Traumatic Brain Injury Health Article

Clinical trials

The National Institute of Neurological Disorders and Stroke (NINDS) supports research on the biological mechanisms of brain injury, strategies to limit brain damage following head trauma, and treatments of TBI that may improve long-term recovery. Research areas include mechanisms of diffuse axonal injury; the role of calcium entry into damaged nerves causing cell death and brain swelling; the toxic effects of glutamate and other nerve chemicals causing excessive nerve excitability; natural processes of brain repair after TBI; the therapeutic use of cyclosporin A or hypothermia to decrease cell death and nerve swelling; and the use of stem cells to repair or replace damaged brain tissue.

NINDS-supported clinical research focuses on enhancing the ability of the brain to adapt to deficits after TBI; improving rehabilitation programs for TBI-related disabilities; and developing treatments for use in the first hours after TBI. Early treatments being investigated include hypothermia for severe TBI in children, magnesium sulfate to protect nerve cells after TBI, and lowering ICP and increasing blood flow to the brain.

To address the specific problems in thinking and communication following TBI, the NINDS is designing new evaluation tools for children, developing computer programs to help rehabilitate children with TBI, and determining the effects of various medications on recovery of speech, language, and cognitive abilities.

The NINDS website (www.clinicaltrials.gov/ct/action/GetStudy) lists specific contact information for ongoing trials. These include hypothermia to treat severe brain injury, open to subjects age 16 to 45 years with nonpenetrating brain injury with a post-resuscitation Glasgow Coma Score less than 8 (contact Emmy R. Miller, PhD, RN, 713-500-6145).

The Prospective Memory in Children with Traumatic Brain Injury study is open to children age 12-18 years, with a post-resuscitation Glasgow Coma Scale score of either 13 to 15 or 3 to 8. Contact information is Stephen R. Mc-Cauley, PhD, 713-798-7479, mccauley@bcm.tmc.edu.

The Measuring Head Impacts in Sports study will test a new device to measure the speed of head impact in football players. The study is open to college football players, age 18–24 years. Contact information is Rick Greenwald, PhD, RGreenwald@simbex.com.

A trial sponsored by Avanir Pharmaceuticals will be testing the safety of the drug AVP-923 in the treatment of uncontrolled laughter and crying associated with TBI as well as with other conditions. Study subjects must be age 18–75 years without any history of major psychiatric disturbance. Contact information varies by state and is available on the website; for Arizona it is Louis DiCave, 602-406-6292, ldicave@chw.edu.

Prognosis

Although the symptoms of minor head injuries often resolve on their own, more than 500,000 head injuries each year are severe enough to require hospitalization; 200,000 are fatal; and 200,000 require institutionalization or other close supervision. Each year in the United States, head injury causes one million head-injured people to be treated in hospital emergency rooms, 270,000 to have moderate or severe TBI, 70,000 to die, and 60,000 to develop epilepsy.

Outcome varies with cause: 91% of TBIs caused by firearms, two-thirds of which may represent suicide attempts, are fatal, compared with only 11% of TBIs from falls. Low Glasgow Coma Scale scores predict a worse outcome from TBI than do high scores.

The Swedish Council on Technology Assessment in Health Care concluded that of 1,000 patients arriving at the hospital with mild head injury, one will die, nine will require surgery or other intervention, and about 80 will have abnormal findings on brain CT and will probably need to be hospitalized.

Immediate complications of TBI may include seizures, enlargement of the fluid-filled chambers within the brain (hydrocephalus or post-traumatic ventricular enlargement), leaks of cerebrospinal fluid, infection, injury to blood vessels or to the nerves supplying the head and neck, pain, bed sores, failure of multiple organ systems, and trauma to other areas of the body.

About one-quarter of patients with brain contusions or hematomas and about half of those with penetrating head injuries develop seizures within the first 24 hours of the injury. Those that do are at increased risk of seizures occurring within one week after TBI.

Hydrocephalus usually occurs within the first year of TBI, and it is associated with deteriorating neurological outcome, impaired consciousness, behavioral changes, poor coordination or balance, loss of bowel and bladder control, or signs of increased ICP.

Long-term survivors of TBI may suffer from persistent problems with behavior, thinking, and communication disabilities, as well as epilepsy; loss of sensation, hearing, vision, taste, or smell; ringing in the ears (tinnitus), coordination problems, and/or paralysis. Recovery from cognitive deficits is most dramatic within the first six months after TBI, and less apparent subsequently.

Memory loss is especially common in severely head-injured patients, with loss of some specific memories and partial inability to form or store new memories. Antero-grade post-traumatic amnesia refers to impaired memory of events that occurred after TBI, while retrograde post-traumatic amnesia refers to impaired memory of events that occurred before the TBI.

Personality changes and behavioral problems may include depression, anxiety, irritability, anger, apathy, paranoia, frustration, agitation, mood swings, aggression, impulsive behaviors or "acting out," social inappropriateness, temper tantrums, difficulty accepting responsibility, and alcohol or drug abuse.

Following TBI, patients may be at increased risk of other long-term problems such as Parkinson's disease, Alzheimer's disease, "punch-drunk" syndrome (dementia pugilistica), and post-traumatic dementia.

Because of all the above problems, some patients may have difficulty returning to work following TBI, as well as problems with school, driving, sports, housework, and social relationships.