Key points

Introduction

Although the original contemplation of concussion originated in Ancient Greece ( Fig. 1 ), public and scientific awareness are finally gaining traction. The scientific establishment now recognizes that the consequences of mild traumatic brain injury (mTBI) might not always be so mild. With ongoing development of basic and clinical science, it becomes possible to provide better prevention, assessment, and treatment for concussions, particularly in higher-risk groups like military personnel, athletes, and pediatric patients.

History of concussions.

Introduction

Although the original contemplation of concussion originated in Ancient Greece ( Fig. 1 ), public and scientific awareness are finally gaining traction. The scientific establishment now recognizes that the consequences of mild traumatic brain injury (mTBI) might not always be so mild. With ongoing development of basic and clinical science, it becomes possible to provide better prevention, assessment, and treatment for concussions, particularly in higher-risk groups like military personnel, athletes, and pediatric patients.

History of concussions.

Definitions

In order to proceed with a discussion of mTBI and concussion, one must establish working definitions, because mTBI and concussion are often used interchangeably. As seen in Table 1 , mTBI is historically based on Glasgow Coma Score (GCS), whereas concussion is a clinical syndrome that may overlap with mild, moderate, and severe TBI.

Epidemiology

Whether from increased awareness or an increased risk, the rate of reported TBI in the United States has been increasing. From 2001 to 2009, the number of annual TBI-related emergency department (ED) visits related to sports and recreation activities increased from 153,375 to 248,418, with the highest rates among young men aged 10 to 19. However, the ED is just the tip of the iceberg, because it is estimated that there are greater than 700,000 mTBIs per year in high school athletes alone, and more than 13% of these are in patients with recurrent concussions.

Sports-related concussions have been on the increase, likely due to both increased recognition and increased power and strength in our athletes. In 2007, Hootman and colleagues analyzed National Collegiate Athletic Association (NCAA) data from 1988 to 2004 regarding all injuries, including concussion. There was no significant change in overall rate of injury; however, concussions did increase significantly over this interval. Surprisingly, women’s soccer had the highest risk of concussion per 1000 athlete exposures with a rate of 0.41, which was not only higher than men’s soccer at 0.28, but on par with men’s football’s risk of 0.37. This finding brought the idea to the forefront that women not only are at risk of concussion but may even be at a higher risk within the same activity compared with their male counterparts. Many theories have been proposed to explain this discrepancy, including hormonal differences, weaker neck muscles, and higher rate of symptom reporting among female athletes. Multiple investigators have confirmed that among comparable sports, in which rules of play are similar, women have a higher rate of concussions.

Pathophysiology

Concussion is a complicated syndrome of microstructural injury and functional impairment. The initial event after impact is dominated by a massive flux of ions and excitatory neurotransmitters, resulting in a metabolic crisis. Rat models show that after fluid percussion injury (FPI), ionic flux of sodium, potassium, and calcium occurs, concomitant with a release of excitatory neurotransmitters, predominantly glutamate. Glutamate then generates further ionic imbalance transiently overwhelming the existing pumps on neurons and surrounding glial cells, whose purpose is to maintain a precise transmembrane ionic gradient. NMDA receptor activation then leads to further calcium influx.

The ionic pumps being activated are ATP driven, and to keep up with ATP depletion, there is immediate hyperglycolysis. As TBI leads to decreased cerebral perfusion, this produces a neurovascular decoupling or metabolic mismatch, with high glucose demand and impaired delivery. This metabolic mismatch is exacerbated by mitochondrial dysfunction caused by secondary effects of calcium influx. Moreover, magnesium is depleted, which persists for days following TBI. This depletion of magnesium is important because in addition to its roles in glycolysis, oxidative generation of ATP, and providing stability to cellular membrane potential, magnesium is an NMDA antagonist. Thus, without magnesium, persistently open NMDA receptors lead to further calcium influx, intensifying the cycle described above.

In adult rats, the acute hypermetabolic state consisting of ion shifts, excitatory neurotransmitter activity, and hyperglycosis is followed by a hypometabolic state lasting 7 to 10 days. During this subacute period, there is upregulation of cytokines and inflammatory genes along with microglial activation. In addition to this inflammation and the metabolic dysfunction, there is microstructural injury. Cytoskeletal damage can alter neurotransmission, and at the severe end, result in axonal disconnection triggered by dismantling of the axonal cytoskeleton via caspases and calpain.

