Cooling May Reduce Seizures in Epilepsy

San Diego, California — Just as certain heart patients wear a pacemaker to correct abnormal cardiac activity, patients with epilepsy may some day have an implanted cooling device that suppresses seizures.

At this year's American Epilepsy Association (AES) 66th Annual Meeting, Japanese researchers reported on a focal brain titanium cooling plate that eradicates seizures in animals without adversely affecting brain function.

The researchers implanted the device over the somatosensory and motor cortex in 2 cats and 2 macaque monkeys, alongside electrocorticography (ECoG) electrodes. The plate has 2 inner water channels and is connected to a component with a pump that keeps circulated water at a target temperature — in this experiment, the target temperature of the cortical surface was 15°C.

The investigators then chemically induced seizures in the animals and recorded brain activity while the animals were awake.

The study found that this approach suppressed electrical epileptic seizures with no apparent changes on ECoG, said one of the researchers, Masami Fujii, MD, PhD, associate professor, and chief, Division of Functional Neurosurgery, Department of Neurosurgery, Yamaguchi University, Japan.

The idea is that patients with epilepsy would eventually be implanted with a similar device that would detect seizure activity and automatically cool the affected area, said Dr. Fujii. But although encouraging, further research still needs to be completed to establish whether this approach is a safe and effective therapeutic intervention for intractable focal epilepsy in patients, he said.

However, Shlomo Shinnar, MD, PhD, professor (neurology pediatrics, epidemiology, and population health) and director, Comprehensive Epilepsy Management Center, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, New York, isn't convinced that cooling the brain in humans wouldn't suppress other brain functions in addition to seizures.

"Brain cooling has been used in the context of hypoxic ischemic insult as a neuroprotectant in babies (with encephalopathy), the so-called 'cooling cap', but at that point, you're willing to put them to sleep for a few days basically to protect them," said Dr. Shinnar. "Whether you can cool the human brain without altering the brain functions you don't wish to alter remains to be seen."

The approach is "very interesting" but remains "very much preclinical," said Dr. Shinnar.

Whole-Body, Pharmaceutical Cooling

Whereas this study looked at invasive focal cooling in preventing seizures, another study presented here investigated the effect on survival and neuronal damage of noninvasive whole-body cooling, and a novel pharmacological approach, in animals in status epilepticus.

For this experiment, researchers induced seizures in 96 adult male rats. After 4.5 hours, half the rats were cooled in a chamber of cold circulating air to a target temperature of 31 to 33°C, whereas the other rats were left at room temperature.

The cooled rats had a significantly better survival rate after 24 hours (82% vs 32%; P < .05; odds ratio for survival, 9.53).

Survival rates at 2.5 months were also better among the cooled rats (50% vs 25%), demonstrating that the benefits are longer-term, said study author Sandipan Pati, MD, epilepsy fellow, Massachusetts General Hospital, Boston.

MRI studies showed that the cooled rats had less hippocampal neuronal damage than the other rats.

The researchers observed similar benefits when they cooled the rats by using a drug in development that blocks cold receptors.

"We found that physical methods of cooling improves neuron damage and improves cognitive outcome and survival, and we also found that pharmacological cooling has the same effect," said Dr. Pati.

Use of drug-induced cooling could help overcome the hurdle of having to intubate patients while cooling them, which can lead to infections and thrombosis in the lungs, said Dr. Pati. "We wondered if there was a smarter, better, way of cooling that doesn't involve intubation."

Dr. Pati envisions that humans with status epilepticus would have to be cooled for at least 1 or 2 days, a period that could carry potential problems.

The current animal study was carried out in advance of a clinical trial, said Dr. Pati.

American Epilepsy Society (AES) 66th Annual Meeting. Abstracts 3.056, 1.044. Presented December 1, 2012.