Traumatic brain injury

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Traumatic brain injury
It’s been a bad month for brains, and particularly for traumatic brain injury:

* A University of Pennsylvania football player who committed suicide at age 21 had the type of brain damage that is linked to depression and suicide in veteran pro footballers. While the cause of Owen Thomas’s suicide may never be fixed, brain damage in such a young player was a chilling reminder of the brain’s fragility.

* Although the National Football League has new rules requiring concussed players be sidelined for their protection, on Sept. 12, two Philadelphia Eagles stayed on the field, despite signs of concussion visible to millions of viewers.

* An estimated 300,000 American veterans of the wars in Iraq and Afghanistan have brain injuries; some severe enough to interfere with memory, speech, thought or movement.

In national security, the national sport, and on the national highways, brains are getting banged. Some estimates say 5 million Americans have some permanent damage from a traumatic brain injury which is due to impact rather than bleeding or loss of blood flow — the causes of stroke.
Eighty two years after dementia pugilistica was diagnosed in boxers, we should not be surprised that impacts in war, car accidents and high-intensity sports are taking a toll on the thinking organ, says Robert John Dempsey, chair of neurological surgery at the University of Wisconsin-Madison. “As we have improved our ability to image brains, and to diagnose dysfunction to include cognition, we have discovered deficits that may have been obvious to family members and physicians.”

ENLARGE

Falls 28%, motor vehicle traffic 20%, struck by/against 19%, Assault 11%, unknown 9%, other 7%, bikes 3%, other transport 2%, suicide 1%

The causes of brain injuries in the United States during six years.

Dempsey says autopsies of people who have had multiple concussions, “suggest there was a permanent injury, a disruption of axons and loss of brain substance.”

The brain shrinkage seen in autopsies of former football players after multiple concussions is called chronic traumatic encephalopathy. This disturbing shrinkage of the brain is linked to severe, deadly brain abnormalities, including memory loss, confusion, paranoia, depression, dementia and Parkinsonism.

Striking younger

After the growing concern about traumatic brain injury among middle-aged football veterans who were paid to endure thousands of blows to the head, the discovery of such damage in the 21-year-old Penn player raised questions for young athletes and their parents, as Robert Stern, a professor of neurology at Boston University, explained to the New York Times. “We don’t know if it’s a specific age, we don’t know if it’s a cumulative number of years of exposure to head trauma, we don’t know what combination of hits to the head set this disease in motion. These are critical issues that need to be answered in order to help guide any dramatic policy changes and individual decisions down the road.”

2 brain sections on top, bottom is miscroscopic view, normal brain has no brown spots, damaged brain has many

Chronic traumatic encephalopathy is marked by concentrations of tau protein, shown here as brown spots. More tau equals more damage. Left: a normal, 65-year-old brain. Right: The brain of former NFL linebacker John Grimsley, who died of a gunshot at age 45 after nine concussions.

Traumatic brain injury can produce many symptoms:

* Poor memory, attention and concentration

* Impulsivity and problems with decisions

* Disorientation and dizziness

* Problems with speaking and communication and

* Movement disorders, including Parkinsonism.

two football players in a tackle, one falling face forward, opponent holding ball falls on head

A 2007 study by University of North Carolina scientists suggests that concussions can follow almost any type of head impact in football, regardless of its strength and location.

A changed picture of brain injury

Until recently, impact was considered less serious than contusions — brain injuries with obvious damage like bleeding and swelling, says Dempsey. “It was considered possible you would not make a full recovery [of movement, speech and vision] from a contusion.”
Until a decade or two ago, Dempsey says, “concussion without a structural disruption was considered a source of transient loss of function, consciousness, confusion, but one where recovery was felt to be complete.”
But when the brains of former pro football players were examined after death, massive damage was blamed for serious problems like depression, confusion and movement disorders.
Today, concussion and contusion seem less like distinct things and more like stages of a continuum of brain injury, Dempsey says. “There is a wave of increasing realization that any injury to the brain should be taken seriously, and that repeated minor injury is cumulative.”

Searching for succor

What can be done in the face of a wave of traumatic brain injuries? The obvious measure, protection and prevention, seems, well, obvious. But ironically, better protection is part of the reason why so many soldiers are returning with brain injuries — body and vehicle armor keeps them alive without always protecting the head.

