Only last year, at the age of 47, Richard Weeden was trapped in a body that could hardly function. Fourteen years earlier, he had been diagnosed with Parkinson's disease, a condition affecting areas of the brain that control movement.

For some time, his symptoms of trembling hands, rigid muscles and slowness of motion had been controlled by medication. But in 1989, he began to experience a common side effect of the drugs, uncontrollable movements called dyskinesias. When he walked, his legs would jerk up and forward, in a bizarre parody of a military goose step, making it impossible to walk in a straight line. Even at rest, his legs constantly writhed and twisted.

Without the medication, Weeden was practically frozen. His hands trembled constantly, and any attempt to move was excruciatingly slow. His balance was so poor that he risked falling whenever he tried to walk. Sometimes he had to move around his home on his hands and knees. Finally, he could not even get out of bed. His wife Betty, a registered nurse, thought she would have to hire an attendant to stay with him during the day while she worked.

'Before Rick got Parkinson's, he was very physically active,' she says. 'We waterskied, we sailed; he loved to do carpentry work around the house. Then slowly, inexorably, he lost everything.'

John Growdon, MD, the MGH neurologist who oversaw Weeden's care, says: 'We were very frustrated with all our efforts to help him with medication. He had only a few minutes every day when he could function at all.'

Today, Weeden's situation has profoundly changed. He walks more than five miles a day. He is able to care for himself and work around the house. While he is not free of Parkinson's symptoms, he is once again an active participant in the lives of his family and friends.

Richard and Betty Weeden

Revival of an Obsolete Operation

This transformation is the result of an operation performed at the MGH, an operation that resulted from a collaboration between an MGH neurosurgeon and a Finnish surgeon who is leading the revival of a procedure thought obsolete decades ago.

The operation, called a pallidotomy, was one of several used during the 1950s and '60s to treat Parkinson's. All these (procedures involved making small lesions (areas of damaged tissue) in parts of the brain involved with motion control. In the pallidotomy, the lesion is placed in an area called the globus pallidus. Through a process that is still not well understood, the operation successfully relieves symptoms for many patients (see sidebar). When medications that produced similar effects without surgery became available in the late '60s, the pallidotomy was abandoned.

Neither drugs nor operations can cure Parkinson's. Eventually patients need higher doses of medication to control their symptoms. Like Richard Weeden, many develop drug-induced dyskinesias and find themselves existing on a precarious edge: motionless without medication, moving uncontrollably with medication.

For the most severely affected patients, surgeons have continued to offer another operation called a thalamotomy. But while that procedure does control tremor and muscle rigidity, it can cause the third major symptom, slowness of movement, to get worse.

Because of this limitation of the thalamotomy, Lauri Laitinen, MD, PhD, a Finnish neurosurgeon working in Sweden, began once more doing pallidotomies in patients with the most severe symptoms. In 1992, he published results showing dramatic results for most patients, sparking interest among many neurosurgeons, including G. Rees Cosgrove, MD , who was about to join the MGH staff.

Dr. Rees Cosgrove

A Series of Frustrations

News about Laitinen's success also spread through support and information networks set up by Parkinson's patients and their families. The Weedens heard about the operation and traveled for an evaluation from their home in Portsmouth, R.I., to a New York teaching hospital that planned to offer the procedure.

A lack of coordination among the staff of the New York center meant that the Weedens had to make several trips to the city and back. When asked to make appointments with several additional doctors, again requiring separate trips, they decided not to return to New York.

Frustrated, the Weedens began to consider traveling to Sweden. At the suggestion of Growdon, they also spoke with Cosgrove, who had joined the MGH staff. While he had experience with the thalomotomy operation, Cosgrove had not yet done any pallidotomies, so he concurred that Weeden's best chance was to seek care from Laitinen.

Weeden was accepted as a patient by Laitinen, and in what was to prove a lucky coincidence, his operation was scheduled at the time when Cosgrove was in Sweden to learn the procedure. Cosgrove observed his treatment and offered to provide followup care back in the United States.

Unfortunately, the results of the first operation in June 1993 were disappointing. Weeden experienced some relief from the Parkinson's symptoms, but it lasted only a few days. Laitinen recommended allowing time for his brain to heal from the operation before deciding on a further course of action.

Pinpointing the problem

MRI examinations taken at the MGH several weeks after Weeden's return pointed to a possible explanation of the problem. 'From what I'd learned about the ideal placement of the lesion, it looked like the position within the globus pallidus was not quite right,' Cosgrove says.

Laitinen agreed with the assessment and accepted an invitation to come to Boston and observe a second procedure earlier this year. The two surgeons independently reviewed detailed preoperative imaging studies, and both agreed on the specific location for the new lesion.

