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Delayed sudden death in an infant following an accidental fall: a case report with review of the literature.

Several controversies exist regarding ultimately lethal head injuries in small children. Death from short falls, timing of head injury, lucid intervals, presence of diffuse axonal injury (DAI), and subdural hematoma (SDH) as marker of DAI are the most recent controversial topics of debate in this evolving field of study. In this area of debate, we present a case of delayed death from a witnessed fall backwards off a bed in a 9-month-old black male child who struck his head on a concrete floor and was independently witnessed as "healthy" postfall for 72 hours until he was discovered dead in bed. Grandmother, babysitter, and mother all independently corroborated under police investigation that the child "acted and behaved normally" after the fall until death. Autopsy showed a linear nondisplaced parietal skull fracture, diastasis of adjacent occipital suture, subgaleal hemorrhage with evidence of aging, small posterior clotting SDH, marked cerebral edema, and a small tear of the midsuperior body of the corpus callosum consistent with focal axonal injury (FAI). No DAI was seen, and there were no retinal hemorrhages. All other causes of death were excluded upon thorough police and medical examiner investigation. Although this seems to be a rare phenomenon, a delayed, seemingly symptom-free interval can occur between a clinically apparent mild head injury and accidental death in a young child.

Accidental Falls↗

[Two cases of isolated ambient cistern hematoma after head injury].

This is a report of two cases of isolated ambient cistern hematoma after head injury. Isolated small hematomas in the ambient cistern after head injury are considered indirect evidence of brain stem injury. In such cases the initial neurological signs are often severe, but the ultimate prognosis is almost always good or excellent. Our patients showed hardly any neurological signs, and their head trauma was not very severe. Isolated ambient hematomas are the result of injury to small vessels or of mild contusions of the brain stem produced by the edge of the tentorium. In case 2, MRI revealed small, high signal intensity near the hematoma, and this sign was interpreted as evidence of mild brain stem injury. We think our patients had very mild brain injuries which were unaccompanied by diffuse axonal injury.

Brain Stem↗

Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage.

Experimental studies have shown that diffuse axonal injury is usually induced by positive or negative acceleration mechanisms. In order to determine the reliability of axonal injury (AI) as a marker of this type of traumatic insult, we compared cases of trauma-induced focal cortical hemorrhage without dural involvement (n = 67) with cases of trauma-induced subdural bleeding without cortical hemorrhage (n = 26). Both groups exhibited a wide range of post-traumatic survival times. The injuries in the first group were caused mainly by direct impact to the head, those in the second by acceleration/deceleration mechanisms. The investigations were based primarily on immunohistochemical demonstration of antibodies targeted to beta-amyloid precursor protein (beta-APP) in the pons as a marker of AI and the results were assessed semiquantitatively. No significant differences were found between the two groups. In both groups AI was detected in 80-100% of cases with survival times of more than 3 h and two thirds of all positive cases showed pronounced positivity. Additional comparison of cases of brain death due to mechanical trauma (n = 14) with cases of brain death due to non-mechanical trauma (n = 18) also disclosed no significant intergroup differences. Finally, investigations of the pons in cases of non-traumatic death due to cerebral hypoxia/ischemia (n = 51) demonstrated AI with the same frequency as in the other groups, although the expression tended to be less pronounced. Our results confirm that beta-APP expression in the pons is a reliable indicator of AI but does not discriminate between injuries caused by traumatic strain or shearing mechanisms and secondary damage due to cerebral hypoxia/ischemia or edema. In the large majority of cases with prolonged post-traumatic survival, it can therefore be assumed that AI in the pons is the consequence of primary and/or secondary events or a combination of both, as is common in non-missile head injury survived for more than 90-120 min. Therefore, positive differentiation of the type of biomechanical event based on this criterion alone is not possible.

Adolescent↗

Thyroid hormones in comatose patients with traumatic brain injury.

