CTE Confirmed in Living Patient for First Time

NOVEMBER 16, 2017
Matt Hoffman
Bennet Omalu, MD, MBA, MPHBennet Omalu, MD, MBA, MPH
A recent advancement in positron emission tomography (PET) scan tracing technology has allowed physicians to identify chronic traumatic encephalopathy (CTE) in living patients for the first time, according to a new study in the journal Neurosurgery.

The study revealed that CTE has an identifiable [F-18]FDNNP “fingerprint” that holds the potential to allow physicians to confirm diagnosis of the degenerative brain disease and other predominant tauopathies – a heretofore unprecedented feat. 

"This is a big step in the right direction,” Bennet Omalu, MD, MBA, MPH, and discoverer of CTE, told MD Magazine. “This is a milestone, period.”

Omalu, professor in the Department of Medical Pathology and Laboratory Medicine at the University of California-Davis’s School of Medicine, said the tracer technology “is telling us that we’re traveling in the right direction."

In the study, Omalu and colleagues examined the patterns of tau and amyloid fibrils in the PET scan of a living patient suspected of having CTE. The tracer has a reported high affinity for ß-pleated sheet fibrillar neuroaggregates, providing the potential for in vivo tau and amyloid fibril visualization.


Results suggested that in vivo identification of CTE substrates in living patients may not only be based on the presence or absence of proteinopathies, but also on the identification of the differential and selective topographic vulnerability unique to CTE, which [F-18]FDDNP-PET may be demonstrating.

"This is a milestone [because] we believed FDDNP should identify CTE in the brain," Omalu said. "The first case we scanned died, and the family was generous enough to call us and to give us his brain. We examined his brain and compared his brain to the data we noted while he was alive, did statistical analysis, and it confirmed that, yes, FDDNP is picking up what it should be picking up."

Previous work by the investigators revealed that brains diagnosed with CTE - a diagnosis normally only possible in the deceased - have been associated with unique patterns of [F-18]FDDNP in PET scans. 

PET scans and [F-18]FDDNP are used widely, and thus, this strategy could be widely implemented, Omalu said, adding that the method "will be done in 4 different hospitals across the country" in a clinical trial that is being planned to test it. The scan's ability ranges beyond CTE confirmation, according to Omalu, as it could also differentiate CTE from Alzheimer’s disease.

In the comparison of the postmortem neuropathological findings with the antemortem imaging results, a high level of correlation was found between the tau regional findings of the [F-18]FDDNP-PET scan and the postmortem autopsy (Spearman-rank order correlation coefficient [rs] =.592; P =.0202). No statistical correlation was identified between amyloid deposition (rs = -.481; P =.0695) or TDP-43 (rs=.433; P =.1066).

The study examined the [F-18]FDDNP-PET scan of the patient at age 59 (52 months pre-death), which showed “mild, global brain atrophy with enlarged ventricles, moderate bilateral hippocampal atrophy, and diffuse white matter hyperintensities,” the authors wrote. At age 61, the patient reportedly began to experience progressive motor deficits, muscle twitches, and decreased muscle mass.

According to the study, the patient was diagnosed with Motor Neuron Disease/Amyotrophic Lateral Sclerosis just 17 months prior to death at age 63, in addition to his presumed diagnosis of CTE. He reportedly experienced progressive dysphagia, progressive neck and limb weakness, and slurred speech, among other symptoms, just prior to death.

Post-death, the patient’s brain was examined for the distribution and density of proteinopathic changes, classified by 4 categories adapted from the Consortium to Establish a Registry for Alzheimer Disease (CERAD): none (0), sparse (1), moderate (2), and frequent (3). Of the 25 regions and subregions examined for tau and amyloid fibrillar neuroaggregates, 5 were categorized as 3+ for both, and 11 were categorized as 3+ for just tau fibrils.

Overall, multiple CTE diagnostic criteria were met as a result of the examination. The authors noted that as a result of these data, further evaluation in the form of clinical trials is needed to provide a proper assessment of [F-18]FDDNP-PET as an adjunct in CTE diagnosis in the living.

"So the next level now is a clinical phase 3 [trial]. We’ve been consulting with the [US Food and Drug Administration] and they are guiding us toward a clinical phase 3," Omalu said. "We’ve developed a study plan - it will last 2 to 3 years. In order to do the phase 3 [trial], we’re going to need $4 to $5 million, because we’re dealing with nuclear material. So the problem is, where do we raise the money from? My hope and prayer is that some generous organization or individual could take a leap of faith, make a difference, and fund this study because that would impact lives."

Since the trial will be short-term, the clinical impact of its findings could be swift. As Omalu noted, the important piece is the ability to "quantify the disease in the living" in order to begin testing treatment modalities.

Omalu said the process to develop a therapy is a 4-phase plan. Stage 1 was to identify the disease, Stage 2 was to have the results confirmed independently, and Stage 3 - "where we are," Omalu said - is to identify CTE in the living brain. Stage 4 is the development of treatment.

Omalu admitted that there could be an existing therapy for CTE - we just may not know it yet. He compared it to HIV therapy— prior to being able to quantify the viral load of HIV in patients, he said, we could not say how medicines would affect the virus. But now, with the ability to measure viral loads, we can see what works. Similarly, the ability to identify tau pathologies in the living brain would allow physicians to expose the patient to treatment, wait 6 months to 1 year, and go back and rescan the patient to see the impact of potential therapies on the tau pathology.

"There are drugs we know that can actually dissolve tau, but the problem is: how are you going to confirm that the drug is doing what it’s supposed to in the brain?" Omalu said. "That is where this scan comes in. No question about it: [there could be existing medicines to treat CTE]." 

Omalu said that one of the biggest effects of this study is the ability to change the narrative around the condition. The conversations around CTE remain morbid, despite the "gold standard" of identification being clinical symptoms, not autopsy.

"What this study does is show a gleam of hope that we’re moving forward with this. We’re moving into the realm of a living person. We’re no longer waiting for you to die, to take your brain and examine it - that sounds very morbid," he said. "So now, we are proposing to change the narrative, that yes, we are hoping to be able to scan, experimentally, living people to quantify, recognize, and identify the pathology in the living brain. What that does is take us to the next step: treatment."

Related Coverage
Sleep Apnea May Increase Alzheimer's Risk
Surgery Decreases Seizures, Increases QOL in Children with Epilepsy
Ibudilast Significantly Slows Brain Atrophy for Progressive MS

Copyright© MD Magazine 2006-2017 Intellisphere, LLC. All Rights Reserved.
$loginModal$