Two conditions make up the largest numbers of patients with movement disorders who might be suitable for radiosurgical treatment. These diseases are Parkinson's disease and essential tremor (familial tremor). In unusual circumstances, movement disorders may also be due to head injuries, brain infections such as encephalitis, or following strokes. Movement disorders take a wide variety of forms. One of the most common movement disorders is tremor.
Parkinson's Disease and Essential Tremor
In Parkinson's disease, the tremor or shaking usually involves the arms and hands and is most prominent when the patient is at rest. In essential or familial tremor, the hands and arms are usually quiet at rest, but if the patient attempts to perform a task, such as picking up a glass of water or writing, then the tremor becomes very noticeable. Tremor can sometimes involve the head and neck and also sometimes involves the legs. Tremor interferes with many normal activities. Patients may be unable to write their name and, for instance, sign checks. They may be unable to drink from a cup or glass without spilling, and they may be unable to cut food with a knife and fork. In addition, patients may be unable to feed themselves, button clothing, comb their hair, or perform almost any movement that involves coordinated control of the hands, fingers and arms.
In essential or familial tremor, the movement disorder is the only aspect of the disease. The only difference between essential tremor and familial tremor is that in the latter, there is a family history with tremor being present in other generations, whereas in essential tremor, there is not. The actual tremor itself is identical in both conditions.
In Parkinson's disease, there are often other movement abnormalities in addition to tremor. These may include bradykinesia (slowness of movement) and rigidity or stiffness in the muscles, which make movements difficult. Also, in Parkinson's disease, there is frequently difficulty with walking because of the slowness and stiffness of movement and because of poor balance and a tendency to fall.
Medications are available for initial treatment of movement disorders. In Parkinson's disease, medications containing L-dopa (levodopa) are the most commonly used. A variety of newer medications may also be effective in the control of Parkinson's disease symptoms. In essential tremor, the beta-blocker family of drugs, which includes Inderal (propranolol) and Mysoline (primidone), may be effective. In general, surgical treatment of any kind, including radiosurgery, is usually reserved for patients whose symptoms cannot be effectively controlled with medications.
Various forms of surgical treatment are available to control movement disorders when medications are ineffective. The surgical procedures available generally fall into two categories: 1) ablative or destructive procedures such as thalamotomy or pallidotomy, and 2) stimulation procedures performed by the implantation of stimulating electrodes within the brain.
Although the exact mechanism of movement disorders is not completely understood, it is clear that in most cases, overactivity in one of two structures within the brain causes movement disorders. This overactivity is located either in the thalamus or in the globus pallidus. Recently, suppression of movement disorders by electrical stimulation in another area, the subthalamic nucleus, has been suggested, but stimulation in this area remains under clinical investigation.
Radiosurgical vs. Radiofrequency Methods
Excessive activity of brain cells in a small part of the thalamus called the ventral intermediate nucleus (VIM) is thought to be responsible for both the tremor of Parkinson's disease and the tremor seen in essential or familial tremor. Its involvement in other forms of tremor varies. The classical surgical method of dealing with tremor has been to destroy this small group of cells (thalamotomy) by passing an especially designed needle into the area and then heating the needle tip with radiofrequency electrical current. The correct area of the brain can be identified by a combination of imaging studies (usually MRI scanning) and electrical recordings made with a tiny wire electrode (microelectrode).
In the 1960's, Lars Leksell, a Swedish neurosurgeon, began to experiment with destroying this area using radiosurgery. Since that time, there has been considerable experience in using radiosurgical methods to treat movement disorders, rather than radiofrequency methods. The advantage of the radiofrequency method is the presumed ability to more carefully locate the exact target using the electrical recording and stimulation methods mentioned previously.
The disadvantage is that it requires passage of a needle electrode through the brain tissue resulting in the possibility of complications such as bleeding and infection, either within or upon the surface of the brain. Unintended injury to other normal structures can lead to complications such as paralysis, loss of feeling, or interference with speech, among others.
Radiosurgical treatment does not require placing any invasive device within the body and must rely therefore on imaging studies such as MRI scanning to correctly localize the target. Some people have felt that the inability to use microelectrode recording and stimulation when radiosurgical procedures are performed is a drawback of those procedures. As we will see, however, the outcome of Gamma Knife radiosurgical procedures is equally effective as that of radiofrequency procedures performed in the thalamus and is considerably safer. Those complications that directly surround an operation such as anesthetic complications, hemorrhage, and infection, do not occur with radiosurgical treatment.
