Regions of cerebral ischemia located by pyridine nucleotide fluorescence.

The fluorescence of the reduced form of the endogenous pyridine nucleotide nicotinamide adenine dinucleotide was used to map regions of ischemia in cat brain. A remarkably microheterogeneous pattern of increased fluorescence resulted from a critical level of incomplete cerebral ischemia. The fluorescence pattern suggests that ischemia occurs initially in microwatershed zones between penetrating cerebral arteries.

Visual field defects in relation to head injury severity. A neuropsychological study.

A total of 159 head-injured patients were classified into four groups based on two acute categories of injury severity (minor-to-moderate and severe) and the subsequent presence or absence of visual field defects (VFDs). They were assessed neuropsychologically within ten to 19 months after injury. Within both minor-to-moderate and severe injury classifications, patients with VFDs were more impaired neuropsychologically and had more frequent acute secondary intracranial complications (brain swelling, intracranial hypertension, and cerebral hyperemia) than patients without VFDs. The findings suggest that the presence of VFDs during the long-term period may be residuals of acute secondary complications indicative of increased neuropsychological deficits after head injury.

Influence of lesions detected by computed tomography on outcome and neuropsychological recovery after severe head injury.

Outcome at 6 months after severe head injury was determined in 117 patients whose computed tomographic (CT) examinations demonstrated diffuse axonal injury (DAI), diffuse swelling (DS), or focal injuries. Neuropsychological sequelae were ascertained from two examinations in 30 of the conscious survivors within the 1st year after injury. Outcome differences varied with the type of CT lesion. DS and focal injuries resulted in more favorable (good recovery) outcomes. Mortality was higher after DAI. Neuropsychological outcome varied with the type of CT lesion and the function measured. Overall differences in memory and learning were revealed among the three CT lesion categories, whereas differences in intelligence and visuomotor functions were not significant. Levels of memory, learning, and visuomotor speed were higher after DS injuries, but improvement was less. Greater improvement of memory, learning, and visuomotor speed occurred after DAI. After focal injuries, visuomotor speed improved, but not recall and learning. The results suggest that the type of injury incurred differentially influences the outcome and the neuropsychological aftermath of severely head-injured adults.

Hospital of the University of Pennsylvania.

The Hospital of the University of Pennsylvania was the first university-owned teaching hospital in the nation. The author briefly reviews its history and association with the other faculties of the University.

The evolving role of the nurse practitioner in neurosurgery.

The authors examine the many important roles for the nurse practitioner in neurosurgery, including patient care in academic departments and private practice, and research and scholarship. The responsibilities of nurse practitioners in a hospital can be varied: they may take some responsibility for all patients on the neurosurgery service, or their assignment may be more specific, such as to the intensive care unit; or they may be assigned to all patients with a specified neurosurgical disorder, such as head injury of intractable pain. Nurse practitioners can become coordinators of clinical research programs, with responsibility for collecting and collating the data and assisting in data analysis and manuscript preparation. Detailed clinical protocols must be developed for nurse practitioners, and those protocols then become the basis for their employment and legal status. Licensure requirements vary greatly among states, and are continuing to change.

Can the out come from head injury be improved?

In the past few years, considerable progress has been made in describing patients with head injuries in such a manner that comparisons in morbidity and mortality can be made among neurosurgical centers according to the seriousness of the injury. Less progress had been made in classifying the type of pathology, especially by computerized tomography. The authors have introduced a classification that includes both the type and the seriousness of the injury. There appear to be two principal causes of the brian damage produced by head injury: 1) mechanical damage to neurons and their processes, especially axons and 2) ischemia. Mechanical damage produces axonal degeneration. Although central regeneration generally is quite limited, perhaps many of the axons damaged by head injury degenerate in continuity, a circumstance in which functional regeneration by axoplasmic outgrowth is much more likely to occur than in most experimental situations where the axons are physically divided. The ischemic brain damage that is so common in head injury appears to be mass lesions and brain swelling that both cause intracranial hypertension. The more the brain swells, and the higher the intracranial pressure, the more difficult it is to control the swelling and the pressure. In patients with acute subdural hematoma in particular, the brian swelling and the high mortality appear to be due to ischemic brain damage. There is recent evidence that the mortality rate in patients with acute subdural hematoma is a function of the time from injury to evacuation of the hematoma. Therefore, outcome from head injury can be improved by the earliest possible removal of space-occupying hematomas and by early, vigorous management of intracranial hypertension.

