Mild Traumatic Brain Injury

Abstract

Mild traumatic brain injury (MTBI) is a significant public health problem worldwide. Injured individuals have an increased relative risk of developing a variety of neuropsychiatric conditions associated with the profile of brain regions typically affected in TBI. Within a neurobiopsychosocial framework, this article reviews what is known about the neuropsychiatric sequelae of MTBI, with an emphasis on recent advances.

Traumatic brain injury (TBI) is a neuropsychiatric disorder that breaks down the remaining barriers between neurology and psychiatry. Broadly speaking, the neurobehavioral effects of TBI include changes in cognition and in personality and an increased relative risk of developing a host of psychiatric disorders. In this article, I review the array of neurobehavioral sequelae associated with mild TBI (MTBI).

Severity of brain injury exists along a continuum that focuses on three parameters: duration and depth of loss of consciousness (LOC), if any; the duration of memory disturbance associated with the event (retrograde and anterograde amnesia); and, if available, the Glasgow Coma Scale (GCS) (1), a simple measure of best speech and language, motor, and oculomotor function. From a clinical perspective, individuals with injuries in which the duration of unconsciousness is less than 30 minutes, the duration of posttraumatic amnesia is less than 24 hours, and the GCS score (1) score is 13–15 out of a possible 15 (with higher scores indicating more normal function) are considered to have had a mild brain injury. When initially seen, these patients may be confused or disoriented and appear lethargic (Table 1).

TABLE 1.

Clinical Indicators of Mild Traumatic Brain Injury^a

Indicator	Duration and Parameters	Comment
Credible event	Need force acting on brain	Must be of sufficient severity to plausibly result in at least an altered level of consciousness. Typical manifestations include incomplete memory for event, confusion, disorientation, and reduced arousal.
Loss of consciousness	0–30 minutes	If unwitnessed, must distinguish from posttraumatic amnesia. Difficult to assess when intubated, sedated, or intoxicated.
Disturbed consciousness	Momentary to several hours	Can fluctuate, wax, and wane. Individual may appear stunned, dazed, confused, or disoriented.
Retrograde amnesia	0 to several hours	Often absent or very brief.
Anterograde amnesia (posttraumatic amnesia)	None to 24 hours	Individual may report patchy recollections. Ends with return of continuous, sequential memory. Difficult to assess when intubated, sedated, or intoxicated.
Neurological signs	Typically transient	May have visual disturbance, language difficulty, or impact seizure. Often no signs evident other than disturbance of consciousness and cognition.
Glasgow Coma Scale	13–15, 30 minutes after the event	Difficult to assess when intubated, sedated, or intoxicated.
Clinical symptoms	Variable	Individual may report headache, nausea, dizziness, sensitivity to light or noise, and cognitive problems.

^aAdapted from McAllister (2).

Numerous efforts have been made to formalize definitions of and diagnostic criteria for MTBI, including those from the Centers for Disease Control and Prevention (CDC) (3), the World Health Organization (WHO) (4), and the American Congress of Rehabilitation Medicine (ACRM) (5). These definitions overlap significantly and have in common that MTBI is caused by a force acting on the brain that results in an alteration in the level of consciousness (manifested by incomplete memory of the event and being confused or disoriented). LOC is not necessary for the diagnosis, although it may occur, with an upper limit of 30 minutes. The ACRM and WHO criteria specify that, if available, the GCS score 30 minutes after injury should be 13–15 (6). Efforts to categorize severity of brain injury have also been a focus in sports medicine, where it is often referred to as sport-related concussion (SRC) (7); however, most clinicians and researchers use the terms MTBI and concussion interchangeably (8).

Epidemiology

Estimates have suggested that each year 1.7 million Americans sustain a TBI (9), a rate of 576 per 100,000 population. With the preceding definitions, MTBI is the most common category of injury severity, accounting for 60%−80% of all TBIs (10, 11). As with TBI in general, mild injury occurs about twice as frequently to males, with increased incidence in the 15–24 and ≥70 age groups (10). Causes of MTBI are similar to those of TBI in general, with falls, motor vehicle accidents, struck or struck-by events, and assaults the most common causes (10, 12).

Estimates of the economic burden of MTBI are difficult to come by, although they are likely quite substantial. On the basis of inflation-adjusted census data from 1995, the CDC in 2006 estimated a total cost of $16.7 billion for MTBI (10, 13). These estimates included only people who sought care in hospitals or emergency departments and were thus an underestimate. They also did not account for the lost productivity of those caring for the patient with MTBI (10).

