How Can Neurologists Diagnose Traumatic Encephalopathy Syndrome?

BOSTON—Proposed diagnostic criteria for probable or possible chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease associated with repetitive brain trauma, include a history of head impacts and various core clinical and supportive features.

Andrew Budson, MD

The preliminary criteria, which were presented by Andrew Budson, MD, Professor of Neurology at Boston University School of Medicine, at the 69th Annual Meeting of the American Academy of Neurology, primarily were designed for research purposes, but can serve as a guide for neurologists for the diagnosis of traumatic encephalopathy syndrome. CTE is a neuropathologic diagnosis, whereas traumatic encephalopathy syndrome is a clinical diagnosis. In addition to presenting the general criteria, Dr. Budson shared diagnostic subtypes, potential biomarkers, and treatment options.

General Criteria

There are five general criteria that patients must meet to receive a diagnosis of traumatic encephalopathy syndrome, said Dr. Budson. First, there must be a history of impacts to the head based on types of injuries (eg, mild or severe traumatic brain injury, concussions, or subconcussive trauma) and sources of exposure, such as military service or involvement in contact sports for a minimum of six years, including at least two years at the college level or higher.

Second, patients must not have another neurologic disorder that likely accounts for the clinical features. Third, clinical features must be present for at least 12 months. The fourth requirement is that at least one core clinical feature (ie, cognitive, behavioral, or mood features) must be present and considered a change from baseline. Finally, at least two of nine supportive features must be present.

Core Clinical and Supportive Features

Of the core clinical features, difficulties in cognition must be reported by the patient, an informant, or a clinician and substantiated by standardized tests. Core behavioral clinical features include emotionally explosive behavior or physical and verbal abuse. Core mood clinical features include feeling overly sad, depressed, or hopeless.

In addition to core clinical features, two of the following supportive features must be present: impulsivity, anxiety, apathy, paranoia, suicidality, headache, motor signs (eg, dysarthria, dysgraphia, or other features of parkinsonism), documented decline for at least a year, or delayed onset of clinical features after a significant head impact exposure (usually at least two years).

Syndrome Subtypes

Patients may have one of four possible traumatic encephalopathy syndrome diagnostic subtypes. A behavioral/mood variant is more common among younger patients, whereas a cognitive variant is more common in older populations, said Dr. Budson. Patients also may have a mixed variant or dementia. Patients with the dementia subtype must have a progressive course of cognitive core clinical features, with or without behavior or mood features. In addition, patients with dementia must have cognitive impairment that interferes with their ability to function independently during normal daily activities.

Biomarkers and Treatment

Cavum septum pellucidum, cavum vergae, or fenestrations on neuroimaging are potential CTE biomarkers, said Dr. Budson. Normal beta amyloid CSF levels, elevated CSF p-tau/tau ratio, negative amyloid imaging, as well as cortical atrophy beyond that expected for age could also be signs of CTE. Potential experimental biomarkers include positive tau imaging and cortical thinning based on MRI.

Once physicians have made a diagnosis of probable or possible CTE, there are several treatments that may benefit patients, although no medications are approved for the treatment of CTE. Cholinesterase inhibitors may help to treat memory impairment, said Dr. Budson. For patients with depression and anxiety, selective serotonin reuptake inhibitors may be helpful. For patients with violent or explosive behavior, atypical neuroleptics may be efficacious. Memantine may benefit patients with moderate or severe dementia. Finally, to manage agitation, a combination of dextromethorphan and quinidine may be a treatment option.

—Erica Tricarico

Suggested Reading

Montenigro PH, Baugh CM, Daneshvar DH, et al. Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome. Alzheimers Res Ther. 2014;6(5):68.