meehan 15 - cte

Authors and Correspondence

• William Meehan III, MD

• Rebekah Mannix, MD, MPH

• Ross Zafonte, MD

• Alvaro Pascual-Leone, MD, PhD

• Correspondence: Dr. Meehan (william.meehan@childrens.harvard.edu)

Abstract

• Recent reports link repetitive head trauma in athletes to various neuropsychiatric disorders.

• Symptoms observed in affected athletes include:

  • Mood disorders

  • Headaches

  • Cognitive difficulties

  • Suicidal ideation

  • Speech difficulties

  • Aggressive behavior

• Pathological findings, referred to as Chronic Traumatic Encephalopathy (CTE), have been observed in some of these athletes postmortem.

• Current hypotheses suggest that both concussions and subconcussive blows contribute to CTE, though not all athletes show these symptoms or pathologies.

• A need for more prospective data and case-control studies is evident to better understand CTE's causes and effects.

Glossary of Terms

• AD: Alzheimer Disease

• ALS: Amyotrophic Lateral Sclerosis

• CTE: Chronic Traumatic Encephalopathy

• FTD: Frontotemporal Dementia

• TDP-43: TAR DNA-binding Protein 43

Historical Context of CTE

• The term CTE is relatively recent; some symptoms have been noted since the early 20th century.

• 1928: Dr. Harrison S. Martland coined the term "punch drunk" for boxers showing symptoms of brain injury, including:

  • Unsteady gait

  • Mental confusion

  • Slowed muscle response

  • Hesitant speech

• The syndrome is progressive, worsening even after cessation of boxing.

Pathological Findings in CTE

• Studies have shown cerebellar atrophy, particularly in the frontal lobes, in those exposed to repetitive head trauma.

• Various studies (e.g., Corsellis et al.) have highlighted the following findings in boxers:

  • Cerebral atrophy

  • Atrophy of mammillary bodies

  • Thinning of hypothalamic floor

  • Dilated lateral ventricles

• The existence of tau-positive neurofibrillary tangles has been associated with the pathology of CTE, differing from Alzheimer’s disease where these typically coincide with amyloid plaques.

Clinical Features of CTE

• Symptoms as described include:

  • Affective disturbances

  • Social instability

  • Memory loss

  • Development of Parkinsonism

  • Progressive cognitive dysfunction

• Increased prevalence of CTE cases reported in athletes from various sports such as football and boxing.

Definition and Characteristics of CTE

• CTE is still underdefined; featured as a neurodegenerative disease resulting from repetitive mild traumatic brain injuries.

• Common characteristics of CTE include:

  • Neurodegenerative syndromes (memory disturbances, mood disorders, motor dysfunction)

  • Pathological criteria (cerebral atrophy, tau-immunoreactive pathology)

• Most definitive diagnoses made postmortem; identifying CTE in living patients is challenging.

Pathologic Characteristics

• Gross features of CTE include:

  • Cortical atrophy, especially in frontal and medial temporal lobes

  • Enlarged lateral and third ventricles

• Cellular features of CTE include:

  • Abundance of tau-positive neurofibrillary tangles throughout key brain regions, particularly in the depths of cortical sulci.

  • Irregularity in distribution termed the "skip phenomenon" complicates diagnosis.

Hypotheses Regarding CTE Pathogenesis

• Various hypotheses exist regarding the relationship between head trauma and neurodegenerative changes:

  • Martland proposed brain injury leads to hemorrhages causing progressive lesions.

  • Other theories suggest that mechanical damage from injuries leads to neurodegeneration and tau protein abnormalities.

  • Neuroimmunological responses and prolonged inflammation post-injury may sustain damage and lead to CTE.

Conclusions and Future Directions

• Current understanding of CTE is limited and calls for more robust studies that compare athletes with and without documented CTE pathologies.

• It's critical to further differentiate between mere associations of injuries and actual causative factors in the development of CTE.