Version May 2024
INTRODUCTION — Mild traumatic brain injury (mTBI), ie, concussion, is common and, while typically benign, has a risk of serious short- and long-term sequelae [1,2]. As a result, it is one of the most important public health problems.
An overview of the sequelae of mTBI is presented here. The evaluation and management of acute mTBI are discussed separately. (See "Acute mild traumatic brain injury (concussion) in adults".)
DEFINITIONS — mTBI occurs with head injury due to contact and/or acceleration/deceleration forces. It is typically defined as mild by a Glasgow Coma Scale (GCS) score of 13 to 15, measured at approximately 30 minutes after the injury (table 1). Some recommend classifying patients with a GCS score of 13 as having a moderate head injury (GCS score of 9 to 12) because they seem more similar with regard to prognosis and incidence of intracranial abnormalities [3-6].
The term "concussion" is often used in the medical literature as a synonym for mTBI. The Quality Standards Subcommittee of the American Academy of Neurology defines concussion as a trauma-induced alteration in mental status that may or may not involve loss of consciousness [7]. Consensus definitions of concussion are discussed in detail separately. (See "Acute mild traumatic brain injury (concussion) in adults", section on 'Definitions'.)
SEQUELAE — The prognosis for complete recovery from mTBI is good for an appropriately managed concussion [1,2]. Nonetheless, there are a variety of short- and long-term sequelae that have important implications.
Second impact syndrome — Second impact syndrome occurs when a person develops altered mental status or loss of consciousness within seconds to minutes of a second concussion when they are still symptomatic from an earlier concussion [8-12]. This is a rare and somewhat controversial but also potentially fatal complication of mild brain injury [13-21].
A 2021 literature review identified only 45 cases, all males between the ages of 10 to 29 (including seven over the age of 20 years). The latency between first and second concussions ranged from less than one hour to five weeks. There were 11 recoveries or favorable outcomes and 19 deaths [22]. It has never been reported in American National Football League (NFL) players.
It is hypothesized that impaired cerebral autoregulation leads to cerebrovascular congestion and malignant cerebral edema with increased intracranial pressure [15,22-25]. There is no specific treatment for this condition; management focuses on mitigating increased intracranial pressure. (See "Evaluation and management of elevated intracranial pressure in adults".)
Return-to-play protocols aim to prevent second impact syndrome. (See "Acute mild traumatic brain injury (concussion) in adults", section on 'Return to play for athletes'.)
Postconcussion syndrome — Postconcussion symptoms may result from brain injury or from trauma involving head and neck structures. These include headache, dizziness (including vertigo and nonspecific dizziness), neuropsychiatric symptoms, cognitive impairment, and sleep dysregulation. These typically develop in the first days after mTBI and generally resolve within a few weeks to a few months. At least one study suggests that a history of a prior concussion, particularly if recent or multiple, is a risk factor for prolonged symptoms after concussion [26]. Repeated concussions can cause cumulative neuropsychologic deficits (ie, increasing severity and duration of mental status abnormalities after each separate incident) [27-29].
Postconcussion syndrome is discussed in more detail separately. (See "Postconcussion syndrome".)
Posttraumatic headaches — Headaches occur in 25 to 78 percent of patients after mTBI [30-33]. According to the International Headache Society (IHS) criteria, the onset of the posttraumatic headaches should be within seven days after the injury [34]. The seven-day onset is arbitrary; some suggest that three months seems a more reasonable latency for onset than does seven days [35]. Headaches may represent a specific injury to the head or neck, may be nonspecific in character, and may have a symptom pattern indistinguishable from other nontraumatic headache syndromes such as migraine and tension headache [36].
The clinical features, evaluation, and treatment of posttraumatic headaches are discussed in detail separately. (See "Post-traumatic headache".)
Sleep disturbances — Sleep-wake disturbances are among the most prevalent and persistent sequelae of mTBI. Patients suffering from TBI of any severity, in both the acute and chronic phases, commonly report excessive daytime sleepiness, increased sleep need, insomnia, and sleep fragmentation (figure 1).
The evaluation and treatment of sleep-wake disturbances after mTBI are discussed in detail separately. (See "Sleep-wake disorders in patients with traumatic brain injury".)
Posttraumatic epilepsy — Data conflict as to whether mTBI is associated with an increased risk of epilepsy. Seizures occurring within the first week of injury are acute symptomatic events and are not considered epilepsy. Half of the seizures consistent with posttraumatic epilepsy will occur in the first year; 80 percent will occur within two years. Prophylactic treatment with antiseizure medications does not prevent posttraumatic epilepsy and is not recommended.
