Deciphering the One-Two Punch: Autism and Epilepsy

EpilepsyUSA explores deeper connect-
ions between Epilepsy and Autism.

Children with autism spectrum disorder (ASD) are ten times as likely to have epilepsy as other children are. And the arrow of causality flies both ways: several epilepsy syndromes, such as infantile spasms, if not treated promptly, result in ASD-like symptoms. Tuberous sclerosis also often starts with seizures, with ASD-like symptoms emerging only later. Only recently have researchers and clinicians from the epilepsy and autism worlds begun working together to explore the deeper connections. Their work is already shedding light on new paths forward for both fields and, most importantly, for the hundreds of thousands of children worldwide who bear both of these heavy burdens. My article about autism and epilepsy, Deciphering the One-Two Punch: Epilepsy and Autism, is the cover story of the current EpilepsyUSA.

Erasing False Memories?

A pill to erase memories?

In Jonah Lehrer's cover story in the current issue of WIRED, he surveys research on the feasibility of using drugs to erase traumatic memories. Each time we remember a particular long-term memory, we take it down from the neurological shelf on which it is stored and make it vulnerable to breakage or change. In fact, the scientists featured in Lehrer's piece pose, memories are inevitably altered (not reinforced) each time they are retrieved. To put them back safely on the shelf, even in their new, altered state, our brains apparently need to make some proteins to lock them safely back in place. But if a PTSD patient, say, recalls a traumatic memory and is simultaneously given a drug that blocks protein synthesis where that memory is stored, Wham! the memory gets whacked before it can be put back on the storage shelf. Voila, the PTSD is gone. The leading candidate drug is a form of protein kinase called PKMzeta. Lehrer, and the neuroscientists he profiles in the piece, seem to expect this technique to become precise, reliable, and safe. That remains to be seen.

The piece is provocative and fun, but Lehrer's makes, I think, a weak argument that since memories are all falible and mutable anyway, there's no real problem with erasing the ones we don't like. Sure memories, and the mechanism by which we keep them, are imperfect. That's why we try so hard to anchor the important ones outside of our brains in other ways: by documenting them and by sharing them with others to keep our perceived reality from drifting too far from the historical one. We can't overestimate the importance of preserving our tenuous link to historical reality, though, either as individuals or as a society. In a world as perilous as ours, we can't afford to forget what's really happened. Remembering with fidelity, hard as it is, is key to moving forward safely and successfully. If we start to whack unpleasant memories, we do so at our collective peril.

Thinking Makes it Go

Illustration by Leandro Castelao

Brains and machines have been flirting for decades, but at several centers around the country they are now getting married. Brain surgeon and neuroscientist Edward Chang is the focus of my story about the union, just out in San Francisco magazine. Chang and his colleagues at the UC Berkeley-UCSF Center for Neural Engineering and Prosthetics (CNEP) are developing brain-computer interfaces, including one that will read words from paralyzed patients' brains and give them voice through a prosthetic device.  Jan Rabaey is developing mirco-arrays that will read electrical signals from the cortex's surface and transmit signals through the skull to devices outside. Michel Maharbiz is even talking about "brain dust," networked wireless nanosensors, each the size of a dust mote, that could be distributed throughout the entire brain like artificial neurons and wirelessly communicate with computers in the outside world. “It’s still a vision for the future, but we think it could work,” he says.

Big Picture on BMI

This week's Big Picture Science examines brain-machine interfaces (BMIs). Guests include engineer of the tiny Jan Rabaey, at the Center for Neural Engineering and Prostheses, who is developing wireless micro-electrode grids that can send signals out of human brains;  Human Connectome researcher Arthur Toga,  a UCLA cartographer of human brain function; UCSF neuroscientist Brad Voytek, who studies attention and memory in ECoG-implanted epilepsy patients; and senior UCSC neurobiologist Michael Gazzaniga, author of the recent book Who's In Charge?: Free Will and the Brain. The interviews are excellent, and the show opens up with my 13-year-old son Leo and me playing Mind Flex, an EEG-based game that we got for Christmas.

Pinpointing the Laughter Zone

Abnormal growths near the part of the
hypothalamus called the mammillary
bodies cause laughing seizures.

There's nothing funny about gelastic epilepsy. It hits young children, worsens with time, and can lead to several devastating seizure types as well as developmental and behavioral problems. But still, the kids who have this very rare epilepsy are laughing. They can't help it.

