ContextApproximately 300 000 sport-related concussions occur annually
in the United States, and the likelihood of serious sequelae may increase
with repeated head injury.ObjectiveTo estimate the incidence of concussion and time to recovery after concussion
in collegiate football players.Design, Setting, and ParticipantsProspective cohort study of 2905 football players from 25 US colleges
were tested at preseason baseline in 1999, 2000, and 2001 on a variety of
measures and followed up prospectively to ascertain concussion occurrence.
Players injured with a concussion were monitored until their concussion symptoms
resolved and were followed up for repeat concussions until completion of their
collegiate football career or until the end of the 2001 football season.Main Outcome MeasuresIncidence of concussion and repeat concusion; type and duration of symptoms
and course of recovery among players who were injured with a concussion during
the seasons.ResultsDuring follow-up of 4251 player-seasons, 184 players (6.3%) had a concussion,
and 12 (6.5%) of these players had a repeat concussion within the same season.
There was an association between reported number of previous concussions and
likelihood of incident concussion. Players reporting a history of 3 or more
previous concussions were 3.0 (95% confidence interval, 1.6-5.6) times more
likely to have an incident concussion than players with no concussion history.
Headache was the most commonly reported symptom at the time of injury (85.2%),
and mean overall symptom duration was 82 hours. Slowed recovery was associated
with a history of multiple previous concussions (30.0% of those with ≥3
previous concussions had symptoms lasting >1 week compared with 14.6% of those
with 1 previous concussion). Of the 12 incident within-season repeat concussions,
11 (91.7%) occurred within 10 days of the first injury, and 9 (75.0%) occurred
within 7 days of the first injury.ConclusionsOur study suggests that players with a history of previous concussions
are more likely to have future concussive injuries than those with no history;
1 in 15 players with a concussion may have additional concussions in the same
playing season; and previous concussions may be associated with slower recovery
of neurological function.

https://jamanetwork.com/journals/jama/articlepdf/197667/JOC30117.pdf

Cumulative Effects Associated With Recurrent Concussion in Collegiate Football Players: The NCAA Concussion Study

Departments of Exercise andSport Science (Drs Guskiewicz and Cantu), Ortho-paedics (Drs Guskiewicz and Marshall), and Epidemi-ology (Dr Marshall), and Injury Prevention ResearchCenter (Drs Guskiewicz and Marshall), University ofNorth Carolina at Chapel Hill; Neuroscience Center,Waukesha Memorial Hospital, Waukesha, Wis (DrMcCrea); Department of Neurology, Medical Collegeof Wisconsin, Milwaukee (Dr McCrea); NeurosurgeryService, Emerson Hospital, Concord, Mass(Dr Cantu); Chicago Neurological Institute (Drs Ran-dolph and Kelly) and Department of Neurology,Northwestern University Feinberg School of Medicine(Dr Kelly), Chicago, Ill; Department of Neurology,Loyola University Medical School, Maywood, Ill (DrRandolph); Department of Neurology, New YorkUniversity School of Medicine, New York (Dr Barr);and Department of Rehabilitation Sciences AthleticTraining Program, Sargent College of Health andRehabilitation Sciences, Boston University, Boston,Mass (Dr Onate).

Cumulative Effects Associated With Recurrent Concussion in Collegiate Football Players

OBJECTIVE: To review the underlying pathophysiologic processes of concussive brain injury and relate these neurometabolic changes to clinical sports-related issues such as injury to the developing brain, overuse injury, and repeated concussion DATA SOURCES: Over 100 articles from both basic science and clinical medical literature selected for relevance to concussive brain injury, postinjury pathophysiology, and recovery of function DATA SYNTHESIS: The primary elements of the pathophysiologic cascade following concussive brain injury include abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function These alterations can be correlated with periods of postconcussion vulnerability and with neurobehavioral abnormalities While the time course of these changes is well understood in experimental animal models, it is only beginning to be characterized following human concussion CONCLUSIONS/RECOMMENDATIONS: Following concussion, cerebral pathophysiology can be adversely affected for days in animals and weeks in humans Significant changes in cerebral glucose metabolism can exist even in head-injured patients with normal Glasgow Coma Scores, underscoring the need for in-depth clinical assessment in an effort to uncover neurocognitive correlates of altered cerebral physiology Improved guidelines for clinical management of concussion may be formulated as the functional significance and duration of these postinjury neurometabolic derangements are better delineated

The Neurometabolic Cascade of Concussion

Early reports of therapeutic hypothermia for severe traumatic brain injury can be traced back to the first half of the 20th century. It is only within the last two decades that clinical studies have demonstrated that therapeutic moderate hypothermia for brief durations can improve patient outcomes following brain injury. The historical background, recent clinical experience, and mechanisms of action of moderate hypothermia are reviewed.

https://www.nejm.org/doi/pdf/10.1056/NEJM199702203360803

Treatment of Traumatic Brain Injury with Moderate Hypothermia

This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

A new model of diffuse brain injury in rats Part I: Pathophysiology and biomechanics

T HE pathogenesis of cerebral concussion has long been debated. The present experiments were undertaken to clarify the nature of acute cerebral disorders resulting from head injury. Concussion was defined by Denny-Brown as a "transitory and reversible nervous reaction with immediate onset following physical stress of sufficient violence and brevity, and characterized by progressive recovery thereafter. ''~ There are two main theories concerning the pathogenesis of concussion: the excitation theory of Walker, e t al., 4a and the paralytic theory of Denny-Brown and Russell2 These two theories, which postulate opposite mechanisms, will be reviewed. Walker and his associates 43 observed the appearance of fast activity in the electroencephalogram (EEG) with little change in amplitude immediately after a compressive impact applied to the exposed dura and brain in experimental animals. This was followed by '"extinction." The EEG changes were frequently accompanied by tonic extension movements of the extremities. They suggested that this type of concussion resulted from excitation of the central nervous system. An opposite view was proposed by Denny-Brown and Russell. Based on experimental observations of concussion produced by a pendulum striking the freely moving head (acceleration concussion), they concluded that this type of concussion was due to temporary paralysis of nervous function. In man, concussion is characterized by transient loss of neural function, accompa-

Cerebral Hemodynamics and Metabolism Following Experimental Head Injury

Ischemic anoxia and cerebral serotonin levels

✓ Severe cerebral ischemia was produced in 25 baboons by clamping the carotid and vertebral arteries bilaterally for 10 minutes. Cerebral hemodynamics and metabolism were monitored throughout. Cerebral anoxia was less severe in animals in which a marked pressor response occurred due to ischemia of the vasomotor center, and a reversible type of brain swelling was usual. In those with more severe ischemic anoxia, progressive cerebral edema was a pathological entity. Evidence is presented that cerebral edema was caused by loss of autoregulation of cerebral blood flow (CBF) concomitant with hyperemia and an increase of water and chloride content of brain tissue. Cerebral edema began when CBF was reduced during occlusion and progressed for several hours after termination of occlusion. Evidence is adduced that uncoupling of oxidative phosphorylation may be an important concomitant of cerebral edema.

Tetsuaki Teraura

Papers

Cerebral Hemodynamics and Metabolism Following Experimental Head Injury

Ischemic anoxia and cerebral serotonin levels

Hemodynamic and metabolic concomitants of brain swelling and cerebral edema due to experimental cerebral infarction

Brain swelling due to experimental cerebral infarction. Changes in vasomotor capacitance and effects of intravenous glycerol.

The effects of a new drug (Hexobendine) on cerebral hemodynamics and oxygen consumption