Posttraumatic seizures and epilepsy are discussed in detail separately. (See "Posttraumatic seizures and epilepsy".)
Posttraumatic vertigo and dizziness — The incidence of posttraumatic vertigo has not been well characterized in prospective studies. Posttraumatic vertigo and dizziness is a substantial contributor to disability after mTBI [37-41].
Head injury may lead to vertigo by a variety of mechanisms, each of which has a relatively distinct clinical syndrome [42,43]. It is important to identify the source of vestibular symptoms in order to appropriately manage the patient [44].
Benign paroxysmal positional vertigo — Benign paroxysmal positional vertigo (BPPV) that occurs after a head injury is presumably caused by shearing and displacement of otoconia, which then settle into one of the semicircular canals, most often the posterior canal.
BPPV produces isolated paroxysms of positionally induced vertigo [45]. There may be a hiatus of weeks and even months between the injury and the onset of BPPV. Evaluation of patients with BPPV after trauma may identify that more than one semicircular canal is involved, a phenomenon that is more common than in patients with idiopathic BPPV (55 versus 6.5 percent in one series) [46,47].
Some but not all studies suggest that BPPV following mTBI may be more difficult to treat than in other settings, require more treatment sessions, and be more prone to recurrences [46,48-51].
The evaluation and management of BPPV is described in detail separately. (See "Benign paroxysmal positional vertigo".)
Convergence insufficiency — Convergence insufficiency (CI) is an increasingly recognized oculomotor impairment following mTBI. In some series, CI is identified in 40 to 55 percent of individuals who are systematically examined after an uncomplicated concussion [52-55]. The pathogenesis or neuroanatomic basis of CI is not well understood.
Patients with CI do not typically report diplopia, but instead have ill-defined dizziness, nonspecific visual complaints (eg, blurred vision, difficulty tracking a moving target), and/or vision-related functional impairments that manifest as reduced performance in school or work. On examination, CI is characterized by a remote near point of convergence and reduced fusional vergence. Outward eye deviation greater at near than at distance is seen in some patients, particularly those with a latent strabismus (picture 1). Not all patients with CI on examination are symptomatic; CI is found in approximately 5 percent of the healthy population [52].
Studies suggest that CI contributes to total symptom burden and neuropsychiatric impairments after mTBI [52]. Observational studies suggest that vision therapy can substantially improve symptoms as well as objective deficits [55].
Other clinical syndromes — In addition to BPPV, described above, other mechanisms of traumatic vestibular system injury include:
●Direct injury to the cochlear and/or vestibular structures usually occurs in the setting of transverse fractures of the temporal bone [56]. Hemotympanum and sensorineural hearing loss often occur along with vertigo. Facial palsy may also occur if the seventh cranial nerve is injured. The symptoms are maximal at onset and progressively improve in most patients over weeks and months due to compensation within the central nervous system.
●Labyrinthine concussion may occur from blunt injury to the membranous labyrinth from hitting the otic capsule [42,43]. This may occur with abrupt changes of head motion not necessarily associated with impact.
Labyrinthine concussion produces acute onset of vertigo and postural instability, often with tinnitus and hearing loss. Symptoms are maximal at the time of symptom onset and improve over days to months, usually somewhat more quickly than with temporal bone fractures, as described above.
●Perilymphatic fistula occurs when trauma causes rupture of the oval or round window and presents with sudden unilateral sensorineural hearing loss and acute, persistent, gradually diminishing vertigo and imbalance. Perilymphatic fistula can be difficult to diagnose and treat. (See "Causes of vertigo", section on 'Perilymphatic fistula'.)
●Vertebral artery dissection may accompany mTBI, and typically produces a lateral medullary infarction or Wallenberg syndrome. Patients present with acute onset of vertigo, which is sustained and often dominates the clinical presentation. Neck pain is common but not invariable. Transient ischemic attacks are relatively infrequent in this setting. While symptoms may develop at the time of injury, it is more common for there to be a delay of a day to a few weeks.
The clinical manifestations of lateral medullary infarction and vertebral artery dissection are discussed in detail separately. (See "Cerebral and cervical artery dissection: Clinical features and diagnosis", section on 'Clinical manifestations' and "Posterior circulation cerebrovascular syndromes", section on 'Lateral medullary infarction'.)
●Vestibular migraine produces episodic vertigo, with episodes typically lasting several minutes to a few hours, some of which are associated with migraine headache and/or other migrainous phenomenon. In one series of 58 active-duty or retired military personnel with dizziness after mTBI, 41 percent were diagnosed with vestibular migraine [43]. (See "Vestibular migraine".)