So what is medicine learning about treating traumatic brain injury? Nobody has a recipe for repairing damage once it’s complete — but traumatic brain injury is not always sudden, and researchers are hot on the trail of techniques that can interrupt the damage process and preserve brain tissue and function.

Room full of people, some in white military uniforms, officer pinning medal on another in a wheelchair

Hospital corpsman Anthony Thompson gets a medal while being treated for a traumatic brain injury caused by an improvised bomb in Iraq.

What do some promising recent studies say about halting or treating traumatic brain injury in animals or people?

Glucose — a sweet solution?

 Silver sedan crashed head-on into tree in an urban setting

Photo: biblicone
Car accidents account for 20 percent of traumatic brain injuries.

Doctors have long worried that an injured brain often contains too much energy in the form of blood sugar, says David Hovda, a professor of neurosurgery and director of Brain Injury Research Center at the University of California at Los Angeles. In stroke victims, a high level glucose in the blood is known to be “really bad because it promotes more damage, and we thought the same thing was true in traumatic brain injuries, so the standard of care became to reduce plasma glucose down to normal.”

But Hovda questions the wisdom of reducing fuel to the brain after trauma. “In animal studies, we began to manipulate serum glucose and found that if we dropped it, brain cells began to show all the signs of being killed by not having enough fuel. When we began to use the same sort of measures in human patients, we discovered the same thing: If we deprive the brain of more glucose, brain cells start to die.”

Hovda says his studies in rodents suggest the brain has complicated fuel needs during recovery. “We believe, but don’t know, that the fuel characteristics are also going to be different, given age, gender, stage of recovery and perhaps the type of injury.”

Military officer in fatigues lying on medical table getting a CT scan, combat boots toward camera

With improved safety gear, more U.S. soldiers are surviving attacks, but then must live with brain injuries.

Hovda says UCLA is in the second year of a five-year project to test the optimum level of plasma glucose after a traumatic brain injury in 20 to 25 patients. Beyond glucose, he will also test other fuels that might support recovery while reducing harm in other parts of the brain. “We’re going to see if we can change their outcome; it’s an efficacy trial, and it’s funded by National Institutes of Health for $5 million.”

If the new approach has promise, Hovda hopes to start a larger trial that would treat traumatic brain injury patients with a variety of intravenous fuels.

Supreme supplements?

Brain injuries can affect small structures like the hippocampus, which is critical to memory and other higher thought processes. In a mouse model of brain injury, Akiva Cohen, an associate professor of pediatrics and neurology at the University of Pennsylvania School of Medicine, has found that dietary supplements may help the hippocampus work after injury.

“We have shown in an animal model that dietary intervention can restore a proper balance of neurochemicals in the injured part of the brain, and simultaneously improves cognitive performance,” says Cohen, who is also a neuroscientist at Children’s Hospital of Philadelphia.

Football player runs into opponent, whose helmet falls away from impact

A 2007 study found that football impacts could reach more than 100 Gs (100 times the acceleration of gravity). That’s equivalent to slamming against a brick wall at 25 mph.

Like many biological processes, the transmission of nerve impulses is tightly controlled. One major neurotransmitter, glutamate, excites neurons, while another, GABA, calms them. An imbalance in these compounds can cause the hippocampus to malfunction, Cohen says.

The imbalance has been concealed because the hippocampus has two pools of the neurotransmitters, and only the smaller pools at synapses (where two brain cells make contact) appear to be altered after injury.

If you study the hippocampus as a whole, Cohen says, “you can’t see the change in smaller, synaptic pool because it’s concealed by a larger pool of the neurotransmitters used for other cellular functions.”

In a study with mice, Cohen found that feeding the mice with branched chain amino acids that are precursors — raw materials — for the two transmitters returned their level at the synapses to normal.

“Once we saw that through feeding, we could bring the concentration back to the level of the control animal, we asked if we could bring back memory, and memory did come back to normal,” Cohen told us. “Memory is a hippocampus-dependent task, and it was only restored because we restored precursors to those two neurotransmitters.”

The team performed electrical tests on brain slices and got normal results if the amino-acid supplements were present.

Even though the supplements “are not really fixing the problem — there are still things wrong in the pathway — we are synthesizing enough new glutamate, and subsequently enough GABA, to restore the synaptic pools, allowing the hippocampus function to return to normal,” Cohen says.