The part of the brain responsible for laughter appears to be located on the underside of the hypothalamus, a place disturbed by all of the growths, called hypothalmic hamartomas, known to cause laughing epilepsy. This discovery was one byproduct of research examining 100 cases of gelastic epilepsy to determine how the locations and sizes of hamartomas resulted in different symptoms and outcomes. The research, recently published in the journal BRAIN, and discussed by a panel of neuroscientists at the AES meeting in Baltimore on Sunday, showed that while variously sized tumors found in proximity to different parts of the hypothalamus had different expressions, all of those causing laughter were adjacent to the part of the hypothalamus known as the mammillary bodies.

"We've known for decades that hamartomas in the hypothalamus cause laughing seizures," said Stanford neurologists Josef Parvizi, lead author of the study. "But that's like saying the problem is coming from a city. We wanted to see exactly which district in that city were involved to help us understand the networks that underlie laughter. Just knowing it was in the hypothalamus was not enough."

Parvizi collaborated with John Kerrigan at the Barrow Neurological Institute in Phoenix, which Parvizi calls "the Mecca for hypothalmic hamartoma research." Their paper, which also examined the different outcomes of children with different sized tumors, and tumors adjacent to different parts of the hypothalamus, concluded that however large they are, and wherever they are located, quick diagnosis and removal of hamartomas is key to a good outcome. "If you let this condition linger," says Parvizi, "you are going to run into trouble." 

Because in many cases the first expression of the disease is laughing seizures, gelastic epilepsy often goes long undiagnosed. Especially, for some reason, in girls. The girls in the study had surgery, on average, about 60 months later than the boys. Why? Parvizi could only speculate: "Maybe because if a boy is laughing it is considered more abnormal than if a girl is. But I don't know." 

Inside the Heads of Epilepsy Patients

On the exhibits floor of  the 75th Anniversary American Epilepsy conference in Baltimore this weekend there are many new ways to get inside the heads of epilepsy patients. NeuroPace, for example, is a brain implant that detects the coming of a seizure and responds with electrical stimulation the part of the brain causing the trouble.  It's a remarkable device...and it was predicted with amazingly high fidelity by Michael Chrichton as far back as 1971 in his novel (later turned into a movie) Terminal Man.  The clinical trial in Chrichton's story don't turn out so well, but its just a novel. Still, let's hope we really know what we're doing as we start installing computers inside of people's heads. There are high hopes, I should say, for NeuroPace. I share them.

Meanwhile, two floors above, in the ballroom of the Baltimore Conference Center neurologist Steven Schachter gave the Judith Hoyer Lecture on Epilepsy. Schachter does some work on high-tech translational medicine at Harvard, where he is a professor of neurology. But he also started the journal Epilepsy and Behavior, was the president of the American Epilepsy Society, and achieved about a half a dozen other things that would put an ordinary epileptologist on the map. Schachter is also the most humane neurologist I've met. He is dedicated to stopping his patients' seizures, yes, but also to helping them wrestle with the other demons that often accompany epilepsy: stigma, employment limitations, loneliness, alienation, depression. He also collects artwork made by people with epilepsy, which he uses both to gain insight into their experience and even to help guide diagnoses and treatment. In a conference that's understandably focused on epileptic brains, Schachter's talk was typically focused on people with epilepsy.

Also part of the Judith Hoyer Lecture was a magnificent performance of a composition by Cynthia Folio.  Titled When the Spirit Catches You, the piece is a musical portrait of a Folio's daughter's seizures. Permormed by the seven-member Relache Ensemble, the piece was moody, caucophenous, dreamy, and melancholy. It ends with a child's music box winding down sadly, but sweetly. It is a moving and engaging piece and I hope it is performed again and again. (A four-minute excerpt of the half-hour-long piece is here.)

Shachter's good talk and Folio's performance were recorded and reportedly will be posted on YouTube, so keep a sharp eye out for them.

For more on the AES's annual meeting in Baltimore, follow Lisa Boyland's good blog on the Epilepsy Foundation site.

Where does "Epilepsy" Come From?

Shakespeare said Caesar had
"the falling sickness" but that
Othello had "epilepsy."

It's still  premature to say where epilepsy itself comes from, but there's a feature on Science Friday's website's "Science Diction" page about the origins of the word. Apparently, "epilepsy" took over describing seizure disorders when the expressions "the falling sickness" and "the sacred disease" fell out of fashion in the early 1600s. Medical historian Howard Markel notes that Shakespeare, in 1599, calls Julius Caesar's seizures symptoms "the falling sickness." Four years later, the Bard's Othello is described as having "fallen into an epilepsy." Those occurrences, Markel argues (on scant evidence, I think), mark the English shift from the old usage to the modern one.

The word "epilepsy" comes from the Greek "epilambanem," which means to "grab," "seize" or "take possession of." Since in those days many people thought epilepsy was caused by spirit possession, the word probably had a double meaning: first, to shake as if grabbed, and second, to be taken over by a spirit.