●Epileptic vertigo is rare, and is usually associated with a temporal lobe focus. Episodes are brief (less than a few minutes), stereotyped, and respond to antiseizure medication (see "Causes of vertigo", section on 'Epileptic vertigo').
Temporal lobe seizures and posttraumatic seizures are discussed in detail separately. (See "Focal epilepsy: Causes and clinical features", section on 'Neocortical temporal lobe epilepsy' and "Posttraumatic seizures and epilepsy".)
●Posttraumatic Meniere disease (MD) has been described in isolated case reports [37,57-59]; it may be that the association is spurious as symptoms reportedly develop months to years after the trauma. Patients with MD present with tinnitus, fluctuating sensorineural hearing loss, and episodic vertigo lasting several minutes to a few hours. The evaluation and treatment of MD is discussed separately. (See "Meniere disease: Evaluation, diagnosis, and management".)
●Cervicogenic dizziness is a controversial and somewhat inconsistently defined entity [60-65]. In case series, commonly described features include neck pain and subjective dizziness, usually in association with a whiplash injury. In many [65-67] but not all cases [61], dizziness seemed to recover in association with treatment of the neck condition, whether that be physical therapy, medications, or surgery.
A specific neuroanatomic basis of this entity is not defined but may involve impaired neck proprioception, which in turn affects vestibular processing [60,61,63,65].
●Nonspecific dizziness is a component of postconcussion syndrome. Sometimes described as vertigo, it may also be characterized by patients as a floating or swaying sensation or as unsteadiness or imbalance [44]. (See "Postconcussion syndrome".)
Evaluation and treatment — Appropriate management of posttraumatic vertigo requires identification of the pathologic mechanism(s) involved [68]. Identification of the most likely underlying pathology is based upon salient clinical features, in particular whether the vertigo is episodic versus sustained and whether there are accompanying symptoms or signs (algorithm 1).
While the approach to the evaluation of posttraumatic vertigo is similar to that of patients who have not had head injury, evaluation (and management) may be complicated by the fact that there may be more than one site and mechanism of vestibular injury in the same patient [68]. (See "Evaluation of the patient with vertigo" and "Causes of vertigo".)
Some case series also indicate that posttraumatic dizziness and vertigo are somewhat more refractory to treatment than their idiopathic counterparts, perhaps because of multiple contributing pathologic injuries [37,42]. However, two small randomized trials suggest that vestibular therapy may provide benefit in this setting [69,70].
See individual topic reviews for treatment of specific clinical syndromes. General symptomatic management of vertigo is discussed separately. (See "Treatment of vertigo".)
Other cranial nerve injuries — The risk of injury to other cranial nerves increases with the severity of brain injury, but these can also occur in mTBI with an incidence of 0.3 percent according to one case series [71]. The distribution is similar to that for moderate or severe head injuries:
●Anosmia and hyposmia, which are often reported by the patient as impaired taste as well as smell, occur following injury to olfactory filaments as they enter the brain through the cribriform plate. While recovery occurs in approximately one-third of patients, loss of smell is likely permanent if present one year after the injury [72]. (See "Taste and olfactory disorders in adults: Anatomy and etiology".)
●Diplopia may result from injury to cranial nerves III, IV, and VI. In the setting of mTBI, injury to cranial nerve IV is most common, followed by VI. Cranial nerve III is less commonly affected by mTBI. (See "Overview of diplopia" and "Fourth cranial nerve (trochlear nerve) palsy", section on 'Traumatic'.)
●Facial pain and occipital neuralgia may occur in association with mTBI. The former usually occurs in the setting of blunt force injury to the trigeminal nerve in the face, such as supraorbital neuropathy, while occipital nerve injury may be indirect from a contiguous musculoskeletal injury in the neck. (See "Overview of craniofacial pain".)
●Facial nerve palsy suggests a possible fracture to the temporal bone, which should be specifically evaluated. (See "Skull fractures in adults".)
Chronic traumatic encephalopathy — Repeated concussions appear to cause cumulative neuropsychologic deficits (ie, increasing severity and duration of mental status abnormalities after each separate incident) [27-29]. Cognitive impairment, psychologic symptoms (behavior and personality changes, depression, suicidality), parkinsonism, and other speech and gait abnormalities are described [73-78].
Epidemiology and pathogenesis — The incidence and prevalence of chronic traumatic encephalopathy (CTE) are unknown, as most studies involve a biased sample. Studies have focused on populations at risk of repetitive TBI, in particular athletes and military personnel.
