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Dear all, In the Autumn issue of the Parkinson's Disease Foundation Newsletter, there appeared a very scholarly article by Dr. Seth Pullman, of New York University, dealing with the current state of the knowledge in pallidotomy and other surgical treatments for Parkinson's disease. For those of you who have not seen this article, I am "pasting" it below. This is the kind of critical research that is necessary before pallidotomy and other such treatments become "mainstream" in the treatment of this disease. I saw no "copyright bug" on this article, so I assume that I am not violating any laws by re-posting it here. ----------------------------------------------------------------- PALLIDOTOMY FOR PARKINSON'S DISEASE Seth L. Pullman, M. D., FRCP(C) Director, Clinical Motor Physiology Laboratory Movement Disorders Group, College of Physicians and Surgeons Columbia-Presbyterian Medical Center New York, NY Introduction: >From the 1940s to the mid-1960s, surgical lesions deep in the movement control centers of the brain were performed to relieve the symptoms of Parkinson's disease. Unfortunately, these early procedures generally met with poor success because localization of deep brain structures was imprecise, and the operations were risky. With the introduction of levodopa in the late 1960s, most of the symptoms of Parkinson's disease were alleviated medically. Medical treatment of Parkinson's disease became the norm. Virtually all surgical procedures fell into disuse. However, by the late 1970s and 1980s, it was found that patients taking levodopa for more than 5-10 years tended to experience a loss of benefit from their medications. Adverse effects such as dyskinesias and "on-off" fluctuations began to occur. Interest in surgical treatment for Parkinson's disease re-emerged. Furthermore, neurosurgical techniques became safer and the ability to obtain images of brain structures with CT, MRI, and PET scans revolutionized the field. Importantly, accurate physiological methods of localizing the movement control centers of the brain were successfully adapted from animal experiments. These developments have led to new surgical approaches for the treatment of Parkinson's disease. Patients must be carefully screened before consideration for pallidotomy. Those with the greatest probability of improvement must be responsive to levodopa but may no longer tolerate side effects such as levodopa-induced dyskinesias. Patients cannot be considered for surgery if they are unresponsive to levodopa. Clinical features that can be improved by pallidotomy are severe tremors, "on-off" fluctuations, bradykinesia, and rigidity. Gait disability is less well treated by pallidotomy. Patients should not be demented or depressed, and must be able to withstand a very long operation. Patients are awake for most of the operation, which can last for up to 10 hours with their heads secured in a metal frame in the operating room. Before the pallidotomy is performed, a brain MRI is taken and the metal frame is gently attached to the head. A CT scan is then obtained to coordinate anatomic regions with hardware landmarks. The patient lies on his or her back with the neck slightly flexed on the operating table. Under local anesthetic, a burr hole is placed in the skull and initial coordinates for the surgery are made. A series of metal guide tubes are positioned such that the electrodes for physiologic recordings and for surgical lesions can be targeted properly. Surface skin electrodes for measuring muscle activity and motion are placed on the arms and legs to document motor activity. Under light anesthesia, several electrode tracks are used to "map" physiologically the boundaries of the deep brain structures to be operated on. Most medical centers performing this specialized surgery find that electro-physiologic monitoring prevents potential errors in lesion placement. In addition, mild electrical stimulation deep in the brain near the visual and motor nerve pathways determines the proximity of these important structures and helps avoid injuring them. After mapping the deep brain structures, surgical lesioning is done using a high temperature electrode pin-pointed at the target. Multiple lesions are usually placed in two or three tracks. Prior to each lesion, low heat testing is used to note visual changes, motor strength and involuntary movements. Lesioning with higher heat levels is then done at each site. Repeated neurologic examinations are performed continuously on the patient, who remains awake throughout the procedure, and guides the surgeon by reporting responses to stimulation. Clinical Results: Clinical measurements such as the Unified Parkinson's Disease Rating Scale (UPDRS) and Core Assessment for Intracerebral Transplantation (CAPIT) are needed for baseline and post-operative evaluation in both the "on" levodopa and "off" levodopa states. Other clinical tests, such as measures of dyskinesias, speech and cognition are also critical for post-operative evaluation. Objective quantification of movement speed and reaction time with computerized methods is very important in measuring results of pallidotomy. Overall, there is 80-100% reduction in dyskinesias after pallidotomy, allowing patients to maintain pre-operative levodopa doses without side effects. Many patients can actually decrease drug doses and maintain sustained improvement. However, it is important to note that best "on" motor scores do not change after pallidotomy. When "off", patients note improvement in almost all activities of daily living, and UPDRS "off" motor scores improve by 20-60%. Tremor can be markedly reduced but may be variable when tremor-related activity is not found during intra-operative physiologic recordings. Rigidity and bradykinesia improvement from 10-45% with clear increases in "off" movement speed. Postural instability, gait and freezing may also show some improvement. Combined experience from all centers performing pallidotomies suggests an overall improvement in "off" scores of about 30%. The effect of pallidotomy, particularly on dyskinetic movements, can be striking and immediate. Patients should be cautioned, however, not to expect "miracles" as the popular press has reported. Long term effects are still being evaluated, but it appears that many patients have shown continued improvement for well over two to three years. Complications: Because general anesthesia is not used, complications related to this technique do not occur in pallidotomy. However, there is a less than one percent risk of serious intra- or post-operative hemorrhage, infection, or death. Because the deep brain regions to be lesioned are adjacent to visual and motor areas in the brain, there is a three to six percent risk of partial blindness or paralysis. Adverse psychological changes such as decreased short term memory, depression and word finding difficulties have occurred in patients after pallidotomy, usually in those with pre-existing symptoms. These complications are more likely to occur when the pallidotomy is done on the left side. Bilateral pallidotomy lesions may result in even greater speech and psychological changes. Other Surgical Procedures for Parkinsonism: Other surgical procedures of potential use in patients with Parkinson's disease include lesioning other deep brain structures (such as thalamotomy), implantation of high frequency electronic stimulators, and neural grafting with transplanted cells. Thalamotomies are highly effective in reducing severe tremors, but are not effective with other symptoms of Parkinson's disease or drug-related dyskinesias. Implanted stimulators hold significant promise but that technique has not been performed enough to make critical assessments at this time. Stimulators have the potential advantage of being able to be turned on and off, but may not treat as large an area of the brain as pallidotomy. Transplantation of fetal grafts into deep brain structures theoretically can be used to replace dopamine loss in Parkinson's disease. Studies are ongoing but clinical effects from transplantation may require at least a year to become evident, and not enough data from patients has been collected to judge the results. Conclusion: Pallidotomy is a relatively safe and effective treatment for carefully screened patients with Parkinson's disease who have levodopa-induced dyskinesias, "on-off" fluctuations, tremors and bradykinesia. Overall, symptoms improve by about 30% with sustained improvement potentially for over two to three years. Gait abnormalities and freezing show less consistent improvement, and peak "on" scores do not improve. Pallidotomies probably should not be performed on patients with significant cognitive impairment and bilateral pallidotomies should be approached with caution due to potential speech and psychological problems. *********************************** ROBERT A. FINK, M. D., F.A.C.S. Neurological Surgery 2500 Milvia Street Suite 222 Berkeley, CA 94704-2636 USA Phone: (510) 849-2555 FAX: (510) 849-2557 WWW: <http://www.dovecom.com/rafink/> "Ex Tristitia Virtus" ***********************************