Liu followed up with 15 of the patients and found that the symptoms continued in one-third of them, and, intriguingly, four of the 15 patients had also developed frequent migraines. Now, he and other researchers believe that migraines, as well as other conditions like epilepsy and viral infections, may be associated with the syndrome. In fact, a 1977 paper in the journal Clinical Pediatrics characterized AWS as a symptom of mononucleosis in three patients, all of whom experienced visual distortions just before the usual telltale signs of the virus kicked in. Likewise, three patients of Todd’s had a family history of migraine, or epilepsy, or both.
One of those researchers, neurologist Owen Pickrell, points out that these conditions may also be associated with epilepsy. Pickrell, who does not work with Liu, is a clinician and genetic researcher at Swansea University in the United Kingdom. His research focuses on epilepsy’s genetic component, but he’s also interested in determining whether there’s a genetic link between epilepsy and AWS.
Over the past 10 years, Pickrell and his research group, led by Mark Rees, a professor of molecular neuroscience at Swansea, have studied roughly 100 families with multiple members who have epilepsy. What recently caught their attention was a family whose members have both epilepsy and AWS. “We thought there might be a genetic link,” Pickrell says. “So, we started to delve into it much deeper, making inroads. We thought if we could figure out what gene causes Alice in Wonderland Syndrome, we could work out what that gene does in the brain, and then we might find links to serious diseases.”
Three years ago, to test their hypothesis, Pickrell and his colleagues began recruiting people who had been diagnosed with AWS and AWLS to donate saliva for genetic analysis. Thus far, 15 people have mailed in their saliva. Pickrell’s team is now in the midst of analyzing the data gleaned from their samples, a project that they say is only a start to more rigorous future research.
Despite the small size of the current study, Pickrell says it has allowed him to get well-acquainted with the syndrome. Among the people in his study and other patients he has spoken to, he says, AWS and AWLS tend to begin between the ages of 5 and 10 and then ebb in the late teenage years. But he says that in other cases he’s come across, including those of some patients with epilepsy, the syndrome may return later in life, either from stress or from the brain changes that naturally occur as a person ages.
Pickrell has also noticed that the symptoms of AWS and AWLS tend to occur at night (as it happened to me, without fail). He suspects that the syndrome may be triggered by a combination of changes in sensory input—like the ebbing of noise and light at nightfall—and the chemical changes that occur in the brain as we near sleep. For example, we depend on sight and sometimes touch to determine the size or distance of an object, Pickrell explains, meaning that if sensory input is disrupted, our perception of that object changes. “So, if you close your eyes and your arm feels small, and then you open your eyes, you get more input, and that tells you your arm is really bigger.”