●Sports-related concussion – Increasing reports of dementia among NFL players with a history of multiple concussions have focused attention on this entity, which has been labeled "chronic traumatic encephalopathy" in this setting [74,79-81]. A convenience sample of deceased NFL players found CTE in 110 of 111 [82]. One cohort study found that neurodegenerative disease-related mortality was three times higher in retired NFL players compared with the general United States population; Alzheimer disease (AD)-related mortality was four times higher [83]. Cumulative effects of repeated concussions have also been implicated in cognitive impairments among college and high school football players [84,85] and poorer neuropsychologic functioning in amateur and professional soccer players [86,87].
Chronic neurologic impairment has also long been recognized as a sequelae of boxing, and has been called "dementia pugilistica" in this setting [88]. The incidence is approximately 20 percent in professional boxers, and is much lower, perhaps negligible, in amateur boxers [89,90]. The number of professional bouts (typically more than 20) appears to be more important than the number of "knockouts" [91]. The total number and type of head blows, particularly if the angle of impact or failure to stabilize the head results in rotational head movements, may be important as well.
●Combat-related TBI – Single as well as multiple combat-related blast injuries in military personnel have also been identified as a precursor to CTE [92-96].
Observational studies are inconclusive but suggest that severity of the TBI event as determined by symptom severity and disability duration appears to increase the risk of CTE [97,98]. However, no threshold of injury with regard to number or severity has been established. The fact that concussion relies on self-report is another limitation of these studies. Age and sex have an undetermined role in predicting risk, although at least one subsequent study suggested that older age at the time of TBI increases the risk of subsequent dementia [97,98].
Apolipoprotein E (APOE) genotype may be a risk factor for CTE as it is for AD. In one series of 30 boxers, APOE genotype was associated with severity of neurologic deficits among high- but not low-exposure boxers [99]. In a similar study of 53 professional football players, older patients with APOE genotype were more likely to have cognitive impairment than those without the APOE genotype [100]. However, other studies suggest that APOE epsilon 4 is not associated with increased burden of neuropsychologic deficits after TBI [101,102]. It has been suggested that recurrent brain injury, and perhaps single brain injuries as well, may activate pathologic mechanisms similar to those that cause brain degeneration in AD [103-105]. Some investigations suggest that trauma may incite a chronic neuroinflammatory response, a mechanism that has also been implicated in AD [106]. However, further investigation is required; similarities and associations between CTE and AD may reflect a coincidence of the two conditions rather than a causal relationship or shared pathogenesis [100].
Neuropathology — CTE is defined pathologically by extensive tau-immunoreactive degenerative changes that are distinct from other tauopathies (such as AD) in their distribution with preferential involvement of the superficial cortical layers [16,73,95,107-109].
In 2016, a consensus panel convened by the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering (NINDS/NIBIB) identified the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern [110]. Supportive but nonspecific p-tau-immunoreactive features and other pathologies of CTE were also identified. These criteria were found to have good agreement between a panel of seven neuropathologists and the diagnosis of CTE [110].
Pathologic findings appear to be specific for CTE. In one study, pathologic findings of CTE were found in 32 percent of brains from 66 individuals with a history of repetitive brain injury and in none of the 198 brains from individuals without this history [111]. A pathologic study in 85 patients found that the severity of pathologic findings could be correlated with the severity of clinical findings [95].
While many consider CTE to be a progressive neurodegenerative disease, the nature of autopsy studies, which are cross-sectional rather than longitudinal, precludes that determination on a pathologic basis [112].
Clinical features — Our understanding of the clinical features of CTE is somewhat limited by the almost exclusive reporting in former professional athletes, thus invoking potential confounding bias [113]. In general, the core clinical features as described include [112]:
●Cognitive impairments – Including memory and executive function
●Behavior abnormalities – Aggression, paranoia, impulsivity
●Mood disorders – Depression, anxiety, suicidality
Neuroimaging — Advanced neuroimaging techniques (diffusion tensor imaging, magnetic resonance [MR] spectroscopy) have demonstrated associated white matter and other abnormalities in these patients; however, further studies are needed to define the sensitivity and specificity of specific findings and patterns of findings [81,85,114,115].
Diagnosis and treatment — At present, there is no specific clinical syndrome, neuroimaging feature, or other biomarker that has been shown to reliably identify patients with CTE.
Similarly, there is no treatment modality that is known to improve long-term outcomes. Symptoms may be managed empirically, as appropriate. (See "Management of neuropsychiatric symptoms of dementia".)
Neurodegenerative disease
●Motor neuron disease – An association between head injury and motor neuron disease is unproven [116]. This concern was raised when higher-than-expected incidences of amyotrophic lateral sclerosis (ALS) were documented in separate reports of Italian soccer players [117], American football and soccer players [118], and Gulf War veterans [119]. However, subsequent studies have not found a definitive association between TBI and ALS [120-124].
