Revealing brain damage from battlefield to playing field
Andrey Nailor, M.D.·Published 17 May 2012·9 min read
Key points
Traumatic brain injury, the signature wound of the Iraq and Afghanistan wars, is doubly cruel: it leaves many victims emotionally shattered and cognitively crippled.
For the new study, published Wednesday in the journal Science Translational Medicine, scientists compared three groups of brains.
There are no approved treatments for traumatic brain injury.
Now the first experiment of its kind documents exactly what "the invisible injury" - at least the kind caused by blast waves or repeated physical impacts - does to the brain: Crumpled axons, which carry signals between neurons; gummed-up neurons like those in Alzheimer's disease; strangled blood vessels.
Traumatic brain injury, the signature wound of the Iraq and Afghanistan wars, is doubly cruel: it leaves many victims emotionally shattered and cognitively crippled. But because mild and moderate brain injuries do not show up on CT or other imaging, doctors and even family members are often skeptical that any real damage exists.
Now the first experiment of its kind documents exactly what "the invisible injury" - at least the kind caused by blast waves or repeated physical impacts - does to the brain: Crumpled axons, which carry signals between neurons; gummed-up neurons like those in Alzheimer's disease; strangled blood vessels.
An injured brain is so littered with the chewed-up remains of neurons and other cells that "it looks like autophagy - the brain eating itself alive," said Lee Goldstein, an Alzheimer's researcher at the Boston University School of Medicine and co-leader of the study.
The discovery promises to help such injuries be taken more seriously, and might lead to preventives or treatments. It comes at a time when both the Pentagon and the National Football League are struggling with the legacy of head injuries.
Tens of thousands of U.S. troops have sustained such injuries and some have committed suicide or other acts of violence. In one horrific case, an Army staff sergeant who had sustained head trauma is accused of murdering 17 Afghan civilians in March.
Most people are unaware of the scope of Traumatic brain injury (TBI) or its overwhelming nature. TBI is a common injury and may be missed initially when the medical team is focused on saving the individual's life. Before medical knowledge and technology advanced to control breathing with respirators and decrease intracranial pressure, which is the pressure in the fluid surrounding the brain, the death rate from traumatic brain injuries was very high. Although the medical technology has advanced significantly, the effects of TBI are significant.
TBI is classified into two categories: mild and severe.
A brain injury can be classified as mild if loss of consciousness and/or confusion and disorientation is shorter than 30 minutes. While MRI and CAT scans are often normal, the individual has cognitive problems such as headache, difficulty thinking, memory problems, attention deficits, mood swings and frustration. These injuries are commonly overlooked. Even though this type of TBI is called "mild", the effect on the family and the injured person can be devastating.
Severe brain injury is associated with loss of consciousness for more than 30 minutes and memory loss after the injury or penetrating skull injury longer than 24 hours. The deficits range from impairment of higher level cognitive functions to comatose states. Survivors may have limited function of arms or legs, abnormal speech or language, loss of thinking ability or emotional problems. The range of injuries and degree of recovery is very variable and varies on an individual basis.
Written and revised by
Andrey Nailor, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
The effects of TBI can be profound. Individuals with severe injuries can be left in long-term unresponsive states. For many people with severe TBI, long-term rehabilitation is often necessary to maximize function and independence. Even with mild TBI, the consequences to a person's life can be dramatic. Change in brain function can have a dramatic impact on family, job, social and community interaction.
The invisibility of many head injuries "is a huge problem," said retired U.S. Army General Peter Chiarelli, chief executive officer of One Mind, a non-profit group promoting brain research. "The ER doc will say, 'why am I wasting my time with this guy when I have people with visible injuries?'"
Adding to the urgency: the recent suicides of former pro football players who sustained head injuries during their playing days. The most recent, former San Diego Chargers linebacker Junior Seau, fatally shot himself earlier this month.
The term traumatic brain injury (TBI) refers to injuries to the brain that are caused by some form of traumatic impact. Traumatic brain injuries usually are caused by a blow to the head, violent shaking or penetration of the brain tissue. Depending on the cause and severity of the brain injury, brain damage can be mild, moderate or severe.
Initial symptoms of a traumatic brain injury may include:
- Headache - Dizziness - Loss of consciousness - Blurred vision - Confusion - Memory loss - Seizures - Paralysis - Coma
In more serious cases of traumatic brain injury, complications can be fatal. While the severity of traumatic brain injuries varies, the long-term effects are often devastating and life-altering.
What is Traumatic Brain Injury?
Traumatic brain injury is sudden, non-congenital physical damage to the brain from an external force that temporarily or permanently disrupts normal brain function. Brain characteristics and functions that can be affected include consciousness, speech and language, memory, mobility, personality and others. Because the brain controls all bodily functions, any damage to the brain, regardless of severity, can impair physical and psychological activity.
MAKING 'THE INVISIBLE INJURY' VISIBLE
For the new study, published Wednesday in the journal Science Translational Medicine, scientists compared three groups of brains. Four came from military veterans who had suffered the blast of an improvised explosive device (IED) or a concussion. Four belonged to young athletes who had concussions. And scores were from mice that had been exposed to a blast akin to that from an IED 17 feet (five meters) away packed with 12 pounds (5.4 kilograms) of TNT, comparable to an IED made from a 120-mm artillery round.
None of the brains had obvious injury. "If you hold them in your hand you don't see any damage," said neuropathologist Ann McKee of the Boston University School of Medicine and the Veterans Affairs New England Healthcare System, co-leader of the new study. "CT and MRI don't see it. It takes a microscope, even an electron microscope."
