Douglas Smith, a professor of neurosurgery at the University of Pennsylvania, has a concise way of summing up where scientists are at in their understanding of concussions and the lasting havoc they can wreak in the brain.
"We're almost up to the starting line," said Smith, who directs UPenn's Center for Brain Injury and Repair.
The point is that while concussions are a well-known phenomenon affecting millions of North Americans annually, the term remains a descriptor of symptoms rather than a precisely understood neurological condition.
Smith likens the word concussion to "consumption," the mysterious wasting ailment of the 19th century that later turned out to be tuberculosis, a disease with a known cause and, eventually, an effective course of treatment. Once the condition was understood, the term consumption faded from the medical vernacular.
More: Read excerpts from Game Change, Ken Dryden's new book on hockey and head injuries
Smith's hope is that scientists can make similar strides with concussions, replacing the cartoon view of a brain being knocked around inside the skull with a detailed picture of what is going on at the cellular level.
"If you don't know the underlying cause, how will you treat it," he asks, pointing out that most medical schools in the United States still teach concussions as a laundry list of signs and symptoms and nothing more.
That view is changing thanks to the growing awareness that at least some concussions can leave the brain impaired over the long term. Meanwhile, studies led by researchers at Boston University suggest that far milder but repeated hits to the head, such as those that occur routinely in contact sports, can lead to the brain-wasting condition known as chronic traumatic encephalopathy, or CTE.
Researchers are now using new tools to probe the brains of those who have experienced concussions to look for subtle changes that would have previously escaped notice. This has reinforced the view that a concussion is akin to a catastrophic electrical failure in the brain's communication network, something like a blackout that takes down the power grid in a major city.
In many cases, the biological equivalent of circuit breakers can be reset and the system apparently resumes as before. In others, there can be hidden but long-term damage from which the brain never fully recovers.
The first job for neuroscientists is understanding how to tell the two situations apart in order to make a diagnosis and plan for treatment. It's a pressing question, and a difficult one because it cannot be approached the way many medical conditions are studied, by relying on animal models.
"The problem is you can't ask a rat if it's experiencing dizziness, or any of the 60 or so other symptoms of concussion," says Charles Tator, professor of neurosurgery at the University of Toronto, senior scientist and director of the Canadian Concussion Centre, Krembil Neuroscience Program, Toronto Western Hospital.
"A lot of this research has to be done in people."
In fact, humans could be almost uniquely vulnerable to concussion, an evolutionary trade-off that comes with having a relatively massive brain tethered at its base in a fluid-filled compartment.
When the head is struck during an impact or fall, the brain can twist or rotate around the brainstem. Scientists have long know that it's rotation rather than linear motion in the brain that brings about the symptoms of concussions, including loss of consciousness. This is thought to be because the rotation stretches the brain's white matter, which is essentially the wiring that connects different brain regions together.
Nerve cells communicate via their axons, long slender structures that convey electrochemical messages in the form of charged ions. When a blow to the head stretches those connections, axons are flooded with ions and the entire system is disrupted. That can account for the immediate and disorienting effects of a concussion, which are cleared away after hours or days. More worrisome is so-called post-concussion syndrome, where the effects may persist for years.
In such cases, it may be that the microscopic architecture inside each axon, which serves like a railway that shuttles proteins up and down its length, has been permanently damaged. Axons swell up with derailed proteins and ultimately die, leading to loss of connections that can slow brain function.
If this scenario proves correct, Smith says, it could help separate those who are likely to experience such damage from those with less serious concussions, "by looking for pieces of axons in their blood." It could also point the way to drugs that bolster axon repair wherever such repair is possible – although clinical trials of such drugs are at least a few years away.
Last year, researchers at the University of Western Ontario in London developed another approach to diagnosing concussions based on metabolites – small molecules in the blood that are the result of cellular processes. While no one metabolite can reveal a concussion, the researchers found that changing patterns in 174 metabolites allowed them to identify test subjects who experienced a concussion with 90-per-cent accuracy. With further research, it may be possible to also estimate the severity of a concussion based on such a blood test, says Doug Fraser, a physician and scientist who led the work. But the challenge remains daunting because the range of outcomes is so great.
"Every brain is different, every injury is different, every person is different," Fraser said. "That makes it a lot more difficult to diagnose."
This challenge is compounded for CTE, a long-term degeneration of the brain that is characterized by cognitive and behaviour issues including depression and aggression, but which currently can only be definitively diagnosed by looking at the brain after death.
While concussions have been linked to CTE, the connection is a complex one and the mechanism remains obscure. But what is abundantly clear from more than 400 brains donated to Boston University's CTE Center by former football players, is that the disease is characterized by the appearance of the tau proteins, which neurons normally rely on to stabilize their internal structure. Researchers speculate that a brain that is repeatedly subjected to blows may be in a constant state of inflammation, trying to repair itself in the short term but ultimately triggering longer-term damage.
The tau protein is at the heart of another Western study, currently heading for publication, in which researchers examined changes in the tau protein found both in CTE as well as in amyotrophic lateral sclerosis, or Lou Gehrig's disease. They were then able to coax the same changes in rat brains that mimic the effects of brain injury.
"We have this really unique window now into understanding what the trauma is," said study leader Michael Strong, who is dean of medicine at Western.
For Michael Alosco, a clinical neuropsychologist, the recent progress is welcome but is tempered with the reality that the number of CTE cases will continue to grow without public education related to the risk and, in professional sports, cultural change.
"It has the potential to be a major public-health concern," he said. "I think a lot of people are now realizing this is a problem we can't ignore."