Acute Post-traumatic Period Research Articles

Basal ganglia hematomas in severely head injured patients: clinicoradiological analysis of 37 cases.

The authors analyzed the clinicoradiological presentation of traumatic basal ganglia hematomas (TBGHs) in severely head injured (SHI) patients. The records of 37 patients (28 male and nine female patients with a mean age of 28 years) in whom computerized tomography (CT) scans revealed TBGHs 2 ml or more in volume were retrospectively reviewed. These cases represented 2.4% of the total series of 1526 SHI patients admitted to the authors' institution between 1979 and 1998. Thirty-five patients (94%) were involved in traffic accidents and only two exhibited a period of lucidity. Associated extracranial injuries were seen in 21 patients (57%) and coagulation disorders in 32 (86%). Skull fracture was present in 10 (43%) of the 23 patients in whom skull x-ray films were obtained. Computerized tomography findings indicated diffuse axonal injury in 27 patients (73%), intraventricular hemorrhage in 22 patients (59%), and subarachnoid hemorrhage in 16 patients (43%). In all but two patients, the TBGHs were visible on the initial CT scan, and in 28 cases (76%) these hematomas were contralateral to the side of impact. Hematoma enlargement over the first few posttraumatic days was noted in 65% of the patients in whom control CT scans had been obtained (22 of 34 patients). Four patients (11%) underwent surgery to remove their TBGHs. Final outcomes were poor: 22 patients (59%) died, two (5%) became vegetative, seven (19%) experienced severe disabilities, and only six patients (16%) made a favorable recovery. Traumatic basal ganglia hematomas are dynamic lesions that tend to enlarge during the acute posttraumatic period. The overall prognosis in this series was poor. Patients in whom the volume of the hematoma was larger than 25 ml and those in whom hematoma volume enlargement or raised intracranial pressure occurred had the worst outcomes, perhaps indicating the need for a more aggressive surgical treatment.

The Novel Compound LOE 908 Attenuates Acute Neuromotor Dysfunction but Not Cognitive Impairment or Cortical Tissue Loss Following Traumatic Brain Injury in Rats

Experimental traumatic brain injury (TBI) initiates massive disturbances in Ca2+ concentrations in the brain that may contribute to neuronal damage. Intracellular Ca2+ may be elevated via influx through voltage-operated cation channels, ligand-gated ionotropic channels, and store-operated cation channels (SOCs). In the present study, we evaluated the neurobehavioral and histological effects of acute posttraumatic administration of (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di[2-(2 ,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a broad spectrum inhibitor of voltage-operated cation channels and SOCs. Male Sprague-Dawley rats (n = 53) were trained in the Morris water maze, anesthetized (60 mg/kg pentobarbital, i.p.), and subjected to lateral fluid percussion brain injury (2.5-2.7 atm; n = 38) or surgery without injury (n = 15). At 15 min postinjury, animals were randomized to receive intravenous administration of either a high dose of LOE 908 (4 mg/kg bolus followed by 160 mg/kg over 24 h; n = 13), a low dose of LOE 908 (2 mg/kg bolus followed by 80 mg/kg over 24 h; n = 12), or vehicle (n = 13). Uninjured controls received the high dose of LOE 908 (n = 8) or vehicle (n = 7). Treatment with either dose of LOE 908 significantly improved neuromotor function at 48 h postinjury when compared to vehicle treatment. Although a significant deficit in visuospatial memory was observed in brain-injured animals at this timepoint when compared to uninjured animals, neither dose of LOE 908 attenuated injury-induced cognitive dysfunction. Histological evaluation revealed that neither dose of LOE 908 affected cortical lesion size at 48 h postinjury. These data suggest that broad spectrum cation channel blockers may be beneficial in the treatment of neurological motor dysfunction when administered in the acute posttraumatic period.

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury.

The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(-/-)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(-/-), n = 10; wt, n = 10] or served as uninjured controls [TNF(-/-), n = 10; wt, n = 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(-/-) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(-/-) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(-/-), n = 20; wt, n = 20] or served as uninjured controls [TNF(-/-), n = 15; wt, n = 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), brain-injured TNF(-/-) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (P < 0. 02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(-/-) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(-/-) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.

Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat.

The activation of poly(ADP-ribose) polymerase, a DNA base excision repair enzyme, is indicative of DNA damage. This enzyme also undergoes site-specific proteolysis during apoptosis. Because both DNA fragmentation and apoptosis are known to occur following experimental brain injury, we investigated the effect of lateral fluid percussion brain injury on poly(ADP-ribose) polymerase activity and cleavage. Male Sprague-Dawley rats (n = 52) were anesthetized, subjected to fluid percussion brain injury of moderate severity (2.5-2.8 atm), and killed at 30 min, 2 h, 6 h, 24 h, 3 days, or 7 days postinjury. Genomic DNA from injured cortex at 24 h, but not at 30 min, was both fragmented and able to stimulate exogenous poly(ADP-ribose) polymerase. Endogenous poly(ADP-ribose) polymerase activity, however, was enhanced in the injured cortex at 30 min but subsequently returned to baseline levels. Slight fragmentation of poly(ADP-ribose) polymerase was detected in the injured cortex in the first 3 days following injury, but significant cleavage was detected at 7 days postinjury. Taken together, these data suggest that poly(ADP-ribose) polymerase-mediated DNA repair is initiated in the acute posttraumatic period but that subsequent poly(ADP-ribose) polymerase activation does not occur, possibly owing to delayed apoptosis-associated proteolysis, which may impair the repair of damaged DNA.

