Significance of intracranial hypertension in severe head injury

Measurements of intracranial pressure (ICP) were begun within hours of injury in 160 patients with severe brain trauma, and continued in the intensive care unit. Some degree of increased ICP (greater than 10 mm Hg) was present on admission in most cases (82%), and in all but two of the 62 patients with intracranial mass lesions requiring surgical decompression; ICP was over 20 mm Hg on admission in 44% of cases, and over 40 mm Hg in 10%. In patients with mass lesions only very high ICP (greater than 40 mm Hg) on admission was significantly associated with a poor neurological picture and outcome from injury, while in patients with diffuse brain injury any increase in ICP above 10 mm Hg was associated with a poorer neurological status and a worse outcome. Despite intensive measures aimed at prevention of intracranial hypertension, ICP rose over 20 mm Hg during the monitoring period in 64 of the 160 patients (40%). Postoperative increases in ICP over 20 mm Hg (mean) were seen in 52% of the patients who had had intracranial masses evacuated, and could not be controlled by therapy in half of these cases. Even in patients without mass lesions, ICP rose above 20 mm Hg in a third of the cases, despite artificial ventilation and steroid therapy. Of the 48 patients who died, severe intracranial hypertension was the primary cause of death in nearly half and even moderately increased ICP (greater than 20 mm Hg) was associated with higher morbidity in patients with mass lesions and those with diffuse brain injury. Measurement of ICP should be included in management of patients with severe head injury.     

Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis

Increased intracranial pressure is a risk factor which may result in secondary brain damage, and affect neurological outcome in head injured patients. In case of diffuse brain lesions, elevated intracranial pressure is characterised by two important features. First, it results from vasogenic or cellular oedema, or from an increase in cerebral blood volume. Second, it is strongly associated to biochemical disorders. The latter may be considered as a direct consequence of the initial traumatic impact, mediating factors of the secondary neurological lesion and the biochemical result of cerebral ischaemia. They contribute to increased intracranial pressure and ischaemia by inducing physiological disorders and cell lesions. They also reflect the degree of cerebral ischaemia. Cerebral acidosis, free radicals and excitatory amicoacids are the main biochemical disorders implicated in this vicious circle leading to neuronal death.     

Does traumatic subarachnoid hemorrhage caused by diffuse brain injury cause delayed ischemic brain damage? Comparison with subarachnoid hemorrhage caused by ruptured intracranial aneurysms

OBJECTIVE: To examine whether traumatic subarachnoid hemorrhage (TSAH) caused by severe diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome, as does aneurysmal subarachnoid hemorrhage (ASAH). METHODS: We examined 99 patients with diffuse brain injury with TSAH and 114 patients with ASAH. Computed tomographic (CT) findings, cerebral blood flow, and neurological outcomes were assessed during the acute and subacute phases and were compared between the two groups. RESULTS: The distribution of subarachnoid hemorrhage on the CT scans differed between the two groups. Unlike ASAH, TSAH was not limited to cisterns surrounding the circle of Willis but extended to supratentorial regions and interhemispheric fissures. Computed tomography-detected subarachnoid hemorrhage disappeared very early with TSAH and gradually with ASAH. In the ASAH group, mean cerebral blood flow decreased to 75% of normal during the acute phase and decreased a further 10% during the subacute phase. In the TSAH group, mean cerebral blood flow decreased to 85% of normal during the acute phase and increased slightly during the subacute phase. Neurological deterioration and in-hospital death peaked on Day 0 in association with TSAH and showed twin peaks in association with ASAH. The incidence of low-density areas on the CT scans was significantly higher with ASAH than with TSAH. All low-density areas on the CT scans of patients with ASAH corresponded to vascular territories, but low-density areas on the CT scans of patients with TSAH were rarely associated with vascular territories and contained deep-seated or gliding contusion types. CONCLUSION: The findings suggest that the incidence of vasospasm is low in association with TSAH and that the cause is different compared with ASAH. There is no evidence that the presence of TSAH in cases of diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome.     

