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Until early last year, no one knew what to do about Mario Della Grotta. A thirty-three-year-old man with a crew cut and a childlike face, Della Grotta was in the grip of one compulsion after another. He washed his hands sixty or seventy times a day. One night he sat in his car for five hours trying to retrace how he'd spent five dollars. He once devoted six hours just to washing the kitchen floor. When his wife was pregnant with their first child, he felt so hopeless he wanted to die.

Doctors at the Brown Medical School describe Della Grotta as having one of the most crippling cases of obsessive-compulsive disorder (OCD) they've ever seen. Between two million and three million Americans suffer from OCD, an illness characterized by obsessive thoughts that something terrible - such as deadly contamination - will happen to them or to someone they love, or by a paralyzing preoccupation with the simplest of worries, such as whether the door is locked at home. For most patients obsessions are accompanied by compulsive rituals - hand washing, for example, or, in Della Grotta's case, repetitive checking - which temporarily ease the anxiety caused by the obsessions. Doctors treat OCD with behavior-modification therapy, with serotonin reuptake inhibitors like Prozac, or with a combination of the two, but for 15 to 20 percent of patients, the treatments don't work.

Mario Della Grotta was one of those patients. Then, on February 5, 2001, he made medical history when Assistant Professor of Clinical Neuroscience Gerhard Friehs drilled two small holes in his skull and threaded four tiny electrodes into Della Grotta's brain. Friehs then connected the electrodes to pacemakers implanted on either side of Della Grotta's chest. The pacemakers would electrically jam the nerve signals in a portion of the brain that is overactive in people suffering from OCD. It was the first-ever use in the United States of an experimental treatment called deep-brain stimulation to treat a psychiatric disorder.

For Della Grotta the results were immediate. While still in the operating room he was able to touch a penny, even though just hours earlier the thought of doing so had terrified him. After he returned to his home in Cumberland, Rhode Island, his symptoms further subsided, and a month after surgery he welcomed his new daughter into the world. A few months ago he was able to start working at a job for the first time in three years, a job that requires him to double-check the records of bank tellers - something he says he could not have handled before. Now he's able to change his daughter's diapers, a great improvement, he says.

"It's wonderful," says his doctor, Benjamin Greenberg, an associate professor of psychiatry and head of a small study that includes Della Grotta. The potential for OCD patients is "unbelievably thrilling," Friehs says. "Seeing their minds get free again without any interference, without making them dumber or harming them - I think it's really fantastic."

 

THE USE of deep-brain stimulation (dbs) represents a major shift in the way psychiatrists conceptualize mental illness. Scientists had evidence as early as 1900 that symptoms of what is now known to be OCD might have a neurological cause. But by the 1970s, when Steven Rasmussen '74, '77 M.D., the head of the OCD clinic at Providence's Butler Hospital, was completing his medical training, Freudian theory dominated the field. Rasmussen, who is also an associate professor of psychiatry at the Brown Medical School, says that most experts back then viewed OCD as a conflict between the superego - the part of the personality responsible for distinguishing between right and wrong - and the id - the unconscious part that controls instinctual needs and drives.

In the mid-1980s scientists looking at the first scans of the living human brain discovered abnormal metabolic activity in the circuits of OCD patients, the first visible evidence that OCD might have a biological, rather than a psychological, root. Around that time, Rasmussen and his colleagues became leaders in treating OCD with behavior-modification therapy and with medication that they'd convinced a drug company to bring to market. Then, in 1993, Rasmussen started testing the safety and efficacy of brain surgery on patients for whom standard treatments did not work. He and his team became the first U.S. physicians to treat OCD with a surgical tool known as the gamma knife, which focuses 210 gamma-ray beams into a single point and burns a tiny hole deep within the brain. The first patient, a Nebraskan named Todd Isaacson, was eighteen years old at the time and so sick that his parents had to feed, dress, and bathe him. The surgery was a success, and Isaacson now hopes to start medical school in the fall.

Today, Rasmussen and his colleagues continue to use the gamma knife on OCD patients from around the country - about forty to date - who turn to Butler Hospital as a last resort. Most are operated on by Associate Professor of Neurosurgery Georg Nor}n, medical director of the New England Gamma Knife Center in Providence, who arrived at the center shortly after Isaacson's surgery. During his medical residency Nor}n worked closely with Lars Leksell, the Swedish neurosurgeon who in the late 1960s invented the gamma knife. Today the tool is used mostly to treat deep-seated brain tumors. Nor}n's work has shown the gamma knife to be safe and, in many cases, effective for OCD patients. The downside is that unlike deep-brain stimulation, the gamma knife creates permanent lesions in the brain.

