailed description and critical analysis are provided of the results of the 10 clinical trials conducted to date in which a randomized prospective controlled design has been used. The issue of the therapeutic time window in acute SCI is discussed. To date, methylprednisolone is the only effective neuroprotective agent that has been established for use in human SCI, and the only therapeutic time window established in human SCI is a maximum trauma-to-treatment time of 8 hours.

Full access

Michael G. Fehlings and Charles H. Tator

The authors conducted an evidence-based review of the literature to evaluate critically the rationale and indications for and the timing of decompressive surgery for the treatment of acute, nonpenetrating spinal cord injury (SCI).

The experimental and clinical literature concerning the role of, and the biological rationale for surgical decompression for acute SCI was reviewed. Clinical studies of nonoperative management of SCI were also examined for comparative purposes. Evidence from clinical trials was categorized as Class I (well-conducted randomized prospective trials), Class II (well-designed comparative clinical studies), or Class III (retrospective studies).

Studies in which animal models of SCI were used consistently demonstrated a beneficial effect of early surgical decompression, although it is difficult to apply these data directly to the clinical setting. The clinical studies provided suggestive (Class III and limited Class II) evidence that decompressive procedures improve neurological recovery after SCI. However, no clear consensus can be inferred from the literature as to the optimum timing of decompressive surgery. Many authors have advocated delayed treatment to avoid medical complications, although there is good evidence from recent Class II trials that early decompressive surgery can be performed safely without added morbidity or mortality.

There is biological evidence from experimental studies in animals that early surgical decompression may improve neurological recovery after SCI, although the relevant interventional timing in humans remains unclear. To date, the role of surgical decompression in patients with SCI is only supported by Class III and limited Class II evidence. Accordingly, decompressive surgery for SCI can only be considered a practice option. Furthermore, analysis of the literature does not allow definite conclusions to be drawn regarding appropriate timing of intervention. Hence, there is a need to conduct well-designed experimental and clinical studies of the timing and neurological results of surgical decompression for the treatment of acute SCI.

Restricted access

Michael G. Fehlings and Charles H. Tator

Object. The authors conducted an evidence-based review of the literature to evaluate critically the rationale and indications for and the timing of decompressive surgery for the treatment of acute, nonpenetrating spinal cord injury (SCI).

Methods. The experimental and clinical literature concerning the role of, and the biological rationale for, surgical decompression for acute SCI was reviewed. Clinical studies of nonoperative management of SCI were also examined for comparative purposes. Evidence from clinical trials was categorized as Class I (well-conducted randomized prospective trials), Class II (well-designed comparative clinical studies), or Class III (retrospective studies).

Examination of studies in which animal models of SCI were used consistently demonstrated a beneficial effect of early decompressive surgery, although it is difficult to apply these data directly to the clinical setting. The clinical studies provided suggestive (Class III and limited Class II) evidence that decompressive procedures improve neurological recovery after SCI. However, no clear consensus can be inferred from the literature as to the optimum timing for decompressive surgery. Many authors have advocated delayed treatment to avoid medical complications, although good evidence from recent Class II trials indicates that early decompressive surgery can be performed safely without causing added morbidity or mortality.

Conclusions. There is biological evidence from experimental studies in animals that early decompressive surgery may improve neurological recovery after SCI, although the relevant interventional timing in humans remains unclear. To date, the role of surgical decompression in patients with SCI is only supported by Class III and limited Class II evidence. Accordingly, decompressive surgery for SCI can only be considered a practice option. Furthermore, analysis of the literature does not allow definite conclusions to be drawn regarding appropriate timing of intervention. Hence, there is a need to conduct well-designed experimental and clinical studies of the timing and neurological results of decompressive surgery for the treatment of acute SCI.

Restricted access

Charles H. Tator and Michael G. Fehlings

✓ In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury.

The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects include early hemorrhagic necrosis leading to major infarction at the injury site.

