✓ Serial studies of visual, auditory, and somatosensory evoked potentials (EP's) obtained from 139 severely head-injured patients up to 1 year after trauma were analyzed to ascertain whether or not EP's can be used to monitor neurological recovery or deterioration following secondary insults. The EP data were analyzed using a grading system of abnormality developed previously, and patients were grouped by the most severe EP abnormality found in any modality during an early study (mean Day 3). The findings showed differential recovery trends depending on the severity of EP abnormality obtained on the initial study and presence of secondary insult. If EP's were normal early after injury, they remained so for up to 1 year, and these patients did well clinically. The EP's that were absent did not improve, and the patients had poor outcomes. Secondary insults did not affect the EP's or the outcomes of patients in these two groups. When EP's that were initially mildly abnormal became normal or remained no worse than mildly abnormal, patients had favorable outcomes in spite of complications. In contrast, deterioration of EP's with secondary insult indicated poor patient outcome. Severe EP abnormalities which improved over time led to favorable outcomes. However, persistence or deterioration of severe abnormalities indicated a poor outcome. Changes in EP's over time were better indicators of outcome than the presence or absence of complications. The results suggest that EP's may be used to assess neural recovery and the consequences of secondary insults to the brain. Four case reports are included to exemplify results.
Pauline G. Newlon, Richard P. Greenberg, Marti S. Hyatt, Gregory G. Enas and Donald P. Becker
Part 2: Autoregulation
J. Paul Muizelaar, John D. Ward, Anthony Marmarou, Pauline G. Newlon and Akihiko Wachi
✓ Autoregulation of cerebral blood flow (“CBF15”) was tested in a series of 26 pediatric patients (mean age 13.2 years) with severe head injury (average Glasgow Coma Scale (GCS) score 5.5) in the acute stage. A baseline 133Xe CBF measurement was performed and then repeated, after blood pressure was increased by 29% with intravenous phenylephrine or decreased by 26% with intravenous trimethaphan camsylate. Correlations were made between CBF and clinical condition, outcome, time after injury, intracranial pressure (ICP), and pressure-volume index (PVI) changes, and the site of injury (hemispheres, diencephalon, or brain stem). The site of injury was determined with multimodality evoked potential measurements. Autoregulation was intact in 22 (59%) of 37 measurements. There was no correlation with GCS score, outcome, time after injury, site of injury, or way of testing (decreasing or increasing blood pressure). Autoregulation was statistically significantly more often impaired when CBF was either below normal −2 standard deviations (SD) (reduced flow) or above normal +2 SD (absolute hyperemia). In cases with intact autoregulation, mean ICP decreased from 17.5 to 15.0 mm Hg with higher blood pressure and increased from 19.0 to 21.3 mm Hg with lower blood pressure. When PVI was measured during the blood pressure manipulations, it was found to change in a direction opposite to the ICP change. The consequences of these findings in the management of ICP problems with blood pressure control are discussed.
Gerrit J. Bouma, J. Paul Muizelaar, Sung C. Choi, Pauline G. Newlon and Harold F. Young
✓ Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 ± 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p < 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF ≤ 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.
Richard P. Greenberg, Pauline G. Newlon, Marti S. Hyatt, Raj K. Narayan and Donald P. Becker
✓ Results of multimodality evoked potential (MEP) studies recorded from 100 comatose patients soon after severe head injury were analyzed prospectively, using a previously established grading system, to assess the prognostic value of MEP's with respect to patient outcome, to evaluate the effect of clinically relevant sequelae of head injury on the prediction of outcome by MEP's, and to describe time to clinical recovery as a function of initial MEP grade. Graded MEP's, when recorded in the first few days after head injury, could predict patient outcome at 1 year with approximately 80% accuracy. Exclusion from the analysis of patients who died from causes unrelated to the brain and those with severe systemic complications that occurred after the evoked potentials were recorded improved the accuracy of outcome prediction to nearly 100%. The presence of a mass lesion requiring surgery reduces the probability of good to moderate outcome for a given MEP grade group by approximately 25% to 40% from that seen in patients without mass lesions. The clinical outcome predicted shortly after head injury by MEP grades may not be realized for many months. Patients with mild MEP abnormality (Grade I or II) generally reach their outcome by 3 to 6 months, whereas those with more severe deficits (Grade III) may not show improvement for at least 1 year.
Antonio A. F. DeSalles, Pauline G. Newlon, Yoichi Katayama, C. Edward Dixon, Donald P. Becker, Henry H. Stonnington and Ronald L. Hayes
✓ Studies in humans have shown that sensory stimuli, presented in the context of certain tasks, can elicit a late positive component (LPC), namely P300, in the scalp-recorded evoked potential believed to reflect neural activity related to attentional processes. A similar LPC has been reported in cats and monkeys. In this study, the LPC of the auditory evoked potential (AEP) in the cat was used to detect impairment in attention to a relevant stimulus after low levels of cerebral concussion produced by a fluid percussion device. A hollow screw (for fluid percussion) and stainless steel screws (for AEP recording) were surgically placed in the skull. After recovery from surgery, animals were trained in the paradigm to obtain an LPC. Pupillary dilation was conditioned to tones. A random sequence of two discriminable tones was presented. The lower tone had a probability of 0.1 and was followed by a tail shock (tone-shock). After 400 to 1000 tone-shock presentations, animals attended to the lower tone stimulus as inferred by selective pupillary dilation. In the AEP an early positive component at 50 to 120 msec related to an alerting response was enhanced, and an LPC at 250 to 450 msec appeared in response to the paired tone-shock. Animals were then subjected to cerebral concussion. Complete recovery of normal reflexes, motor coordination, and orienting response was seen within 2 hours after injury. The LPC was suppressed for a period of at least 3 days, suggesting that low magnitudes of brain injury can disrupt higher-order neural activities. This disruption can persist despite recovery of other neurological functions.
John D. Ward, Donald P. Becker, J. Douglas Miller, Sung C. Choi, Anthony Marmarou, Cheryl Wood, Pauline G. Newlon and Richard Keenan
✓ In certain subgroups of severely head-injured patients, the mortality rate remains unacceptably high. The authors describe a randomized, controlled trial of prophylactic pentobarbital therapy in a group of these patients. Pentobarbital was started as soon as possible after the head injury, regardless of the intracranial pressure (ICP), and was continued for a prescribed period of time. The study included 53 consecutive head-injured patients over the age of 12 years, who had either an acute intradural hematoma (subdural and/or intracerebral, large enough to warrant surgical decompression), or no mass lesion but whose best motor response was abnormal flexion or extension. All patients in the study were randomly assigned to a control group (26 cases) or a pentobarbital-treated group (27 cases) once the diagnosis had been made and informed consent obtained. All patients were treated with the same protocol of aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care, with close follow-up monitoring. The randomization was effective in producing a close match between the control and treated groups with respect to age, sex distribution, cause of injury, neurological status, intracranial lesions, prevalence of early systemic insults, midline shift, and initial ICP. Outcome was essentially the same in each group. There was no difference between groups in the incidence of elevated ICP, the duration of ICP elevation, or the response of ICP elevations to treatment. Arterial hypotension occurred in 14 patients (54%) in the treated group and only two patients (7percnt;) in the untreated group. Based on these data the authors cannot recommend the prophylactic use of pentobarbital coma in the treatment of patients with severe head injury. They also believe that its use is accompanied by significant side effects which can potentially worsen the condition of a patient with severe head injury.