Assessing baroreflex sensitivity in post-myocardial infarction patients: comparison of spectral and phenylephrine techniques

OBJECTIVE: To comparatively assess outcome of patients undergoing monitoring and management of cerebral extraction of oxygen along with cerebral perfusion pressure vs. outcome of patients undergoing monitoring and management of cerebral perfusion pressure alone in severe acute brain trauma. DESIGN: Prospective, interventional study. SETTING: Intensive care unit of a university hospital. PATIENTS: Adults (n = 353) with severe acute brain trauma. A group of 178 patients underwent continuous monitoring and management of cerebral extraction of oxygen and cerebral perfusion pressure, while a control group of 175 patients underwent monitoring and management of cerebral perfusion pressure only. INTERVENTIONS: Routine neuroemergency procedures. MEASUREMENTS AND MAIN RESULTS: The two groups of patients were matched with regard to age, postresuscitation Glasgow Coma Scale scores, rates of acute surgical intracranial hematomas and brain swelling, pupillary abnormalities, early hypotensive events (before intensive care monitoring), as well as initial levels of intracranial pressure and cerebral perfusion pressure. Outcome at 6 months post injury was significantly better (p < .00005) in the 178 patients undergoing monitoring and management of cerebral extraction of oxygen along with cerebral perfusion pressure, than in the control group of 175 patients undergoing monitoring and management of cerebral perfusion pressure alone. CONCLUSION: In patients with severe acute brain trauma and intracranial hypertension associated with compromised cerebrospinal fluid spaces, monitoring and managing cerebral extraction of oxygen in conjunction with cerebral perfusion pressure result in better outcome than when cerebral perfusion pressure is managed alone.     

Evaluation of acute mental status change in the nonhead injured trauma patient

Acute mental status change in the first 24 hours after trauma is uncommon in nonhead injured patients who initially present with a normal sensorium. Although arterial hypoxemia is the classic etiology for such a mental status change, three less common etiologies should always be considered: cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis. Prompt diagnosis and appropriate treatment can significantly improve patient morbidity and mortality. Three nonhead injured trauma patients are described illustrating cerebral fat embolism, blunt carotid artery injury, and vertebrobasilar artery thrombosis as causes of acute mental status change. Each patient initially presented with a clear sensorium, but subsequently developed neurological deficits within 24 hours after admission. All had a normal admission CT scan of the head. MRI or conventional arteriography was diagnostic in each case. Any patient who is initially lucid and subsequently develops a neurological deficit, or a patient whose neurological status does not correlate with brain CT findings should undergo immediate evaluation for possible cerebral fat embolism or cervical vessel injury. An algorithm for management of nonhead injured trauma patients with acute mental status deterioration is presented.     

Penetrating head injury caused by weed--case report

A case of penetrating head injury caused by weed was reported. A 69-year-old man fell from a bicycle and was stuck by the hard stalk of weed through the right nasal cavity. On admission the patient was fully alert and with no neurological deficits. The weed was pulled out at an out-patient department and then he became semicomatose and hemiplegic on the left side together with an occurrence of nasal bleeding. Subsequent computed tomographic (CT) scan showed an intracerebral hematoma in the right frontal lobe. The hematoma was immediately evacuated and the dural defect, lateral to the cribriform plate, was closed. It is stressed that neuroradiological evaluation with CT scan and/or magnetic resonance imaging (MRI) is mandatory because an information about an anatomical location of penetrating objects and intracranial complications are essential to a decision-making of surgical strategy. The objects should be urgently removed in a surgical exposure of the intracranial lesion and the contused brain should be debrided with a repair of the lacerated dura mater.     

Intraoperative jugular desaturation during surgery for traumatic intracranial hematomas

