AUTHOR: Joseph S. Kass, MD, JD, FAAN
Chronic traumatic encephalopathy (CTE) is a pathologically defined neurogenerative disorder often found in athletes and veterans that is associated with repetitive concussive or subconcussive head injury. CTE presents with cognitive, psychiatric, and sometimes motor symptoms.
Traumatic encephalopathy syndrome (clinical diagnosis)
Dementia pugilistica (older term)
Punch drunk syndrome (older term)
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The incidence and prevalence of CTE are currently unknown. In the largest CTE case series to date, of 202 deceased individuals who had a significant history of repetitive head trauma related to either contact sports or military service, Mez et al1 reported that CTE was diagnosed in 177 former professional football players (87% of the cases) and, more specifically, in 110/111 (99%) of the former National Football League (NFL) players. The authors noted that the study was limited by ascertainment bias because individuals with symptoms consistent with possible CTE were much more likely to participate in the brain donation program, and therefore the true frequency of CTE pathology is unknown.
- A study of CTE in the brains of military personnel revealed that CTE was infrequently found and was usually reflected by minimal neuropathologic changes. Risk ratios for CTE were numerically higher among decedents who had contact-sports exposures in civilian life than among those who had blast exposure or other military TBI but the small number of CTE cases and wide confidence intervals precluded causal conclusions.2
- Among participants with severe CTE pathology, 89% had behavior, mood symptoms, or both, 95% had cognitive symptoms, and 85% had signs of dementia.
CTE may present early (20s to 30s) or later (50s to 60s) in adulthood. The relationship with sex is unknown.
Repetitive head injuries leading to concussions or subconcussive injuries are the strongest risk factor for the development of CTE. Athletes, veterans, and victims of repetitive head trauma are at highest risk. Although repetitive head trauma is required for CTE to develop, head trauma alone is insufficient. The search for genetic and environmental risk factors is underway.
CTE causes progressive cognitive, behavior, and mood changes and may even lead to motor deficits. CTE is a delayed presentation of repetitive concussive or subconcussive injuries and should not be confused with acute or postacute sequelae of traumatic brain injury (TBI). The most common cognitive domains affected are memory and executive function. The most common presenting symptoms in patients with autopsy-confirmed CTE are listed in Table E1. Because CTE is a pathologic diagnosis currently made only postmortem, a search for in vivo biomarkers is underway. Patients with a clinical syndrome thought to be the consequence of repetitive blows to the head are considered for research purposes to have traumatic encephalopathy syndrome (TES). Some TES patients are found postmortem to have CTE, whereas others may have other forms of neurodegeneration or even psychiatric conditions lacking specific neurodegenerative pathology. Like CTE, TES does not refer to either the acute or postacute sequelae of TBI such as concussion, postconcussive syndrome, or moderate to severe TBI. TES can take one of four clinical types: (1) Behavioral/mood variant, occurring in younger patients; (2) cognitive variant, occurring later in life; (3) a mixed variant; and (4) a dementia variant.
Table E1 Clinical Features at Initial Presentation of Patients With Autopsy-Confirmed Chronic Traumatic Encephalopathy
Reprinted with permission from Budson AE, Solomon PR: Memory loss, Alzheimer’s disease, and dementia: a practical guide for clinicians, ed 2, Edinburgh, UK, 2016, Elsevier Health Sciences, using data from Stern RA et al: Clinical presentation of chronic traumatic encephalopathy, Neurology 81(13):1122-1129, 2013. https://doi:10.1212/ WNL.0b013e3182a55f7f.
The behavioral/mood variant first presents early in life (later 20s to 30s), with primarily psychiatric and behavioral manifestations such as depression, anxiety, paranoia, impulsivity, explosivity, and aggression. Cognitive problems are more common as the disease progresses. The cognitive and dementia forms present later in life (50s to 60s), with impairment in episodic memory, attention, and executive function. Currently it is thought that CTE progresses in four stages with increasing severity along each stage. Symptoms progress from headaches, attention problems, and depression to explosivity, aggression, dementia, and suicidality as the disease progresses.
Physical examination findings are not always present in CTE but may include symptoms of parkinsonism and motor dysfunction, such as gait disturbance, tremors, ataxia, and dysarthria. These have been found to be particularly more common in boxers.
CTE may present similarly to the behavioral variant of frontotemporal dementia (bvFTD), but CTE patients, in addition to their history of repetitive or subconcussive head injury, experience more memory loss than patients with bvFTD. Alzheimer disease (AD) should be in the differential diagnosis for memory loss, but in addition to the apathy or irritability that may be seen in both AD and CTE, CTE patients have explosivity and disinhibition not typically seen in AD. CTE patients with dementia may also develop parkinsonism, raising the possibility of dementia with Lewy bodies (DLB), but parkinsonism is late and rare in CTE. Rapid eye movement (REM) behavior disorder is typical of DLB but not a feature of CTE, and disinhibition and explosivity are features of CTE not associated with DLB.
The frequency, severity, and total exposure to head trauma and the exact pathophysiologic mechanism by which repetitive head trauma causes CTE in CTE are active areas of research.
- Head injury is a necessary but insufficient risk factor for developing CTE; other exposure and genetic risk factors are under investigation.
- Currently, no validated clinical diagnostic criteria for CTE exist, although research diagnostic criteria have been developed.
- Concussion is a clinical syndrome of impaired brain function, typically affecting memory and orientation, with or without loss of consciousness that results from head injury.
- CTE is defined by neuropathology: Perivascular aggregation of phosphorylated tau protein within neurons and astrocytes that begins in the depths of sulci and progresses to involve the medial temporal lobes and other parts of the brain.
CTE is thought to occur as result of repetitive head injuries. Definitive diagnosis is made only through autopsy. Neurofibrillary tangles and p-tau aggregates may be found around blood vessels and in deep cortical sulci, amygdala, hippocampus, brain stem, and cerebellum depending on the stage of the disease.
