Cerebral palsy is a particularly frustrating disease to treat. Although the neuropathologic conditions that produce the symptoms are well known, this knowledge has not led to any curative surgical treatment. Consequently, the neurosurgeon has had little to offer in management of these patients. My own experience is typical of recently trained neurosurgeons: I saw no cerebral palsy patients as a resident, even during rotations on pediatric neurology. In a few centers, neurosurgical ablative procedures have been tried to reduce the movement abnormalities in athetoid cerebral victims. Results of such procedures have been reported as moderately favorable, but this type of ablative neurosurgery using stereotaxis has never been very popular in the United States.
In 1971, Dr. Irving Cooper drastically changed the involvement of neurosurgeons in the treatment of cerebral palsy by introducing a new operation designed to reduce spasticity: chronic cerebellar stimulation. His initial report of success aroused considerable interest in the neurosurgical community as well as in the general press, which enthusiastically supported the "new brain pacemaker" that could relieve the problems of cerebral palsy. The neurosurgical community is quite used to reports of such "breakthroughs," and consequently chronic cerebellar stimulation has been greeted with considerable skepticism; the surgeons are awaiting the long-term results of such intervention. In this article I wish to review the original rationale for the implant procedure and indicate the current status of clinical studies of the efficacy of this treatment.
The use of cerebellar stimulation in man has been made possible by the development of suitable ways for chronically stimulating the nervous system and muscular tissue. The cardiac pacemakers are, of course, the most widely used electrical implants. Other examples are the phrenic nerve stimulators for quadriparetic patients, spinal cord stimulators for bladder control for quadriplegic patients, and dorsal column stimulators for relieving pain.
Common to all these systems are a tissuecompatible electrode capable of being stimulated electrically over extended periods of time and an implanted device necessary for regulating the current flow. Unlike the cardiac pacemakers, the systems used for neurologic purposes have the battery external to the patient and use a radiofrequency generator and antenna to signal the implanted radiofrequency receiver. This implanted unit in turn sends the electricity to the electrodes (Figure 1). The combination of an external control device and battery with the implant system was necessary because of the higher energy requirements for neurologic stimulation (a regular cardiac batterywould run down too fast) and the need for controlling the signals over a much wider range of frequency and voltages. As electronic systems become miniaturized and batteries are made stronger, it is quite likely that an acceptable, totally implantable unit for neurologic purposes will be developed.
This type of equipment became generally available in the late 1960s, and stimulating areas of the central nervous system then became a practical possibility. Dr. Cooper had a long-standing interest in movement disorders and the underlying physiologic abnormalities. His reason for believing that electrical stimulation to the superior surface of the cerebellum might decrease abnormal movements and rigidity in the cerebral palsy patients came from a long line of experimental findings that go back to the 1890s.
Charles Sherrington, Nobel Prize winner in physiology, had demonstrated before the turn of the century that stimulation of the nervous system could markedly reduce rigidity in cats and monkeys. Sherrington needed an animal preparation in which abnormal tone and posturing were present, and for that reason the decerebrate preparation was developed. Using faradic stimulation, Sherrington found that several regions of the nervous system could markedly diminish the postural abnormalities and rigidity. The two most prominent were the superior cerebellum and the dorsal columns of the spinal cord.
Over the next 50 years this phenomenon was examined in great detail, and Dow and Moruzzi in their classic book on the cerebellum,1 published in the late 1950s, summarized many of these findings. Rates of stimulation, voltage, and precise anatomic location were important in producing the effect. The physiologic pathways that may be involved were not clarified until the 1960s, when investigators showed that the Purkinje cells of the cerebellar cortex have a marked inhibitory effect on the deep cerebellar nuclei. These deep nuclei send signals to the brainstem that regulate tone in the extremities through the alpha and gamma motor neuron systems (Figure 2). It was believed that stimulation to the surface of the cerebellum fired Purkinje cells, which inhibited the chain of neurons from deep cerebellar nuclei to the spinal cord motoneurons.
It now appears that the situation is much more complicated. But in any case, in 1971, Dr. Cooper combined the knowledge of cerebellar physiology with the newly developed means of stimulating the nervous system and implanted cerebellar-stimulating devices in a number of patients with cerebral palsy. He also implanted the devices in several patients with epilepsy, because he felt that the inhibitory output of the cerebellum could be employed to reduce seizure activity. The theoretic justification for this application rested on the experimental data of several investigators, who had shown that the electroencephalogram and seizure foci in animals could be affected by cerebellar stimulation.