Traumatic intracranial hematomas which are present on hospital admission or which develop during the hospital course are associated with a worse neurological outcome than diffuse injuries. The purpose of this study was to monitor jugular venous oxygen saturation (Sjvo2) during surgery for evacuation of traumatic intracranial mass lesions, to determine the incidence and the causes of jugular venous desaturation, and to assess the usefulness of Sjvo2 monitoring in this setting. Twenty-five severely head injured patients were monitored during 27 surgical procedures. At the start of the surgical procedure, the median Sjvo2 was 47% (range 25%-89%). Seventeen (63%) of the patients had a Sjvo2 less than 50%. Five patients had extremely low Sjvo2 values (< or = 30%). Upon evacuation of the intracranial hematoma, there was a significant (P < 0.001) increase in the median Sjvo2 to 65% (range 50%-88%). Intracranial hypertension was the primary cause of the low Sjvo2, as confirmed by the response to surgical evacuation. Hypotension (mean arterial pressure < 80 mm Hg) was a contributing factor in seven of the cases of jugular desaturation. The definitive treatment of a traumatic intracranial hematoma is surgical evacuation. However, during the period prior to evacuation of the hematoma, jugular venous desaturation was common, suggesting that monitoring Sjvo2 might provide useful information about the adequacy of cerebral perfusion.     

The management of severe traumatic brain injury

An approach to the initial evaluation, resuscitation, and treatment of the patient with severe traumatic brain injury is presented in terms of the underlying physiology and literature support. The primary importance of rapid and complete systemic resuscitation in terms of the "ABCs" is stressed, with the goal of optimizing cerebral perfusion and preventing secondary insults to the injured brain. The integration of brain-specific treatments and diagnostic maneuvers into resuscitation protocols is discussed, including the role of mannitol and hyperventilation as well as the prioritization of CT imaging of the brain.     

Jugular venous desaturation and outcome after head injury

Early experience with continuous monitoring of jugular venous oxygen saturation (SjvO2) suggested that this technology might allow early identification of global cerebral ischaemia in patients with severe head injury. The purpose of the present study was to examine the relationship between episodes of jugular venous desaturation and neurological outcome. One hundred and sixteen severely head-injured patients had continuous monitoring of SjvO2 during days 1-5 after injury. Episodes of jugular venous desaturation (SjvO2 < 50% for more than 10 minutes) were prospectively identified, and the incidence of desaturation was correlated with neurological outcome: 77 episodes of desaturation occurred in 46 of the 116 patients; 27 had one episode and 19 had multiple episodes of desaturation. The causes of these episodes were systemic (n = 36), cerebral (n = 35), or both (n = 6). Most of the episodes were less than 1 hour in duration, and it is probable that many of them would not have been detected without continuous measurement of SjvO2. Episodes of desaturation were most common on day 1 after injury, and were twice as common in patients with a reduced cerebral blood flow as in patients with a normal or elevated cerebral blood flow. The occurrence of jugular venous desaturation was strongly associated with a poor neurological outcome. The percentage of patients with a poor neurological outcome was 90% with multiple episodes of desaturation and 74% in patients with one desaturation, compared to 55% in patients with no episodes of desaturation. When adjusted for all co-variates that were found to be significant, including age, Glasgow coma score, papillary reactivity, type of injury, lowest recorded cerebral perfusion pressure, and highest recorded temperature, the incidence of desaturation remained significantly associated with a poor outcome. Although a cause and effect relationship with outcome cannot be established in this study, the data suggest that monitoring SvO2 might allow early identification and therefore treatment of many types of secondary injury to the brain.     

Correlation of cerebral blood flow with outcome in head injured patients

In order to determine the relationship of cerebral blood flow (CBF) to the clinical outcome of head injury, serial determinations of CBF were performed by the intravenous Xenon technique in 24 patients. The patients were of mixed injury severity and were classified into four groups depending on the neurological exam at the time of each CBF study. All eight patients who were lethargic on admission demonstrated increases in their minimally depressed CBF as they improved to normal status. Eleven patients in deep stupor or coma ultimately recovered. Ten of these patients initially had moderate to profound decreases in CBF which improved as recovery occurred. The single exception was an adolescent whose initial CBF was high but became normal at recovery. Five comatose patients died. In four of these, already depressed CBF fell even lower, while one adolescent with initially increased CBF developed very low CBF preterminally. The data presented in this report demonstrated a good correlation between CBF and clinical outcome. In every one of the adult survivors, depressed CBF increased as the patient recovered to normal status. All adults who died showed a deterioration of CBF as the neurological status worsened. The only exceptions were two adolescents who initially showed high CBF values. In the adolescent who died, CBF dropped to low levels while in the survivor a normal CBF was achieved. Thus in adults a traumatic brain injury was associated with depressed CBF which increased with recovery or decreased further with deterioration while the reaction to injury was quite different in the younger brain.     

