MRI Brings Back Pallidotomy

Usually medical technology advances with ever new and improved procedures. In the case of Parkinsonís disease, however, an old technique has been rediscovered, thanks to the precision provided by magnetic resonance imaging (MRI) and brain mapping.

Pallidotomy is surgical removal of the brain tissue that causes Parkinsonís symptoms. Major pallidotomy programs are offered at three medical centers: Emory University in Atlanta, where the physiological monitoring that accompanies the surgery was developed; the University of Toronto; and New York University. The procedure is offered at many other facilities, but these three centers are the most consistent in their use of localization strategies and long-term follow-up.

Parkinsonís disease gradually impairs the bodyís ability to move smoothly. Normally, the nervous system coordinates the functioning of muscle groups so that an action such as standing is possible without jerks and twitches. Some people with Parkinsonís disease also develop tremors, especially of the hands. The most common manifestations are slow physical motion, a shuffling gait and a face often described as masklike, with a characteristic rigidity that results from increasing muscle tone. We donít really know the cause of the disease, but it has been attributed to viral infection or exposure to pollutants. We do know that it is common. "Itís estimated that between a million and a million and a half people have Parkinsonís disease," said Dr. Paul Maestrone, director of scientific and medical affairs at the American Parkinsonís Disease Association, headquartered in Staten Island, N.Y.

But that may be underestimated. "Parkinsonís is not a reportable disease because it isnít contagious, so the information on incidence is not as accurate," he added.

The defect causing Parkinsonís symptoms is a deficit of nerve cells that produce the neurotransmitter dopamine, in a part of the brain called the substantia nigra. The lack of dopamine increases activity in a region called the globus pallidus interna, prompting it to send out inhibitory signals to muscles and causing the disorderís muscular rigidity and slowed movements.

Pallidotomy is directed to the globus pallidusñand itís a small target. "The globus pallidus is about 1/2 in. in diameter, and pallidotomy targets about a quarter of that space, the part that is farthest back. It is a very discrete, precise lesion that must be made," said Dr. Enrico Fazzini, director of the Parkinsonís Disease Center at NYU. Somehow, destroying cells here restores normal movement to some degree in about 80 percent of patients undergoing the procedure.

The seed of the idea for pallidotomy was sown, researchers say, in 1817, when James B. Parkinson, for whom the disease was named, noted that a patientís tremor lessened after a stroke. He hypothesized that the damage from the stroke somehow righted the wrong causing the tremor.

In the 1950s, a New York surgeon accidentally tied off an artery serving the globus pallidus, and again, the patientís Parkinsonís symptoms improved. A flurry of reports confirming the finding followed, but they tended to be anecdotal. Still, pallidotomy as a surgical procedure became available in 1954.

Then a fantastic development in Parkinsonís treatment made pallidotomy seem too invasiveñthe discovery that the drug levodopa can restore the deficient dopamine levels. "Pallidotomy was performed in the 1950s and 1960s, but it wasnít used for 15 years or more after levodopa was introduced for the treatment of Parkinsonís disease," said Maestrone.

Levodopa was a breakthrough because dopamine is too bulky to cross the blood-brain barrier. Chemically different from dopamine, levodopa can cross the barrier and is then convened to dopamine. But levodopa therapy does not target only the globus pallidus ñdopamine reaches many brain regions, a phenomenon that would become troublesome.

Through the 1960s and 1970s, levodopa appeared to be a wonder drug. Then physicians discovered that it stopped working after a few years in about two-thirds of patients. Patients also responded to levodopa in an "on-off" manner, responding at times and not responding at others within the course of a day. Ironically, the drug also produces grotesque movements, often of the face and arms, called dyskinesia.

Levodopaís success, however, told researchers through the 1980s more about Parkinsonís disease because the drug allowed people to live longer. Levodopa also revealed the effects of flooding the brain with dopamine, suggesting that perhaps a more targeted approach would have fewer side effects and last longer.

And so, in the 1990s, it was back to the idea of the 1950s to selectively destroy parts of the brain, but with a twistñnew technology to direct the treatment. "Improvements in mapping techniques, including MRI and CT scanning, allowed neurosurgeons to visualize the area of the globus pallidus," said Roger Rizzo, director of the pallidotomy program at the University of Texas-Houston Health Science Center.

To guide pallidotomy, MRI is used with a recording of the electrical activity of brain neurons as they fire nerve impulses. The approach is called multimodality correlative imaging. MRI, with stereotactic tomographic imaging and software of neuroanatomy, provides the neuroradiological component, and electrophysiological targeting acquires characteristic "signatures" of certain groups of neurons firing.

"MRI is part of the correctly done procedure and is most important in identifying the site to be destroyed in the brain," explained Maestrone.

During the procedure, the patientís head is positioned in a frame, and a small hole is drilled in the top of the skull. A microelectrode connected to speakers in the operating room is extended through the hole. As it probes, the sounds of neurons firing fill the room. Simultaneously, MRI visually tracks the electrical activity. The patient, sedated but responsive, is asked to move certain body parts, and the neuron firings are followed.

Within two to three hours, the team has a good idea of the location of the globus pallidus. "Through MRI and hearing the sounds, the surgeon can make the lesion in the exact spot that can help relieve symptoms of Parkinsonís disease," noted NYUís Fazzini. A lesioning electrode replaces the searching electrode, and it emits heat that selectively destroys cells. The procedure is painless.

Fazzini has followed patients undergoing pallidotomy in its current manifestation for as long as 4 1/2 years. Results are encouraging. "It improves the slowness, stiffness, tremors and involuntary movements from the medication," he said. For the 20 percent of patients who do not improve or do so only transiently, the site of the lesion was often slightly off, he added.

The surgery, however, cannot slow the dementia and loss of balance that are also part of the disease. "Balance and cognition are so complex, involving so many parts of the brain, that you wouldnít expect a simple lesion to help them," remarked Fazzini.

He described one patient as fairly typical, a teacher in his 40s who often experienced the on-off phenomenon in front of his students. When levodopa worked too well, his right arm would shoot forward, and his right leg would kick up, quite on their own. Yet when in the "off" state, the leg dragged. "After surgery, his right side is normal. To his classes, it seems a miracle," Fazzini said.

At the Texas program administered at Hermann Hospital, a third to a half of interested patients qualify for the procedure, according to Dr. Gage Van Horn, professor in the department of neurology. He added that the average patient is between the ages of 49 and 75 and has been ill for at least ten years.

"Pallidotomy is usually used where medical treatment is no longer effective," said Maestrone. People most likely to benefit from the procedure have intractable dyskinesia and the on-off response to the drug, wrote Drs. Christopher Goetz and Nico Diederich of Rush Presbyterian St. Lukeís Medical Center in Chicago, in the May issue of Nature Medicine. Patients not likely to benefit are those who never responded well to levodopa, do not show the on-off response and have severe tremors.

The procedure isnít a cure, Fazzini said, but can make life much easier. "If you pick the right patients and do the right surgery, it really helps a great deal."

feedback form | permissions | international | locate your campus rep | request a review copy

digital solutions | publish with us | customer service | mhhe home

---

Copyright ©2001 The McGraw-Hill Companies.
Any use is subject to the Terms of Use and Privacy Policy.
McGraw-Hill Higher Education is one of the many fine businesses of the The McGraw-Hill Companies.