In a neuropathologic autopsy study of 12 former athletes with pathologically confirmed CTE, three also had motor neuron disease [125]. These three, along with seven others, were found to have abundant TDP-43-positive inclusions and neurites in the spinal cord as well. In one study, 24 patients with ALS and a history of head injury had similar rates of disease progression and neuropathologic findings compared with patients with ALS and no head injury [126].
●Others – Whether TBI is associated with neurodegenerative disease remains speculative. One study found cognitive decline by age 70 years was greater for male veterans with a history of TBI than those without [127]. In a pooled analysis of clinical and neuropathologic data, TBI with loss of consciousness was associated with risk for Lewy body accumulation but not Alzheimer pathology [128].
LATE MORTALITY — At least one cohort study found higher mortality rates in patients with mTBI 13 to 15 years after mTBI (eg, 27.9 versus 13.2 per 1000 per year) [129,130]. It is uncertain whether lifestyle factors or potential neuropathologic changes account for this observation; however, causes of death were similar among patients and controls. By contrast, other cohort studies have not found late increases in mortality after mTBI [131,132], although one of these found that recent TBI (within the past two years) was associated with a higher mortality rate [131].
PREVENTION OF TRAUMATIC BRAIN INJURY — The combined acute and chronic morbidity associated with mTBI suggests placing a premium on reducing the number of concussions. Individuals, particularly older patients, who have had one head injury are at increased risk of recurrent head injury [131].
Use of sport-specific helmets has been found to reduce head injuries in sports such as baseball, ice hockey, rugby, and alpine skiing and snowboarding [133-136]. However, these case-control studies leave open the possibility that the observed effects associated with voluntary use of a helmet are the result of general risk-avoidant behavior rather than the helmet itself. By contrast, helmets have not been found to reduce the rate of head injury in soccer players [137]. Furthermore, in some cases, use of protective equipment may adversely affect playing behavior, encouraging risky behavior, so that the risk of injury actually increases [138,139]. While American football helmets are widely used, there is no standard for helmet construction to prevent concussions [140].
Bicycle and motorcycle helmets reduce the severity of accident-related head injuries. (See "Bicycle injuries in children: Prevention".)
The National Football League (NFL) has made changes to rules, emphasizing player safety. As an example, in 2009, the return-to-play-from-concussion guideline was amended and blows to the head of a defenseless receiver were prohibited. During the 2010 NFL season, there was increased discipline (increased enforcement, large fines, and possible suspensions) for helmet-to-helmet contact in violation of players' safety rules and a change where the ball is immediately blown dead if a ball-carrier's helmet comes off during a play.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Increased intracranial pressure and moderate-to-severe traumatic brain injury" and "Society guideline links: Minor head trauma and concussion".)
SUMMARY AND RECOMMENDATIONS
●Definitions – Mild traumatic brain injury (mTBI) occurs with head injury due to contact and/or acceleration/deceleration forces. It is typically defined as mild by a Glasgow Coma Scale (GCS) score of 13 to 15, measured at approximately 30 minutes after the injury (table 1). The term "concussion" is often used as a synonym for mTBI. (See "Acute mild traumatic brain injury (concussion) in adults".)
●Second impact syndrome – This is a rare but potentially life-threatening phenomenon when diffuse cerebral swelling develops in the setting of a second concussion that has occurred when the patient is still symptomatic from an earlier concussion. (See 'Second impact syndrome' above.)
●Posttraumatic vertigo and dizziness – These can be a substantial contributor to disability after mTBI. Head injury may lead to vertigo by a variety of mechanisms (including direct injury to the vestibular apparatus, migraine, and others), each associated with a different clinical syndrome.
Treatment is guided by identification of the underlying mechanism. An approach to the evaluation of posttraumatic vertigo is presented in the algorithm (algorithm 1). (See 'Posttraumatic vertigo and dizziness' above.)
●Other sequelae – Other complications include postconcussion syndrome, headaches, epilepsy, sleep disturbances, and other cranial nerve deficits. (See 'Sequelae' above.)
Recurrent TBI may also lead to chronic neuropsychologic impairments known as chronic traumatic encephalopathy (CTE). (See 'Chronic traumatic encephalopathy' above.)
●Prevention – While the risks of repeated concussions are not well defined, there is sufficient evidence to support measures that limit repeated injuries. However, the efficacy of individual measures such as helmets is uncertain. (See 'Prevention of traumatic brain injury' above.)
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