These posttraumatic vascular effects can be treated. Systemic normotension can be restored with volume expansion or vasopressors, and spinal cord blood flow can be improved with dopamine, steroids, nimodipine, or volume expansion. The combination of nimodipine and volume expansion improves posttraumatic spinal cord blood flow and spinal cord function measured by evoked potentials. These results provide strong evidence that posttraumatic ischemia is an important secondary mechanism of injury, and that it can be counteracted.

Full access

Charles H. Tator, Michael Fehlings, Kevin Thorpe and Wayne Taylor

A multicenter retrospective study was performed in 36 participating North American centers to examine the use and timing of surgery in the treatment of acute spinal cord injury (SCI). The study was conducted to obtain information required for the planning of a randomized controlled trial of early compared with late decompressive surgery.

The records of all patients aged 16 to 75 years with acute SCI who were admitted to the 36 centers within 24 hours of injury over a 9-month period (August 1994 to April 1995) were examined to obtain data on admission variables, methods of diagnosis, use of traction, and surgical variables including type and timing of surgery.

A total of 585 patients with acute SCI or cauda equina injury were admitted to these centers, although approximately half were ultimately excluded because they did not meet inclusion criteria. Common causes for exclusion were late admission, age, gunshot wound, and an absence of spinal cord compression demonstrated on imaging studies. Thus, only approximately 50% of acute SCI patients would be eligible for inclusion in a study of acute decompressive procedures. Although 100% of patient underwent computerized tomography (CT) scaning, only 54% underwent magnetic resonance imaging, and CT myelography was performed in only 6%. Complete neurological injuries (American Spinal Injury Association Grade A) were present in 57.8%. Traction was applied in only 47% of patients with cervical injuries, of which only 42% demonstrated successful decompression by traction. Neurological deterioration occurred in 8.1% of patients after traction. Surgery was performed in 65.4% of patients. The timing of surgery varied widely: less than 24 hours in 23.5% of patients; 25 to 48 hours in 15.8%; 48 to 96 hours in 19.0%; and 5 days or longer in 41.7% of patients.

These data indicate that whereas surgery is commonly performed in patients with acute SCI, one-third of the cases are managed nonoperatively, and there is very little agreement on the optimum timing of surgical treatment. The results of this study confirm the need for a randomized controlled trial to determine the optimum timing of surgical decompressive procedures in patients with SCI.

Restricted access

Michael G. Fehlings, Charles H. Tator and R. Dean Linden

✓ Recent work has indicated that direct-current (DC) fields may promote recovery after acute spinal cord injury. In the present experiments, the therapeutic value of an applied DC field was studied in 40 rats with clip compression injuries of the cord at C7–T1. The rats were randomly allocated to one of four groups including 10 rats each: two groups received a 17-gm cord injury and two groups a 53-gm injury. One group at each injury severity received implantation of a treatment (14 µA) DC stimulator and the other group a control (0 µA) stimulator. Clinical neurological function was assessed weekly by the inclined-plane technique. At 8 weeks after injury, motor and somatosensory evoked potentials (MEP's and SSEP's) were recorded, and the axonal tracer horseradish peroxidase (HRP) was introduced into the cord at T-6. The total number of HRP-labeled cells was counted in every sixth coronal section through the brain stem and motor cortex. All outcome parameters were assessed blindly.

In the 17-gm group, there were no significant differences in any outcome measure between control and treated rats. In contrast, in the 53-gm group, the inclined-plane scores, the amplitude of the MEP's, and the number of labeled cells in the red nucleus, raphé nuclei, and vestibular nuclei were greater in treated than in control rats. These data strongly indicate that an applied DC field can produce functional neurological and anatomical improvement in rats with acute spinal cord injuries.

Restricted access

Michael G. Fehlings, Charles H. Tator and R. Dean Linden

✓ There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40.

The preinjury physiological parameters, including the SCBF at T-1 (mean ± standard error of the mean: 56.84 ± 4.51 ml/100 gm/min), were not significantly different (p > 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 ± 2.99 ml/100 gm/min; p < 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p < 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p < 0.0001), and the SSEP (p < 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 ± 6.09 ml/100 gm/min; p < 0.003) and improved the MEP-C (p < 0.0001), MEP-N (p < 0.04), and SSEP (p < 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p < 0.0001) and somatosensory tracts (p < 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.

