Chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is thought to result from mild repetitive head injury. The diagnosis can only be made by neuropathological examination.

Terminology

Chronic traumatic encephalopathy refers to a specific neuropathological diagnosis, often made post-mortem ¹⁰. Traumatic encephalopathy syndrome refers to the clinical syndrome presumed to be associated with these neuropathological changes ¹⁰.

Epidemiology

The exact incidence and prevalence are unknown. It is most commonly seen in amateur and professional contact/collision sports players where repetitive head injury is common (e.g. boxing, American football, rugby, ice hockey), as well as in military personnel exposed to explosive blasts and victims of domestic violence ^1,3,10. 

Clinical presentation

Symptoms have an insidious onset, most often years after the initial injuries, with loss of attention/concentration and episodic memory ¹⁰. This can progress, in some cases in 2-3 years, to include motor symptoms such as impaired gait (including parkinsonism), impaired executive function, neurobehavioural dysregulation, lack of insight, and poor judgment ^1,2,4,10. 

Pathology

Although the details remain to be elucidated, there is mounting evidence that reactive gliosis and redistribution of aquaporin 4 molecules, leading to disruption of transparenchymal CSF clearance of interstitial beta-amyloid via the glymphatic system may be a key component ⁸.

Macroscopic appearance

There is generalized cerebral atrophy with more pronounced atrophy of the frontal and temporal lobes (including mesial temporal lobe) as well as the thalamus, hypothalamus, and mammillary bodies. A cavum septum pellucidum may be present ².  

Microscopic appearance

Chronic traumatic encephalopathy is characterized by the presence of neurofibrillary tangles and TDP-43 binding protein in subcortical and perivascular regions, often with reactive astrocytes and microglia ⁷. 

Radiographic features

MRI

Imaging features of chronic traumatic encephalopathy are non-specific, but the following may be seen ^4,7:

• generalized cortical atrophy

• hippocampal atrophy

• vermian atrophy

• cavum septum pellucidum

• features of diffuse axonal injury (e.g. microhemorrhages)

Treatment and prognosis

No disease-modifying treatment exists and thus management is supportive ⁹.

History and etymology

This syndrome was first recognized in boxers in 1928, and has been known as "punch drunk" and "dementia pugilistica".

Differential diagnosis

There is clinical and imaging overlap of chronic traumatic encephalopathy with other neurodegenerative diseases. Traumatic brain injury is a risk factor for their development (i.e. not just chronic traumatic encephalopathy) and should be considered in the differential diagnosis ^5,6:

• Alzheimer disease

• amyotrophic lateral sclerosis

• frontotemporal dementia

• Parkinson disease