Chronic traumatic encephalopathy (CTE) occurs as a result of repetitive mild traumatic brain injury (TBI) with a progressive neurodegenerative pathology. CTE was first identified as “punch drunk” syndrome by Martland in 1928, who reported severe neuropsychiatric symptoms in a group of boxers.1
The disease process involves accumulation of phosphorylated tau (p-tau) in the sulci and peri-vascular region, with accompanying gliosis. CTE neuropathological progression is described in four stages. In stage I, there are few loci of p-tau in the sulci of lateral frontal cortices. The advancement of the disease involves areas of the brain including the temporal and parietal lobes as well as the insula. By stage 4, there is global spread of p-tau, as well as phosphorylated 43 kDa TAR DNA binding protein (TDP-43).
Although there is no consensus on the clinical characteristics of CTE, McKee and colleagues2 proposed a set of clinical symptoms corresponding to each of four neuropathological stages.
Stage 1. A typical CTE patient is either clinically asymptomatic or may complain of mild short-term memory deficits, or depressive symptoms. Mild aggressive symptoms have also been reported.
Stage 2. Mood and behavioral symptoms are more severe and may include explosive behavioral outbursts and more severe depressive symptoms.
Stage 3. Patients typically display more cognitive deficits, ranging from memory loss to executive and visuospatial functioning deficits as well as symptoms of apathy.
Stage 4. Patients have profound language deficits, psychotic symptoms such as paranoia as well as motor deficits and parkinsonism.
Further attempts at clinical classification of CTE patients were made by Stern and colleagues.3 The researchers looked at 36 male patients with pathologically confirmed CTE, who did not have any comorbid neurodegenerative diseases; histories were provided by next of kin informants retrospectively. There were two distinct emergent clinical subgroups: the younger group initially presented with behavioral/mood symptoms, while the older group presented with mainly cognitive symptoms. Cognitive deficits eventually developed in the younger group, whereas there were significantly less mood and behavioral symptoms in the older group as time went by. Furthermore, the younger group of patients were significantly more physically violent and behaviorally disinhibited. It is important to note that approximately one-quarter of these patients did not have memory symptoms. However, as the researchers noted, these two clinical subtypes may not be representative of the wider spectrum of all CTE patients.
In a more extensive study, Mez and colleagues4 examined 202 American football players; 177 of these players had a confirmed CTE diagnosis. The mean age at the time of death was 67 years; the mean number of years of playing football was 15.1. Study subjects were divided into mild and severe neuropathology groups. The vast majority from both groups suffered from behavioral and mood symptoms, as retrospectively reported by next of kin (96% from the mild CTE subgroup vs 89% from severe CTE subgroup). Similarly, most of the patients in both groups had cognitive symptoms (85% in the mild subgroup vs 95% in the severe subgroup). Moreover, 33% of patients in the first group displayed signs of dementia compared with 85% of the second group who had signs of dementia.
Findings suggest an association between cumulative repetitive head impacts and the development of neuropsychiatric symptoms including depression, behavioral dysregulation, executive functioning deficits, and cognitive impairment in adulthood.5 The age at the time of exposure to repetitive head impacts is another distinct risk factor for development of neurocognitive deficits in later adulthood.
Dr Fesharaki-Zadeh is Instructor of Psychiatry and Neurology, Boyer Center of Molecular Medicine, Yale University, New Haven, CT. He reports no conflicts of interest concerning the subject matter of this article.
1. Martland HS. Punch drunk. JAMA. 1928;91:1103-1107.
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