Correlation of computed tomography findings and serum brain damage markers following severe head injury

The objective of our study was to investigate the association between the initial levels of serum S-100B protein and neuron specific enolase and the severity of radiologically visible brain damage and outcome after severe head injury. Admission computed tomography (CT) scans of forty-four patients with severe head injury were analysed. Initial levels of S-100B protein and neuron specific enolase were compared between the different outcome groups at 6 month, the different categories of the Marshall classification, the presence of traumatic subarachnoid haemorrhage, the type of haematoma and the volume of contusion. Serum S-100B was significantly higher in patients with unfavourable outcome (1.1 micrograms/l versus 0.3 microgram/l, p < 0.005, Mann-Whitney U test). In diffuse injury, unfavourable outcome significantly increased with higher Marshall grades (p < 0.05). There was a significant correlation between the four grades of diffuse injury and initial serum S-100B protein (r = 0.48, p < 0.001). Patients with focal mass lesions and a favourable outcome after 6 month had significantly lower S-100B values than those who had an unfavourable outcome (0.51 microgram/l versus 1.3 micrograms/l, p < 0.05). A significant correlation was demonstrated between the volume of contusion visible on CT scans and serum S-100B (r = 0.58, p < 0.001). In our study, initial serum S-100B protein was a powerful predictor of outcome even within the same category of radiologically visible brain damage. Serum S-100B protein may provide independent information about the severity of primary brain damage after head injury.     

Severe head trauma. Review of the factors influencing the prognosis

A series of 72 severely head injured patients are reported, 24 (33%) with surgical intracranial hematomas. All patients were intensively cared for under the same therapeutic regime; intracranial pressure (ICP) was monitored and treated if increased. The series mortality was 39%. Uncontrollable increase of ICP (UI-ICP), always fatal, was observed in 18% of patients and in 13 of 28 deaths (46%); the incidence of UI-ICP among deaths was higher in patients less than in those more than 40 years old (55% vs 25%). Patients with UI-ICP were frequently deeply comatose and with arterial hypotension on admission; almost all died in the first days. Patients directly admitted from the scene with well staffed Life Flight Helicopter Emergency Care compared with those directly admitted from the scene with different type of ambulance service (paramedics, police, firemen and private) had a mortality rate significantly less (20% vs 54%) and an incidence of UI-ICP strongly lower both among patients (5% vs 29%) and among deaths (25% vs 54%). Thus in this small series intensive care after admission was not effective to obtain good results if patients had received poor preadmission emergency care. Review of the literature on main clinical predictors of outcome in severe head injury, have made possible some observations. Ischemic and intracranial hypertension brain lesions were generally present in patients killed by head trauma; while diffuse axonal injury, frequently responsible for vegetative, severe disability survival and late deaths, was observed only in 20-30% of postmortem examinations. Old age, poor neurological status and cardiocirculatory and respiratory disturbances prior to and upon admission positively worsened the outcome, while intracranial hematomas had a more variable predictive value. Intracranial hypertension was a definitively ominous predictor only if very high when the risk to be or become uncontrollable seems to be much elevated. UI-ICP, often fatal despite any aggressive therapy, was the single most frequent killer after severe head injury, responsible for about half of all deaths after admission. The different outcome among severe head injury series could be conceivably related to a different frequency of UI-ICP. Besides the severity of head injury and delay and mode of admission, we suggest that preadmission respiratory and cardiocirculatory and the quality of emergency medical system could strongly affect the incidence of uncontrollable increase of ICP in admitted patients and thus the mortality rate and favorable recovery of the series. The advanced preadmission emergency care service with intensive care after admission could significantly explain the better results often observed in severe head injury series.     