With that scrutiny the damage was clear. Specialized cells called astrocytes extended what BU's Goldstein called "little feet" that wrapped themselves around blood vessels. Axons crumbled and wound up in cellular garbage cans. Long strings of proteins called tau formed, as seen in Alzheimer's disease.
The damage was strikingly similar to what scientists have seen in the brains of ex-football players who had sustained head injuries and, after death, were found to have chronic traumatic encephalopathy (CTE), the condition once known as boxer's dementia.
CTE can cause depression, aggression, impulsivity and memory loss and has been linked to suicide. "Men become very aggressive, develop a hair-trigger temper, and their judgment is off," said Goldstein. "These are all part and parcel of damage to the brain."
Age offered no protection. In the new study, the athletes ranged in age from 17 to 27 when they died. They are the youngest head-injury victims ever found with CTE.
Until this study, scientists could not be sure that head injuries, from an IED or a linebacker, caused the brain or behavioral changes. That's where the lab mice came in. While anesthetized and in a special tube, they were exposed to blasts akin to those suffered by U.S. troops in Iraq and Afghanistan.
Even though a shock wave barreled through the animals' skulls at 336 miles per hour, "there was no bleeding, no contusions, no rips in the tissue," said Goldstein, who led the mouse part of the study. "They looked for all the world like what we see in human cases of traumatic brain injury - the invisible injury that people have been talking about since World War One."
The mice's behavior changed, too: they could not remember or learn as well after the blast as before it. "This matches what veterans (exposed to IEDs) say: 'I'm thinking slow and I can't remember,'" said Goldstein.
The three lines of evidence - from veterans, athletes and lab mice - suggest a common mechanism by which head injury causes CTE and CTE impairs mental function.
Blasts in a war zone and head trauma on a gridiron both break axons and stretch neurons, said McKee, a football fan who has four bobble-head dolls of retired NFL quarterback Brett Favre in her office. That stretching makes their membranes more porous, allowing calcium ions to flood into the neuron and activating enzymes that alter tau proteins just as they are altered in Alzheimer's. As a result, said McKee, "the neuron is no longer functional."
{pagebreak}
It may not even take such dramatic impacts to impair mental skills. A second study released on Wednesday showed that some college football and hockey players had lower scores on thinking and memory tests after a season of enduring repeated but minor hits to the head.
The players, outfitted with special helmets that measured head impacts, experienced an average of 469 during the season, scientists led by Thomas McAllister of the Geisel School of Medicine at Dartmouth reported in the journal Neurology.
TREATING AND PREVENTING
There are no approved treatments for traumatic brain injury. One experimental drug from BHR Pharma, a subsidiary of Besins Healthcare SA, is in the last stage of human testing.
But the study suggests the military should re-examine soldiers' protective gear. Heavy helmets that protect against impacts and even bullets "are like putting a bowling ball on top of a match stick," said Goldstein, exacerbating the destructive acceleration and deceleration from a blast wave.
According to the CDC (Centers for Disease Control and Prevention), USA:
- About one third of injury related American deaths are linked to TBI - About 230,000 hospitalizations occur annually in the USA as a result of TBI - 1.1 million Americans are treated for TBI and released from an emergency department - Almost 2% of the US population lives with TBI-related disabilities - About 2 million American adults and children suffer from traumatic brain injury annually - 50,000 patients die annually in America as a result of TBI - Every 15 seconds one American man, woman or child sustains a significant traumatic brain injury - The total number of individuals with TBI who are not seen in an emergency department, or who do not receive any care is unknown - Direct medical costs and indirect costs, such as lost productivity of TBI totaled an estimated $60 billion in the USA in 2000
- Among American children aged up to 14 years, TBI results in an estimated:
Scientists have not managed thus far to identify effective medications to improve outcomes for such patients, despite the extent of the problem.
The CDC also reports that the main causes of TBI are falls (28%), motor vehicle traffic crashes (20%), struck by/against events (19%), and assaults (11%).
When the mice's heads were immobilized, though, an identical blast produced no brain damage. That finding "has invaluable implications for future safety measures," said psychologist Jennifer Wilde of the University of Oxford, who was not involved in the study. Namely: "special helmets to help keep soldiers heads still during a blast."
The results also suggest that head trauma should be treated immediately instead of waiting for symptoms. The BU scientists "are working on field-deployable treatments," Goldstein said, including anti-inflammatory drugs and agents that target leaky blood vessels.
The U.S. military tries "to identify TBI as soon as possible and provide effective treatment," said Pentagon spokesperson Cynthia Smith. That policy pertains "regardless of whether the injury is obvious and severe, or subtle and hidden." All service members in a vehicle collision or rollover or within 150 feet of a blast undergo a mandatory medical evaluation.
The new study also confirms the physical reality of psychological illnesses that the military and others have sometimes dismissed. "Post-traumatic stress disorder has been regarded as a purely psychological illness, because we've been looking at brains with CT and MRI," said neuropathologist Bennet Omalu, chief medical examiner of San Joaquin County in California and co-founder of the Brain Injury Research Institute. BIRI hopes to examine Seau's brain, which the BU lab is also in the running for.
"CT and MRI don't have the resolution to show the cellular and sub-cellular changes you can get from a concussion or sub-concussive injury," said Omalu. "Now we can see that PTSD is likely to be a manifestation of traumatic brain damage."
News
