Jon P. Williams, DO, PhD

Traumatic brain injury (TBI) is ubiquitous and is increasingly being recognized in both the media and diverse clinical practices because of significant prevalence and morbidity. It is estimated that approximately 5.3 million people in the US have TBI-related disability.

 In the US, up to 1.7 million people sustain a TBI every year, of which 1.4 million are treated in emergency departments, yielding 275,000 hospitalizations and 52,000 fatalities, with an overall cost of $76.5 billion.

 Males are at increased risk for sustaining TBIs.

More than 70% of the cases of TBI are mild (mTBI), which makes this subgroup of particular clinical interest. The cost of managing mTBI in the first year ($4600) is much less than that for managing moderate or severe TBI ($36,000), but because the vast majority of brain injury cases are mild, they are the main contributor to cumulative costs.

Many clinicians are uncomfortable with the diagnosis and management of mTBI-probably because of the lack of validated and standardized treatments as well as a poor understanding of the natural history of TBI. Considerable overlap exists between TBI and disorders in cognition, behavior, and personality, which can provide even greater clinical challenges for health care professionals.

This review on mTBI focuses on the clinical and pathophysiologic features of this disease process and on current treatment guidelines and prognosis.

Brain trauma categorization takes into consideration injury severity, pathoanatomic damage, physical mechanism, and pathophysiology. Traditional schemes for diagnosis and grading of TBI severity have incorporated some combination of Glasgow Coma Scale (GCS) score, posttraumatic amnesia duration, duration of loss of consciousness, and presence of other clinical symptoms following a head injury. However, a universally accepted definition of mTBI has proved elusive. A recently published review of mTBI literature revealed approximately 40 different definitions used by various authors and organization.

 The issue is clouded further by the use of the term “concussion,” which is sometimes used synonymously with mTBI but at other times is considered a specific subset of mTBI.

In this review, we avoid the use of the term “concussion” and discuss mTBI as defined by DSM-5: initial GCS score of 13 to 15, posttraumatic amnesia of less than 24 hours, and loss of consciousness of less than 30 minutes. This definition is in keeping with the most widely used definitions, which have evolved from multiple working groups, including the American Congress of Rehabilitation Medicine and the World Health Organization.

The exact pathophysiology of mTBI remains under investigation and is a complex biophysical process, as are the mechanisms by which external forces cause damage to the brain. The general pathological process begins immediately following the injury with a significant release of neurotransmitters and concomitant ionic gradient shifts. To restore membrane potentials, energy requirements increase in the setting of mildly reduced blood flow. In mTBI, this does not lead to ischemia. However, anaerobic energy production and subsequent lactic acidosis may ensue.

Findings also suggest that TBI involves damage to the blood-brain barrier.

 Both animal models and postmortem examination of mild brain injury have revealed structural pathological changes, which indicate the presence of microscopic axonal injury.

 Diffusion tensor imaging and magnetization transfer imaging can detect subtle changes in white matter integrity following an mTBI.

Several mechanisms of injury contribute to mTBI occurrence. mTBIs in participants in contact sports and among active duty military personel with combat exposure have recently become a focus of attention. In the US, the annual incidence of sport-related mTBI exceeds 1.6 million cases, and up to 10% of returning US Army infantry soldiers have met criteria for mTBI.

 The broad pervasiveness of mTBI demonstrated by these figures predicts a high likelihood of psychiatric comorbidities. Indeed, several studies have demonstrated an increased rate of neurobehavioral and psychiatric illness following an mTBI.

Following an mTBI, patients may experience many symptoms that might contribute to the diagnosis of neurocognitive disorder due to TBI. These may include difficulties in complex attention, executive ability, learning and memory, information processing, and social cognition. Additional associated features may consist of perturbations in both mood (irritability, easy frustration, anxiety, affective lability) and personality (disinhibition, apathy, aggression).

Physical symptoms include headache, fatigue, sleep disruption, tinnitus, photosensitivity, and reduced tolerance to psychotropic medications. Patients with mTBI are at greater risk for MDD and for panic disorder than are people in the general population.

 After adjusting for concomitant depression and PTSD, the only residual symptom was headache in soldiers who had sustained an mTBI with associated loss of consciousness.

 Both depression and PTSD can have overlapping symptoms with mTBI and may contribute to much of the morbidity associated with mTBI.

The initial management of mTBI poses a diagnostic challenge to the physician who must balance the concern for excluding serious intracranial pathology versus increasing exposure to radiation as well as the cost of unneeded medical workup. The previously discussed lack of a universally accepted definition for mTBI also makes interpretation and application of available guidelines and recommendations difficult.

Several organizations have published guidelines regarding the management of mTBI: the American College of Emergency Physicians (ACEP)/CDC guidelines in 2008, the Department of Veterans Affairs (VA)/Department of Defense (DoD) guidelines in 2009, and the Eastern Association for the Surgery of Trauma (EAST) practice guidelines in 2012.

 While there are differences in the way each guideline defines mTBI, each is in agreement that there must be a mechanism of injury involving an external force that results in a physiological alteration of brain function. Most also agree that the GCS score should be 13 to 15, any loss of consciousness should be less than 30 minutes, and posttraumatic amnesia should be less than 24 hours. The ACEP/CDC and EAST guidelines focus primarily on the evaluation and management of mTBI in the acute setting, while the VA/DoD guidelines are intended for patients within the VA/DoD system.

Beyond the evaluation and management of mTBI in the acute setting, validated and broadly applicable treatment guidelines are lacking. A recent meta-analysis that reviewed 15 clinical trials of various interventions aimed at reducing the severity and duration of mTBI symptoms suggested an overall lack of data to support any intervention for the management of mTBI.