The objective was to study if thyroid hormones, cortisol, prolactin and brain injury marker levels were changed in traumatic brain injury (TBI) patients with changing levels of consciousness. We estimated the above named parameters in 32 patients (27 men and 5 women aged 11-55). Admission Glasgow Coma Score was < 8. Follow-up period--30 days. The length of coma was 3 to 25 days. There were significant decreases in TSH, TBG, FT3 and F_levels (p < 0.05, for each) and a T3 increase (as compared to very low preceding values) on day 1 before emergence from coma and considerable post-coma increase in TBG, FT3, TSH and F levels (p < 0.001 each) on days 1-3 in patients with diffuse axonal injury (DAI). In patients with contusions and epidural and subdural hematomas (CH) T3 and T4 levels continued to fall until 4-6 postcoma days. TSH values significantly increased up to average normal ranges (p < 0.05) on days "-" 2 and "-" 1 before emergence from coma and remained so. Significantly lower levels of TSH, F and PRL were found in patients with CH in the mostly remote period (on days "-" 12-"-" 8) before emergence from coma in comparison with DAI patients. In blood the following correlations of examined parameters were established: between NSE and T3 (r = -0.39), NSE and FT3 (r = -0.59), TNF alpha and TBG (r = -0.64), TNF alpha and T3 (r = -0.3) and S-100 and T3 (r = -0.3) (p < 0.05, for each). The results obtained confirmed a low T3 syndrome in comatose TBI patients. We demonstrated an objective and informative interdependence: the turning-point moment of the emergence from coma was accompanied by significant changes of examined hormone levels and brain injury marker levels. The results may serve as a base for recommending monitoring FT3 and T3 levels simultaneously with that of other injury markers and adequate T3 replacement therapy in the early posttraumatic period.

Adolescent↗

Traumatic brain axonal injury produces sustained decline in intracellular free magnesium concentration.

Decline in brain intracellular free magnesium concentration following experimental traumatic brain injury has been widely reported in a number of studies. However, to date, these studies have been confined to focal models of brain injury and temporally limited to the immediate 8-h period post-trauma. Recently, a new model of impact-acceleration brain injury has been developed which produces nonfocal diffuse axonal injury more typical of severe clinical trauma. The present study has used phosphorus magnetic resonance spectroscopy and the rotarod motor test to characterise magnesium homeostasis and neurologic outcome over a period of 8 days after induction of severe impact-acceleration injury in rats. Severe impact-acceleration induced injury resulted in a highly significant and sustained decline in intracellular free magnesium concentration that was apparent for 4 days post-trauma with recovery to preinjury levels by day six. There were no significant changes in pH or ATP concentration at any time point post-injury. All animals demonstrated a significant neurologic deficit over the assessment period. The extended period of magnesium decline after severe diffuse brain trauma suggests that repeated administration may be required for pharmacotherapies targeted at restoring magnesium homeostasis.

Animals↗

Electrocardiographic changes after head trauma.

We report the case of a patient who developed, a few days after a closed head injury, marked electrocardiographic changes mimicking an acute coronary event, in the absence of actual cardiac damage. The electrocardiographic changes were fully reversible, paralleling the neurologic status. Neuroimaging examinations excluded subarachnoid hemorrhage or space-occupying hematoma, but demonstrated diffuse axonal injury using susceptibility-weighted magnetic resonance techniques. This kind of traumatic brain injury thus may be responsible for a pseudo-acute myocardial ischemic syndrome.

Adult↗

Head injury in man and experimental animals: clinical aspects.

Clinical studies have demonstrated that, with regard to death, the two worst types of head injury are subdural haematoma (SDH) and diffuse axonal injury (DAI). These two have different mechanisms of causation; SDH occurs much more commonly in non-vehicular injuries, especially falls, while DAI is caused, almost exclusively by vehicular mechanisms. The production of these two types of injury in non-impact acceleration models helps to explain these causal differences, but also shows that both injuries share a common mechanical cause, differing only in degree. SDH is due to vascular injury that is caused by relatively short duration angular acceleration loading at high rates of acceleration. These are the circumstances that occur in falls where the head rapidly decelerates because of impact to firm, unyielding surfaces. DAI is also due to angular acceleration of the head, but occurs most readily when the head moves coronally and it only occurs when the acceleration duration is longer and the rate of acceleration lower than conditions that produce SDH. These conditions are met in vehicle occupants where impact to deformable or padded surfaces lengthens the deceleration and decreases its rate. In DAI the principal mechanical damage is to the brain itself (mainly to axons) while in SDH the primary damage occurs to surface blood vessels. Now that models of the two most important types of head injury have been created in the laboratory, it is hoped that a better understanding of their pathophysiology will result in new strategies to affect protection from their occurrence and in improved treatment when they do occur.

