Parkinson's disease surgery
Techniques currently used in the surgical treatment of Parkinson's (PD) include thalamotomy, pallidotomy, deep brain stimulation and fetal cell transplant.
One of the first treatments was stereotactic thalamic surgery. With the advent of levodopa [medication for Parkinson's disease] in the early 1970s, the number of these procedures fell dramatically.
After more than 20 years of experience with levodopa therapy, it became clear that some people respond poorly, and that in others treatment is limited by the development of drug-induced side effects or by benefits becoming unpredictable. (People with early-onset PD have a very strong possibility of developing complications within a very short time.) With advanced brain-mapping technology, surgical techniques have developed significantly, and considerable interest has been generated in the current role of stereotactic surgery.
Interest has also evolved in the area of tissue transplants, which have progressed from the use of adrenal tissue to fetal tissue. This last procedure has raised contentious issues which are being debated in various parts of the world.
Stereotactic surgery
was first used in 1947 by Spiegel and Wycis for tremor. Initially lesions were made in the part of the brain known as the pallidum but in the mid '50s the target moved to the thalamus and this target proved better for tremor. A lesion made in the left thalamus suppressed tremor on the right side and vice versa. This procedure gave some patients relief from tremor but other symptoms persisted; if the patient needed surgery on both sides, complications such as problems with speech often occurred.
Thalamotomy
(in the ventrolateral part of the thalamic nucleus) has long-lasting effects in reducing or eliminating tremor on the opposite side and is used where there is severe, disabling tremor, preferably unilateral (and unaccompanied by marked bradykinesia), that is unresponsive to drug therapy. Deep-brain stimulation may be used on the second side. Bilateral surgery is rare and bradykinesia (slowness of movement) may increase following thalamotomy, when tremor is obliterated. This is one of the reasons for pallidotomy becoming more popular.
Pallidotomy
(in the ventroposterio-lateral area of the globus pallidus) is reported to improve bradykinesia (rigidity and akinesia), walking, hand function and verbal skills; there is significant benefit on dyskinesias opposite to the side lesioned and the pain generated by these. There is concern about bilateral surgery, and the long-term effects on cognition (mental processes) are unknown. Reports on the effect of pallidotomy on cognitive functions are varied. One study showed significant improvement in recall, verbal, visual and general memory.
Deep brain stimulation
(DBS) is a reversible therapy using small implanted programmable electrodes to block brain signals that cause disabling tremor. Surgery involves insertion of one or more electrodes into the thalamus, pallidum or subthalamic region (on the contralateral side to the tremor), using an MRI scan for accuracy. It is left in position and attached to a battery-operated, high-frequency-current generator. The first stage is exact placement under local anaesthesia, allowing external testing over several days.
The second stage involves implantation of the 'pacemaker' beneath the skin of the upper chest wall (the subclavicular area). Stimulation is then controlled by the patient using a hand-held magnet. Bilateral DBS is possible. Side effects are mild and reversible when stimulation is discontinued. Effects can be long-lasting and tuning can be varied to allow optimal results with few complications (some dysarthria — speech problems — and balance impairment have been observed but can be reversed with tuning). No cognitive changes have been recorded.
In American, Australian and French studies of patients with severe tremor, improvements were significant in terms of patient satisfaction, functional improvement and reduction of tremor.
Fetal cell transplants
were first performed in Mexico in 1987. This operation involved using tissue from an aborted fetus and transplanting it into the brain of the patient. First results demonstrated that fetal tissue had properties not present in adrenal tissue (the first tissue used for transplants). Fetal tissue could remain alive and actively continue to grow after transplant and developed into whatever cells were needed at the site of the transplant. Also the risk of rejection was minimal.Swedish scientists then began to experiment and were soon followed by the Americans. The Swedish experiments were made public in the February 1990 edition of the journal Science, and stated that transplantation of fetal cells produced 'marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease' (Science 1990, 247:574-7).
The patient showed a marked reduction in rigidity 2 months after the operation and a reduction in 'off-time' was noted such that 'off' periods were either non-existent or experienced only once a day. By the fifth month there was a marked increase in the speed of movement shown by the patient in all flexion movements, and few parkinsonian symptoms were evident even 4 hours after levodopa intake.
Experiments at the Colorado University and Yale University involving fetal tissue transplants on PD patients have also shown marked improvements in patients who have had the surgery. Dr Freed of Colorado University published an article in 1990 in Archives of Neurology, reporting on his first patient to receive the transplant.
Before the operation, the patient was unable to walk without a cane or crutches, spent more than 30 per cent of his day in an 'off' state and was taking medication every 2 hours. Eighteen months after the operation, he reported being able to walk on his own when in his own home and using only a cane for outings, an improvement in speech and voice volume, that his tremor had cleared and that there was 45 per cent reduction in medication.
In March 1988, the American administration banned the funding of any medical research that involved fetal tissue. This has severely restricted American efforts to study the effects of this procedure on PD patients.
Post-mortem evidence showed transplant survival and reinervation (restoration of nerve control) by grafted tissue. The increased striatal dopaminergic function correlated with improved clinical performance in the 'off' state.
A 7-year study by Freed et al (1988) showed improvement up to 4 years after transplant. It seems that the ethical issues are too great to allow the full instigation of this surgery as a treatment. Also the financial aspect needs to be taken into consideration.
At this time fetal tissue implantation must still be considered as experimental rather than proven. It is important for patients with Parkinson's disease not to build up false hopes about transplantation. Many of the seemingly encouraging results have been refuted and it seems unlikely that this procedure will be a realistic treatment option. Future developments are more likely to be related to providing the brain with a renewable source of neurotransmitters and trophic (growth) factors.
Last Reviewed: 18 July 2002
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