Effect of longer, deeper cooling for newborns with neurological condition

 As a neonatal neurologist involved in the program at The Womans Hospital, its amazing to care for these babies in the NICU and to see them later in the office.

Sadly, there is a limit to the efficiacy of the treatment.

JR

Effect of longer, deeper cooling for newborns with neurological condition

Date:

December 23, 2014

Source:

JAMA - Journal of the American Medical Association

Among full-term newborns with moderate or severe hypoxic ischemic encephalopathy (damage to cells in the central nervous system from inadequate oxygen), receiving deeper or longer duration cooling did not reduce risk of neonatal intensive care unit death, compared to usual care, according to a study in the December 24/31 issue of JAMA.

Hypoxic ischemic encephalopathy is an important cause of childhood neurodevelopmental deficits among infants born at full-term. Hypothermia (reduced body temperature) at 33.5°C for 72 hours reduces death or disability, according to background information in the article. Longer cooling and deeper cooling has been found to be neuroprotective in animal models.

Seetha Shankaran, M.D., of Wayne State University, Detroit, and colleagues conducted a study in which full-term infants were randomly assigned to four hypothermia groups: 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours, to examine if longer duration and deeper cooling would improve outcomes at 18 to 22 months. Infants admitted to the neonatal intensive care until within 6 hours of birth were candidates for the study when seizures or moderate or severe encephalopathy was present. The trial was closed for safety and futility issues and included 364 infants (of 726 planned).

Mortality in the neonatal intensive care unit (NICU) was 7 percent for the 33.5°C for 72 hours group, 14 percent for the 32.0°C for 72 hours group, 16 percent for the 33.5°C for 120 hours group, and 17 percent for the 32.0°C for 120 hours group.

Among neonates with moderate hypoxic ischemic encephalopathy, death in the NICU occurred in 4 percent in the 72 hours group; 8 percent in the 120 hours group; 7 percent in the 33.5°C group; and in 5 percent in the 32.0°C group. Among neonates with severe hypoxic ischemic encephalopathy, deaths in the NICU occurred in 34 percent in the 72 hours group; 42 percent in the 120 hours group; 31 percent in the 33.5°C group; and in 44 percent in the 32.0°C group.

Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1 percent in the 120 hours group vs 3 percent in the 72 hours group. Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2 percent.

Full article here

Brain Cooling May Prevent Epilepsy Induced by Trauma

A study in rats showing brain cooling after trauma may prevent seizures brought on by the trauma.

In the weeks, months and years after a severe head injury, patients often experience epileptic seizures that are difficult to control. A new study in rats suggests that gently cooling the brain after injury may prevent these seizures.

"Traumatic head injury is the leading cause of acquired epilepsy in young adults, and in many cases the seizures can't be controlled with medication," says senior author Matthew Smyth, MD, associate professor of neurological surgery and of pediatrics at Washington University School of Medicine in St. Louis. "If we can confirm cooling's effectiveness in human trials, this approach may give us a safe and relatively simple way to prevent epilepsy in these patients."

The researchers reported their findings in Annals of Neurology.

Cooling the brain to protect it from injury is not a new concept. Cooling slows down the metabolic activity of nerve cells, and scientists think this may make it easier for brain cells to survive the stresses of an injury.

Doctors currently cool infants whose brains may have had inadequate access to blood or oxygen during birth. They also cool some heart attack patients to reduce peripheral brain damage when the heart stops beating.

Smyth has been exploring the possibility of using cooling to prevent seizures or reduce their severity.

"Warmer brain cells seem to be more electrically active, and that may increase the likelihood of abnormal electrical discharges that can coalesce to form a seizure," Smyth says. "Cooling should have the opposite effect."

Smyth and colleagues at the University of Washington and the University of Minnesota test potential therapies in a rat model of brain injury. These rats develop chronic seizures weeks after the injury.

Researchers devised a headset that cools the rat brain. They were originally testing its ability to stop seizures when they noticed that cooling seemed to be not only stopping but also preventing seizures.

Scientists redesigned the study to focus on prevention. Under the new protocols, they put headsets on some of the rats that cooled their brains by less than 4 degrees Fahrenheit. Another group of rats wore headsets that did nothing. Scientists who were unaware of which rats they were observing monitored them for seizures during treatment and after the headsets were removed.

Rats that wore the inactive headset had progressively longer and more severe seizures weeks after the injury, but rats whose brains had been cooled only experienced a few very brief seizures as long as four months after injury.

Brain injury also tends to reduce cell activity at the site of the trauma, but the cooling headsets restored the normal activity levels of these cells.

The study is the first to reduce injury-related seizures without drugs, according to Smyth, who is director of the Pediatric Epilepsy Surgery program at St. Louis Children's Hospital.

"Our results show that the brain changes that cause this type of epilepsy happen in the days and weeks after injury, not at the moment of injury or when the symptoms of epilepsy begin," says Smyth. "If clinical trials confirm that cooling has similar effects in humans, it could change the way we treat patients with head injuries, and for the first time reduce the chance of developing epilepsy after brain injury."

Smyth and his colleagues have been testing cooling devices in humans in the operating room, and are planning a multi-institutional trial of an implanted focal brain cooling device to evaluate the efficacy of cooling on established seizures.

Read more here