That's one reason the Butler team started testing DBS. Deep-brain stimulation was discovered by accident in 1987 while a French neurosurgeon was using an electrical probe in the brain of a patient with Parkinson's disease. The doctor was surprised to find that when an electrical current accidentally touched the section of the brain called the thalamus, the patient's tremors stopped. The U.S. Food and Drug Administration has now approved the use of DBS for the treatment of two illnesses: essential tremor and Parkinson's; it is being used in clinical trials for other illnesses. Friehs, who has been performing DBS surgery on Parkinson's patients since 1997, became eager to use the surgery for OCD after scientists in Belgium did so in 1999. Greenberg, Friehs, and their colleagues received funding from the National Alliance for Research on Schizophrenia and Depression and from the pacemaker manufacturer Medtronic to conduct a study of DBS on five OCD patients. Patients such as Della Grotta turned to Greenberg after years of unsuccessful treatment.

The principle behind both the gamma-knife and DBS treatments is to correct what scientists have found to be higher-than-normal metabolic brain activity in obsessive-compulsive patients. Specifically, the surgeries target the electrochemical connections between two areas: the orbital and medial frontal cortex and places deep in the brain called the ventral striatum and the midline thalamus. In normally functioning people, the job of the orbital and medial frontal cortex is to constantly assess, at any given moment, whether a situation is likely to be good or bad for them, then to tell the ventral striatum and midline thalamus what behavior to perform as a result. Milliseconds later, the places deep in the brain send information back to the frontal cortex and the process begins again. "It's kind of a circuit loop," Rasmussen says. Because this part of the brain is overactive in OCD patients, they become obsessed with the question, worrying excessively, and for no rational reason, that something terrible is going to happen. The gamma knife severs the connections between the two areas of the brain. DBS, by comparison, electrically jams the nerve impulses in the connections so their messages are not transmitted.

Rasmussen sees advantages and disadvantages to each approach. The gamma knife is almost entirely noninvasive, so patients can return home the night of the surgery. One patient went waterskiing the next day, Rasmussen says; another competed for his black-belt in karate the next day. About 10 percent of gamma-knife patients suffer from headaches after the procedure, Rasmussen says, and a much rarer side effect is apathy and decreased motivation. On the other hand, Rasmussen says that 55 percent of gamma-knife patients report that they're much or very much improved. "They have been given another chance in life," he says. Patients start to see results after six months to a year.

The more invasive DBS surgery is physically tougher on patients, who must usually stay overnight in the hospital. Recovery takes a week or two, and risks include hemorrhage (in 2 to 3 percent of cases) and infection (in 3 to 5 percent). The great advantage of DBS is that the surgery is reversible. If it's unsuccessful, doctors can remove or simply turn off the electrodes. Gamma-knife lesions, by contrast, are permanent. With DBS, physicians also have the ability to fine-tune the treatment. After surgery each patient meets regularly with Greenberg, who experiments with the pacemakers until he finds an optimal level of electrical stimulation.

"Then it's just a waiting game," says behavioral therapist Richard Marsland, a registered nurse at Butler who works with OCD patients. Early results from Belgium, where doctors are now following four OCD patients, suggest that DBS may have the same success rate as the gamma-knife procedure. In his own patients, Greenberg has seen anxiety levels and mood start to improve immediately after the stimulators are turned on, but obsessions and compulsions take longer to subside.

In view of each surgery's advantages, and the similarity of results, Rasmussen believes it's too early to tell whether one of the surgeries is superior to the other. He even has trouble advising patients on which to choose. "This is all very new research," he says.

 

FOR THE PEOPLE who live with ocd, surgery can be like waking up from a ten-year nightmare. Asked to describe her life as an OCD sufferer, Gerry, a gamma-knife patient who lives outside New York City (her last name is withheld at her request), says: "If you could imagine hell on earth, that would pretty much sum it up. You wake up every day and say, ԔThis is a good day to die.'" In her compulsion to kill germs, Gerry, who is in her fifties, would empty a can of Lysol every day and wash her hands up to 200 times over the same period. When she brushed against a garbage can or a person who'd just sneezed, she'd rush to the shower and stay there until the water ran cold. One day she came across a pool of vomit in a building and avoided the spot for the next two years.

"The medicine definitely helped," she says of the medication prescribed to her, "but not enough to function, not enough to get off the couch." Her children did not bring friends to the house. Her husband took on all the responsibilities of parenthood. "It's not an individual disease," she says. "It destroys the entire family."

Gerry came to Rhode Island for gamma-knife surgery in November 1999. She noticed an improvement eight months later, around the time her husband left her. "You're actually afraid to test yourself, to go to these places you're terrified of," she says. But when she saw vomit in her church one day, she returned that same day without thinking twice. She also lost most of the 100 pounds she'd gained as a side effect of her medication, and returned to college. "I was told I was going to be sick the rest of my life," she says. "Dr. Rasmussen, he was the answer to my prayers."

Physicians caution their patients that radical surgery cannot "cure" the disorder. "Even the best medication cannot change your behavior," says Todd Isaacson, the first gamma-knife patient. "It's something you have to do yourself." He says the surgery relieved some of his obsessions and made it easier to train himself to stop the compulsive rituals that had come to dominate his life. Before surgery, Isaacson lived with what he describes as a "constant feeling of impending doom that you can't really put your finger on." His underlying fear, as illogical as it seems to him today, was offending God. If he stepped on an ant on the sidewalk, he'd pray for two hours. To temporarily ease his fear, he developed a ritual for every step of every activity, from walking to eating to getting out of bed. "He looked like he was in slow motion," Rasmussen says.

