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Histopathologic consequences of moderate concussion in an animal model: correlations with duration of unconsciousness.

Although duration of unconsciousness is commonly used as a prognostic index following traumatic brain injury (TBI), few controlled studies have statistically evaluated the relationship between unconsciousness and histologic pathology, particularly after moderate head injury. Using a pendulum-striker concussive device, a reproducible model of TBI in rats was developed. This model is uncomplicated by skull fractures, contusions, or experimenter-induced craniotomies. In the present study, the severity of the histopathology observed in this model of moderate closed-head injury at 48 h posttrauma is linearly related to the duration of unconsciousness (p < 0.0001). The pathology, assessed with a silver stain for neurodegeneration, is particularly striking if unconsciousness persists for 4 minutes or more. These data suggest that the initial period of unconsciousness may be a useful predictor of clinical brain histopathology associated with moderate closed-head injury, predicting either the degree of pathology and/or the rate it progresses if left untreated.

Animals↗

Serum biochemical markers for post-concussion syndrome in patients with mild traumatic brain injury.

Mild traumatic brain injury (MTBI) is a major public health problem in the United States. A significant subset of MTBI patients develop persistent and distressing neurological, cognitive, and behavioral symptoms, known as the post-concussion syndrome (PCS). To date, multiple studies have assessed the relationship between brain-related proteins found in the serum at the time of injury, and the development of PCS. We conducted a systematic review of prospective cohort studies that assessed the ability of serum biochemical markers to predict PCS after MTBI. A total of 11 studies assessing three different potential biochemical markers of PCS--S100 proteins, neuron-specific enolase (NSE), and cleaved Tau protein (CTP)--met selection criteria. Of these markers, S100 appeared to be the best researched. We conclude that no biomarker has consistently demonstrated the ability to predict PCS after MTBI. A combination of clinical factors in conjunction with biochemical markers may be necessary to develop a comprehensive decision rule that more accurately predicts PCS after MTBI.

Animals↗

Death due to concussion and alcohol.

We encountered 5 deaths following blunt trauma to the face and head in which the injuries were predominantly soft tissue in nature with absence of skull fractures, intracranial bleeding, or detectable injury to the brain. All individuals were intoxicated, with blood ethanol levels ranging from 0.22 to 0.33 g/dl. We feel that in these deaths, ethanol augmentation of the effects of concussive brain injury, with resultant posttraumatic apnea, was the mechanism of death.

Adult↗

A flask full of jelly: the first in vitro model of concussive head injury--1830.

IN 1830, THE French Military Surgeon Jean-Pierre Gama reported an experiment planned to unravel the mechanical events caused by head injury. His model was a round glass flask with a long neck filled with a gelatinous substance that resembled the consistency of the brain. Thumping the walls of the flask caused the movement of thin wires embedded in the "brain-like" material, thought to represent the spread of forces within the brain. Gama thought that he could thus observe oscillatory and vibratory movements of the wires representing the effects of concussion without visible structural brain lesions. Although it was crudely constructed, entirely subjective as to evaluation of results, and lacking the essential instrumentation that only modern technology can provide, this hypothesis-driven pioneer experiment should be regarded as the first to use the novel approach of physical modeling of the brain. Even today, this approach has not been fully exploited.

Brain Concussion↗

New treatments for concussion: the next millennium beckons.

As increased understanding of the pathophysiology of mild traumatic brain injury and concussion develops, so the scientific rationale for interventional pharmacological therapy becomes paramount. A number of agents have been postulated or have been the subject of anecdotal noncontrolled trials. This paper reviews the published evidence in this regard. To date no effective pharmacological therapy exists that satisfies Class I evidence-based medicine criteria.

Athletic Injuries↗

Cyclooxygenase products of arachidonic acid metabolism in cat cerebral cortex after experimental concussive brain injury.