Vertebrobasilar spasm: a significant cause of neurological deficit in head injury.

Cerebral vasospasm in the anterior circulation has been recognized as a significant factor in the sequelae of head injury; however, vertebrobasilar spasm resulting from trauma has received much less attention. In the past year we have observed six patients where spasm in the major vessels of the posterior circulation was primarily or in part responsible for the neurological deficit. In such cases, the neurological examination may suggest a supratentorial mass with herniation and, in three of our cases, burr holes or carotid angiography were performed first. However, in every instance neurological signs present on admission indicated primary brain-stem dysfunction. In each of the six cases vertebral angiography demonstrated significant spasm in either the vertebral or basilar arteries. Intracranial pressure was monitored in each of the six patients and did not exceed 25 mm Hg in any. In cases of head injury where the neurological examination indicates brain-stem dysfunction inconsistent with or after a supratentorial mass has been excluded, vertebral angiography may aid in the diagnosis and subsequent management of such patients.

Relationship of acute CBF and ICP findings to neuropsychological outcome in severe head injury.

Neuropsychological outcome within 1 year after severe head injury was examined in 42 conscious survivors and correlated with acute measurements of cerebral blood flow (CBF) and intracranial pressure (ICP). During acute coma, CBF was elevated in 23 patients, indicating hyperemia, and was reduced in the remaining 19 cases. Intracranial hypertension (ICP 20 mm Hg or greater) was present acutely in 15 patients and absent in 27. Occurrences of hyperemia and intracranial hypertension were significantly related. During chronic recovery, neuropsychological dysfunction was found in all cases. However, patients with hyperemia revealed greater impairment of overall intellectual and memory functions than did those with reduced flow, while patients with intracranial hypertension showed greater memory deficit than did those without ICP elevations. The results suggest that early pathophysiological events can influence subsequent neuropsychological outcome, and that chronic recovery is not homogeneous in young severely head-injured adults.

Relation of cerebral blood flow to neurological status and outcome in head-injured patients.

Noninvasive studies of regional cerebral blood flow (CBF) were performed on 36 head-injured patients in varying degrees of coma, using the intravenous xenon-133 method. Serial examinations, averaging four per patient, were begun during the acute phase of illness and continued until death of recovery of normal consciousness. Comparison of the initial and final studies revealed that CBF declined to very low levels in all nine patients who died, and remained subnormal in a patient with persistent vegetative state. In contrast, 25 of 26 patients who recovered consciousness showed increases in blood flow. Because of the presence of both reduced and elevated blood flows on the initial study, CBF was not predictive of outcome. Absolute or relative hyperemia, observed in nine acute cases, was associated with either diffuse cerebral swelling (observed on computerized tomography) or recovery from systemic shock. Cerebral metabolic studies in hyperemic patients yielded a very low oxygen uptake and arteriovenous oxygen difference, indicating that the high blood flow was a true "luxury perfusion." When instances of presumed luxury perfusion were excluded, CBF was positively correlated with level of consciousness, assessed on a four-point coma scale.

Experimental cerebral oligemia and ischemia produced by intracranial hypertension. Part 2: Brain morphology.

The authors studied the morphological sequelae of 15 minutes of cerebral oligemia (20 torr cerebral perfusion pressure) and complete cerebral ischemia produced by raised intracranial pressure in rabbits. Ischemic cell change was present in five of seven ischemic animals; it was most extensive in the striatum and hippocampus, with only a few ischemic nerve cells in the thalamus and neocortex. The brains of control and oligemic animals were normal. These results indicate the following: 1) ischemia is a more severe insult than oligemia; 2) compression ischemia results in a pattern of damage that differs from that produced by other types of ischemia; and 3) the method used to reduce cerebral perfusion pressure is an important factor in determining the pattern and extent of brain damage produced.

