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Experts Gain Ground in CTE Diagnosis

<ѻý class="mpt-content-deck">— NIH working group says perivascular tau deposition is hallmark feature of chronic traumatic encephalopathy.
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WASHINGTON -- A consensus conference has established neuropathological criteria for diagnosing chronic traumatic encephalopathy (CTE), researchers reported here.

The panel of neuropathology experts identified tau accumulation in neurons and neurites in a perivascular pattern that they said is specific to the disease, , of Boston University, reported during a poster presentation here at the American Academy of Neurology meeting.

"I think this puts to rest the idea that CTE is not a distinctive disease," McKee told ѻý. "It's a major step forward."

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • A panel of neuropathologists released consensus criteria for the neuropathologic diagnosis of chronic traumatic encephalopathy, which includes tau accumulation in perivascular neurons and neurites -- the finding most specific for the disease.

, of NorthShore University HealthSystem near Chicago agreed that it was "an important step." He was not involved in the poster by McKee's group, but he has developed a potential screening method for CTE.

"This helps clarify the level of our understanding based on our limited but important experience with CTE," Bailes said. "This defines, crystalizes, and objectifies some of the uncertainties of CTE, and establishes by expert consensus the standards for the neuropathological tissue diagnosis of CTE."

One of the major criticisms of CTE is that it may not be its own disease; that it can't be distinguished from cognitive impairment or Alzheimer's disease. In April 2013, the NIH launched a major effort to define the pathologic characteristics of CTE, with a goal of one day being able to use imaging tools to examine patients for CTE while they're still alive (currently the diagnosis can only be made by autopsy).

Part of that effort was the consensus conference, held in Boston in February 2015. Eight neuropathologists reviewed some 700 slides taken from 19 brain regions of 25 patients. Some of them were CTE cases, while some showed other tauopathies including Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, primary age-related tauopathy, and parkinsonism dementia complex of Guam.

McKee said they had very high inter-rater agreement for the diagnosis of CTE.

The feature that was considered most specific for CTE was a distribution of tau in neurons and neurites around blood vessels. It was a feature that made it distinct from other tauopathies, McKee said.

Additionally, this hallmark was only seen in patients who'd had brain trauma, particularly in those who'd had multiple episodes of it, she said.

The group also listed supportive criteria for a diagnosis of CTE, as well as findings that were considered exclusions to the diagnosis.

McKee said the criteria constitute the first step in the process of fully characterizing the neuropathology of CTE, though she acknowledged that several questions remain. For instance, the involvement of the spinal cord, neuronal cell loss, gliosis, inflammation, and hemosiderin deposition, are unknown.

Also, there are no clear and specific pathologic stages of the disorder, and amyloid and TDP-43 pathologies need to be further characterized.

The group also noted that it is "especially important" for neurologists to understand that it isn't yet possible to correlate clinical symptoms or future brain health with the signature pathologic feature of CTE.

McKee noted that other criticism of the CTE diagnosis has been that there's no definitive proof that trauma is the underlying cause of the observed lesions.

"From our point of view, you can't prove causality in a human study. You can't knock people over the head and ask them to donate their brain. This is as close as we're going to get with a human study, and that this panel endorsed trauma as the etiology, I think that is a major step forward," she said.

The full paper from the consensus group will be published in the near future.

Disclosures

The study was supported by NINDS and NIBIB cooperative agreement.

McKee disclosed no financial relationships with industry.

Primary Source

American Academy of Neurology

Source Reference: McKee AC, et al "Preliminary results of the NINDS/NIBIB consensus meeting to evaluate pathological criteria for the diagnosis of CTE" AAN 2015; Abstract P2.178.