Previous studies have suggested that following experimental fluid percussion brain injury, increased prostaglandin (PG) synthesis, with its concomitant production of oxygen free radicals, causes functional and morphological abnormalities of the cerebral arterioles. The purpose of this study was to chemically determine if PGs are altered following this injury. To facilitate interpretation of neurochemical measurements the cats were ventilated, blood pressure was measured, and a cranial window, for microscopic observation of pial arteriolar diameter was inserted. PG levels were determined in quick-frozen cortical tissue removed from control and 3 groups of injured cats at 1.5, 8,0, and 60 min after injury. Analysis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was performed by HPLC and GC/MS. The control levels of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were 216 +/- 44, 210 +/- 48, and 48 +/- 12 ng/g wet weight, respectively. Following injury, produced by a 22 ms increase in intracranial pressure, the pial arterioles dilated irreversibly and a transient hypertensive response occurred, thereby producing hyperemia. During the maximum hyperemic response, the total PGs were 75% of control. At 8 min after injury, when blood pressure returned to control level, the PGs were 158% of control and PGs fell to 111% of control at 60 min. These experiments supported our previous studies implicating increased PG synthesis in te genesis of the physiologic and morphologic sequelae of experimental concussive brain injury.

Animals↗

Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury.

Traumatic brain injury is a well-recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven-month-old mice were randomized to receive either regular chow or chow-supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post-injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E-treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Abeta peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Alphabeta accumulation and behavioral impairments in the Tg2576 mice.

Amyloid↗

The physician survey on the post-concussion and whiplash syndromes.

BACKGROUND: The post-concussion syndrome (PCS) and whiplash syndrome (WS) have been controversial topics among physicians for many decades. There is little information available on the opinions and practices of physicians. METHODS: In June of 1992, we performed a national survey by mail of the four physician groups most commonly treating these problems. The number of respondents and response rates were as follows: family physicians, 118, 16%; neurologists, 100, 21%; neurosurgeons, 97, 23%; orthopedists, 82, 13%. The survey instrument contained items on demographics, definitions, causation, prognosis, medico-legal aspects, testing, and treatment. RESULTS: Only a minority of respondents believe that PCS and WS are clearly defined syndromes. A substantial minority report that psychogenic and litigation factors are most responsible for the conditions. Most of the physicians believe that PCS and WS have a 3-6 month recovery time. A significant minority concur that symptoms of the two syndromes resolve when litigation is settled. Most of the physicians order tests to rule out pathology although a minority order tests to reassure patients or because of litigation concerns. Only a minority of respondents believe that effective treatments are available. Not surprisingly, a multitude of conventional and unconventional treatments are sometimes recommended. CONCLUSIONS: Many aspects of PCS and WS are controversial among treating physicians. This controversy can have a profound impact on the quality and cost of patient care. Ongoing research is required to discover more effective treatments for mild brain injury and chronic pain.

Brain Concussion↗

Post-concussion syndrome. Brain damage, constitutional characteristics and environmental reactions.

A 9-year-old boy was referred for child-psychiatric examination because of failure in school, restlessness, impulsiveness and concentration difficulties. The symptomatology was ascribed to a previous severe head injury and defined as a post-concussion syndrome. During the examination it was found that he had an identical twin brother without a history of brain-damage. A comparison of the patient and his twin brother with the same examination methods at the age of 9 and 18 gave similar results. These indicate that factors other than brain damage also could explain a clinical picture with school failure, restlessness, impulsiveness and concentration difficulties in a schoolboy. The question arises whether a clinical picture of this kind are the symptoms of stress among vulnerable boys in reaction to excessive demands from their psychosocial environment.

Adolescent↗

Cerebral concussion in the monkey: an experimental model.

A statistically significant experimental model has been developed for reproducing head injury by impact in the monkey. Results with 80 monkeys subjected to occipital impact under specified conditions ( duration of phenomena, 1 to 10 milliseconds) enable the construction of curves relating the production of experimental cerebral concussion in 10, 50, and 90 percent of the monkeys to the average impulse of the blow in pounds-seconds, as well as to the average linear acceleration of the head. These curves are proposed as a baseline from which blows to various parts of the head, as well as nonimpacting impulsive loads, can be studied under various conditions of protection and according to varioucs time regimes.