Neuropathophysiology

Changes in Brain Structure

As with more severe injury, MTBI is associated with damage to neurons, axons, and cerebral vasculature. Animal models of brain injury using a variety of paradigms across several species (14–18) have suggested that the neuropathology of brain injury occurs along a spectrum that mirrors the spectrum of clinical severities.

Evidence of neuropathology associated with human MTBI is limited to convenience samples of individuals who sustain an MTBI, die shortly thereafter of an unrelated cause, and are autopsied. For example, Oppenheimer (19) reported destruction of myelin, axonal retraction bulbs (beadlike structures at the proximal end of a ruptured axon), and aggregates of small reactive glial cells (indicating recent tissue injury) in a variety of brain regions of five patients with minor or trivial injuries. Blumbergs et al. (20) reported multifocal axonal injury in five individuals who had sustained mild injuries with periods of unconsciousness as brief as one minute. Bigler (21) described subtle neurocognitive and neuropathological abnormalities in a 47-year-old man who died of unrelated causes seven months after an MTBI.

Changes in Brain Function

Both animal and human studies have suggested that MTBI impairs the normal balance between cellular energy demand and supply with subsequent metabolic disruption (22, 23). MTBI causes significant changes in intracellular and extracellular concentrations of potassium, sodium, calcium, and magnesium ions. Restoration of these altered ionic gradients requires a significant increase in energy expenditure that is initially met by hyperglycolysis. However, ongoing energy demand requires an increase in blood flow. The normal coupling of increased energy demand to increased cerebral blood flow (and hence increased energy supply) can be disrupted after MTBI, resulting in a mismatch of supply and demand (24–28).

Role of Neuroimaging

From a clinical perspective, neuroimaging informs our understanding of the pathophysiology of MTBI, as well as assists with clinical management. Computed tomography (CT) scanning is the most commonly used imaging modality in the management of TBI because of its widespread availability, ease and speed of image acquisition, and sensitivity to detecting acute hemorrhage. However, only 5%−10% of individuals with MTBI and GCS scores of 15 have abnormal CT scans (29–31). Individuals with GCS scores of 13 or 14 have a higher frequency of abnormal findings on CT scans, ranging from 20% to 35% (32–35).

MRI-based methods, particularly using more recent image acquisition techniques such as susceptibility-weighted imaging (36) and diffusion tensor imaging (DTI) (37, 38), are better at detecting the diffuse axonal injury and small hemorrhages that are generally believed to be the neuropathological substrate of MTBI (36, 39). For example, a recent study showed that 28% of individuals admitted to level 1 trauma centers with MTBI and normal CT scans had abnormal MRI studies when scanned within two weeks of injury and that the presence of abnormalities on MRI scans significantly improved prediction of outcome three months after injury (40).

From a research perspective, several other imaging techniques show promise for informing our understanding of the neuropathophysiology of MTBI. Diffusion imaging techniques such as DTI may be of use in demonstrating abnormalities of white matter pathways and connectivity (38, 41–43). Of note is that changes in DTI parameters have been shown to occur both acutely (42) and chronically (38) and, in some studies, to correlate with cognitive performance (37, 44).

Functional MRI also shows promise in clarifying some of the underlying symptoms of TBI (45). Functional MRI studies have suggested that within one month of being injured, individuals with MTBI show aberrant patterns of activation of working memory circuitry (46–48). The MTBI group’s cognitive performance did not differ from that of a healthy control group, but the MTBI group reported significantly more cognitive and memory complaints. One interpretation is that people with MTBI experience problems with the allocation of memory processing resources and label this as memory trouble. Additional work has suggested that alterations in frontal catecholaminergic signaling may underlie these changes (47, 49, 50).

Clinical Picture

Overview

MTBI results in a complex array of neuropsychiatric sequelae, including problems with cognition, mood, sensorimotor function, sleep, and emotional regulation. Fortunately, for most individuals, these signs and symptoms are typically short-lived, with resolution over a period of one to several weeks. However, several factors can alter the trajectory of this recovery, and there is a small group of individuals for whom recovery can be incomplete.

Acute Sequelae

Cognitive sequelae.