Before sitting in a chair, for example, Isaacson would tap the armrest a certain number of times, then tap his leg, then tap the chair again, then hop up and down. It took fifteen minutes to sit down, and another fifteen to get up again. Isaacson recalls that he believed it was morally wrong to move too quickly or do things too easily. In fact, it took him so long to eat a plate of food that his weight dropped to eighty pounds and his parents started pouring the nutritional drink Ensure down his throat. "In my mind," he says, "I was afraid [that] if I enjoyed food too much, it would offend God somehow, because there are so many in the world who don't have enough to eat."

The surgery helped him learn to act - and think - as other people would in a given situation. "I remember asking the behavioral therapist, ԈHow do you wash your hands?' " he says. "It had been so long since I'd washed my hands in a normal fashion." Isaacson has also been working on his social skills, which lapsed after he dropped out of high school and stopped leaving the house. His recovery process included volunteering at Butler Hospital, where he learned to socialize with coworkers in the office and at lunch in the cafeteria. Even today, Isaacson has noticed that he's not as socialized as his peers, but he isn't worried: practicing social skills, he says, will be far easier than overcoming OCD. Eventually, he left Rhode Island and returned to Nebraska, where he earned his high school equivalency degree and obtained a driver's license. Now a senior at Creighton University, he is awaiting word on his medical school applications. Isaacson intends to practice family medicine with an emphasis on treating OCD and other anxiety disorders.

Della Grotta, the first DBS patient, says he still loses about four hours a day to obsessions and compulsive rituals, down from eighteen on his worst days. He is now a devoted patient of behavioral therapy; during sessions he practices such tasks as making deliberate mistakes in his handwriting. "I still have my ups and downs," he says, "but I can see light at the end of the tunnel."

 

AROUD THE TIME when della grotta returned from the hospital with two circular scars peeking out from beneath his crew cut, the Wall Street Journal published an article about the promise of deep-brain stimulation as a treatment for various brain disorders. One neurologist told the newspaper, "We're at the cusp of a new era." Rasmussen, though, is more reserved.

He and his colleagues emphasize that surgery is an option only for the most seriously ill. "We are far from having a cure or a treatment for OCD," Friehs says. "We do not want people to get overly excited." According to Rasmussen, only one or two of every ten OCD sufferers in the United States seek treatment. He believes that of those who don't respond to behavioral therapy or drugs, only around 10,000 have symptoms severe enough to meet the standards for the operations.

Friehs also worries that desperate patients will seek surgical treatment from psychiatrists who are not experts in OCD and from surgeons who don't have experience performing the DBS procedure. Adding to his worry, he says, are medical centers around the world that advertise deep-brain stimulation to OCD patients even though none of their doctors has ever performed it.

Rasmussen and his fellow researchers hope to learn enough about the circuitry of the brain to someday develop even more sophisticated surgeries, ones that are safe and effective enough to treat patients with less debilitating OCD. That, Rasmussen believes, could vastly improve the quality of life for those who experience the weight gain and sexual dysfunction that are unfortunate side effects of some OCD medication.

More research could also open the door to treating other disorders using deep-brain stimulation or gamma-knife surgery. In fact, a team of doctors led by Professor of Psychiatry Lawrence Price is about to become the first in the world to test DBS as a treatment for patients suffering from clinical depression. And a small number of scientists around the world are testing DBS for epilepsy, chronic pain, and dystonia (abnormal involuntary movements, such as tremors or body jerks). Such work could even conceivably lead to the use of the surgeries to treat eating disorders, addictions, and obesity.

The next step for Rasmussen and his team, however, is to do more research and clinical testing on OCD. Much is still unknown about the biological underpinnings of the disorder, and as a result, Rasmussen and Greenberg are not altogether certain why the surgical techniques are so effective. They don't yet understand, for example, how deep-brain stimulation jams or modulates the electrical signals of the brain, or whether the electrodes inserted there could be more effective if inserted in a slightly different location. "It would be very unlikely that on our first try we came up with the optimal way to do this," Greenberg says.

Funding for researching such surgeries can be difficult to come by. Up to now, the Brown physicians have not sought grant money from the National Institutes of Health. Public agencies, Rasmussen believes, have been reluctant to support surgery for the mentally ill ever since frontal lobotomy was discredited in the 1950s. Rasmussen hopes to overcome the political obstacles to federal funding soon, paving the way for larger-scale research and testing. He's optimistic, given the promising outcome of the work his team has done so far.

Besides, he adds, lobotomy is a crude procedure that has little in common with the surgeries of today. Far from attacking the brain's entire frontal lobe, today's surgeons use state-of-the-art imaging to pinpoint minuscule locations for surgery. Most importantly, lobotomies left patients with dulled minds, while the surgeries on patients like Della Grotta and Todd Isaacson have unencumbered their minds and set them free.


Emily Gold is the BAM's senior writer.




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