As Cohen searches for funding for a human trial, he notes that the mice received leucine, isoleucine and valine. “These are essential amino acids, you have to eat them, but if you don’t need them, you will just get rid of them. There are athletes who take these supplements for strength training.”

The Why Files was intrigued by the notion that simple lenses could substantially reduce symptoms of traumatic brain injury, and Rosner recommended that we phone former patient Penelope Frenette, 31.

Frenette said that after a car accident four years ago, she made the rounds of treatments, and saw an immediate improvement while visiting Debby Feinberg, a Birmingham, Mich., optometrist. “It was such a dramatic difference! The first time I put on a pair of prisms, I started bawling. I could see straight!”

Penelope’s Story

Penelope Frenette describes how prism glasses reduced the symptoms of a brain injury after a car crash.


Vision Specialists of Birmingham

Previously, Frenette says, her balance was so poor that her apartment “was filled with grease marks where I had to hold the walls. Now I can walk around my home. I feel stable.”

The prisms allowed her to resume reading, with a guide under the lines of print. “I’m in love with reading,” she says. “It’s made my life completely enriched. We all have to have an escape, reality can be rough sometimes.”

Seizures that were triggered by “over stimulation from noise or lights, or any sort of visual movement” are less common, Frenette says, and she says she is again driving, although with limitations. “That’s a huge thing for me.”

A visionary idea

It sounds too good to be true, but a Michigan research group has published a study showing that simple corrective lenses can reduce headache, neck ache, and dizziness — common symptoms of traumatic brain injury. “We came into this backward,” says Mark Rosner, an adjunct clinical instructor in emergency medicine at the University of Michigan, who worked with optometrists who were treating the same symptoms in people without brain injury.

 X-ray of human skull with large dark hole, toward back left of head

Image: Jmh649
A CT scan of the head after a traumatic brain injury. Arrow shows a damaged, empty space.

“We found that the post-concussion visual symptoms pretty much crossed over with the symptoms we were already treating in headachy, dizzy people,” Rosner says.

The problem seems to be rooted in a brain malfunction that prevents the eyes from converging, so one eye aims slightly above or below the other. The misalignment can cause words to bounce around on the page.

The working hypothesis, Rosner says, is that “There’s a faulty signal from the brain that is trying to vertically diverge the eyes, and that makes them double the image, but other parts of the brain say ‘You can’t do that! You are giving us double imagery!'”

The resulting tug of war between the muscles that raises and lower the eyes causes tension and headaches, Rosner says.

The divergence is subtle, but detectable, and in many cases, it can be cured with prismatic eyeglasses, Rosner contends. Many patients even notice their headache and neck ache start to subside during a 20-minute trial period in the office.

Like regular eyeglasses, the lenses are used continually; the goal is not to retrain the brain but to correct the misalignment.

A published study of 43 patients1, for whom Rosner and his colleagues had complete records, found a 72 percent reduction in several symptoms of traumatic brain injury, based on a subjective scale.

The majority of the patients had had a motor vehicle accident, Rosner says, but falls, strokes or and blast injuries to veterans were also represented.

As Rosner and colleagues struggle to get the word out on their simple treatment, he says prism glasses are helpful, but not a panacea. “These people do have other injuries. I would love to tell you this would fix all traumatic brain injuries. It cannot do that, but it does do a lot.”

– David J. Tenenbaum

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Terry Devitt, editor; S.V. Medaris, designer/illustrator; Jenny Seifert, project assistant; David J. Tenenbaum, feature writer; Amy Toburen, content development executive

Bibliography

  1. Identification of Binocular Vision Dysfunction (Vertical Heterophoria) in Traumatic Brain Injury Patients and Effects of Individualized Prismatic Spectacle Lenses in the Treatment of Postconcussive Symptoms: A Retrospective Analysis, Jennifer E. Doble et al, PM R 2010;2:244-253
  2. U. Penn football suicide.
  3. Combat brain injury.
  4. Inner Enemy (click on Recon in left-side menu, then choose Inner Enemy).
  5. Defense Centers of Excellence: traumatic brain injuries.
  6. Defense and veterans brain injury center.
  7. Brainline.
  8. CDC: TBI prevention and control.
  9. Brain Injury Association of America.
  10. International Brain Injury Association.
  11. High tech football helmets.
  12. Football physics.
  13. Head injuries in football.