Terminally differentiated human neurons survive and integrate following transplantation into the traumatically injured rat brain.

The present study evaluated the survival and integration of human postmitotic neurons (hNT) following transplantation into the traumatically injured rodent brain. Anesthetized male Sprague-Dawley rats (n = 47) were subjected to lateral fluid percussion brain injury of moderate severity (2.4-2.6 atm). Sham animals (n = 28) were surgically prepared, but did not receive brain injury. At 24 h following injury or sham surgery, the rats were re-anesthetized and approximately 100,000 hNT cells (freshly cultured or previously frozen) or vehicle were stereotactically injected into the ipsilateral cortex. Animals were examined for neuromotor function at 48 h, 7 days, and 14 days posttransplantation using a standard battery of motor tests. Animals were sacrificed at 2 weeks postinjury and viability of hNT grafts was assessed by Nissl staining and MOC-1 immunohistochemistry, which recognizes human neural cell adhesion molecules (NCAM) expressed on hNT cells. Transplanted hNT grafts remained viable in 83% of brain-injured animals at 2 weeks following transplantation of either fresh or frozen hNT cells. Glial fibrillary acidic protein (GFAP) immunohistochemistry revealed a marked increase in the number of reactive astrocytes following brain injury in both vehicle and hNT implanted animals. These reactive astrocytes appeared not to impede grafted cells from sending projections into host tissue. Despite the survival of transplanted cells in the traumatically injured brain, hNT cells had no significant effect on posttraumatic neurologic motor function during the acute posttraumatic period. Since hNT cells are transfectable, prolonged survival of these transplanted cells in the posttraumatic milieu suggests that grafted hNT cells may be a suitable means for delivery of therapeutic, exogenous proteins into the CNS for treatment of traumatic brain injury.

Sequential computerized tomography changes and related final outcome in severe head injury patients.

The authors analysed the serial computerized tomography (CT) findings in a large series of severely head injured patients in order to assess the variability in gross intracranial pathology through the acute posttraumatic period and determine the most common patterns of CT change. A second aim was to compare the prognostic significance of the different CT diagnostic categories used in the study (Traumatic Coma Data Bank CT pathological classification) when gleaned either from the initial (postadmission) or the control CT scans, and determine the extent to which having a second CT scan provides more prognostic information than only one scan. 92 patients (13.3% of the total population) died soon after injury. Of the 587 who survived long enough to have at least one control CT scan 23.6% developed new diffuse brain swelling, and 20.9% new focal mass lesions most of which had to be evacuated. The relative risk for requiring a delayed operation as related to the diagnostic category established by using the initial CT scans was by decreasing order: diffuse injury IV (30.7%), diffuse injury III (30.5%), non evacuated mass (20%), evacuated mass (20.2%), diffuse injury II (12.1%), and diffuse injury I (8.6%). Overall, 51.2% of the patients developed significant CT changes (for worse or better) occurring either spontaneously or following surgery, and their final outcomes were more closely related to the control than to the initial CT diagnoses. In fact, the final outcome was more accurately predicted by using the control CT scans (81.2% of the cases) than by using the initial CT scans (71.5% of the cases only). Since the majority of relevant CT changes developed within 48 hours after injury a pathological categorization made by using an early control CT scan seems to be most useful for prognostic purposes. Prognosis associated with the CT pathological categories used in the study was similar independently of the moment of the acute posttraumatic period at which diagnoses were made.

Ruptured hemidiaphragm: Unusual late presentation

Diaphragmatic injuries may be undiagnosed in the acute posttraumatic period and may remain unrecognized despite a variety of chronic symptoms, until eventual emergency department presentation with an intestinal obstruction. We present a case of a female who experienced chronic chest pain during coitus that eventuated in an acute admission with an intrathoracic mesentero-axial volvulus of the stomach, 8 months after a motor vehicle accident. The literature regarding delayed presentation of a ruptured hemidiaphragm is reviewed.

The influence of the mechanism of cervical spine injury on the degree of the spinal cord lesion

In the years 1965 to 1988, 1687 patients with cervical spine injury were treated in the acute post-traumatic period. In the analysed material commonest cause for the injury was by a flexion mechanism (48%), less frequently compressive (26%), and by a hyperextension mechanism (26%). Radiological changes were related, to some extent, with the patients age. Compression and flexion fractures occur most often in young people, dislocations in older ones, and injuries caused by hyperextension in, most often, elderly age (average age 53 years). The mechanism of the injury influences the degree of the nervous system injury. Serious consequences usually occur with crushing of a vertebral body. Serious neurological disturbance may occur with a flexion mechanism; and rarely such serious neurological disturbances accompany injuries caused by a compression mechanism. There was a complete lesion of the spinal cord in only 11% of patients. Neurological improvement was achieved in 51% of patients; 31% had no improvement, and 18% of patients died during treatment. The best results were observed in the group of typical compression fractures (neurological improvement--81%), whereas the poorest was found in patients with a crush type of fracture (improvement in 17%, mortality 18%), and in those with dislocation (improvement in 25%, mortality rate--23%).