Raj K. Narayan, Tina M. Narayan, David A. Katz, Paul L. Kornblith and Genesio Murano
✓ Urokinase (UK), a potent thrombolytic agent, was tested in a rabbit model for safety and efficacy in lysing intracranial hematomas. Intracerebral-intraventricular (IC-IV) hematomas were created by stereotaxically injecting 0.2 ml of clotted human blood into the frontal lobe and lateral ventricle of a total of 57 anesthetized adult New Zealand White rabbits (weighing 1.6 to 2.5 kg). Control animals received 0.2 ml of normal saline injected into the clot, and the experimental group received an equal volume of UK solution (50,000 units/ml) immediately after the clot injection. Some animals were sacrificed at 3 hours and others at 24 hours postinjection. At 3 hours, clot lysis had been achieved in nine (90%) of 10 UK-treated animals as compared to one (14%) of seven controls. By 24 hours, clots had been lysed in 10 (83%) of 12 UK-treated animals and in two (33%) of six controls. Overall, clot lysis was demonstrated in 19 (86%) of the 22 UK-treated animals and in only three (23%) of the 13 controls (p < 0.001). There was no significant difference in results between these animals and a further set of 22 rabbits that were treated with UK or saline 24 hours after clot injection. There was no histological evidence of damage or inflammation noted on careful light microscopic examination of three to five sections from each brain, although findings consistent with encephalitozoonosis, an incidental protozoan infestation, were encountered in four animals. These studies suggest that UK may be safely and effectively employed for the lysis of intracranial hematomas in this animal model, and that a delay in therapy of up to 24 hours does not significantly compromise its efficacy.
J. Stuart Crutchfield, Raj K. Narayan, Claudia S. Robertson and Lloyd H. Michael
✓ The fiberoptic device is a relatively new type of intracranial pressure (ICP) monitor which appears to offer certain advantages over conventional monitoring systems, particularly its ability to measure brain parenchymal pressures. This study was undertaken to analyze the accuracy and drift characteristics of the fiberoptic device and to compare pressures in the subdural, intraparenchymal, and intraventricular compartments. The device was accurate to ± 3 mm Hg over a 0- to 30-mm Hg range in vitro. The maximum daily drift was ± 2.5 mm Hg, with an average daily drift of ± 0.6 mm Hg and an average drift over a 5-day period of ± 2.1 mm Hg. In vivo, the pressures and waveform characteristics obtained with the fiberoptic device and with a strain-gauge transducer connected to a ventriculostomy were very similar. Alterations in ICP were induced by various therapeutic and pathological manipulations, and the pressures in the three intracranial compartments were compared. Changes in ICP appeared to be reflected simultaneously and equally in all three compartments. Furthermore, changes in ICP secondary to a unilateral mass lesion were identical in both supratentorial parenchymal compartments when measured simultaneously. It is concluded that the fiberoptic device is an accurate and reliable system for ICP monitoring; the pressures recorded in the subdural, intraparenchymal, and intraventricular compartments paralleled each other in all of the physiological and pathological states tested. Although the drift associated with this device is less than that reported for previously available systems, its maximal cumulative drift over a 5-day period of ± 6 mm Hg is significant. Since the fiberoptic device cannot be recalibrated in situ, it is suggested that the device be replaced if monitoring is to be continued for periods longer than 5 days.
Sung C. Choi, Raj K. Narayan, Randy L. Anderson and John D. Ward
✓ Data from 523 patients admitted to the Medical College of Virginia with severe head injury and known 6-month outcomes were analyzed in order to determine the optimal combination of early-available prognostic factors. Twenty-one prognostic indicators noted in the emergency room at admission were used to predict outcomes into four categories: good, moderately disabled, severely disabled, or vegetative/dead. A combination of the patient's age (in years), the best motor response (graded in the usual six-point scale), and pupillary response (in both eyes) was found to be the most accurate indicator. The model correctly predicted outcome into one of the four outcome categories in 78% of cases (“specifically accurate predictions”). If predictions into an outcome category adjacent to the actual outcome were accepted, this model was accurate in 90% of cases (“grossly accurate predictions”). A set of three simple graphs based on this model can be used for rapid early estimation of probable outcome in a severely head-injured patient at admission.
Sourabh Mukherjee, Chad Beck, Narayan Yoganandan and Raj D. Rao
To determine the incidence of and assess the risk factors associated with neurological injury in motor vehicle occupants who sustain fractures of the thoracolumbar spine.
In this study, the authors queried medical, vehicle, and crash data elements from the Crash Injury Research and Engineering Network (CIREN), a prospectively gathered multicenter database compiled from Level I trauma centers. Subjects had fractures involving the T1–L5 vertebral segments, an Abbreviated Injury Scale (AIS) score of ≥ 3, or injury to 2 body regions with an AIS score of ≥ 2 in each region. Demographic parameters obtained for all subjects included age, sex, height, body weight, and body mass index. Clinical parameters obtained included the level of the injured vertebra and the level and type of spinal cord injury. Vehicular crash data included vehicle make, seatbelt type, and usage and appropriate use of the seatbelt. Crash data parameters included the principal direction of force, change in velocity on impact (ΔV), airbag deployment, and vehicle rollover. The authors performed a univariate analysis of the incidence and the odds of sustaining spinal neurological injury associated with major thoracolumbar fractures with respect to the demographic, clinical, and crash parameters.
