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Pallidotomy vs Medical Therapy for Parkinson’s Disease
Abstract & Commentary
Source: Vitek JL, et al. Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol. 2003;53:558-569.
Surgical treatment for Parkinson’s disease has become increasingly used as a modality of treatment. Nevertheless, the efficacy and its long-term outcomes as compared to medical therapy are not well established. In the present report, 36 patients with Parkinson’s disease were randomized to either medical therapy (n = 18) or unilateral GPi pallidotomy (n = 18). Vitek and associates followed as a primary outcome variable the change in the total Unified Parkinson’s Disease Rating Scale (UPDRS) score at 6 months of follow-up. At 6 months, the patients receiving pallidotomy had a statistically significant reduction of 32% in the total UPDRS score, as compared to those on medical therapy who showed a 5% increase. The patients who received surgery showed improvement in all the cardinal motor signs of Parkinson’s disease including tremor, rigidity, bradykinesia, gait, and balance. Drug-induced dyskinesias were also markedly improved. The improvement was greatest on the side contralateral to the lesion; however, there was also a significant improvement ipsilateral to the lesion for bradykinesia, rigidity, and drug-induced dyskinesias. A total of 20 patients have been followed for 2 years to assess the long-term effects on clinical outcome. These patients have shown sustained improvement on the UPDRS "off" motor scale, as well as complications of therapy subscores. Sustained improvement was only seen for tremor, rigidity, bradykinesia, percent on time, and drug-induced dyskinesias.
As discussed in prior issues, there are a number of advances, which are taking place for the treatment of Parkinson’s disease. These include neuroprotective strategies, neurorestoration strategies with GDNF, as well as neuroreplacement with stem cells. The fourth advance in treatment, which has become highly used over the past several years, is surgical treatment. The major modalities, which have been studied, are lesions in the globus pallidus interna (Gpi) and deep-brain stimulation in the subthalamic nucleus. The present report is one of the best controlled and evaluated studies of the effects of GPi pallidotomy in PD patients. Vitek et al have clearly documented improvement at 6 months as compared to medical therapy and demonstrated that the benefits were sustained for 2 years of follow-up. A previous trial in a multicenter study did not report follow-up longer than 6 months. An earlier study without microelectrode recording reported results similar to those in the present results at 6-12 months of follow-up, but by 2 years the patients had largely returned to baseline levels of functioning. Vitek et al, therefore, feel that using microelectrodes to localize lesions is very important in obtaining successful long-term improvement. A number of other groups found sustained long-term benefit with unilateral pallidotomy. A few of the prior studies showed effects only on certain symptoms in Parkinson’s patients. For instance, one showed an effect on bradykinesia but only a moderate effect on tremor, and another reported little effect on tremor but a significant effect on rigidity. Others reported improvement of both tremor and bradykinesia. The present report showed improvement in all clinical variables. Particularly notable was improvement in balance, which is usually resistant to drug therapies. Vitek et al observed improvement in dyskinesias. This has been one of the most consistent outcomes with pallidotomy in the GPi. Vitek et al note that the lesions, which are effective, may be localized to different parts of the GPi. It is known that the circuitry into these different portions differs. It was reported that tremor was alleviated to a significantly greater degree, with lesions placed more posteriorly in the GPi whereas rigidity was alleviated with more anteriorly placed lesions. Vitek et al note that it is important to avoid lesioning the GPe. The one patient in the present cohort who did not improve after pallidotomy had a lesion that involved a large portion of the posterior portion of GPe. Similarly, in another study in which pallidotomy was reported to have little benefit, the reported lesion size was considerably larger, and there may have been partial involvement of GPe. Another factor, which they evaluated, was the age of the patients in response to outcome from pallidotomy. Vitek et al observed that there was a clear and significant relationship of age to clinical outcome with younger patients showing significantly more improvement than older patients independent of disease duration. This is consistent with a prior report from Lang and associates, who reported greater improvement for patients younger than 65 vs those older than 65.1
Overall, this study provides clear evidence that pallidotomy is an effective treatment for the motor symptoms associated with advanced Parkinson’s disease, and can provide lasting benefits on both ipsilateral as well as contralateral rigidity, bradykinesia, and drug-induced dyskinesia. These data provide further evidence that this is a useful treatment modality for advanced Parkinson’s disease. — M. Flint Beal
Dr. Beal is Professor and Chairman; Department of Neurology; Cornell University Medical College, New York, NY.
1. Lang AE, et al. N Engl J Med. 1997;337:1036-1042.