Only one placebo-controlled trial of 1-desamino-8-D-arginine vassopressin (DDAVP), administered intranasally, showed significant improvement on memory tasks on day 3 following an mTBI.

 However, this was a small study with narrow statistical significance, and no other benefit was found on 3 other cognitive domains. Another treatment strategy, such as providing standardized information to patients following TBI, failed to show any change in the severity or duration of symptoms.

 However, coordinated follow-up of patients along with standardized information, when aggregated, did not statistically show improved outcomes.

Caution is warranted for athletes who sustain an mTBI: another head injury in close proximity to the first can lead to significant cerebral edema with catastrophic outcomes (second impact syndrome). The evidence for this syndrome is sparse and primarily anecdotal, but there are many reported cases in the literature. The mechanism is putatively ascribed to loss of auto-regulation of cerebral blood flow after the second impact.

The return-to-play guidelines appear reasonable, given the concern for catastrophic second impact syndrome. There is less evidence to support a recommendation of bed rest. Theoretically, the brain is at risk for oligemia. Animal studies have shown decreased markers of plasticity following post-TBI exercise.

 However the translation of bed rest to improved human TBI outcomes has not produced consistent results. A retrospective study of student athletes, characterized a subject’s activity level into 1 of 5 categories, with the most extreme being “no school or exercise activity” and “school activity and return to competition.”

 The middle group included school activity with light physical activity and had the best cognitive functioning results. However, a randomized, controlled study of strict bed rest versus no bed rest found no difference in recovery at 2 weeks, 3 months, and 6 months after an mTBI.

 This study suggested that bed rest during the first 2 weeks may provide some palliative effect with less subjective dizziness, but otherwise there was no overall difference in the groups.

Although the landscape of mTBI pathophysiology and resultant comorbidity is inherently complex, prognostic data remain consistently encouraging. In general, patients with mTBI fare well, with most symptoms resolved 3 months after the injury. This is in line with the clinical observation that the majority who suffer sports-related or even combat-related mTBI tend to return to baseline. Although the 5-year risk of seizure after mTBI is somewhat increased, the absolute risk remains quite low (0.7%). There is no conclusive evidence that mTBI predisposes to intracranial neoplasia or dementia.

There remains a significant burden of less tangible deficits in the adult mTBI population because of ongoing disability and associated compensation claims. The lines blur between situations meeting criteria for neurocognitive disorder due to mTBI and malingering.

Evidence also suggests an interaction between mTBI and PTSD, which yields an exaggeration of symptoms in populations with both.

 Psychosocial comorbidities predating or following mTBI (ie, litigation, ADHD, bipolar disorder, chronic benzodiazepine use, malingering) contribute significantly to the severity of post-mTBI symptoms.

Although additional studies are needed, the available facts indicate that for the majority of mTBI patients, there will be no long-term sequelae. These facts also suggest that a significant proportion of ongoing mTBI symptoms can be seen because of psychosocial comorbidities that interact with mTBI. Therefore, a rational treatment strategy should focus on patient reassurance, recognition, and mitigation of social stressors in addition to treatment of psychiatric symptoms.

The direct influence of mTBI on personality and psychiatric morbidity is difficult to determine, particularly because cognitive changes may represent various components of the experience or understanding of the event, rather than any inherent physical injury process. Residual deficits, if any, may be more or less realized by any given patient. And although a clear correlation with psychiatric diagnoses and compensation efforts exists, a subset of patients who are subjectively and/or objectively cognitively affected after an mTBI may not manifest with full diagnostic criteria for mental illness and may not pursue significant compensation or alternative gains.

The constellation of symptoms in each patient must be synthesized and treated appropriately in a multidisciplinary fashion. Close attention to the clinical presentation should prompt consideration of therapy, even when diagnostic criteria for a defined psychiatric condition are not met. In the end, long-term follow-up using a team approach that includes behavioral health and other specialists, coordinated by an engaged primary care physician, is likely to provide the most benefit to the patient.

Future research about the management of mTBI is needed to answer many remaining clinical questions. The ideal use of imaging and biomarkers in diagnosis and prognosis beyond the acute setting remains unclear, as does the optimal timing and duration of various therapies for mTBI symptoms.

mTBI is a common clinical entity that is caused by a variety of common life situations and carries the potential for significant neuropsychiatric comorbidities. Effective strategies from recent guidelines exist for initial management and gradual return to activity, but there is a lack of widely accepted guidelines for management outside the acute phase.

The prognosis is generally favorable across age groups. However, one of the most challenging aspects of mTBI is the potential for prolonged reporting of associated symptoms, which may be augmented in situations that are linked to psychosocial comorbidities or potential compensation issues. Future goals for research are to more quickly identify and objectively detect persistence of mTBI sequelae and to guide further improvement in treatment strategies.

Dr Willis and Dr Williams are Neurology Residents; Dr Sladky is Neurology Program Director and Staff Neurologist; and Dr McClean is Neurology Assistant Program Director and Staff Neurologist in the department of neurology at the San Antonio Military Medical Center at Fort Sam Houston in Texas. The authors report no conflicts of interest concerning the subject matter of this article.

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Articles

A considerable overlap exists between TBI and disorders in cognition, behavior, and personality, which can provide even greater clinical challenges. More than 70% of the cases of TBI are mild, which makes this subgroup of particular clinical interest.

Author | Jon P. Williams, DO, PhD

Articles

Management of Mild Traumatic Brain Injury