Individuals with mild brain injury report problems with short-term memory, attention, and slowed thinking and can be distinguished from those in a healthy control group on measures of speed of information processing, attention and memory, and performance consistency in the first week or so after the injury (4, 51–54), even in the absence of subjective complaints (55–57). Studies of cognitive testing one and three months after injury have shown progressive diminution of group differences in cognition. Studies of elite athletes with SRC (56) have suggested that most in this population are symptom free and have returned to their baseline cognitive function within seven to 10 days. Such good outcomes are not universally found, however. For example, even in the National Collegiate Athletic Association study of SRC (56), approximately 10% of the athletes did not recover fully within the typical one-week time frame (56), and Ellemberg et al. (58) found evidence of poorer cognitive function six to eight months after a single concussion in a small sample of collegiate female soccer players compared with teammates without concussions (control). In an emergency department cohort, Heitger et al. (51) found persistent deficits in verbal learning at both three and six months after injury.

Postconcussive symptoms.

In addition to the cognitive sequelae, a variety of sensorimotor, emotional, and behavioral sequelae are associated with mild brain injury. Complaints of headache, disequilibrium, sensitivity to noise and light, fatigue, sleep disturbance, irritability, and depression are common and are reported by 80%−100% of patients (54, 59). These symptoms are common in more severe injuries as well and thus are not pathognomonic for MTBI (59–63). Depending on the cohort studied, surprisingly high rates of symptoms may be present three months or more after injury (54, 64), although these symptoms may not be specific to the MTBI per se, because studies that include a control group of persons with “other injury” do not always show between-group differences (59).

Chronic Sequelae

Cognitive sequelae.

The long-term cognitive sequelae of MTBI are a subject of ongoing discussion. Several meta-analyses have suggested that at a group level, cognitive recovery after MTBI is largely complete by three months postinjury (65–70). Two systematic reviews also speak to this issue. The WHO report on MTBI (4) reviewed 427 studies of prognosis after MTBI (studies of children as well as adults were included) and concluded that there was strong evidence for cognitive dysfunction shortly after injury (from days to one week) and that there was strong and consistent evidence that these deficits resolve at the group level by three months after injury. However, a more recent Institute of Medicine report on brain injury (71) concluded that there was a sufficient number of contradictory studies to prevent a firm conclusion about long-term cognitive deficits.

Postconcussive symptoms.

Although the frequency and intensity of postconcussive symptoms improves with time, careful assessment often reveals a surprisingly high rate of symptoms. McCullagh et al. (72) found significant rates of persistent symptoms five to six months after MTBI, with almost half of the 57 participants reporting dizziness and headache and almost three fourths reporting fatigue. Furthermore, more than 50% of those with GCS scores of 13–15 met General Health Questionnaire (73) criteria for psychiatric “caseness” indicative of significant psychological distress. In a carefully designed dual-cohort study (MTBI and matched control group with other injuries), Kraus et al. (74) found that 83% of the MTBI cohort reported at least one complaint six months after injury and had a mean of 4.3 complaints. Headaches, dizziness, vision difficulties, memory or learning problems, and alcohol intolerance occurred at higher rates among the MTBI cohort.

Several studies have suggested elevated symptom rates even one year after MTBI, especially in cohorts drawn from emergency departments (60, 75). Dikmen et al. (59), combining data from several of their previous studies of TBI, reported that 44% of hospitalized persons in the uncomplicated MTBI group (without CT scan abnormalities) noted three or more symptoms that were new or worse since the injury, whereas 24% of the “other injury” control group had three or more symptoms. Among those with complicated MTBI, 50% reported three or more symptoms, a significant difference from the control group. Attributing the cause of symptoms or cognitive impairment to an MTBI must be done with caution. As Satz et al. (76) and others (77–80) have pointed out, it is important to consider the effects of other system injuries, as well as the base rate of typical postconcussive symptoms in the general population. In a recent report from the TRACK-TBI study, a third of MTBI patients had Glasgow Outcome Scale-Extended scores of ≤6 (out of a possible 8, with scores of 7–8 indicating good recovery), signifying incomplete or poor recovery three months after injury (81). This cohort was drawn from level 1 trauma centers and consisted largely of hospitalized individuals, 25% of whom had GCS scores of 13–14; 44% were judged to have complicated MTBI (abnormal CT findings).

Is There a Postconcussive Syndrome?