Neurological deficit associated with thoracolumbar fracture was most frequent at extremes of age; the highest rates were in the 0- to 10-year (26.7% [4 of 15]) and 70- to 80-year (18.4% [7 of 38]) age groups. Underweight occupants (OR 3.52 [CI 1.055–11.7]) and obese occupants (OR 3.27 [CI 1.28–8.31]) both had higher odds of sustaining spinal cord injury than occupants with a normal body mass index. The highest risk of neurological injury existed in crashes in which airbags deployed and the occupant was not restrained by a seatbelt (OR 2.35 [CI 0.087–1.62]). Reduction in the risk of neurological injuries occurred when 3-point seatbelts were used correctly in conjunction with the deployment of airbags (OR 0.34 [CI 1.3–6.6]) compared with the occupants who were not restrained by a seatbelt and for whom airbags were not deployed. Crashes with a ΔV greater than 50 km/hour had a significantly higher risk of spinal cord injury (OR 3.45 [CI 0.136–0.617]) than those at lower ΔV values.
Deployment of airbags was protective against neurological injury only when used in conjunction with 3-point seatbelts. Vehicle occupants who were either obese or underweight, very young or elderly, and those in crashes with a ΔV greater than 50 km/hour were at higher risk of thoracolumbar neurological injury. Neurological injury at thoracic and lumbar levels was associated with multiple factors, including the incidence of fatality, occupant factors such as age and body habitus, energy at impact, and direction of impact. Current vehicle safety technologies are geared toward a normative body morphology and need to be reevaluated for various body morphologies and torso compliances to lower the risk of neurological injury resulting from thoracolumbar fractures.
Benjamin H. Venger, Richard K. Simpson and Raj K. Narayan
✓ Associated injuries to the neck, chest, or abdomen are found in approximately one-quarter of all civilians with penetrating spinal cord or cauda equina injuries. While the value of and indications for general surgical exploration and repair of these injuries are fairly self-evident, the value of neurosurgical intervention in terms of neurological outcome and infection prophylaxis remains the subject of debate. To study this issue, 160 civilian patients with penetrating spinal injuries and neurological deficits were retrospectively reviewed. Associated injuries of the esophagus, trachea, bronchi, or bowel were seen in 107 individuals (67%); 33 (31%) of these patients had abdominal injuries, 25 (23%) had neck injuries, 23 (21%) had thoracic injuries, and 26 (24%) had injuries occurring at multiple sites. Of these 107 patients, 67 (63%) had complete neurological injuries and the remaining 40 (37%) demonstrated incomplete deficits. All 107 patients underwent surgical exploration and repair of their visceral injuries; in 19 of them a neurosurgical procedure was also performed for decompression of the neural elements and/or debridement of the wound. Regardless of the presence of associated visceral injuries, the mechanism of injury, and the extent of the neurological deficit, no statistically significant difference in neurological outcome was found in patients with or without neurosurgical intervention. Complications associated with neurological injury were reported in 17 (11%) of the total group of 160 patients. Four (21%) of the 19 patients who had neurosurgical intervention suffered a related complication, compared to only six (7%) of the 88 patients who were managed conservatively (p < 0.05). Within the limitations of a retrospective review, the results of this study do not clearly support the value of routine neurosurgical intervention as an adjunct to general surgical repair in cases of spinal injury associated with penetrating visceral trauma.
Claudia S. Robertson, Robert G. Grossman, J. Clay Goodman and Raj K. Narayan
✓ Cerebral ischemia is a common mechanism of secondary brain injury following severe head injury. The cerebral metabolic rate of oxygen (CMRO2) and of lactate (CMRL), as well as cerebral blood flow (CBF) were measured daily for 5 days after head injury in 44 comatose head-injured patients to determine if metabolic changes could identify the patients who would develop cerebral infarction. Of 41 patients whose CBF remained at levels regarded as adequate to prevent infarction (CBF ≥ 0.2 ml/gm/min), the six who showed a cerebral infarction on computerized tomography (CT) scans exhibited characteristic cerebral metabolic patterns: a CMRO2 of less than 0.6 µmol/gm/min on one or more of the days monitored, and markedly elevated cerebral lactate production (CMRL < −0.06 µmol/gm/min) on Days 1 and/or 2 after injury. Patients who had no areas of infarction on serial CT scans typically had a CMRO2 of 0.6 µmol/gm/min or higher and a low cerebral lactate production. Measurement of CMRO2 and CMRL can be obtained at the bedside and can indicate the presence of an evolving ischemic infarct after head injury.
Duncan K. Fischer, Terence L. Chen and Raj K. Narayan
✓ Various strategies have been used to identify and characterize the antigens associated with human brain tumors. These approaches have included the raising of polyclonal and monoclonal antibodies against tumor antigens and, more recently, efforts toward the direct biochemical identification of such proteins. This review summarizes the progress made in this area, suggests reasons for the broad antigenic cross-reactivity and heterogeneity revealed by these studies, and proposes additional methods for deciphering the complex antigenic composition of human brain tumors.