Although most of this neurometabolic cascade has only been demonstrated in humans after severe TBI, there is a cerebrovascular effect demonstrable after both severe and mTBI. It has been proposed that concussion symptoms acutely and subacutely are related to this metabolic mismatch, which can be demonstrated in vivo with depressed cerebral blood flow (CBF), both acutely and persisting up to 30 days after injury. Meier and colleagues also demonstrated this depressed CBF at days 1 and 7 after injury with recovery in most subjects by 1 month. Those with persistent symptoms beyond 1 month were more likely to have persistently depressed CBF.

Clinical diagnosis of the acute concussion

In order to accurately diagnose concussion, one must learn its common signs and symptoms and determine which tools are accurate and validated for assisting in this clinical diagnosis.

Of 544 high school sports concussions, the most common acute symptoms were headache in 93.4%, dizziness/unsteadiness in 74.6%, difficulty concentrating in 56.6%, vision changes including sensitivity to light in 37.5%, nausea in 28.9%, drowsiness in 26.5%, and amnesia in 24.3%. Loss of consciousness was only present in 4.6% of their patients. In college athletes, the average number of symptoms and symptom resolution time do not differ by sex. However, a larger proportion of concussions in male athletes included amnesia and disorientation, whereas female athletes were more likely to report headache, excess drowsiness, and nausea/vomiting.

There is no sign, symptom, or clinical tool that is 100% sensitive or specific for diagnosing a concussion. It remains a largely clinical diagnosis, and for this reason, the most important rule is “When in doubt, sit them out” to protect against the increased risk for a repeat concussion.

The provider should also be aware of available clinical tools to be used on the sideline or in clinic to aid in triage and diagnosis ( Table 2 ). Tests are best used in combination. Most tests are intended for evaluation in a quieter location other than the sideline, although symptom checklists, Maddock’s questions, and King-Devick have been used on the sideline or in locker rooms and clinics.

Neuropsychological testing

A comprehensive examination of concussion patients would be incomplete without a thorough neuropsychological examination. The foundation of applying neuropsychological testing to concussed athletes began with Dr Jeffrey Barth in the 1980s. In 2008, Broglio and Puetz published a meta-analysis of neuropsychological testing and showed that along with postural tests and symptom reporting, neurocognitive functioning was significantly depressed acutely and generally remained affected to a lesser degree for at least 14 days.

Computerized cognitive testing (CCT) is becoming widespread in a sports setting, with no particular brand showing a clear superiority. The main advantages of CCT are administration to large groups of athletes simultaneously, automated randomization of tests (alternate forms), accurate measurements of response and reaction time, and straightforward scoring and data storage, whereas traditional pen and paper testing advantages are increased face-to-face time allowing customizable tests by the tester, the ability to judge fluency and verbal memory, the opportunity to take appropriate breaks, and extensive normative data for many demographic groups. As with any assessment tool, clinical context and judgment must be used when interpreting CCT, which is best done in consultation with a neuropsychologist. Studies have shown decreased CCT scores associated with orthopedic injury or even urge to void, rather than concussion.

Acute imaging

Most mTBIs have no CT imaging findings. The Canadian Head CT Rule was directed to solve this dilemma. Of 3121 adults with mTBI, 8% of patients had a clinically important brain injury (any acute finding on computed tomography [CT] requiring admission or neurologic follow-up); 1% required neurosurgical intervention, and 4% were found with clinically unimportant lesions (mostly small SAH or contusions not needing intervention, determined insignificant with no intervention needed and doing well at 14-day follow-up). The investigators found 5 high-risk features: failure to reach GCS of 15 within 2 hours of presentation, suspected open skull fracture, sign of basal skull fracture, vomiting greater than 2 episodes, or age greater than 65 years. In addition, there were 2 medium-risk factors: retrograde amnesia greater than 30 minutes and dangerous injury mechanism. Any single high-risk factor was 100% sensitive for the patient needing neurosurgical intervention, and medium-risk factors were 98.4% sensitive for a clinically important brain injury. In combination, the rule was found to be 92% sensitive for any injury on CT, including “clinically unimportant” lesions.

The New Orleans Criteria necessitates imaging for any patients with age greater than 60, vomiting, headache, intoxication, persistent anterograde amnesia, evidence of trauma above clavicle, or a seizure on presentation. When compared with the New Orleans Criteria, the Canadian CT rule was found to have greater specificity for clinically important head trauma leading to less imaging and lower costs.