Acceleration↗

Sequelae of minor head injury: the natural history of post-concussive symptoms and their relationship to loss of consciousness and follow-up.

The character and natural history of post-concussive symptoms were studied in two subject groups: patients admitted to hospital for observation following brief loss of consciousness (LOC) as a result of head injury and patients who attended the accident unit after head injury but not were not admitted. Follow-up data were obtained from the hospitalized group at standardized out-patient interview and from the non-hospitalized group by postal questionnaire. Two- and 12-week data are presented on 24 hospitalized and 58 non-hospitalized patients. The type and frequency of symptoms was similar in the two groups and rank ordering was significantly correlated. However, the reduction in symptom scores (number of symptoms) 12 weeks post-injury was significantly greater in the hospitalized than the non-hospitalized group. The possible significance of this is discussed.

Adolescent↗

A study of the effect of legal settlement on post-concussion symptoms.

Forty-four consecutive patients with concussion for whom a medico-legal report had been written were followed up for 3-4 years after their accidents. Three cases were still pending at the end of the study. Fifty-seven per cent complained of symptoms when the medico-legal reports were written (mean interval from accident 12.9 months), 39% had symptoms at the time of settlement (mean interval 22.1 months) and 34% had symptoms one year later. When these results were compared with a general series from the same department some years earlier, it was found that the symptoms at the time of writing the reports were not significantly different from symptoms at 6 weeks in the earlier series, but the symptoms one year after settlement were almost two-and-a-half times greater than the symptoms at 12 months in the general series. No evidence could be found to suggest any organic basis for the higher symptom rate in the litigation series. It is suggested that the litigation process itself is a factor in the persistence of symptoms and this effect continues after legal settlement has been reached. Early settlement of the cases might significantly reduce morbidity.

Accidents↗

Caffeine impairs short-term neurological outcome after concussive head injury in rats.

OBJECTIVE: Adenosine is an endogenous neuroprotective agent that is released during ischemia, hypoxia, epilepsy, and ischemic brain injury. Caffeine is a receptor antagonist for adenosine that might interfere with the neuroprotective effect of adenosine in ischemic-hypoxic conditions. An investigation was undertaken to study the effect of caffeine on neurological function, edema formation, and blood-brain barrier permeability after experimental head injury in rats. METHODS: Adult female Wistar rats classified into different groups received caffeine intraperitoneally at doses of 0, 50, 100, and 150 mg/kg body weight. Thirty minutes after the caffeine treatment, the animals were subjected to concussive head injury (CHI) administered by a controlled cortical impact device. Neurological severity score was recorded in each rat at 2 hours after CHI. Specific gravity, water content (as an indicator of edema), and blood-brain barrier impairment were analyzed in the cortical tissue surrounding the injury site. The levels of myeloperoxidase and malondialdehyde in the cortical region were measured as indicators of neutrophil infiltration and lipid peroxidation, respectively. RESULTS: A significant increase in righting latency and neurological deficiency after CHI was observed in caffeine-treated rats as compared with untreated animals. Although no deaths occurred in the rats exposed to CHI after pretreatment with saline, pretreatment with caffeine caused significant mortality of animals after trauma in a dose-dependent manner. Caffeine also exacerbated neutrophil infiltration, edema, and disruption of blood-brain barrier in the traumatic cortex. Light microscopy of brain revealed more severe hemorrhage and neuronal degeneration in the injured hemisphere of caffeine-treated rats as compared with rats in the injury-alone group. A significant increase in malondialdehyde in the brain of injured rats treated with caffeine before CHI clearly indicated the role of oxidative stress. CONCLUSION: Caffeine adversely affects outcome after CHI, possibly as a result of blockade of adenosine receptors. The findings also point toward the involvement of free radical-mediated neuronal damage in caffeine-induced exacerbation of neurotrauma.