Accidents, Traffic↗

Neuronal changes in the arcuate and hypoglossal nuclei of brain stem induced by head injury.

In head injury, assessing the damage not only to the cerebrum and the cerebellum but also to the brain stem is very important. In this paper, we report neuronal changes of the arcuate nucleus (ARC) and the hypoglossal nucleus (HN) in the brain stem. We investigated these changes immunohistochemically with antibodies against microtubule-associated protein 2 (MAP2), muscarinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos), and the 72 kD heat-shock protein (HSP70). We measured the percentage of immunopositive neurons among the total neurons of the ARC and the HN. The investigation of neuronal changes in relation to the type of head injury showed different results. In cases of tonsillar herniation, immunoreactivity to MAP2 and mAChR in the ARC was significantly lower than in the HN (p < 0.01). Moreover, MAP2, HSP70 and c-Fos reactivities in the ARC were significantly lower than in other types of head injuries (p < 0.01). In the HN, diffuse axonal injury produced slightly higher immunoreactivity to mAChR and c-Fos (p < 0.1). Our observations indicate that immunohistochemical examination of brain stem nuclei can provide useful information for estimating damage to the brain stem.

Adolescent↗

Intraparenchymal and intraventricular hemorrhage without mass effect in traumatic coma.

A group of 57-head injured patients showing computerized tomographic (CT) findings compatible with "diffuse brain injury" or of the so called "diffuse axonal injury" is analyzed. Thirty-four patients showed intraparenchymal hemorrhage in the CT scan study, 8 intraventricular hemorrhage and 15 patients had both intraparenchymal and intraventricular hemorrhage. Forty percent (23/57) of those with these findings had associated intracranial focal lesions. The deep nuclei are the most common location of intraparenchymal hemorrhage. Signs of brain stem hemorrhage were seen in 9 patients. Forty-nine percent of patients in this series had a good outcome. Old age (greater than 60), abnormal motor response, abnormal eye signs, associated with focal lesions, and evidence of brain stem hemorrhage are reliable prognostic parameters for a grave outcome.

Adolescent↗

Prognostic role of proton magnetic resonance spectroscopy in acute traumatic brain injury.

Proton magnetic resonance spectroscopy (MRS) is being used to evaluate individuals after acute traumatic brain injury. These studies have shown that changes in certain brain metabolites are associated with poor neurologic outcomes. The majority of MRS studies have been obtained relatively late after injury, but there have been a few reports of use early after injury to assist with outcome prediction. Altered brain metabolites may be sensitive indicators of injury and thus provide additional prognostic information when spectroscopy is done early after injury. This technology may provide a noninvasive means to evaluate early excitotoxic injury, and show changes associated with both neuronal injury and membrane disruption secondary to diffuse axonal injury. This article will review the technology of MRS, discuss its role in patient assessment after traumatic brain injury, and present a summary of our published and ongoing research.

Adolescent↗

Fatal head injury in children.

A comprehensive neuropathological study was undertaken on 87 children aged between 2 and 15 years with fatal head injuries to identify those features which occurred at the time of head injury (fractured skull, contusions, intracranial haematoma and diffuse axonal injury) and those which were subsequently produced by complicating processes (hypoxic brain damage, raised intracranial pressure, infection and brain swelling). The types of brain brain damage identified were remarkably similar to those seen in adults. The only difference was the prevalence of diffuse brain swelling in children.

Adolescent↗

Cognitive rehabilitation interventions for executive function: moving from bench to bedside in patients with traumatic brain injury.

Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed.

Animals↗

Cerebral injuries and intracranial hemorrhages as a result of trauma.

