What is Chronic Traumatic Encephalopathy (CTE)?

Chronic Traumatic Encephalopathy (CTE)

Chronic Traumatic Encephalopathy (CTE) is a progressive neurodegenerative disease characterized by abnormal accumulation of hyperphosphorylated tau protein in neurons and astrocytes, occurring in individuals with a history of repetitive head trauma, including concussions and subconcussive impacts. 1

Pathology and Mechanism

CTE is defined by distinct neuropathological findings:

• Pathognomonic features:

  • Perivascular hyperphosphorylated tau deposits in neurons, astrocytes, and cell processes
  • Patchy distribution at the depths of cortical sulci
  • Neurofibrillary tangles and abnormal neurites 1, 2

• Additional pathological findings:

  • Cerebral atrophy, particularly in frontal and temporal lobes
  • Cavum septi pellucidi with fenestrations
  • Shrinkage of mammillary bodies
  • TDP-43 proteinopathy in >85% of cases 3, 2

The pathological changes begin focally and progressively spread to involve superficial cortical layers before becoming widespread, affecting medial temporal lobe structures, diencephalon, and brainstem 2.

Risk Factors and Epidemiology

CTE is strongly associated with:

• Repetitive head trauma, including concussions and subconcussive impacts 4
• Contact sports participation, including:
  • American football (99% of former NFL players in one study)
  • Boxing ("dementia pugilistica")
  • Ice hockey, soccer, rugby, wrestling 1
• Military service with blast exposure 1

Importantly, the number of years of exposure to repetitive head trauma, rather than the number of diagnosed concussions, appears to be the most significant risk factor for CTE development 5. This suggests that chronic, repetitive head impacts, even without concussive symptoms, drive disease progression.

Clinical Presentation

CTE typically presents after a latency period of 14-15 years following exposure to repetitive head trauma 5. Clinical manifestations include:

• Early symptoms:

  • Irritability and impulsivity
  • Aggression and depression
  • Short-term memory loss
  • Increased suicidality 2

• Progressive symptoms:

  • Cognitive deficits and executive dysfunction
  • Behavioral and personality changes
  • Parkinsonism
  • Memory impairment progressing to dementia
  • In some cases, motor neuron disease 3, 2

Diagnosis

Currently, CTE can only be definitively diagnosed through post-mortem neuropathological examination 1, 6. No validated biomarkers or clinical criteria exist for diagnosing CTE in living individuals.

The McKee criteria, developed by expert neuropathologists, confirm CTE as a unique neurodegenerative disease with pathognomonic lesions found only in individuals exposed to brain trauma 1.

Research efforts are underway to develop biomarkers for in vivo diagnosis, including:

• Advanced neuroimaging techniques
• Cerebrospinal fluid and blood-based biomarkers 4, 1

Management

Without disease-modifying treatments available, management focuses on symptom control:

• Non-pharmacological approaches:

  • Cognitive rehabilitation
  • Behavioral therapy
  • Physical exercise
  • Sleep hygiene optimization 6

• Pharmacological management of specific symptoms:

  • Depression and mood disturbances
  • Cognitive impairment
  • Behavioral issues
  • Sleep disorders 6

Prevention

Prevention remains the most effective approach:

• Reducing exposure to repetitive head trauma
• Proper enforcement of rules prohibiting dangerous techniques like spear tackling in contact sports 4
• Neck muscle strengthening to potentially reduce concussion risk 4
• Delaying return to play after concussion until complete symptom resolution 4

Research Directions

Current research priorities include:

• Development of in vivo diagnostic biomarkers
• Understanding the role of genetic factors and other modifiers
• Investigating the relationship between CTE and other neurodegenerative conditions
• Exploring potential disease-modifying treatments 1, 6

Important Caveats

• The true prevalence of CTE remains unknown due to selection bias in brain donation programs
• Not all individuals with repetitive head trauma develop CTE
• The minimum threshold of head trauma exposure needed to trigger CTE is unclear
• The contribution of other factors (age, genetics, substance use) to CTE development requires further investigation 2