The Pediatric Emergency Care Applied Research Network (PECARN) resolved to differentiate low-risk pediatric mTBIs from those with clinically significant injury. This algorithm rules imaging out for patients with normal mental status, no loss of consciousness, no vomiting, a nonsevere injury mechanism, no signs of basilar skull fracture, and no severe headache. The negative predictive value was 99.5% with zero missed neurosurgical interventions. Externally validated in 2014, the investigators found that “none of the children with a clinically important TBI were classified as very low risk by the PECARN TBI prediction rules.”

Acute MRI, while promising in several research studies comparing a cohort with clinical concussion with a control cohort, does not yet provide additional diagnostic or prognostic power in the evaluation of an individual patient. A study compared 75 mTBI patients to a control group with sprained ankles. CT and MRI were performed on all subjects, and MR sequences included not only fluid attenuated inversion recovery, T2 weighted imaging, susceptibility-weighted imaging, and diffusion-weighted imaging, but also diffusion tensor imaging (DTI). No significant differences were found between the 2 groups. Moreover, no differences were found in patients who turned out to have prolonged symptoms at 1 month, with the investigators suggesting there was no prognostic value of acute MRI with DTI.

Conversely, the TRACK-TBI study enrolled 135 patients with mTBI who presented to a level I trauma center. All patients enrolled received a CT scan and an “early MRI” (at 12 ± 3.9 days). Thirty-seven (27%) patients had abnormal head CT (31 intracranial, 6 isolated skull fractures). Of the 98 patients with negative head CTs, 28% had abnormal MRIs (23 hemorrhagic axonal injury, 3 contusions, 4 extra axial hematomas). Outside of socioeconomic and CT findings, the strongest predictor of poor outcome was MRI presence of one or more brain contusions or the presence of diffuse axonal injury.

Repeat injury

The first step in management is always to remove the patient from any scenario where they risk further impact/contact to decrease risk of a second concussion, which has been associated with greater symptoms and prolonged recovery. In a prospective cohort study with 2905 NCAA football players, 184 had concussions, 12 had a second concussion in the same season, and 11 of 12 repeat concussions occurred within 10 days of the first injury.

Moreover, following concussive brain injury in an animal model, there is a window of metabolic vulnerability. A single mTBI resulted in significantly decreased cerebral metabolic rate of glucose (CMRglc), which returned to those of sham injuries by day 3. When a second mTBI was introduced within 24 hours of the first, CMRglc was further depressed, and recovery was prolonged. However, if the 2 impacts were introduced 120 hours apart, the CMRglc values recovered as if they were single impacts. In addition, the 24-hour repeat TBI (rTBI) rats had memory deficits beyond day 3, unlike the single mTBI or 120-hour rTBI animals. This study demonstrated increased physiologic risk during the metabolic window of vulnerability, with normal recovery if injuries were further apart.

In humans, magnetic resonance spectroscopy (MRS) was used to examine effects of concussion on brain metabolism. Concussed athletes had significantly depressed metabolite ratios of N-acetylaspartate to creatinine or choline, lowest at day 3, and recovering to baseline by day 30. Athletes all reported symptom freedom between days 3 and 15 despite persistent metabolic changes on MRS. In a separate study, patients who had a second concussive injury before the 15-day mark did not recover NAA peaks until 45 days after injury. These data mirror that of Prins and colleagues in that the compounded injury produced a more severe metabolic depression than the first, and required longer to recover.

Second impact syndrome

Second Impact Syndrome (SIS) remains a controversial subject. It was first reported in 1984 by Saunders and Harbaugh, who described massive, fatal, cerebral edema after a second mTBI before recovery from a first mTBI. In this initial case report, a 19-year-old football player, who allegedly suffered a concussion from a fight, returned to play 4 days later and suffered additional mTBI. This second concussion resulted in massive cerebral edema and death.

McCrory argues that SIS is overreported, based on a recall bias of the first TBI, and that it shows a clear geographic bias, given no reports of this syndrome outside of the United States. If SIS were a risk in the general population, youth boxers should be at particular risk from this syndrome. Massive cerebral swelling after mTBI does occur rarely but may not always require repeated impacts. Multiple case reports have recounted disproportionate cerebral edema to a single mild head injury in patients with a personal or family history of hemiplegic migraine related to a familial or de novo mutation in one of the CACNA1A calcium channel subunit genes. Based on current understanding of concussion pathophysiology, other types of ion channel dysfunction are plausible contributing mechanisms.