There is a good deal of confusion surrounding the use of the term postconcussive syndrome. Some clinicians use it to describe any symptom or symptoms experienced at any point after an MTBI. Others limit use of the term to individuals who have persistent complaints after an MTBI. The issue is further confounded by the ICD-10 diagnosis of postconcussion syndrome (82) and the observation that postconcussive symptoms are not specific to TBI and have been found to occur at high rates in the general population (83). Rather than conceptualizing postconcussive symptoms as a syndrome, it may be more accurate to assert that there is a set of common, albeit nonspecific, symptoms that occur with variable frequency depending on a specific injury profile and relevant premorbid factors. This is more than a semantic issue because the different views carry treatment implications. With a syndromic approach, the implication is that a common underlying mechanism is responsible for all symptoms (be it neural damage, depression, or compensation seeking), and the clinician should look for a treatment that will ameliorate the entire syndrome. With the alternative view (many symptoms with different causes, albeit dating to the same initiating injury event), the implication is that the clinician should examine each symptom and diagnose and treat the different sources of distress (e.g., dizziness related to labyrinthine trauma or headache resulting from cervical muscle strain). Clinical experience suggests that individuals who experience multiple symptoms shortly after an injury can show improvement in all, some, or none of the symptoms over time, arguing against the syndrome view.

Predictors of Delayed or Incomplete Recovery

A study by Rutherford et al. (84) suggests that 10%−15% of individuals have persistent or chronic problems. However, the definition of poor outcome or delayed recovery varies. Some have defined poor outcome as persistent trouble at three months, some at six months, others at more than a year. In the SRC literature, poor outcome may be failure to return to play after three weeks. One must also clarify the indicator of poor outcome. If poor outcome is defined in terms of self-reported symptoms and distress, the literature cited previously suggests that approximately 33%−50% will have problems at three months (85, 86) and a similar percentage at six months (74, 87) and even at 12 months (59). Limiting conclusions from most of these studies is the absence of preinjury baseline data (thus, change scores are not available), the nonspecific nature of the symptoms, and the high rates of occurrence in other injury (non-TBI) populations.

Certain factors, however, appear to predict a poorer prognosis (Table 2). For example, recent work with military populations has suggested that the presence of comorbid psychiatric disorders such as depression and posttraumatic stress disorder (PTSD) may account for much of the distress of individuals who also have MTBI and have persistent symptoms (107, 108). Age at time of injury appears to play a role in terms of both symptoms and neuropsychological function (59, 88). Intuitively, it would seem that repetitive injuries would be associated with persistent symptoms, and certainly studies of contact athletes would suggest that for some groups this holds true (99). It is possible that specific genetic profiles contribute to response to neurotrauma and cognitive outcomes (101, 109, 110).

TABLE 2.

Factors Associated With Delayed Recovery or Poor Outcome^a

Indicator	Representative References	Commentb
Increased age at injury (>60)	(88)	True of all injury severities.
Premorbid psychiatric illness	(89, 90)	Depression, anxiety, and substance abuse are common.
Development of psychiatric illness after injury (e.g., depression, posttraumatic stress disorder)	(91–95)	Fairly consistent association between axis 1 diagnosis and increased levels of postconcussive symptoms and other outcome measures.
Compensation or litigation	(68, 96–98)	Not a universal finding. Association should not be misinterpreted as causation.
Repetitive injuries	(64, 99, 100)	Evidence is somewhat indirect and tentative—comes from both sports injury literature and early emergency department populations (64, 71).
Selected polymorphic alleles (e.g. ANKK1, APOE e4)	(2, 101, 102)	Several large ongoing studies should shed further light on this.
Abnormal acute neuroimaging	(89, 103, 104)	“Complicated MTBI” has outcomes more similar to moderate traumatic brain injury (TBI).
Expectation of poor outcome	(105, 106)	Expectation of poor outcome or severity of complications is associated with poor recovery.
Extracranial injuries and high initial symptom load	(87)	Extracranial injuries may prolong need for treatment and delay return to work but not necessarily increase postconcussive symptoms (80).

^aAdapted from McAllister (2).

^bMTBI, mild traumatic brain injury.

The role that compensation seeking plays in outcome is controversial (111), and the literature on this topic is divided and confounded by methodological concerns (64, 112–115). Litigation and compensation proceedings are typically highly adversarial and are associated with anxiety and distress (96, 97, 116) and more severe initial symptoms (and thus, perhaps, more severe injuries and more likelihood of seeking compensation) (89). Meta-analyses (68, 98) have suggested that compensation is associated with higher symptom distress. In the WHO report, Carroll et al. (4) concluded that compensation and litigation are consistent predictors of delayed outcome. The conclusion that desire for compensation causes the symptoms does not necessarily follow from a simple association. There are numerous reasons for apparent poor effort or negative response bias on tests of cognitive function, and malingering should not immediately be assumed. Inconsistent performance must be interpreted in the context of such factors as fatigue, medication effects, and medical or comorbid psychiatric conditions.