Figure 1. Device used for chronic cerebellar stimulation unhke cardiac pacemakers, it has external battery (left) because of hign output needed for neurologic stimulation The energy is transmitted from the external generator to the implanted receiver (right)
Figure 2. Schematic diagram of the brain stem and cerebellum Signals from Purkinje cells m the cerebellar cortex affect deep cerebellar nuclei, which send signals to the brain-stem regulating tone in the extremities through the alpha and gamma motor neuron systems.
Dr. Cooper's initial reports of success with this technique prompted a number of other studies to gauge its long-term effectiveness. Most of his evaluations of patients' motor function were made through rhe use of neurologic rating scales and reports from patients and their families. He reviewed his experience with more than one hundred patients, and published two books on the subject.2"' Overall, two-thirds of his patients derived some benefits from cerebellar stimulation. Only moderate functional gains were found in most of the patients who improved, but in a few, dramatic changes were seen.
I became involved with the procedure five years ago. The mother of a severely disabled, quadriplegic seven-year-old child with cerebral palsyasked me whether I would be willing to try the implant operation. After considerable discussion as to the risks of the procedure and the newness of this approach we went ahead with the operation.
It became clear after the procedure that it was going to be extremely difficult to evaluate the results objectively because of the enormous enthusiasm that the family had for the procedure. They felt that there were definite changes in the tone and posture and that the child was much improved with stimulation. I agreed in part with their assessment, but was nor sure how much of a change there was or how much of this could be attributed to the stimulation.
To answer these questions, objective tests would have to be developed and applied repeatedly over months and years. Furthermore, double-blind tests, on and off stimulation, would have to be run. This complex testing required the cooperation of a number of laboratories at Rush Medical Center.
To grade motor function and development reflexes, a rating scale - the Milani-Comparetti - was used by our physical therapist. This test is well suited to gauge changes in reflexes that might affect motor skills and has the advantage of a clearly defined, reproducible testing procedure.
Speech was assessed by taking serial recordings before and after stimulation. These tapes were analyzed for intelligibility and other speech qualities in a blind fashion, and the objective characteristics, such as pitch and pause times, were quantitated.
Since the procedure was supposed to decrease muscle rone and reduce "spasticity," we needed special tests of these functions that could be applied to severely affected cerebral palsy patients. To measure muscle rigidity, a new test was devised in the Motor Control Laboratory. The foot was oscillated up and down and the resistance of the muscles to this stretch was measured. At the same time, the muscle response to the stretch as shown on the electromyogram (EMG) was recorded. Further special tests of the excitability of the spinal motor neurons (H and F reflexes) were performed in the EMG laboratory.
We now have made implants on 16 patients, and all of these tests are being conducted on each of them. Only half of the double-blind evaluations have now been completed, but we can already draw some conclusions. These are some of them.
We are sure from our studies that cerebellar stimulation does indeed affect motor control. It is not simply a complex, expensive placebo. A most convincing example was provided by a patient with dystonic neck posturing. When the right side of the cerebellum was stimulated at a high rate he developed marked increase in neck turning. Stimulation at a low rate on the other side of the cerebellum caused reduction of the muscle tone. So we were able to make someone worse or better, depending on the site and rate of stimulation. (This, incidentally, was the only patient in our series to get worse with stimulation.)
In examining the electrical and mechanical properties of these patients' muscles with our objective tests, and in the double-blind studies, we learned that two-thirds of our patients showed changes as a result of cerebellar stimulation. Unfortunately, however, the modification of these signs of "spasticity" did not always translate into changes in motor function that were helpful to the patient. Only half of the patients who demonstrated significant changes in the laboratory showed significant functional improvement.
In surveying the results of all 16 patients, it was apparent that the spastic-athetoid and spasticquadriparetic patients made the greatest strides following cerebellar stimulation, as opposed to the purely athetoid. This is not surprising in view of the fact that the operation is supposed to reduce motor tone and that the dystonic athetoid patients already have high to low tone. The tests of speech showed a small but objective overall improvement, and, in a few patients, intelligibility of speech was markedly better. We could not predict, on the basis of speech impairment or type of cerebral palsy, which patients would improve the most.
