Progressive Focal Gray Matter Volume Loss in a Former High School Football Player: A Possible Magnetic Resonance Imaging Volumetric Signature for Chronic Traumatic Encephalopathy

Authors: Cyrus A. Raji, MD, PhD; David A. Merrill, MD, PhD; Jorge R. Barrio, PhD; Bennet Omalu, MD, MPH; Gary W. Small, MD

American Journal of Geriatric Psychiatry, October 2016

Introduction

The connection between American football, repetitive head trauma, and traumatic brain injury (TBI) has become a growing focus in both medical research and public health. Historically, athletes exposed to repeated concussions were described as suffering from “punch-drunk syndrome,” a condition now understood as chronic traumatic encephalopathy (CTE).

While most confirmed CTE cases have been found in former NFL players, emerging evidence suggests that high school and college athletes may also be at risk. Because definitive diagnosis of CTE requires autopsy, identifying premortem imaging biomarkers is critical for earlier detection and intervention.

This case study presents a 51-year-old former high school football player with a history of multiple concussions, progressive cognitive decline, and psychiatric symptoms. Volumetric MRI with Neuroreader® revealed focal gray matter loss that may represent a potential MRI signature for CTE.

Case Presentation

Clinical History

• Patient: 51-year-old male, former high school running back and defensive end.
• Concussion history: Estimated ~900 head impacts over 3 years of high school play, including at least one major concussion with loss of consciousness.
• Symptoms (10-year progression):
  • Declining attention and memory
  • Mood lability and depression (without suicidal ideation)
  • Impulse control issues and “cognitive voids”
  • Job loss due to concentration difficulties

The patient was previously diagnosed with ADHD and bipolar disorder type II, though symptoms did not fully align with those conditions.

Neuropsychological Testing

• Global cognition: Normal
• Executive function: Impaired (Stroop test – 16th percentile)
• Memory performance: Normal (55th percentile)

Neuroimaging Findings

The patient underwent two MRI scans (2012 and 2016), analyzed with Neuroreader® for quantitative volumetrics.

Key Results

• 14% total gray matter loss over 4 years.
• Greatest decline in:
  • Midbrain
  • Ventral diencephalon
  • Frontal lobes
• No atrophy in temporal or parietal lobes (rules out Alzheimer’s and frontotemporal dementia).
• Cavum septum pellucidum detected (nonspecific, but often reported in CTE).
• MRI also revealed old petechial hemorrhages and gliosis in frontal and parietal-temporal white matter.

Correlation with PET Imaging

• Atrophy patterns aligned with FDDNP-PET findings of tau accumulation in other suspected CTE cases, particularly in the frontal lobes, brainstem, and diencephalon.

Discussion

This case may represent the first documented example of progressive volumetric MRI changes in a high school football player with suspected CTE.

Key Insights

1. Distinct volumetric signature: Progressive atrophy localized to brainstem, diencephalon, and frontal lobes, sparing hippocampus and temporal lobes.
2. Differential diagnosis:
   • Alzheimer’s disease ruled out (no hippocampal or temporal lobe loss).
   • Frontotemporal dementia ruled out (temporal lobes preserved).
   • Bipolar disorder unlikely (no hippocampal or cerebellar volume loss).
3. Psychiatric symptoms: Executive dysfunction and mood lability aligned with frontal lobe atrophy.
4. Protective factors: Patient’s normal hippocampal volume and preserved memory may reflect lifestyle habits (regular exercise, omega-3 diet).

Implications for Sports and Public Health

• CTE risk extends beyond professional football—this case highlights possible long-term effects in high school athletes.
• Volumetric MRI with Neuroreader® could serve as a premortem biomarker for CTE, allowing clinicians to:
  • Track progression of atrophy
  • Differentiate CTE from Alzheimer’s, FTD, or psychiatric disorders
  • Guide early intervention and treatment strategies
• Reinforces the importance of concussion safety protocols at all levels of play (high school, college, professional).

Conclusion

This case demonstrates that longitudinal volumetric MRI can reveal progressive focal brain atrophy in a former high school football player with suspected CTE. The findings support the potential of quantitative neuroimaging as a diagnostic tool for premortem identification of CTE and highlight the urgent need for preventive measures in contact sports.