Chronic Traumatic Encephalopathy: A Clinical Perspective.

The concept of chronic traumatic encephalopathy (CTE) has dramatically altered neuroscientific thinking about potential relationships between traumatic brain injury (TBI) and dementia, two of the more prevalent health challenges facing medicine and society. Whereas these disorders both feature cognitive impairment, a plausible link between them was relatively obscure until the past decade, when widely publicized neuropathological data began to appear describing a dementia syndrome in people who had been exposed to repetitive mild TBI (mTBI) (1). This condition was noted to feature prominent cerebral tauopathy and was referred to as CTE (1). The term CTE had actually been first proposed in the 1940s (2, 3) but garnered little attention outside of medical professionals whose work focused primarily on sports and TBI. In contrast, the reintroduction of the idea immediately attracted the attention of a wide range of medical professionals and at the same time generated significant health concerns among the general public. This phenomenon has in large part been related to media coverage regarding a poorly operationalized cluster of symptoms and outcomes that were hypothesized to be related to cerebral tauopathy identified in brains of former professional athletes. In turn, this sense of alarm has ledmany individuals with repetitive mTBI from a variety of exposure settings to suspect that they have CTE because of symptoms similar to those of people who were later found to have the condition at autopsy. Some people may even suspect that they have CTE after a single mTBI. Such individuals may be markedly distressed by their self-diagnosis, or by having had this diagnosis suggested by a medical professional. In turn, they frequently turn to clinicians, seeking validation for their suffering while at the same time expressing concerns that they have an incurable disease. Facing this dilemma, those who care for these individuals would be well advised to step back and consider the phenomenon of CTE from a broad evidence-based perspective that maintains the patient’s well-being as the foremost priority. A fact about which all agree is the existence of a neuropathological entity that has been termed CTE, although postmortem criteria are not always consistently defined. Autopsy has provided key information about tauopathy and other brain changes observed after multiple mTBIs in athletes andmilitary veterans, leading to energetic investigation of what appears to be a disease similar or identical to the older entity described in retired boxers known as dementia pugilistica (4). The essential point for clinicians, however, is that no method exists for making the diagnosis of CTE during life. Brain biopsy could potentially disclose neuropathological features of CTE but is prohibitively hazardous as a procedure given that no effective treatment to modify the presumed neuropathology is available. Clinical criteria have been proposed, but despite much investigation, no such criteria have been agreed upon for identifying CTE in living patients who may be at risk (5, 6). Similarly, while efforts to visualize the accumulation of tau in the living brain using positron emission tomography have yielded some useful information (7), as of this writing, no neuroimaging technique can be used to confirm that CTE actually exists in a person with worrisome symptoms and exposure to repetitive mTBI (8). What then is a clinician to do? One unresolved issue is that the clinical features thought to be associated with CTE have varied over time. Speech, movement, and memory disturbances were historically reported in autopsy-identified cases of dementia pugilistica, but alterations in personality and emotional expression, along with cognitive decline, have been the clinical focus of CTE cases (8). The literature has not yet provided an explanation that reconciles these varying clinical manifestations, although a neuropsychiatric perspective has likely added more detail to the clinical profile of recent cases. Whereas dementia pugilistica and CTE share enough clinical pathological features to invite the notion that they are the same disease, it is not yet firmly established that the disorder linked to boxing several decades ago is the same one now being described in former professional athletes and military veterans. Other more vexing problems exist. CTE describes a constellation of neuropathological signs purportedly associated with repetitive mTBI and manifesting as a neurodegenerative dementia, but not only is consensus lacking on the symptoms and signs of this dementia, it is not clear how common the diseasemay be or the extent towhich TBI alone accounts for its development (5, 9). How many people have the neuropathology of CTE with no symptoms and how many have symptoms without the neuropathology remain unanswered questions. Fewer than 400 cases of CTE have been described, and the absence of prevalence data means that it is premature to generalizefindings onCTE to the larger