Experimental cerebral oligemia and ischemia produced by intracranial hypertension. Part 1: Pathophysiology, electroencephalography, cerebral blood flow, blood-brain barrier, and neurological function.

Cerebral blood flow, electrical activity, and neurological function were studied in rabbits subjected to either 15 minutes of oligemia (20 torr cerebral perfusion pressure) or complete cerebral ischemia produced by cisterna magna infusion. During oligemia, flow was reduced from 68.4 +/- 4.2 ml/100 gm/min to 26.3 +/- 4.4 (p less than .01), and during ischemia animals had no proven flow. By 5 minutes after oligemia or ischemia significant symmetrical hyperemia occurred and there was no evidence of the no-reflow phenomenon. The electroencephalogram became isoelectric significantly later and returned significantly sooner in oligemia than in ischemia. Oligemic animals had earlier and better return of neurological function than their ischemic counterparts, although postinsult hypocapnia improved functional recovery in both groups. These experiments do not support the concept that oligemia is a more severe insult than complete ischemia. In intracranial hypertension produced by this model, the no-reflow phenomenon does not occur.

Experimental cerebral oligemia and ischemia produced by intracranial hypertension. Part 3: Brain energy metabolism.

The authors studied the effect on cortical metabolites of intracranial hypertension produced by the infusion of mock cerebrospinal fluid into the cisterna magna in rabbits subjected to 15 minutes of cerebral oligemia (20 torr) or 15 minutes of complete ischemia. In both groups high-energy metabolites were exhausted within the first 5 minutes of the 15-minute insult. Significant recovery of the high-energy intermediates occurred within 15 minutes of reperfusion, well before return of electroencephalogram (EEG) activity. Continued reperfusion, during which electrical activity and function were returning, brought only moderate improvement in energy metabolites. In contrast, severe lactic acidosis persisted at least 15 minutes after insult, but was reduced by the time EEG activity returned. At no time were there striking differences in metabolites between the oligemic and ischemic groups. These results indicate that recovery in general, and the significantly earlier recovery of oligemic as compared to ischemic animals, cannot be explained on the basis of energy supply. Whether the persistence of lactic acidosis is an important factor limiting return of function requires further study.

Relationship of early cerebral blood flow and metabolism to outcome in acute head injury.

Cerebral blood flow (CBF) measurements were obtained acutely in 96 comatose patients with closed head injury, using the intravenous 133Xe technique. Arteriojugular venous oxygen differences and cerebral metabolic rate for oxygen (CMRO2) were determined in a subgroup of 66 patients. The relationship between each of these variables and outcome at 6 months was analyzed, using the Glasgow Outcome Scale. The CMRO2 was significantly depressed in patients who subsequently died or remained in a vegetative state, whereas higher values were obtained in patients who later regained consciousness. Although CBF was not predictive of outcome in the total sample, omission of patients with acute hyperemia resulted in a significant relationship that paralleled the metabolic findings. Follow-up studies in the survivors revealed a correlation between CBF and degree of functional recovery, the lowest blood flows being obtained among patients with severe disability. Age, initial Glasgow Coma Scale score, and occurrence of intracranial hypertension were each found to be predictive of outcome, thus confirming previous reports. When these variables were combined with CMRO2 in a logistic regression analysis, the probability of recovery was correctly predicted in 82% of the cases. The CMRO2 was relatively independent of the other prognostic indicators and, next to age, contributed most to the prediction.

Hemorrhage in bilateral choroid plexus hemangiomas demonstrated by computed tomography. Case report.

The authors present a case in which bilateral posttraumatic hemorrhages in choroid plexus hemangiomas were demonstrated by computed tomography and histopathological study.

Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension.

