What is the diagnostic approach for Chronic Traumatic Encephalopathy (CTE)?

Diagnostic Approach to Chronic Traumatic Encephalopathy (CTE)

Currently, definitive diagnosis of CTE can only be made post-mortem through neuropathological examination demonstrating a unique pattern of p-tau deposition. 1

Clinical Assessment

• History:

  • Document substantial exposure to repetitive head impacts from:
    • Contact sports (football, boxing, hockey, soccer, rugby)
    • Military service
    • Other causes of repeated head trauma 1
  • Assess for core clinical features:
    • Cognitive impairment (episodic memory and/or executive function)
    • Neurobehavioral dysregulation (poor emotional/behavioral control)
    • Progressive course of symptoms 1

• Clinical Presentation:

  • Cognitive symptoms: Memory problems, executive dysfunction
  • Behavioral symptoms: Explosiveness, impulsivity, rage, violent outbursts, emotional lability
  • Other symptoms may include: Depression, suicidal thoughts, personality changes 2, 3

Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES)

The National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for TES requires:

1. Substantial exposure to repetitive head impacts
2. Core clinical features of cognitive impairment and/or neurobehavioral dysregulation
3. Progressive symptom course
4. Clinical features not fully explained by other neurologic, psychiatric, or medical conditions 1

Imaging Studies

• MRI:

  • Recommended sequences: 3D T1 volumetric, FLAIR, T2-weighted, and diffusion-weighted imaging 1
  • May show cerebral atrophy, cavum septi pellucidi with fenestrations, and shrinkage of mammillary bodies 2
  • Limited utility in early or mild cases 1
  • Class I recommendation: Only perform MRI in patients with persistent, new, or worsening symptoms 1

• Advanced Neuroimaging Techniques (Research Stage):

  • Tau PET imaging (investigational) 1, 4
  • Diffusion Tensor Imaging (DTI) to assess white matter integrity 5, 4
  • Functional MRI (fMRI) 5, 4
  • Magnetic Resonance Spectroscopy (MRS) 4
  • Susceptibility Weighted Imaging (SWI) 4

Biomarkers (Research Stage)

• Blood-based biomarkers being investigated:

  • Phosphorylated tau (p-tau)
  • Neurofilament light chain (NfL)
  • TREM2
  • CCL11
  • GFAP 4

• CSF biomarkers (investigational):

  • Tau proteins
  • Amyloid markers 6, 4

Differential Diagnosis

Rule out other conditions that may mimic CTE symptoms:

• Alzheimer's disease
• Frontotemporal dementia
• Lewy body dementia
• Vascular cognitive impairment
• Psychiatric disorders (depression, PTSD)
• Other causes of traumatic brain injury 1, 7

Important Caveats

• Clinical diagnosis of CTE is not currently possible - TES criteria are primarily for research purposes 1
• TES criteria should be used cautiously in clinical and medicolegal settings 1
• Avoid equating TES diagnosis with CTE pathology 1
• Current diagnostic approaches have high sensitivity (97.3%) but low specificity (20.2%) 1
• The DIAGNOSE CTE Research Project is ongoing to develop and validate in vivo biomarkers for CTE diagnosis 6

Clinical Approach Algorithm

1. Screen individuals with history of repetitive head impacts and cognitive/behavioral symptoms
2. Exclude other neurological, psychiatric, or medical conditions
3. Document progressive course of symptoms
4. Consider MRI if symptoms are persistent, new, or worsening
5. Apply TES research criteria if appropriate
6. Refer to specialists with expertise in traumatic brain injury and neurodegenerative disorders
7. Consider research participation in biomarker development studies

Remember that while clinical suspicion may be high in certain cases, definitive diagnosis remains a post-mortem finding until validated biomarkers are established.