Experimental Radiation Treatment for OCD Hits a Snag

by Tom Valeo

April 18, 2011

A form of brain surgery that uses radiation to destroy spots of tissue in the brain gives significant relief to some people with disabling obsessive-compulsive disorder (OCD). But the surgical team with the most experience performing this technique has called a temporary halt to it until long-term side effects that have appeared recently can be studied.

“We’re on hiatus now with the gamma knife,” said Steven Rasmussen of Brown University, referring to the machine that delivers the radiation. “Three of the last 20 patients have developed a brain cyst, which we never saw before. The new gamma knife delivers a slightly different distribution of radiation, and we think that caused the cysts in these patients. None of our first 36 patients developed this adverse effect.”

Surgeons at the University of Pittsburgh, however, have found no cysts in their gamma knife patients in nearly five years of follow-up, and continue to perform the procedure. In fact, in January they published a paper in the journal Neurosurgery reporting that three patients who had the gamma knife surgery experienced reductions in their obsessions and compulsions ranging from 30 percent to 80 percent “with no adverse effects.”

The gamma knife directs more than 200 thin beams of gamma radiation at different angles toward a single point in a person's brain. While each beam delivers a trivial amount of radiation, the spot where they converge receives enough energy to destroy that tissue, making the gamma knife a precision tool for attacking small tumors, malformed blood vessels, and other brain disorders without opening the skull.

Beginning in the mid-1990s, Rasmussen and Benjamin Greenberg, both faculty members at the Brown University Medical School, thought that creating a tiny lesion in the brain’s anterior capsule might relieve the symptoms of OCD.

The anterior capsule consists of a bundle of fibers linking the orbital and medial regions of the frontal cortex to regions deep within the brain, including the thalamus. In most people, the frontal cortex assesses input from other brain regions, including regions that generate signals when something is amiss in the environment. The frontal cortex then either devises a response or decides nothing is wrong. Either way, the warning signal fades.

In people with OCD, these warning signals are thought to form a repetitive loop that constantly alerts the frontal lobes that something is wrong, creating a persistent sense that something terrible is about to happen. This results in relentless urges to correct the problem.

Frontal lobotomy, which flourished for about two decades after World War II, was a crude technique that severed massive numbers of fibers in the frontal lobes, often producing marked changes in behavior, such as apathy, emotional flatness, and lack of normal inhibition. Doctors noticed, however, that lobotomy patients with severe OCD sometimes displayed a dramatic reduction in symptoms. Rasmussen and Greenberg suspected that the surgury severed the fibers that maintained the alarm circuit in people with severe OCD. Brown University had recently acquired a gamma knife, which they believed they could use to make a discrete lesion that would sever only the fibers responsible for OCD.

Identifying the precise location of those fibers, however, proved to be a challenge.

“We put a single lesion in the place we thought would be most likely to give us the therapeutic benefit with the fewest side-effects,” Rasmussen recalled of the first efforts to treat OCD with the gamma knife. “We did 15 patients. At the end of a year, only one out of 15 got better. That was very disappointing.”

They went back and put a second lesion below the first, and eight of the 15 got better.

“Subsequently we started to do two lesions on each side,” Rasmussen said. “Thirty-six patients later, it looked like we were getting about a 70 percent response rate in these incredibly refractory patients.”

A good response consists of at least a 30 percent reduction in OCD symptoms as measured by the Yale-Brown obsessive compulsive scale, along with other improvements in quality of life. In one follow-up study, three out of five patients showed a slight decline in their ability to multitask—a sign of possible deficits in executive function. But overall , the changes produced by gamma knife surgery have improved life dramatically for many patients, including Gerry Radano, who wrote about her treatment in a book titled, Contaminated: My Journey Out of Obsessive Compulsive Disorder, published in 2007. During her second pregnancy, with her mother dying of cancer, Radano became obsessed with germs and contamination.

“I spent every waking moment washing my hands, spraying Lysol, changing my ‘contaminated’ clothes, and suffering from panic attacks while crying over the devastation taking place that I felt powerless to stop,” she wrote. “It was as if someone had seized my mind and was destroying it one brain cell at a time.”

Suddenly the former flight attendant who had traveled the world didn’t want to leave her house. As her children grew up she lost her career, spent time in three psychiatric hospitals, tried every known medication for OCD as well as cognitive behavioral therapy, and contemplated suicide.

After 10 years of suffering she approached Rasmussen and qualified for the experimental gamma knife surgery. Although improvement didn’t appear right away, her symptoms gradually subsided over several months. She washed less frequently, used fewer cans of Lysol to kill the germs she dreaded, and experienced few panic attacks. “Still far from perfect,” she admitted, “but I was getting there.”

She declined to be interviewed for this article, saying she didn’t want to encourage people to seek the surgery at a time when Rasmussen and his colleagues are not performing it, but she maintains a website, where she provides resources for people with OCD, and offers her services as a speaker on the subject.

The Brown University Medical Center eventually purchased a new gamma knife, and Rasmussen and his colleagues performed the surgery on another 20 people with OCD using the new machine. During a 5-year follow-up, they discovered a significant cyst in the brain of one of the patients treated with the new gamma knife. Later they found cysts in two other patients.

Now they’re re-evaluating the procedure, and exploring whether one shot of radiation would achieve the same results as two while eliminating the problem of cysts. “These patients are extremely ill, but 3 cysts out of 20 patients is too high of a risk to continue with a double shot of radiation, so right now we’re evaluating the safety of proceeding with a single shot lesion.”

Meanwhile, surgeons at the University of Pittsburgh continue to perform the surgery without significant side effects, according to Douglas Kondziolka, lead author of the recent paper in Neurosurgery.

“Gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects,” the authors concluded. After nearly five years of follow-up, some patients continue to show a significant reduction in symptoms, with no sign of cognitive deficits.

The cysts that Rasmussen has found in three of his patients do not worry Kondziolka, a professor of radiation oncology and vice-chairman of neurological surgery at the University of Pittsburgh.

“Cystic degeneration can occur after any form of radiosurgery, but is very rare,” he said. “The radiosurgical lesion will lead to tissue cavitation, which can cause a microcyst. Should extracellular fluid accumulate, then a larger cyst could form, and this could potentially require treatment, but this should be very rare. In other cases of lesional radiosurgery, such as thalamotomy for movement disorders—and I have done more than 100—I have not seen it ever.”