It should be noted in considering our results that if we had simply taken the assessment of patients' families, the treatment would have been considered almost 100 per cent effective. None of the implanted patients has stopped using the device, and all feel that they have been changed for the better - at least in some ways - with stimulation. This is in spite of the fact that some patients could not tell correctly if the stimulator was on or off during the double-blind period. This underlines the need for objective testing by investigators if we are to get a realistic evaluation of the operation.
The various investigators examining this procedure have by no means exhausted possibilities for its application. It may well be that we are not using the best stimulation parameters or stimulating in the precise places that we should for optimal effects. For example, Dr. Larson in Milwaukee has devised a different electrode arrangement that passes more current through the cerebellum and he feels that this is more effective in reducing rigidity and improves the overall response. As with any new procedure being used on a diverse population of patients, a considerable amount of time will be needed to sort out which patients might benefit from the procedure and whether the procedure is good enough to justify doing it in view of the risks of neurosurgery. Fortunately, the operative risks are low and the implanted units have held up well over time.
At the present time at our hospital we are restricting the procedure to patients who meet the following criteria:
(1) The child must have normal or near-normal intelligence, so that he can take advantage of any motor improvements that might come with stimulation.
(2) Spasticity must be present, by which we mean increased tone in extremities.
(3) The motor disability must be severe enough to warrant the small but definite risks of surgery.
It is equally important to determine if the family can be entrusted with carrying out the stimulation program and cooperating with our testing procedures over a number of years. Since we have not been impressed with the changes in athetosis with stimulation, we have decided not to implant any more patients with this type of cerebral palsy.
One can look at the overall results with disappointment or guarded optimism. The procedure certainly does not live up to the National Enquirer's claims of making the paralyzed walk. Nor does it meet the expectations of patients who want a "cure" for cerebral palsy. On the other hand, it is a totally new approach to central-nervous-system motor disorders and is a research procedure that is truly in its infancy. It would be a shame not to explore fully the potentials of the new technique, to clarify the indications for its use, and to objectively evaluate the group of over 1,000 patients who have already been implanted.
Many new surgical procedures seem to go through several stages of development. Initially there is enormous enthusiasm and great publicity. It is then tried by other investigators. They report some failures, and there is overall skepticism and disappointment in the medical community. Finally, there is a sorting-out period, when the proper indications for the surgery are found and improvements made in the operation. It then finds its place in overall treatment.
At the present time we seem to be in the mild, disillusioned period, and I think it will be a number of years before we can sort out all the proper indications for the procedure. After all, it has taken a long period of time for the orthopedic procedures to find their rightful place in the treatment of cerebral palsy, and it may take a similarly long period of time for cerebellar stimulation to assume its proper role. Even if it eventually proves not be effective enough for general use, the concept of stimulation of the brain to overcome neurologic damage will have changed our thinking about ways to treat cerebral palsy.
1. Dow, R. S., and Moruzzi, G. The Physiology and Pathology of the Cerebellum. Minneapolis: The University of Minnesota Press, 1958.
2. Cooper, LS. (ed.). The Cerebellum, Epilepsy, and Behavior. New York: Plenum Press, 1974.
3. Cooper, I. S. (ed.). Cerebellar Stimulation in Man. New York: Raven Press, 1978.
A SELECTED READING LIST FOR PEDIATRICIANS WISHING MORE INFORMATION
Fisher, M. A., and Penn, R. D. Evidence for changes in segmental motoneurone pools by chronic cerebellar stimulation and its clinical significance. J. Neurol. Neurosurg. Psychiatry 41 (1978), 630-635.
Gildenberg, P. L. (ed.). Safety and clinical efficacy of implanted neuroaugmentative devices. Appi. Neurophysiol. 40 (1977), 67-241.
Gottlieb, G. L., Agarwal, G. C, and Penn, R. D. Sinusoidal oscillation of the ankle as a means of evaluating the spastic patient. J. Neurol. Neurosurg. Psychiatry 41 32-39.
Penn, R. D., and Etzel, M. L. Chronic cerebellar stimulation and developmental reflexes. J. Neurosurg. 46 (1978), 506-511.
Penn. R. D., Gottlieb, G. L., and Agarwal, G. C Cerebellar stimulation in man: quantitative changes in spasticity. J. Neurosurg. 48 (1978), 779-786.
Ratusnik, D. L., Wolfe, V. I., Penn, R. D., and Schewitz, S. Effects on speech of chronic cerebellar stimulation in cerebral palsy. J. Neurosurg. 48 (1978), 876-882.