In the operating room, Cosgrove made a tiny hole in the skull and inserted a needle-like probe that carries an electrical current into the brain. The electrode is insulated to allow current to pass out at the tip only. Depending on how much current is applied, the electrode can stimulate, inactivate or destroy the cells it touches. In Weeden's case, the probe was passed into the globus pallidus on the left side of the brain, which affects movement on the right side of the body.

Because no pain-sensing nerves are located inside the brain, patients remain awake during the operation, under local anesthesia. With the help of the patient, the surgeon can further confirm the target for the operation and avoid damaging crucial nearby structures. 'We talk to the patients during the procedure and do a number of intraoperative tests,' Cosgrove explains. 'By passing a small current through the brain, we can see improvement in function right away.'

When the electrode is in the right spot, a stronger current is applied that destroys cells in a small area. Weeden recalls the moment: 'Dr. Cosgrove was doing the operation, and Dr. Laitinen was asking me to move my right leg to see if the probe was in the right place. They agreed that the position was right, and Dr. Laitinen said to me, 'You're not going to have any trouble with that leg again.' I was skeptical, but since then it has been rock steady. I haven't had any dyskinesia in that leg at all.'

Improved mobility, balance

Weeden's entire right side, which was most seriously affected before the operation, has improved remarkably, and his sense of balance also has returned. Although he still takes medication to con-

trol symptoms on the left side and has some dyskinesia in that leg, he and his wife are delighted with his restored mobility.

'There are so many things you take for granted when you're healthy. I couldn't even roll myself over in bed at night, much less get up to go to the bathroom,' he says. 'Now I take care of the house myself and make the meals. I can get out for a walk every day. To me, that's just wonderful.'

The pallidotomy is not a cure for Parkinson's; symptoms can eventually return as the degenerative process that underlies the disease continues. But the operation will most likely give Weeden several additional years of functional mobility. And if symptoms on his left side worsen significantly, the operation can be repeated on the untreated right side of the brain for a few more years of relief.

'Rick's improvement has been like a miracle, and we're so grateful to Dr. Cosgrove, Dr. Laitinen, and everybody at the MGH,' Betty Weeden says. 'The nurses who cared for Rick were just fantastic. Before this operation I felt like I didn't have my husband any more; I was a nurse taking care of a patient. Now I have my husband back.'

Trying to Restore the Balance

Parkinson's disease is caused by the death of certain brain cells secreting a chemical called dopamine, one of several neurotransmitters that carry signals between brain cells. Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement.

Without enough dopamine, this balance is upset. People begin to exhibit the typical symptoms of Parkinson's disease -- a trembling of the hands or head, increasing rigidity of muscles, and a slowness of motion. The disease typically appears in older people, with most being diagnosed in their 50s or 60s, and usually continues to worsen throughout life. Some patients, like Richard Weeden, develop symptoms much earlier.

John Penney, MD, an MGH neurologist, evaluates Parkinson's patients for surgery. He notes that several conditions can produce symptoms of the disease -- including infections of the brain, certain drugs, and brain injury (as in the case of boxer Muhammad Ali). But the ultimate cause of true Parkinson's disease is still a mystery.

For decades, neurosurgeons tried to relieve the involuntary movements of conditions like Parkinson's by operating on parts of the brain involved with motion control. As more was learned about brain anatomy, attention was directed toward a cluster of deep-brain structures, including the basal ganglia, the thalamus, and the globus pallidus. These form a 'circuit' that transfers motion-related signals from the brain to the spinal cord and thus to the rest of the body.

In the late 1940s, introduction of a technique called stereotactic surgery made operating on the brain much safer. Stereotaxis uses a metal frame to hold a patient's head absolutely still during imaging studies and the operation. Measurements can be taken to precisely locate structures within the brain, and delicate instruments inserted through a tiny hole in the skull to remove or destroy tissue.

With less risk of damaging healthy brain tissue, surgeons used stereotactic surgery to control the symptoms of Parkinson's by creating small lesions within these brain structures. While such operations were used to treat advanced Parkinson's symptoms during the 1950s and '60s, they were largely abandoned when drug treatment became available. One of the operations, the thalamotomy, did continue to be offered, and now pallidotomy, creation of a lesion in the globus pallidus, is being revived for selected patients.

'This operation is not for everyone,' says John Growdon, MD, MGH neurologist. 'Most patients are treated successfully with medication. But each patient is unique, and a few, like Mr. Weeden, develop exaggerated responses to the drugs that can be just as disabling as the illness. Without this operation, there isn't much else we can offer such seriously affected patients.'