Association With Psychiatric Illness

TBI in general, including MTBI, increases the risk for developing a variety of psychiatric disorders that can contribute to significant disability after the injury (60, 75, 117–121). The presence of these disorders can serve to accentuate or increase the degree of distress associated with lingering symptoms, and successful treatment of comorbid conditions can result in a significant reduction in postconcussive symptoms (122, 123).

Depressive symptoms are a common complication of TBI (91, 92, 124, 125). There are fewer studies of MTBI specifically, although the literature available suggests that depressive symptoms co-occur equally with MTBI (115). Many postconcussive symptoms such as subjective slowing, irritability, fatigue, and sleep disturbance can be consistent with a depressive syndrome, even when patients may not endorse explicit items such as “depressed mood.” Mania can occur after MTBI but is less common than emergence of depressive symptoms (126–130).

Anxiety is very common after TBI (117, 121, 131). As with depression, there is an overlap between some postconcussive symptoms and generalized anxiety disorder (GAD) symptoms. For example, many patients endorse complaints of headache, dizziness, blurred vision, irritability, and sensitivity to noise or light after mild brain injury (54, 59, 132). Fann et al. (133) reported that 24% of their sample (the majority of whom had MTBI) evaluated two to three years after injury met criteria for GAD. Hibbard et al. (118) also found high rates of several different anxiety disorders (PTSD, 19%; obsessive-compulsive disorder, 15%; panic disorder, 14%; GAD, 9%) in their sample of individuals with mixed injury severity.

There is an increasing awareness of the relationship between PTSD and brain injury in both civilian and military populations (134, 135). Bryant and Harvey (136–138) have reported a series of studies of individuals hospitalized after motor vehicle accidents, some with and some without MTBI. Their results suggest that PTSD is quite common in the context of MTBI (approximately 20%), that acute stress disorder is a good predictor of those who go on to develop PTSD six months after injury, and that the TBI group with PTSD was significantly more symptomatic than the TBI group without PTSD. These findings suggest that PTSD can amplify postconcussive symptoms after an MTBI and complicate recovery. In their sample with MTBI (LOC <15 minutes), Mayou et al. (139) found that an astonishing 48% of those with definite LOC had PTSD three months after injury, and one third of their subjects with MTBI had PTSD one year after injury.

The conflicts in Iraq and Afghanistan have spurred an interest in the relationship between psychological and biomechanical trauma, particularly in military populations (134, 140, 141). Two articles highlight the interaction of biomechanical and psychological trauma. Hoge et al. (107) reported that indicators of more severe MTBI were associated with higher rates of PTSD among service members returning from the war in Iraq. Schneiderman et al. (108) found that MTBI incurred during combat approximately doubled the risk for PTSD and that a PTSD diagnosis was the strongest factor associated with persistent postconcussive symptoms. The brain regions thought to play a role in the genesis of PTSD (e.g., hippocampus, amygdala, medial and orbital frontal cortices) overlap considerably with brain regions vulnerable to injury associated with typical biomechanical trauma (hippocampus, frontal cortex, and frontal subcortical white matter) (134), suggesting that shared neurobiological mechanisms may underlie the frequent comorbid presentation of TBI and PTSD.

