Parkinson's Disease:
A New Surgical Approach Provides Hope

"I'm a new man," declared David Crawford, who for 12 years suffered the increasingly debilitating effects of Parkinson's disease. Unable to function or even move without assistance, Crawford recently underwent 18-hour surgery at Beth Israel Hospital in Boston in the hope of being able once again to do the simplest of things of life -- all on his own. This surgery, using microelectrode recording from individual neurons in the brain, is the newest hope for sufferers of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease that affects the functioning of the basal ganglia, a brain area that contributes to the control of movement. The disease is caused by the death of nerve cells in the brain that produce dopamine, a chemical messenger. When the supply of dopamine is depleted, the function of the basal ganglia is disrupted and its ability to control movement deteriorates. The result is that PD patients experience moderate rigidity, difficulty in initiating movements and slowness in executing them, and a rhythmical tremor at rest.

To improve motor functions, PD patients are usually treated with Levadopa (marketed as Sinemet), which replaces dopamine in the brain. However, as the disease progresses, Levadopa treatment loses its efficacy, and patients lose their ability to initiate movement on their own -- they "freeze." At this point, the amount of medication needed to enable movement is so high that it leaves the patient no choice other than to be in constant motion -- motion of a nature that involves abnormal involuntary movements, long-lasting painful muscle contractions, and sudden jerky movements.

Such constant and uncontrollable movement makes it difficult for patients to care for themselves and perform simple tasks of daily life such as eating without choking, drinking without spilling, speaking audibly, or holding a grandchild. It becomes almost impossible to walk without falling, to sit still, to prepare a meal or empty the trash, or to drive a car. At night, the constant movement makes it difficult to sleep, have sex or even share the bed with a partner; yet it is necessary so that the patient can talk to a spouse, change position, and get up once awake. The toll these difficulties take on the spirits is devastating.

At this stage, the best alternative is surgery. For years, a surgical procedure has been used to destroy the part of the brain containing the nerve cells that generate the neurological symptoms exhibited in Parkinson's Disease. This procedure locates the general area to destroy by a process of elimination: using microstimulation (tiny electrical charges) to identify the functions of the cells in the areas surrounding the target area. The surgeons then destroy some part of the area roughly defined by the microstimulation. The imprecision of this procedure, however, puts the patient at substantial risk of paralysis or loss of vision.

A new high-precision, low-risk procedure is currently in use at a handful of hospitals throughout the country. Based on anatomical and physiological studies of the basal ganglia, this procedure, called "pallidotomy," uses information provided by microelectrode recording of the activity of individual neurons to pinpoint the exact area to be destroyed. With this precision, only cells located deep in the basal ganglia, in an area called the globus pallidus (Gpi), are destroyed, leaving surrounding areas unharmed.

"I knew about the other surgery, but I wasn't willing to take the risk. When I heard about this new procedure, I knew I had nothing to lose and everything to gain," Crawford explained in his first meeting with the surgical team.

To locate the Gpi and its borders accurately before destroying it, several techniques are used in concert. First, a stereotaxic frame (a large metal head brace that enables geometric location of brain areas) is attached to the head of the patient under local anesthesia, and computed tomographic (CAT) and magnetic resonance imaging (MRI) scans are made. The anatomical information provided by these images is used to refine the stereotaxic coordinates of the Gpi; this narrows down the position of the area to be destroyed. Next, a single hole is made in the skull to allow the introduction of a recording microelectrode into the Gpi. This microelectrode is fastened to a hydraulic microdrive (an instrument that advances the electrode in small, precise steps). The tip is advanced one-thousandth of a millimeter at a time in order to identify individual neurons and to record their activity.

Because the activity of the Gpi neurons differs from the activity of neurons in the adjacent areas, repeated repositioning of the recording microelectrode makes it possible to distinguish target from nontarget areas and thereby locate and map the borders of the Gpi. This is a complex task, however, in that the differences in neuronal activity are often too small to distinguish by the commonly used techniques of listening to their activity or by observing their spikes on the oscilloscope. Therefore, to identify properly the different types of neurons, we developed a computerized on-line statistical analysis system that averages neuronal activity and displays it graphically within seconds (Figure 1).

The information provided by this system helps the neurophysiologist identify the target area boundaries for the safest and most precise lesioning (cell destruction) in the Gpi, and the neurosurgeon lesions it (Figure 2, below) by heating the target (60 seconds, 80 degrees Celsius) through an uninsulated tip of a probe.

The rationale for this procedure stems from findings that the depletion of dopamine interferes with the signals that reach the Gpi from other parts of the basal ganglia, causing Gpi neurons to receive fewer inhibitory signals from one part of the basal ganglia and more excitatory signals from another. As a result, neurons in the internal part of the globus pallidus become hyperactive. Hyperactive Gpi neurons are thought to play a key role in interfering with the execution of voluntary movement; therefore, destroying them allows the initiation and control of voluntary movements. The result is a patient who can function once again with low doses of Levadopa and who is free of complications or side effects.

To date, hundreds of PD patients throughout the U.S. have undergone this operation in hopes of alleviating the miserable choice between being "frozen" or being in constant uncontrollable movement. David Crawford's new lease on life speaks for itself. With a significantly reduced amount of medication, he walks without falling, sleeps normally, and enjoys doing the little tasks of everyday life. He can now initiate movement on his own when and how he wishes. He is, once again, living life as an independent, well-functioning individual. *

Dr. Burstein is Assistant Professor of Neurobiology and Anesthesia at Harvard Medical School and Beth Israel Hospital.