Cerebral blood flow (CBF) measurements were made in 75 adult patients with closed head injuries (mean Glasgow Coma Scale score 6.2) using the xenon-133 intravenous injection method with eight detectors over each hemisphere. All patients were studied acutely within 96 hours of trauma, and repeatedly observed until death or recovery (total of 361 examinations). Arteriojugular venous oxygen differences (AVDO2) were obtained in 55 of the patients, which permitted assessment of the balance between metabolism and blood flow, and provided estimates of cerebral metabolic rate for oxygen (CMRO2). Based on mean regional CBF, the patients were classified into two groups: those who exhibited hyperemia on one or more examinations, and those who had a consistently reduced flow during their acute illness. "Hyperemia" was defined as a normal or supernormal CBF in the presence of coma, a definition that was independently confirmed by narrow AVDO2's indicative of "luxury perfusion". During coma, all patients showed a significant depression in CMRO2. Forty-one patients (55%) developed an acute hyperemia with an average duration of 3 days, while 34 patients (45%) consistently had subnormal flows. Although more prevalent in younger patients, hyperemia was found at all age levels (15 to 85 years). There was a highly significant association between hyperemia and the occurrence of intracranial hypertension, defined as an intracranial pressure above 20 mm Hg. Patients with reduced flow showed little or no evidence of global cerebral ischemia, but instead revealed the expected coupling of CBF and metabolism. The CBF responses to hyperventilation were generally preserved, with the hyperemic patients being slightly more reactive. In 10 patients with reduced flow, hyperventilation resulted in wide AVDO2's suggestive of ischemia.

Effects of increased ICP on brain phosphocreatine and lactate determined by simultaneous 1H and 31P NMR spectroscopy.

In order to study the metabolic events surrounding ischemia induced by the graded increase of cerebrospinal fluid (CSF) pressure, the technique of simultaneous phosphorus-31- and hydrogen-1-enhanced nuclear magnetic resonance spectroscopy was applied to five cats as intracranial pressure (ICP) was gradually raised by the instillation of mock CSF. Threshold lactate rose at an average cerebral perfusion pressure (CPP) of 49 torr, and, in general, preceded a threshold decrease in phosphocreatine, which was observed at an average CPP of 29 torr. There was considerable variation among cats in the CPP at which failure of brain energy metabolism occurred, however, suggesting differences in the autoregulatory curves. It is concluded that, with elevated ICP, there is no universally "safe" CPP at which brain energy metabolism may be assumed to be uncompromised.

Computerized tomography, magnetic resonance imaging, and positron emission tomography in the study of brain trauma. Preliminary observations.

Results of computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), xenon-133 measurement of cerebral blood flow (CBF), and neuropsychological assessments are described in three head-injured patients. The patients were selected because they presented with intracranial hemorrhage diagnosed by CT. Two of the patients were studied acutely and again approximately 6 months later. In the acute stage, MRI was superior to CT in identifying the precise location and extent of intracranial hemorrhage and associated edema. Small subdural hematomas diagnosed on MRI were missed with CT scanning. The extent of apparent encephalomalacia in the chronic stages of injury was also better defined with MRI. Positron emission tomography showed disturbances of glucose metabolism that extended beyond the structural abnormalities demonstrated by MRI and CT; anterior temporal lobe dysfunction was particularly evident in all three patients. Regional CBF studies failed to detect a number of the abnormalities seen on MRI and CT, and even ignored the metabolic dysfunction evident on PET that should have been accompanied by changes in regional CBF. The neuropsychological studies localized frontal lesions, but did not reveal abnormalities attributable to the structural lesions and the reduced metabolism in the anterior temporal lobes.

Influence of injury severity on quality of survival after head injury.

The relationship between severity of injury [as determined by the Glasgow Coma Scale (GCS)] and the quality of survival (as determined by neuropsychological measurements and work return) were investigated in 54 conscious survivors within 16 months following head injury. While severely head injured (GCS less than or equal to 8) patients had more neuropsychological impairments in areas of intelligence, attention, memory, visuomotor speed, and motor skills than those with mild injuries (GCS greater than 8), performances after both types of injury were below normative levels in areas of learning, memory, and visuomotor speed. Unemployment increased after both severe and mild injuries, while employment status changed more frequently after severe injuries. Age had a minimal effect on neuropsychological and employment outcomes after minor head injuries (GCS greater than 13). The findings suggest that regardless of acute severity, closed head injury influences long-term quality of survival.