Animals↗

Cerebellar concussion--three case reports.

Three patients with transient cerebellar dysfunction following head injury are described. Acute cerebellar signs, such as ataxia, nystagmus, and dysarthria, occurred just after trauma and resolved gradually, disappearing in every patient. Cerebrospinal fluid and computed tomography examinations were normal but magnetic resonance imaging and single photon emission computed tomography revealed cerebellar lesions. These findings distinguish cerebellar concussion from cerebellar contusion and suggest that the synergistic effect of trauma and ischemia may be the pathophysiological basis of this unusual syndrome.

Accidental Falls↗

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: I. Biomechanical properties.

This study presents a new device for producing experimental, concussive head injury together with a detailed description of biomechanical features of fluid percussion brain injury in the cat. Anaesthetized cats were subjected to multiple (N = 3) or single injuries (N = 87). The variables studied in repeated injury experiments included the volume of fluid injected intracranially, rate of fluid flow, and the associated pressure transients recorded extracranially in the injury device and intracranially at supratentorial and infratentorial sites. Peak fluid flow increased with increasing volumes of fluid loaded intracranially. Extracranial pressure peaks and durations increased when volume loading was increased. Extracranial and intracranial pressure transients were similar at all recording sites. The form of pressure transients recorded in single injury experiments was similar to that recorded in multiple injury experiments. In single injury experiments, the extracranial pressure peaks and durations also increased with increased intracranial fluid volume loading. The slopes describing the relationships between intracranial volume loading and extracranial pressure transients were significantly different in single and multiple injury experiments. Details of the design and use of the head injury device are also discussed.

Animals↗

A new model of concussive brain injury in the cat produced by extradural fluid volume loading: II. Physiological and neuropathological observations.

This study examined physiological and histopathological changes in the cat produced by a new experimental fluid injury device. Spontaneously breathing (N = 14) and artificially ventilated (N = 45) cats were subjected to systemically varied magnitudes of fluid percussion brain injury. Within certain injury ranges, increasing magnitudes of fluid percussion injury produced increasing durations of apnea, as well as greater transient increases in mean arterial blood pressure, intracranial pressure and cerebral perfusion pressure. Acute increases in intracranial pressure may have been related to cerebral vasodilatation produced by the systemic hypertension following brain injury. Injuries associated with pressure transients greater than 10 atm ms produced concussive responses, including irreversible apnea in spontaneously breathing cats and temporary pupillary dilatation, increases in heart rate and mean arterial blood pressure in artificially ventilated cats. Injuries greater than 39 atm ms frequently produced histopathological and physiological indices of significant irreversible brain damage, including fixed and dilated pupils, systemic cardiovascular hypotension and deteriorating blood gases. Injury magnitudes less than 20 atm ms did not produce macroscopic evidence of histopathology, intermediate injury ranges produced increasing evidence of subarachnoid and petechial hemorrhage while injury levels greater than 40 atm ms frequently produced significant histopathology including massive hematomas. Injury greater than 10 atm ms resulted in opening of the blood-brain barrier, as assessed by extravasation of horseradish peroxidase. Injury greater than 19 atm ms produced suppression of EEG amplitudes which did not recover for up to 40 minutes after injury. These data provide detailed information on the physiological and histopathological consequences of fluid percussion injury in the cat and indicate that this modified fluid percussion apparatus can produce graded levels of brain injury similar to those previously reported for fluid percussion injury.

Animals↗

A survey of treatments for post-concussion syndrome.

A survey of the members of the National Academy of Neuropsychology and the International Neuropsychological Society was conducted on current treatment approaches for post-concussion syndrome. The interventions that were found useful most frequently included education about the effects of head injury, reassurance that the symptoms are part of the normal recovery process, and support in coping with reactions to the symptoms. Graded resumption of activity, antidepressant medication, and cognitive restructuring were also regarded as useful. The relationships between type of treatment, factors contributing to the syndrome, ratings of treatment effectiveness, and duration of treatment were discussed.

Adaptation, Psychological↗