It should be strongly noted that radiosurgery with the LINAC technology is not recommended for any type of movement disorder as the machines can not reach the precision of the Gamma Knife and potential harm will be done to the patient.
Both radiofrequency and radiosurgical thalamotomy can be expected to relieve tremor in about 85% of patients. In some patients, the tremor is markedly suppressed but not totally relieved and in other patients, the tremor is completely relieved. Examples of a patient's handwriting before and after a thalamotomy was performed with the Gamma Knife machine. Virtually all of the treatment of movement disorders using radiosurgery has been with the Gamma Knife. There is little or no experience in using the other forms of radiosurgery, that is, the linear accelerator or heavy particle beam radiosurgery, to make such lesions for treatment of movement disorders.
Therefore, results achieved with Gamma Knife may not be indicative of results achieved with other types of radiosurgical equipment. The Gamma Knife is designed to perform this type of treatment. We have performed more than 200 thalamotomies for the relief of tremor over a period of more than eight years. Only two relatively mild side effects have been seen in these 200 patients. Both involve mild weakness or coordination difficulty in the side of the body opposite to the thalamotomy. No other complications of any kind have been seen in any of the other patients.
For radiofrequency thalamotomy, the complication rate has been variously estimated from as low as five percent to as high as 20% or 25%. These complications can include paralysis, loss of feeling, difficulties with speech and, in a rare case, severe hemorrhage requiring a major operation (craniotomy) to remove a large blood clot within the brain or on the surface of the brain. It is our belief that radiosurgical thalamotomy with the Gamma Knife offers the safest method for treatment of tremor. Figure 3 shows a lesion created in the thalamus by radiosurgical thalamotomy.
Deep Brain Stimulation
Recently, there has been considerable attention to the use of deep brain stimulation to treat tremor. The success rate with this method is about equal to that of thalamotomy performed either by the radiofrequency or radiosurgical method. Deep brain stimulation requires, however, a permanent implantation of stimulating hardware (wires and battery) within the brain and the body. The potential for hardware related complications such as wire breakage, dislocation of the wires, the need for frequent reprogramming of the batteries and the eventual failure and need for replacement of the batteries, in addition to the relatively high cost of the hardware, in our opinion, limit the practical usage of deep brain stimulation.
Deep brain stimulation may be particularly useful if a thalamotomy has been performed previously on one side and one is interested in controlling tremor on the other side. Performing a bilateral or two-sided thalamotomy increases the risk considerably. This risk may be lowered by performing a thalamotomy on one side and then placing a deep brain stimulator on the other side.
The other area of the brain involved in movement disorders is the globus pallidus. Overactivity in this structure generally produces the slowness of movement and stiffness seen in Parkinson's disease patients. The globus pallidus generally is not thought to play any role in familial or essential tremor. The pallidotomy procedure, which destroys a portion of the globus pallidus can be performed by either radiofrequency or Gamma Knife approaches. Once again, we are unaware of any significant experience with either linear accelerator or particle beam radiosurgery for the performance of pallidotomy.
We have performed nearly 100 pallidotomies in the past eight years using the Gamma Knife. The success rate closely approximates that which can be obtained with the radiofrequency method. As the radiosurgical pallidotomy technique was being developed, some complications occurred more frequently than one would have expected with the radiofrequency method. However, during the past 60 patients, only a single complication, a partial visual loss, has occurred. No other complications of any kind have been seen. We believe that radiosurgical pallidotomy is as effective as radiofrequency pallidotomy and considerably safer.
Recently, information has been published on the use of deep brain stimulation in the globus pallidus, as well. This method has been employed primarily in Europe and is currently not approved by the Food & Drug Administration of the United States for use here. As mentioned previously, there has been recent interest in deep brain stimulation in an area called the subthalamic nucleus. Most of this work has also been done in Europe and currently deep brain stimulation also is not approved for use in the United States, although some experimental applications are currently being carried out.
By the end of 1998, it had been reported that 814 patients had received Gamma Knife treatment for Parkinson's disease at all Gamma Knife centers throughout the world, and a significant number of additional patients had received treatment for essential tremor and other forms of tremor. The interest in using radiosurgery to treat movement disorders is increasing. It is attractive to patients and their families because of its effectiveness and safety. Many radiosurgical centers perform the procedures on an outpatient basis and, at maximum, an overnight stay is required. Patients are able to return to normal activities immediately without the recovery period generally required after an open skull procedure, such as a radiofrequency thalamotomy or deep brain stimulator implantation.