Sport-Related Concussion

SRC is, by virtually any definition, an MTBI, although it is often considered to fall on the milder end of the MTBI continuum. Nevertheless, over the past decade SRC has become acknowledged as a significant public health concern in the United States and worldwide. The CDC has estimated that between 1.6 and 3.8 million Americans sustain an SRC each year and that because of underreporting, this is probably an underestimate (142). Furthermore, it is now recognized that repetitive SRC and perhaps repetitive head impacts, associated in the past primarily with boxing (143) but more recently with other contact sports, may be associated with a neurodegenerative condition referred to as chronic traumatic encephalopathy (CTE) (99, 144). Publicity attending the deaths of and neuropathological findings for several high-profile professional athletes (145–147) and class action lawsuits brought on behalf of former National Football League and National Hockey League players (148) have fueled concern among players, parents, legislatures, and sport governing bodies. Questions are now being raised about how many concussions are too many: Are some individuals more vulnerable to the effects of concussion and, if so, why; is concussion the proper metric of injury, or should more attention be paid to the number and magnitude of repetitive head impacts; is MTBI an exposure or an initiating event for long-term sequelae over the life span; and should certain sports such as football be banned (149–152)? To date, the basis for the concerns consists of a growing but highly selective sample of athletes with a diverse array of neuropsychiatric symptoms who have died and then been autopsied by a single group. Only in the past year have formal neuropathological criteria been agreed on (153). Thus, there is a significant need for more population-based studies to ascertain the true risks inherent in contact sport participation. Unfortunately, CTE remains a pathological diagnosis, although attempts are being made to operationalize clinical staging criteria for individuals with suspected CTE (154). With respect to exposure to repetitive head impacts, relatively little data is available as of yet on which to base conclusions. A recent formative review of this topic (155) concluded that to date there is no firm evidence that repetitive impact exposure is detrimental, although clearly there is a need to address this concern given the public health implications.

Treatment Issues

In general, the prognosis for recovery from MTBI is very good, and thus treatment interventions generally consist of those designed to prevent the development of persistent symptoms and those that target specific symptoms or disorders that have become evident after an MTBI (156). The former typically involve psychoeducational interventions; the latter may consist of medication or cognitive-behavioral interventions. At the risk of stating the obvious, however, the foundation of the approach to patients with mild brain injury is a proper evaluation.

Evaluation

Significant effort must be expended to clarify premorbid history. In particular, one must look for a prior history of brain injury, which can be seen in as much as 30% of patients (64, 71), as well as substance abuse and other psychiatric disorders that are risk factors for TBI (60, 75, 117–120). Interviews with significant others can be invaluable in gaining a clearer picture of these issues.

Signs and symptoms attributed to the injury must be clearly defined, as well as any changes in symptoms as a function of time from the injury. The profile of the injury itself must be outlined, including the type of injury; the presence or absence of LOC and its duration; and the presence, absence, and duration of any retrograde and anterograde amnesia. Corroborative information, including accounts from observers, emergency medical technicians, ambulance and emergency department personnel, and inpatient hospital records, can be invaluable. When evaluating these records, phrases such as “normal mental status” without sufficient documentation do not eliminate the possibility that there were cognitive changes. This is particularly true when the emergency team is distracted by trauma to other parts of the body (157). The presence and location of complications such as depressed skull fractures, cerebral contusions, and hematomas should be noted because of potential prognostic implications. The neurodiagnostic tests done and the timing in relation to the injury should be clarified and the reports or actual studies obtained. If they have not been performed, an MRI and a careful neuropsychological evaluation may be considered. Such studies, however, are not always abnormal in the presence of brain injury, especially if they are performed well after the event. Furthermore, even when abnormal, these studies may not reveal abnormalities that are pathognomonic for mild brain injury. Because few patients have these tests performed both before and after their injury, it is difficult to be certain that such abnormalities were caused by the traumatic event in question. As Binder et al. (158) have pointed out, it is normal to perform poorly on some number of tests administered as part of a battery (158).

All of this information can then be integrated with findings from the clinical interview to determine the consistency of the history and examination with the known sequelae of mild brain injury. This process should determine the presence or absence of one or more of the specific syndromes outlined earlier, including postconcussive symptoms, depression, anxiety syndromes, PTSD, and psychotic syndromes. Treatment should then follow rationally from this diagnostic scheme.

Psychoeducation

For patients with active neurobehavioral sequelae, often the most effective intervention or means of preventing poor recovery, is a careful explanation of the pathophysiology, typical sequelae, and time course of recovery associated with minor brain injury (156, 159–165). Problems with slowing, attention, and memory, especially in the first three to six months, should be described. The potential for longer-term difficulties should be mentioned but not overemphasized. The overall tone should be that of expectant recovery. This explanation should occur soon after the injury and is best done in the presence of family, friends, or significant others. Setting realistic goals for return to major activities can be a difficult process that must be individualized for each patient. Unfortunately, clinicians often become involved in the later stages of the process, by which time there is frequently an unpleasant dynamic in which one or more individuals (family, friends, employers, insurance carriers, health care workers) may be questioning the validity of the patient’s complaints on the basis of the seemingly minor nature of the injury and the patient’s healthy appearance. Validating the patient’s complaints without unduly fostering illness behavior can be a difficult and lengthy process. Attempts to take a more problem-based approach seem to have been less successful to date (166, 167).

