Until now, the diagnosis of CTE could only be confirmed when it was no longer of any use to the patient, namely at autopsy. Researchers have now been able to identify MRI markers so that those affected could benefit from the correct classification during their lifetime.
Chronic traumatic encephalopathy (CTE) can develop after repeated head trauma, a progressive neurodegenerative tauopathy for which there was previously no way of detecting it in the living. Our understanding of the clinical manifestations of CTE has improved, but still lags behind other tauopathies. A groundbreaking study now reports that there are, after all, specific characteristics in structural magnetic resonance imaging (MRI) that would allow a diagnosis to be made while the patient is alive.1
"That would be great!" writes one physician in a reader comment on the medical portal Medscape.2 "When CTE started to become known, one of my patients was a former NFL football lineman. His official diagnosis was 'schizophrenia' - but it was clear that this was for want of anything better - and he probably died with that diagnosis. But today it is clear (to me) that he had CTE - and a clear diagnosis could have helped him have a much better quality of life. The way things were going for him, he had lost everything: his farm, his family, his friends, his ability to earn a living - everything."
According to neuropathological criteria, four stages of CTE are defined, describing a progressive accumulation of hyperphosphorylated tau (pTau). The type and distribution of tau pathology in CTE appears to be different from that in Alzheimer's disease. Also, there is no accumulation of ß-amyloid plaques in CTE.2
Shrinkage of the frontal and temporal lobes is considered the initial and most striking characteristic of CTE. Finally, in stage IV, there are diffusely distributed tau lesions and tangles throughout the cortex, as well as neuronal demise and gliosis in the frontal and temporal brains.
A recent study examined 55 men during their lifetime with an autopsy-confirmed CTE, 45 of whom were stage III/IV. All had in common a history of repeated trauma to the head. Almost all (52/55) had been football players, two ice hockey players and one man had been through military operations and combat.
After correction for age at imaging, the cognitively symptomatic men with confirmed CTE had significantly more severe frontal, temporal and hippocampal atrophy and almost 7-fold higher odds of having a CSP (cavity of septum pellucidum or pseudoventricle) on lifetime MRI compared to 31 cognitively unremarkable controls. However, the presence of a CSP is only significant in combination with the shrinkage of the frontal lobe (a CSP alone is also sporadically found in the general population of elderly people). In addition, higher atrophy scores on MRI were associated with more severe pTau accumulation in 14 regions at autopsy.
Nearly two-thirds of the CTE brain donors (n = 36) had another neurodegenerative disease in parallel. However, the effect sizes remained similar even when patients with frontotemporal lobar degeneration or Alzheimer's disease were excluded.
If these findings are validated by prospective clinicopathological correlation studies, the use of structural MRI could become a valuable tool to aid in the diagnosis of CTE during a patient’s lifetime, the researchers hope.
In another reader comment, a psychologist expresses her gratitude for this work, writing, "I am a survivor of a severe traumatic brain injury 23 years ago and have suffered multiple falls and concussions from my head injury. I welcome this news very much. I don't want to wait until I die to have an autopsy to do something I could have done now."2
However, experts who were not involved in the study argue that the results should not be overestimated. Frontal-temporal atrophy is not a specific feature of CTE. It is also conceivable that the MRI findings reflect a craniocerebral trauma rather than CTE. Tau-PET imaging is potentially a better candidate than MRI for the new gold standard of CTE diagnosis.
However, the most critical dissenting voice goes even further, suggesting that the association of tau with atrophy is not surprising and still need not say anything about how or whether the tau pathology observed in CTE contributes to the clinical expression of symptoms.2
References:
1. Alosco, M. L. et al. Structural MRI profiles and tau correlates of atrophy in autopsy-confirmed CTE. Alzheimer's Research & Therapy 13, 193 (2021).
2. MRI Key to Diagnosing CTE in Living Patients? Medscape http://www.medscape.com/viewarticle/964345.