A new, simple blood test for serious consequences of mild brain injury, or concussion, may be on the horizon thanks to experts at the University of Pennsylvania.
Working together with colleagues at Glasgow University, U.K., Douglas H. Smith, M.D., and his team are developing a test because the signs of concussion can be subtle, making diagnosis hard. Some patients will also suffer long-term symptoms such as memory problems.
In previous research, the team found that high blood levels of a brain protein called alpha II-spectrin N-terminal fragment (SNTF) is linked to greater problems in recovery. Their new work has taken this further by examining the origins and effects of this protein.
SNTF is made in damaged nerve fibers deep in the brain, they explain, in a condition known as diffuse axonal injury. This form of injury cannot be seen on standard brain scans because concussed brains rarely show bleeding, bruising, or other obvious abnormalities. But microscopic examination of the brain in severe and fatal traumatic brain injury cases often shows numerous swollen, degenerating, and even fully disconnected axons throughout the white matter.
In tests on patients with severe traumatic brain injury, levels of SNTF were again closely linked to diffuse axonal injury. The team also found that a diffuse axonal injury can produce a wide range of damaging effects on axons, the long portions of nerve cells.
Unlike injury to discrete brain regions, axonal injury affects the way in which networks of the brain communicate with one another. Areas of the brain communicate via pathways made of axons and send information within and between brain regions.
Details of the study are published in the journal Acta Neuropathologica. Said Smith, “Our findings also confirm that even relatively mild, concussion-type brain impacts can cause permanent damage of this kind.”
Dr. William Stewart of Glasgow University added, “Our work represents a major step forward towards developing a biologically plausible blood test that could be used to detect concussion and direct injury management. A blood test for SNTF could allow doctors to diagnose concussion and to predict those that might have prolonged symptoms.”
The team believes their discoveries will “provide insight into a more comprehensive approach to the neuropathological assessment of diffuse axonal injury.”
Drs. Smith and Stewart focus on the public perception of concussion in a recent article in The Lancet Neurology. They write, “Despite Hollywood films and endless news headlines about concussion, there remains remarkable confusion over the underlying pathology.
“Contrary to the all too common animations illustrating the brain slamming back and forth inside the skull, the principal mechanical basis of concussion is likely to be head rotational acceleration,” they write. “A consequence of these rotational forces is rapid deformation of the brain resulting in tissue damage, particularly to vulnerable white matter axons.”
Normally, axons can stretch to at least twice their resting length and relax back, unharmed, write the authors. “However, very rapid stretching, such as that which occurs with concussion, results in components of the axon becoming stiffer, resulting in breakage of axonal microtubules, a pathology known as diffuse axonal injury, leading to protein accumulation at sites of injury.”
The diffuse axonal injury-associated proteins, namely tau and amyloid precursor protein, are responsible for both the acute injury of concussion and also, in severe cases, the neurodegeneration seen in chronic traumatic encephalopathy.
They conclude that “remarkable knowledge gaps remain” in our understanding of concussion. “Most notably, we are really only at the beginning of deciphering the underlying causes, one important candidate being diffuse axonal injury.”
The same team has previously investigated long-term neurodegeneration caused by traumatic brain injury. This can include progressive axonal degeneration that can continue years after the original injury. It may also play a role in the development of Alzheimer’s disease.
“Although historically ignored as a major health issue, traumatic brain injury is a leading cause of illness and death internationally, with significant socio-economic implications,” they warn in the journal Experimental Neurology.
“There is considerable evidence indicating just a single traumatic brain injury may be associated with the later onset of neurodegenerative disorders, including Alzheimer’s disease,” they write, adding that, damage to axons “may have a role in this development of Alzheimer-like pathologies.”
Johnson, V. E. et al. SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury. Acta Neuropathologica, 20 November 2015 doi: 10.1007/S00401-015-1506-0
Smith, D. O. and Stewart, W. Tackling concussion, beyond Hollywood. The Lancet Neurology, June 2016 doi: 10.1016/S1474-4422(16)30037-0
Johnson, V. E. et al. Axonal Pathology in Traumatic Brain Injury. Experimental Neurology, August 2013 doi: 10.1016/j.expneurol.2012.01.013