Cerebral injuries refer to an actual injury to the brain matter. Injuries seen are concussion, contusion, or diffuse axonal injury. Bleeding into any of the meningeal spaces, brain, or ventricles is known as intracranial hemorrhage. Seldom do cerebral injuries appear as distinct entities but rather as a combination of injuries. The neurologic dysfunction is the sum total of the injury. The significance of the initial injury lies in the development of secondary events, such as edema, hemorrhage, and swelling. These events may lead to further deterioration and neurologic dysfunction. Treatment is directed at preservation of brain homeostasis and prevention of secondary injury. Controlled hyperventilation is the mainstay in the treatment of increased ICP. Other therapies include barbiturate coma and the use of corticosteroids to reduce ICP. Nursing interventions focus on methods to promote cerebral perfusion and support other body systems affected by immobility and altered level of consciousness. Planning nursing care and activities to the patient's ICP and CPP responses is indicated.

Brain Injuries↗

Real-time PCR quantitation of FE65 a beta-amyloid precursor protein-binding protein after traumatic brain injury in rats.

In cases of traumatic brain injury (TBI) in which the patient survived for only a short period of time and was without macroscopic changes at autopsy, it is difficult to diagnose TBI. To detect early diagnostic markers of diffuse axonal injury (DAI), real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in an experimental head trauma model of rat was chosen. The beta-amyloid precursor protein (beta-APP) is a well-known diagnostic marker of DAI which can be detected by immunolabeling as early as 1.5 h after injury. beta-APP has a binding protein, FE65, which is expressed in the brain of Alzheimer's disease patients along with beta-APP, but no involvement with brain injury has been reported. Neuron-specific enolase (NSE) is also a useful marker of DAI. We found that FE65 expression increased dramatically as early as 30 min after injury and decreased after peaking 1 h post-injury, although NSE showed no significant changes. These results suggest that real-time PCR of FE65 mRNA is useful for the diagnosis of DAI in forensic cases.

Amyloid beta-Protein Precursor↗

The impact of acute hyponatraemia on severe traumatic brain injury in rats.

The effect of experimental acute hyponatraemia on severe traumatic brain injury (TBI) was studied in a modified impact-acceleration model. The cortical contusional volume was quantified by image analysis on serial sections, injured axons were visualized and quantified by beta-Amyloid Precursor Protein (beta-APP) immunohistochemical staining. Regional brain water content was estimated by the wet-dry weight method. The experiment was conducted in Group I (injury only) and Group II (injury followed by acute hyponatraemia). Comparison between the two groups showed that acute hyponatraemia significantly increased contusional volume (3.24 +/- 0.70 mm3 vs. 1.80 +/- 0.65 mm3, P = 0.009) and the number of injured axons (128.7 +/- 44.3 vs. 41.7 +/- 50.1, P = 0.04) in the right thalamus & basal ganglia region. Water content of the brain stem region was also significantly increased by acute hyponatraemia (73.71 +/- 0.14% vs. 72.28 +/- 0.93%, P = 0.004). These results suggest that acute hyponatraemia potentiates secondary brain damage in severe TBI by augmentation of both focal contusion and diffuse axonal injury. The injured brain stem region is more susceptible to edema formation induced by experimental acute hyponatraemia.

Amyloid beta-Protein Precursor↗

Freeze-fracture and cytochemical evidence for structural and functional alteration in the axolemma and myelin sheath of adult guinea pig optic nerve fibers after stretch injury.

Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal axolemma. By 4 h, there was novel labeling for Ca-ATPase membrane pump activity at the same site. There was loss of IMPs from the nodal axolemma extending over several hours after injury. There was loss of both membrane pump Ca-ATPase and p-nitro-phenylphosphatase (p-NPPase) activity of the node. There was loss of ecto-Ca-ATPase activity but increased labeling for p-NPPase activity at sites of dissociation of compacted myelin. Quantitative freeze-fracture demonstrated statistically significant changes in membrane structure. We provide support for the hypothesis that structural and functional changes occur in the axolemma and myelin sheath at nondisruptive axonal injury.

4-Nitrophenylphosphatase↗

Functional reorganisation of memory after traumatic brain injury: a study with H(2)(15)0 positron emission tomography.

OBJECTIVE: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval. METHODS: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H(2)(15)0 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed. RESULTS: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI. CONCLUSIONS: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes.

Adult↗