Medication Approaches

Medication approaches to the sequelae of MTBI have generally taken three broad forms: amelioration of psychiatric complications, amelioration of specific symptoms (e.g., headache, dizziness, and sleep disturbances), and approaches to cognitive complaints. At this time, there are no Food and Drug Administration–approved pharmacological interventions specific to MTBI. Thus, approaches typically mirror those used for idiopathic psychiatric disorders. Several general principles should be borne in mind when prescribing psychotropic agents. Most important, the vast majority of individuals with MTBI will recover without needing medication, and no studies have been done with MTBI populations to determine whether a given medication alters the rate of recovery. Thus, most individuals should be reassured and encouraged to let recovery occur over time. If medications are warranted, the clinician should bear in mind that many of these individuals seem to be more sensitive to common psychotropic side effects such as sedation, psychomotor slowing, and cognitive impairment (such as impairments of recent memory and attention). Although few data are available to confirm this phenomenon, most clinicians working with patients with TBI have noted this tendency for increased side effects and a resultant narrowing of the benefit-to-toxicity ratio. In general, it is prudent to use lower starting and (often) final doses and to prolong the titration intervals (168–170). With respect to amelioration of psychiatric complications, the same general approaches taken in the noninjured population are typically used, although therapeutic efficacy studies are lacking for this group (170).

The treatment of postconcussive cognitive symptoms can be challenging. Most studies to date have focused on efforts to alter catecholaminergic and cholinergic signaling mechanisms as mediators of the attentional and memory domains vulnerable to injury in TBI (171, 172). Several dopamine agonists, including bromocriptine and stimulants, particularly those with dopamine agonist properties such as methylphenidate, amphetamine, and levodopa, have been used to treat various cognitive and behavioral sequelae of TBI and other acquired brain injuries (169, 173–177).

Multiple studies have demonstrated that cholinergic augmentation, generally using one of several cholinesterase inhibitors (e.g., physostigmine or donepezil), can improve TBI-induced memory deficits even in the late postinjury period (longer than one year) for some TBI survivors (178–182). Arciniegas and colleagues have advanced the theory that cholinergic mechanisms play a critical role, particularly in certain attentional deficits after TBI (183), and they have reported successful use of donepezil with some individuals with TBI (184). Thus, there appears to be increasing evidence, both theoretical and clinical, suggesting that the cautious, empirical use of cholinergic and catecholaminergic agents is warranted for the treatment of chronic memory and attentional deficits.

Summary

Mild brain injury is a significant public health problem. It can result in an array of common neurobehavioral sequelae. Several points are worth highlighting: Limited human data and more extensive animal data have suggested that mild brain injury produces neuropathological changes to a lesser extent but that these changes are of similar quality and location to those seen with more severe brain injury. Mild brain injury is associated with impairments in speed of information processing, attention, and memory. These deficits are most pronounced in the initial days to weeks after the injury. Most patients show a rapid, progressive improvement over the subsequent one to three months. A small percentage of patients have demonstrable long-term sequelae.

A variety of predictable cognitive, somatic, and behavioral complaints, known as postconcussive symptoms, are seen subsequent to brain injury of all levels of severity. These symptoms occur predictably after MTBI but also after more severe injury and in other injury settings. Thus, they are not specific to MTBI. After mild brain injury, most patients show progressive resolution of these symptoms over the subsequent one to three months. A small but significant percentage have persistent symptoms for 12 months or longer.

Several factors may be associated with poor outcome or delayed recovery, including a history of prior brain injury, older age at time of injury, certain complications (such as depressed skull fracture or CT evidence of cerebral contusions or hemorrhages), preexisting psychiatric illness or postinjury development of psychiatric illness, injury to other body systems, and certain psychosocial factors.

Mild brain injury has been associated with the new onset of discrete psychiatric disorders, including depression and PTSD. The brain injury may result in atypical clinical presentations, heightened sensitivity to standard psychotropic agents, and a somewhat more refractory course, although these observations must be considered tentative. Treatment of the neuropsychiatric sequelae involves careful assessment of premorbid function, psychosocial context, and injury profile. Psychoeducational strategies, supportive psychotherapy, and judicious use of appropriate psychotropic agents can be beneficial.