Restricted access

Charles H. Tator, Michael Fehlings, Kevin Thorpe and Wayne Taylor

Object. A multicenter retrospective study was performed in 36 North American centers to examine the use and timing of surgery in patients who have sustained acute spinal cord injury (SCI). The study was performed to obtain information required for the planning of a randomized controlled trial in which early and late decompressive surgery are compared.

Methods. The records of all patients aged 16 to 75 years with acute SCI admitted to 36 centers within 24 hours of injury over a 9-month period in 1994 and 1995 were examined to obtain data on admission variables, methods of diagnosis, use of traction, and surgical variables including type and timing of surgery.

A total of 585 patients with acute SCI or cauda equina injury were admitted to participating centers, although approximately half were ultimately excluded because they did not meet inclusion criteria. Common causes for exclusion were late admission, age, gunshot wound, and absence of signs of compression on imaging studies. Thus, only approximately 50% of patients with acute SCI would be eligible for inclusion in a study of acute decompressive surgery. Although all patients underwent computerized tomography (CT) scanning, only 54% underwent magnetic resonance imaging, and CT myelography was performed in only 6%. Complete neurological injuries (American Spinal Injury Association Grade A) were present in 57.8%. Traction was applied in only 47% of patients who sustained cervical injury, in whom decompressive traction was successful in only 42% of cases. Neurological deterioration occurred in 8.1% of cases after traction. Surgery was performed in 65.4% of patients. The timing of surgery varied widely: less than 24 hours postinjury in 23.5%, between 25 and 48 hours postinjury in 15.8%, between 48 and 96 hours in 19%, and more than 5 days postinjury in 41.7% of patients.

Conclusions. These data indicate that although surgery is commonly performed in patients with acute SCI, one third of cases are managed nonoperatively, and there is very little agreement on the optimum timing of surgical treatment. The results of this study confirm the need for a randomized controlled trial to assess the optimum timing of decompressive surgery in SCI.

Restricted access

R. John Hurlbert, Charles H. Tator, Michael G. Fehlings, Greg Niznik and R. Dean Linden

✓ Although the assessment of spinal cord function by electrophysiological techniques has become important in both clinical and research environments, current monitoring methods do not completely evaluate all tracts in the spinal cord. Somatosensory and motor evoked potentials primarily reflect dorsal column and pyramidal tract integrity, respectively, but do not directly assess the status of the ventral funiculus. The present study was undertaken to evaluate the use of evoked potentials, elicited by direct cerebellar stimulation, in monitoring the ventral component of the rodent spinal cord. Twenty-nine rats underwent epidural anodal stimulation directly over the cerebellar cortex, with recording of evoked responses from the lower thoracic spinal cord, both sciatic nerves, and/or both gastrocnemius muscles. Stimulation parameters were varied to establish normative characteristics. The pathways conducting these “posterior fossa evoked potentials” were determined after creation of various lesions of the cervical spinal cord.

The evoked potential recorded from the thoracic spinal cord consisted of five positive (P1 to P5) and five negative (N1 to N5) peaks. The average conduction velocity (± standard deviation) of the earliest wave (P1) was 53 ± 4 m/sec, with a latency of 1.24 ± 0.10 msec. The other components followed within 4 msec from stimulus onset. Unilateral cerebellar stimulation resulted in bilateral sciatic nerve and gastrocnemius muscle responses; there were no significant differences (p > 0.05) in the thresholds, amplitudes, or latencies of these responses elicited by right- versus left-sided stimulation. Recordings performed following creation of selective lesions of the cervical cord indicated that the thoracic response was carried primarily in the ventral funiculus while the sciatic and gastrocnemius responses were mediated through the dorsal half of the spinal cord. It is concluded that the posterior fossa evoked potential has research value as a method of monitoring pathways within the ventral spinal cord of the rat, and should be useful in the study of spinal cord injury.