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Chronic traumatic encephalopathy (CTE) remains a diagnosis that can only be made during autopsy, but consensus criteria for a clinical syndrome associated with CTE that can be diagnosed during life have been proposed.

New (TES) from the National Institute of Neurological Disorders and Stroke (NINDS) are the first research criteria developed for the clinical disorder associated with CTE, reported Robert Stern, PhD, of Boston University, and co-authors in Neurology.

"The publication of these criteria is another important step that will enable scientists to fill knowledge gaps, including a better understanding of CTE's clinical features and natural history, incidence and prevalence, as well as the causes and risk factors for developing this neurodegenerative disease," said NINDS director Walter Koroshetz, MD, in a statement.

CTE is associated with a history of repetitive head impacts (RHIs), including those sustained in contact or collision sports like American football and boxing. It can be by the presence of hyperphosphorylated tau (p-tau) in a unique pattern.

The NINDS expert panel, part of the ongoing project, aimed to provide researchers with detailed criteria for diagnosing study participants with TES with a "provisional level of certainty" that an individual would have CTE brain pathology.

Under the new criteria, a person diagnosed with TES for research purposes must have both substantial exposure to RHIs and core clinical features not fully accounted for by other conditions. If these criteria are met, the individual's level of functioning is graded, including assessing for dementia.

Substantial exposure to RHIs can be from contact sports, military repetitive blasts, or other sources like domestic violence, head banging, and vocational activities. These head impacts can be with or without clinical symptoms or signs of concussion or traumatic brain injury. Thresholds for football, where most CTE research has been conducted, include a minimum of 5 years of organized American football, with 2 or more of those years played at the high school level or beyond.

Core clinical features include progressive cognitive impairment involving episodic memory or executive functioning, or neurobehavioral dysregulation including explosiveness, impulsivity, rage, violent outbursts, and emotional lability, or both.

These changes in cognition or behavior must not be fully accounted for by pre-existing, established, or acquired neurodegenerative disorders or non-degenerative nervous system, medical, or psychiatric disorders and conditions. "Comorbid diagnosis of another neurodegenerative disease, substance use disorder, post-traumatic stress disorder (PTSD), or mood or anxiety disorders does not exclude TES," Stern and co-authors wrote. "The determination if other conditions more fully account for the core clinical features often may require extensive evaluation."

It's important to note these symptoms of TES are nonspecific, observed Lili-Naz Hazrati, MD, PhD, of the Hospital for Sick Children in Toronto, and Nicole Schwab, MSc, of the University of Toronto, in an .

"RHIs are a risk factor of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's, ALS, and others for which the clinical symptoms heavily overlap with TES," Hazrati and Schwab wrote. "Symptoms of TES are also common in the general population, reflecting patients with chronic pain, suicidality, and mood disorders." Moreover, the neuropathology of CTE is not entirely clear nor universally agreed upon, they noted.

Importantly, TES diagnostic criteria are for researchers, not clinicians, the editorialists emphasized. "With the uncertainties surrounding CTE pathology and TES, the clinician's priority should be treating clinical symptoms to improve patient quality of life," they wrote.

"Currently no biomarkers nor disease modifying treatments for CTE exist, however treatments for many symptoms of CTE do," Hazrati and Schwab pointed out. "It is crucial that clinicians do not give a premortem diagnosis of CTE, as this can cause harm and lead to worsened symptoms, mental health, and even suicide."

Diagnostic criteria for TES will be updated as new research information becomes available, Stern said in a statement: "It is expected that biomarkers, such as PET scans and blood tests currently being studied in the DIAGNOSE CTE research project, will be integrated into the criteria to improve diagnostic accuracy in the next few years, resulting in the appropriate use of the criteria to diagnose patients in the clinic."

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