Sudden Unexpected (Unexplained) Death in Epilepsy (SUDEP) refers to the unexpected death of a person with epilepsy, who was otherwise healthy, and for whom no other cause of death can be found. Between 500 and 1,000 people with epilepsy die of SUDEP in the UK each year. It is thought that these deaths are in most cases related to a severe convulsive seizure affecting vital functions such as breathing or heart rhythm. Despite ongoing research, risk factors for SUDEP are only partly understood. One of the theories put forward in the last few years is that some of those who die unexpectedly have a genetic predisposition to both sudden death and epilepsy.

In our November 2009 enewsletter we saw how scientists at Baylor College of Medicine, in Texas, had discovered a gene, which if mutated, could predispose people with epilepsy to SUDEP. This gene is known as KCNQ1 and it encodes a potassium channel called KvLQT1.

Now, the same researchers have revealed that mutation of a second gene, encoding another type of potassium channel called Kv1.1, might also predispose people with epilepsy to SUDEP. Mutation of the Kv1.1 gene in humans is associated with spontaneous seizures, abnormal muscle movements, and coordination problems. The team's latest findings suggest that Kv1.1 channels are also required for proper heart function.

In this study, the scientists bred mice that lacked the gene for Kv1.1. Previous research has shown that a lack of Kv1.1 causes severe epilepsy, involuntary movement and premature death in these animal models (which is very similar to the effect of mutated Kv1.1 in humans). The team was interested in finding out why animals lacking Kv1.1 die and whether Kv1.1 is a possible risk factor for SUDEP.

The researchers recorded electrical signals from the brains and hearts of the animal models, to determine where and how the lethal abnormalities originated. They found that the hearts of these models skipped beats intermittently, and during seizures, their heart beats became even more erratic and in some cases stopped beating (which often proved fatal). This suggests that a lack of Kv1.1 channels causes disordered signaling between the brain and the heart.

After examining a control group of healthy animals, the scientists discovered that Kv1.1 channels are present in the brain and the vagus nerve (a bundle of axons that helps to regulate heart rhythms), but are barely detectable in the heart. In the models lacking Kv1.1 channels, it appeared that signals being sent from the brain to the heart, via the vagus nerve, were in disarray.

Dr Edward Glasscock, first author of the study, commented "In mice without Kv1.1 channels, we think the vagus nerve loses control and sends extra nerve impulses to the heart, telling it to slow down -- and even stop beating -- when it shouldn't."

These results are encouraging, because they have the potential to uncover some of the mysteries surrounding SUDEP. It remains to be seen whether a mutated Kv1.1 gene in humans has the same effect as it does in animal models; however if this is found to be the case, people with epilepsy could potentially be screened for this mutation in the future, to identify those at risk of sudden death.

The long term goal is for all people predisposed to SUDEP to be identified, and for preventative action to be taken. There could be many genes associated with SUDEP yet to be discovered, which is why continuing research is so important.

Read more here