Transcranial Doppler in vertebrobasilar vasospasm after subarachnoid hemorrhage

OBJECTIVE: The primary objective of this study was to assess the incidence of vertebrobasilar vasospasm after subarachnoid hemorrhage (SAH) by means of transcranial Doppler ultrasonography and to evaluate the clinical significance of this phenomenon. The secondary objective was to analyze the different factors influencing the development, the severity, and the duration of vertebrobasilar vasospasm. METHODS: Fifty-seven patients with traumatic SAH and 44 patients with spontaneous SAH were evaluated and monitored by means of transcranial Doppler ultrasonography. Vasospasm of the anterior and middle cerebral arteries was defined by mean flow velocities (FVs) exceeding 120 cm per second and at least three times the FV of the internal carotid artery. Vasospasm of the basilar and vertebral arteries was defined by a mean FV exceeding 60 cm per second. RESULTS: Vasospasm of the anterior or middle cerebral arteries was found in 27 patients and was associated with vertebrobasilar spasm in 20 patients. FVs in anterior circulation vessels were neither related to the cause of the SAH nor did they correlate with the outcome. Forty-six patients (45.5%) had FVs exceeding 60 cm per second and 25 (24.8%) had FVs exceeding 85 cm per second. In 10 of these patients, direct or computed tomographic angiography showed arterial narrowing involving the vertebrobasilar system, whereas in 21 more patients, computed tomography disclosed a cerebral infarction involving the vertebrobasilar vascular territory. Vertebral artery FVs in this group were twice that of the ipsilateral carotid artery. Vertebrobasilar vasospasm was significantly more frequent after head injury, although it was not related to the type of intracranial lesion or the Glasgow Coma Scale score at admission. It did correlate, however, with outcome (P < 0.0001) and with the intensity of SAH (P < 0.0001). Delayed neurological deterioration occurred in 14 patients and was significantly more frequent in patients with basilar artery FVs above 85 cm per second (P < 0.001). Prognosis, however, could not be reliably predicted by FVs in the basilar artery, even when an FV of 110 cm per second was chosen for prediction criterion. CONCLUSION: These results suggest that vertebrobasilar vasospasm is more common than previously thought, especially in association with head injury, with which it may significantly contribute to brain stem ischemic lesions and therefore justify specific therapeutic measures.     

Cerebrospinal fluid tissue factor and thrombin-antithrombin III complex as indicators of tissue injury after subarachnoid hemorrhage

BACKGROUND AND PURPOSE: No marker that reflects and predicts brain injury due to subarachnoid hemorrhage (SAH) and cerebral vasospasm has been reported. We hypothesized that membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) in the cerebrospinal fluid (CSF) of patients with SAH become markers indicating brain injury. To evaluate the hypothesis, we correlated levels of mTF and TAT in the CSF of patients with SAH with clinical severity, the degree of SAH, and outcome. METHODS: We assayed CSF mTF, TAT and myelin basic protein (MBP) in patients with SAH at intervals that included days 0 to 4 and days 5 to 9 after ictus. Classification of clinical severity of disease on admission was based on Hunt and Hess grade, degree of SAH on CT on Fisher's grading, and outcome 3 months after SAH on the Glasgow Outcome Scale. RESULTS: In the interval from days 0 to 4, mTF and TAT correlated with Hunt and Hess and Fisher grades, and occurrence of cerebral infarction due to vasospasm. Only mTF correlated significantly in this period with outcome. TAT, mTF, and MBP all correlated significantly with each other. From days 5 to 9, only mTF correlated with cerebral infarction, infarction volume, MBP levels, and outcome. CONCLUSIONS: Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.     

Hemispheric cerebral atrophy after traumatic extra-axial hematoma in adults

The relationship between traumatic extra-axial hematomas and cerebral atrophy was investigated in 42 adult patients aged between 15 and 50 years who required removal of extra-axial hematomas. These patients were followed up by serial computed tomography for more than 6 months after head injury. Nine of these patients developed cerebral atrophy. Their Glasgow Coma Scale score on admission was 6.4 +/- 2.8 (mean +/- SD). The score of the patients without cerebral atrophy was 9.6 +/- 3.3 (p < 0.01). These patients had three extradural and six subdural hematomas. All patients with cerebral atrophy had cerebral swelling postoperatively, more prominent in the hemisphere ipsilateral to the hematoma in seven patients. This swelling was associated with global hypodensity and persisted for 10.4 +/- 2.9 days. The severity of cerebral atrophy was more prominent in the hemisphere ipsilateral to the hematoma in five of these seven patients. Extra-axial hematoma in patients with severe head injury can induce hemispheric cerebral atrophy in the underlying cerebral hemisphere.     

