Donald P. Becker

Traumatic Acute Subdural Hematoma — Major Mortality Reduction in Comatose Patients Treated within Four Hours

To discover which factors contributed to recovery after surgical intracranial decompression, we reviewed the records of 82 consecutive comatose patients with traumatic acute subdural hematoma (ASDH) who were treated in a single center under a uniform protocol. The delay from injury to operation was the factor of greatest therapeutic importance. Patients who underwent surgery within the first four hours had a 30 per cent mortality rate, as compared with 90 percent in those who had surgery after four hours (P less than 0.0001). Other important prognostic variables included results of the initial neurologic examination, sex, multimodality-evoked potentials, and postoperative intracranial pressure (ICP). If all patients with traumatic ASDH were taken directly to hospitals equipped to diagnose and remove the hematoma within four hours of injury, mortality rates could be reduced considerably.

Improved confidence of outcome prediction in severe head injury A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEPs), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEPs represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state

Following cerebral concussion, in which there is no evidence of direct morphological damage, cells are exposed to an increase in extracellular potassium as well as an accumulation of calcium. This concussion-induced ionic flux most likely alters the cellular energy demands thereby modifying metabolic processes. To investigate the metabolic changes after cerebral concussion, local cerebral metabolic rates for glucose (lCMRglc) utilizing [14C]2-deoxy-D-glucose were studied in rats (n = 98; 250-300 g) immediately, 30 min, 6 h, 1, 2, 3, 5 and 10 days following a unilateral frontoparietal fluid percussion (F-P) injury (3.7-4.3 atm). Compared to sham controls, animals exhibited bilateral hypermetabolism immediately following brain injury. However, this effect was more pronounced in structures ipsilateral to the site of F-P and was especially marked for the cerebral cortex (46.6-30.1% higher than control) and hippocampus (90.1-84.4% higher than control). By 30 min post-trauma many ipsilateral regions still showed evidence of hypermetabolism, although their lCMRglc had subsided. Beginning as early as 6 h following injury many regions within the ipsilateral cortex and hippocampus went into a state of metabolic depression (16.4-33.7% of control) which lasted for as long as 5 days. These results indicate that, although not mechanically damaged from the insult, cells exposed to concussive injury dramatically alter their metabolic functioning. This period of post-concussive metabolic dysfunction may delineate a period of time, following injury, during which cells are functionally compromised.

Axonal Change in Minor Head Injury

Anterograde axonal transport of horseradish peroxidase (HRP) in selected cerebral and cerebellar efferents was studied in cats subjected to minor head injury. After trauma, the animals were allowed to survive from one to 24 hours, when they were perfused with aldehydes and processed for the light and electron microscopic visualization of the peroxidase reaction product. By light microscopy, the brain injury elicited an initial intra-axonal peroxidase pooling. With longer post-traumatic survival, HRP pooling increased in size, demonstrated frequent tabulation, and ultimately formed large ball- or club-like swellings which suggested frank axonal separation from the distal axonal segment. Ultrastructural examination revealed that the initial intra-axonal peroxidase pooling was associated with organelle accumulation which occurred without any other form of axonal change or related parenchymal or vascular damage. This accumulation of organelles increased with time and was associated with conspicuous axonal swelling. Ultimately these organelle-laden swellings lost continuity with the distal axonal segment and the axonal swelling was either completely invested by a thin myelin sheath or protruded without myelin investment into the brain parenchyma. This study suggests that axonal change is a consistent feature of minor head injury. Since these axonal changes occurred without any evidence of focal parenchymal or vascular damage, minor brain injury may ultimately disrupt axons without physically shearing or tearing them.

Concussive brain injury is associated with a prolonged accumulation of calcium : a 45Ca autoradiographic study

In order to determine the extent and duration of calcium (Ca2+) flux following a lateral fluid percussion brain injury in the rat, 45Ca autoradiography was used to study animals immediately, 6, 24 and 96 h after the insult. In addition, cell suspension studies were conducted to determine the extent of cellular flux of 45Ca. Optical density and/or scintillation counting was utilized to provide a relative measure of 45Ca accumulation within 20 different structures. The results indicated that in animals who exhibited no gross morphological damage, 45Ca accumulation following injury was exhibited primarily within the ipsilateral cerebral cortex, dorsal hippocampus and striatum. This accumulation continued for several days returning to control levels by the 4th day after injury. In animals who sustained morphological damage, the contusion site exhibited a marked accumulation of 45Ca which did not resolve spontaneously over the course of 4 days. We conclude from this work that Ca2+ flux is a major component of this experimental model of traumatic injury. Furthermore, that depending on the extent of cell damage, the accumulation of Ca2+ is regionally different. Finally, that even in an injury which by itself does not produce gross morphological tissue damage, accumulation of Ca2+ can continue for at least 48 h.

Increased vulnerability of the midly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury

Abstract Fasted Wistar rats were subjected to either a mild mechanical injury, 6 min of transient forebrain ischemia, or a mild mechanical injury followed 1 h later by 6 min of forebrain ischemia. EEG and evoked potentials were assessed intermittently and morphological analyses were performed after 7 das postinjury survival. In all groups complete qualitative recovery of electrical activity and general behavior was observed with 7-day survival. However, rats subjected to combined concussion and ischemia displayed EEG spike activity and a delayed return of EEG and evoked potentials during acute recovery not evident in other groups. No overt neuronal cells loss was seen in trauma alone and was minimal or absent in ischemia alone. However, extensive bilateral CA1 and subicular pyramidal cell loss was found in the septal and mid-dorsal hippocampi in the combined trauma and ischemia group. In contrast, no overt axonal injury was found in any group. We conclude that even mild mechanical injury can potentiate selective ischemic hippocampal neuronal necrosis in the absence of overt axonal injury. This potentiation also occurs in conjunction with more generalized electrophysiological disturbances such as EEG evidence of postischemic neuronal hyperactivity suggesting that mild concussion may also decrease the threshold for post-ischemic neuronal excitation. These results suggest the potential of this model for examining common or different injury mechanisms in mechanical and ischemic brain injury.

Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat : a cytochrome oxidase histochemistry study

Utilizing a lateral fluid percussion injury as a model of cerebral concussion, rats were studied histochemically measuring the degree of cytochrome oxidase activity present within different structures at different times following injury. After concussion, the cerebral cortex ipsilateral to the site of injury exhibited a diffuse decrease in its level of chromotome oxidase (CO) activity beginning at as soon as one day and lasting for up to 10 days after the insult. The ipsilateral dorsal hippocampus also exhibited an injury-induced decrease in CO activity, however, it was not as severe as in the cortex. These results indicate that oxidative metabolism is depressed primarily within the cerebral cortex and hippocampus for several days following a cerebral concussion. We propose that this period of metabolic depression may delineate a period of time during which the injured brain is unable to function normally and thus would be vulnerable to a second insult.

Early detection of vasospasm after acute subarachnoid hemorrhage using continuous EEG ICU monitoring.

The neurologic morbidity of delayed ischemic deficits from vasospasm following aneurysmal subarachnoid hemorrhage (SAH) continues to be the most debilitating complication from this devastating illness. Neurologic critical care is focused on recognition and treatment of these secondary insults but often the treatment is withheld until an irreversible deficit becomes manifest. Continuous EEG (cEEG) monitoring provides a unique potential to recognize early secondary insults and offers an opportunity for early intervention. We studied 32 SAH patients using cEEG and trending of the quantitative measure, relative alpha (RA), to determine if reductions in RA variability occurred with documented vasospasm. In 19/19 patients with angiographically documented vasospasm, we found that RA variability was decreased by a mean of two grades and improved with resolution of vasospasm. In 10/19 this reduction in RA variability preceded the diagnosis of vasospasm by a mean of 2.9 days (SD 1.73). The positive predictive and negative predictive values are 76% and 100%, respectively. Non-diagnostic clinical signs at the time of RA variability reduction and vasospasm were present in 12/19 patients. Thus decreased RA variability is able to provide early detection of neurologic complications such as vasospasm in patients before clear clinical symptoms and signs occur.

Relationships Between Choline Magnetic Resonance Spectroscopy, Apparent Diffusion Coefficient and Quantitative Histopathology in Human Glioma

This study sought to correlate quantitative presurgical proton magnetic resonance spectroscopic imaging (1H- MRSI) and diffusion imaging (DI) results with quantitative histopathological features of resected glioma tissue. The primary hypotheses were (1) glioma choline signal correlates with cell density, (2) glioma apparent diffusion coefficient (ADC) correlates inversely with cell density, (3) glioma choline signal correlates with cell proliferative index. Eighteen adult glioma patients were preoperatively imaged with 1H-MRSI and DI as part of clinically-indicated MRI evaluations. Cell density and proliferative index readings were made on surgical specimens obtained at surgery performed within 12 days of the radiologic scans. The resected tissue location was identified by comparing preoperative and postoperative MRI. The tumor to contralateral normalized choline signal ratio (nCho) and the ADC from resected tumor regions were measured from the preoperative imaging data. Counts of nuclei per high power field in 5–10 fields provided a quantitative measure of cell density. MIB-1 immunohistochemistry provided an index of the proportion of proliferating cells. There was a statistically significant inverse linear correlation between glioma ADC and cell density. There was also a statistically significant linear correlation between the glioma nCho and the cell density. The nCho measure did not significantly correlate with proliferative index. The results indicate that both ADC and spectroscopic choline measures are related to glioma cell density. Therefore they may prove useful for differentiating dense cellular neoplastic lesions from those that contain large proportions of acellular necrotic space.

Administration of Excitatory Amino Acid Antagonists via Microdialysis Attenuates the Increase in Glucose Utilization Seen following Concussive Brain Injury

Immediately following concussive brain injury, cells exhibit an increase of energy demand represented by the activation of glucose utilization. We have proposed that this trauma-induced hypermetabolism reflects the effort of cells to restore normal ionic balance disrupted by massive ionic fluxes through transmitter-gated ion channels. In the present study, changes in local CMRglc following fluid-percussion concussive injury were determined using [14C]2-deoxy-d-glucose autoradiography, and the effects of in situ administration (via microdialysis) of excitatory amino acid (EAA) antagonists [kynurenic acid (KYN), 2-amino-5-phosphonovaleric acid (APV; 100 μM, 1 mM, and 10 mM), and 6-cyano-7-nitroquinoxaline-2,3-dine (CNQX; 300 μM, 1 mM, and 10 mM] on glucose utilization were investigated. Animals that did not receive dialysis showed a remarkable increase (up to 181% of normal control) in cortical glucose utilization following injury. In contrast, this high demand for glucose was reduced in areas infiltrated with KYN, APV, and CNQX. These results indicate that EAA-activated ion channels are involved in the posttraumatic increase in glucose utilization, reflecting the energy demand of cells required to drive pumping mechanisms against an ionic perturbation seen immediately following the concussive injury. The effects of KYN, APV, and CNQX suggest that although all subtypes of the glutamate receptor appear to be involved in this phenomenon, N-methyl-d-aspartate-activated channels may play a major role.