Traumatic intracerebral hematoma with stable neurological deficit

The possibility of an intracerebral hematoma may be overlooked in the presence of a "fixed" neurologic deficit. The clinical complex that is emphasized is composed of (a) ipsilateral cranial trauma, (b) early development of focal neurological deficit, (c) a plateau in the subsequent course of the disease, (d) the delayed appearance of a positive radioactive isotope scan, and (e) a focal area of distorted vessels in angiographic studies. The availability of the computer tomographic scan has made the diagnosis of intracerebral hematomas more certain but it is important that the possibility of a hematoma be considered and pertinent investigations be performed. Even after diagnosis, an operative procedure may be delayed in patients who are neurologically stable. In the five cases presented, the diagnosis of cerebral contusion led to a delay in operative evacuation which was associated with improvement in the previously stable neurological deficit.     

Traumatic brain contusions: a clinical role for the kinin antagonist CP-0127

Focal cerebral contusions can be dynamic and expansive, leading to delayed neurological deterioration. Due to the high mortality associated with such cerebral contusions, our standard practice had evolved into evacuating contusions in patients who had a deterioration in level of consciousness, lesions > 30 cc and CT suggestion of raised ICP. Experimental brain edema studies have implicated kinins in causing 2 degrees brain swelling. CP-0127 (Bradycor), a specific bradykinin antagonist, has been found to reduce cerebral edema in a cold lesion model in rats. In a randomized, single blind pilot study, a 7 day infusion of CP-0127 (3.0 micrograms/kg/min) was compared to placebo in patients with focal cerebral contusions presenting within 24-96 hours of closed head injury with an initial GCS 9-14. The ICP, GCS, and vital signs were monitored hourly. The total lesion burden (TLB) was measured on serial CT scans. There were no differences in age, baseline GCS, TLB, initial ICP, or laboratory findings between the two groups (n = 20). The mean (+/- s.d.) rise in peak ICP from baseline was greater in the placebo group than with CP-0127 (21.9 +/- 4.7 vs 9.5 +/- 2.0, P = 0.018). In addition, the mean reduction in GCS in the placebo group was significantly greater than in the CP-0127 group (4 +/- 1.0 vs 0.6 +/- 0.4, P = 0.002). Significantly raised ICP and clinically significant neurological deterioration occurred in 7/9 patients on placebo (77%) and only in 1 patient (9%; n = 11) on CP-0127, mandating surgery (P = 0.005). There were no adverse drug reactions, significant changes in vital signs or variations in the laboratory values. The cerebral perfusion pressure was adequately maintained in all patients irrespective of therapy. These preliminary results with CP-0127 provide supporting evidence that the kinin-kallikrein system could be involved in cerebral edema. In this study, treatment with CP-0127 appeared to alter the natural history of traumatic brain contusions by preventing the 2 degrees brain swelling. In addition, CP-0127 obviated the need for surgery in the majority of treated patients. CP-0127 could act on the cerebral vasculature to limit dys-autoregulation and brain swelling or on the blood brain barrier to reduce cerebral edema.     

The effect of associated injuries, blood loss, and oxygen debt on death and disability in blunt traumatic brain injury: the need for early physiologic predictors of severity

Studies of 4590 patients with blunt trauma injuries admitted to a Level I Trauma Center, have shown that 37% had a blunt traumatic brain injury (BTBI). Of these brain injured patients 60% has an associated other injury. Examination of mortality has shown that those with an isolated brain injury had an 11% mortality compared with 21.8% in those with an associated systemic injury. Further investigation demonstrated that the cause of the increased mortality was related to the blood loss associated with the injuries and that when hypovolemic shock resulted, mortality rose from 12.8 to 62%. The severity of the associated injuries effect on the brain injured patient could be estimated by a parameter of oxygen debt, the base deficit and this allowed for a quantitative estimate of the probability of death as an index of severity. A combined linear logistic model using the admission Glasgow Coma Score (GCS) as a measure of brain injury and the base deficit as a measure of physiologic injury provides such a predictive score. The effect of associated injuries in patients with moderate brain injury (AIS 2,3) was to increase the average total cost of medical care in the first year of injury by three-fold ($12,489 to $36,177) and for severe brain injury (AIS 4,5) to increase average cost from $59,000 in isolated BTBI to $90,000 in BTBI with associated injury. The high incidence of brain injuries in motor vehicle crashes (MVC) caused by lateral impacts and their association with other side-impact injuries (lungs, spleen, kidney, and pelvic fractures) in which large blood volume losses are common, focuses attention on the need for side impact protection standards that simultaneously protect brain, thoracoabdominal viscera, and pelvis as a means of reducing the severity and cost of lateral impact MVCs.     

The role of phospholipases, cyclooxygenases, and lipoxygenases in cerebral ischemic/traumatic injuries

Free fatty acids (FFAs) are elevated in the brain following both ischemic and traumatic injury. Phospholipase activation, with the subsequent release of FFAs from membrane phospholipids, is the likely mechanism. In addition to phospholipases A1, B, C, and D, there are at least 19 groups of PLA2, including multiple cytosolic, calcium independent, and secretory isoforms. Phospholipase activity can be regulated by calcium, by phosphorylation, and by agonists binding to G-protein-coupled receptors. These enzymes normally function in the physiological remodeling of cellular membranes, whereby FFAs are removed by phospholipase activity and then reacylated with a different FFA. However, reductions in the cell's ability to maintain normal metabolic function and the resultant fall in ATP levels can cause the failure of reacylation of membrane phospholipids. Alterations to membrane phospholipids would be expected to compromise many cellular functions, including the ability to accumulate excitotoxic amino acids. This review presents evidence for a central role of phospholipases and their products in the etiology of damage following injury to the brain. Phospholipase expression and activity is increased in animal models of cerebral ischemia and trauma. FFA release from the in vivo rat brain is reduced following the application of selective phospholipase inhibitors, and this inhibition also decreases the severity of cortical damage following forebrain ischemia, focal (middle cerebral artery occlusion) ischemia, and cerebral trauma. Mice with knockouts of PLA2 have decreased infarct volumes. Human data demonstrate a correlation between the elevation of CSF FFAs and worsened outcome following stroke, traumatic brain injury, and subarachnoid hemorrhage. The released FFAs, especially arachidonic and docosahexaenoic acids, together with the production of lysophospholipids, can initiate a chain of events which may be responsible for the development of neuronal damage. Inhibitors of both cyclooxygenase and lipoxygenase pathways have been shown to reduce cerebral deficits following ischemia and trauma. These results suggest therapeutic strategies to reduce morbidity following cerebral injury using selective inhibitors of phospholipases, cyclooxygenases, and lipoxygenases, underlining the need for further investigation of their role in the development of cerebral damage.     

Hyperglycemia increases neurological damage and behavioral deficits from post-traumatic secondary ischemic insults

The effects of post-traumatic administration of glucose 2.0 g/kg was compared to saline infusion with and without control of brain temperature at 37 degrees C on behavioral and histological measures of brain injury after controlled cortical impact injury complicated by a secondary ischemic insult. The glucose infusion increased blood glucose concentration from 114 +/- 4 to 341 +/- 76 mg/dl prior to the secondary ischemic insult. The resulting outcome measures were significantly worse in the glucose infusion group than in either control group. Mortality rate was significantly increased by the glucose administration, from 0% to 55% (p < 0.001). The median contusion volume was increased from 7.9 to 64.2 by glucose administration (p < 0.001) and the neuronal loss in the CA1 and CA3 areas of the hippocampus were greater in the glucose infusion group. In the animals that survived for the 2 weeks of behavioral studies, the duration of beam balance was shorter; the percent of animals that could balance on the beam for at least 60 s was less, the percent of animals that could perform the beam-walking task was less, and the length of time required to find the platform in the Morris water maze task was longer in the glucose infusion group. These studies demonstrate that the infusion of glucose after the cortical impact injury significantly increases the damage caused by post-traumatic ischemic insults. The adverse effect on neurological outcome could not be explained by the temperature effects of glucose infusion.