The Neurosciences Institute, which is associated with Good Samaritan Hospital in Los Angeles, sponsored a symposium on Nov. 2-3, 1996 in Rancho Mirage, CA. Dr. Chance made her presentation there. I thank Carole Hilton for making this information available to the Parkinsn archives. Clinical follow-up of Post-Pallidotomy and Neurotransplantation Patients - Dr. Janet Chance The treatment of Parkinson's disease is continuing to change. Initially there was little to offer, but surgery and ablative techniques were performed for severe tremor and rigidity. The development of L-Dopa revolutionized the management of Parkinson's disease and surgery fell into disuse. The next great breakthrough was the development of an animal model (MPP+ induced) and we are now seeing results from this with the development of more selective Dopamine agonists and the COMT inhibitors. However, none of the drugs currently available have any significant effect on the disease process. Consequently, as the patients progress they require more complex drug regimens and medication side effects, especially the long term side effects of L-Dopa, may become intolerable to both patient and care giver. For a number of patients, currently a small and highly selective group, surgical treatment has again become an alternative. With the advent of microsurgical techniques, a clearer understanding of the anatomic microstructure and patho- physiologic function of the basal ganglia, the lesions can be made with far greater precision. Stereotactic radio frequency oblation, electrophysiologic stimulation and computer integration of MR images with stereotactic frames have minimized morbidity. Current procedures available include thalamotomy and VIM stimulation (primarily for tremors), medial pallidotomy and neural grafting. It is with the latter two procedures, or rather the post operative management, that I wish to deal. Studies of basal ganglia connections have shown that output from the striatum to GPi occurs over two pathways, the direct and the indirect. The direct pathway inhibits GPi. The indirect pathway by disinhibition of excitatory subthalimopallidal neurons stimulates GPi. Lack of dopamine ultimately results in decreased activity in the direct pathway and increased activity in the indirect pathway, resulting in excessive inhibition of thalamo cortical neurons. Based on this, pallidotomy should improve the symptoms of Parkinson's disease. Results, however, have been somewhat mixed. The most dramatic effect is the profound reduction in L dopa induced dyskinesia contralateral to the lesion. A degree of ipsilateral improvement is also seen. I will discuss follow up in five patients who had unilateral or bilateral pallidotomy. In summary, all patients had cessation or near complete cessation of dyskinesia contralateral to the lesion with a moderate decrease in ipsilateral dyskinesia. Two of five patients had a moderate decrease in rigidity. There was no significant functional improvement in bradykinesia, although rapid successive movements did increase in amplitude. Speech and postural reflexes were unchanged in all patients. Gait improved in that the severe dyskinesias ceased. There was no significant decrease in Sinemet requirements in any patient, but it was significantly better tolerated. It was possible to decrease by 25 to 30 percent the requirement for Dopamine agonists, Amantidine and anticholinergics. Four of five patients were extremely satisfied with their outcome, citing the reduction of dyskinesia as the most pleasing aspect. Perioperative morbidity consisted of transient left facial weakness in patient number two. Patient number four was briefly hospitalized three weeks post operatively with what was initially thought to be stroke but turned out to be exhaustion. He had been playing on the beach all day with his grandchildren and staying up until the small hours of the morning with his children. MR during his admission appeared to show subacute damage to the left pallidum and the patient had had a right pallidotomy. Approximately three months post operatively patient number three developed apraxia of eye opening. It is not clear that this is directly connected to the surgery, but the patient had a good response to Baclofen. Follow up in these patients ranges from three months to three years and four of the five patients remain very satisfied. Disease progression was not affected and the patients did not have a decrease in their Sinemet requirements, but found that they tolerated it much better. it has been possible to increase the dosage without significant side effects. Bilateral fetal implants were performed on three patients, each receiving four to six donors per side. In contrast to the pallidotomy subjects, two of the three patients had a very stormy course for the first six months post operatively. Initially there was a significant increase in symptoms with marked bradykinesia, tremor, unpredictable freezing and an increase in "off" time. In addition to this, patient number three developed hiccup and confusion, which cleared within one month. By 2-1/2 months post implant, patients one and three developed major depressive episodes, with anxiety, rumination, hopelessness and anhedonia. Both patients required psychiatric intervention. During this period both patients felt they were making no progress despite clinical evidence to the contrary. In month six both patients improved, almost overnight, with cessation of depression, optimism and resumption of previously pleasurable activities. From month two on, motor function was slowly improving in all patients, although need for Sinemet did not decrease significantly. There was an improvement in "on" time and less unpredictable freezing. At month nine, patient two, her pre-operative status with a slightly lower dose of Sinemet, resumed living alone. Patient three had a significant decrease in "off" time and was able to spend considerable time on his computer and ham radio. At one year post implant patient two continued to feel well. Patient one had returned to work and patient three was doing well with reduction in tremor compared to preoperative status, and with a decrease in "off" time. He was somewhat discouraged in that his Sinemet requirement was unchanged from preoperatively. During the first year post implant all patients - especially one and three - needed a considerable amount of care. Phone calls from them or their families were frequent, sometimes daily, and office visits were also increased in number. This was maximal in the first six months. It became evident that peer support was necessary and was found to be extremely helpful by the patients involved. We have established an informal "buddy" system for future neural transplant patients and their families which will start preoperatively. The initial worsening in these patients was likely due to a combination of the mechanical effects of the implant placement, together with edema. The depression is more difficult to explain. The Yale Group did not find a clear relationship between depression and neural transplant. However, neither of my patients had any prior history of psychiatric illness and in both patients the improvement was abrupt and quite striking, occurring at six months post implant. They both saw the same psychiatrist, who was also impressed by the similarity between them. In summary, both procedures are useful in a small and carefully selected group of patients. Pallidotomy is particularly helpful for dyskinesias, the patients tolerate the procedure well, and post operative management is simple. Neural transplant is more problematic. Peer support is essential, best managed on a "buddy" system starting preoperatively and involving the care giver as well. Depression does appear to be a significant problem and this merits further exploration. However, it also appears to be relatively self-limited, clearing within six months. BIBLIOGRAPHY 1. Neurosurgical Horizons in Parkinsons Disease; Goetz, C.G., et al. Neurology 1993; 43:l-7 2. The Role of Surgery in Parkinsons Disease Management Olanow, C.W.; Marsden, C.D; Lang, A.E.; Goetz, C.G. Neurology 1994; 44 (suppl. 1): S17-S20 3. Ventroposterolateral Pallidotomy Laitinen, L.V. - Stereotact Functional Neurosurgery 1994; 62:41-52 4. Pallidotomy for Parkinsons Disease Laitinen, L.V. - Neurosurgical Clinics of North America 1995; 6:105-112 5. Sterotactic Ventral Pallidotomy for Parkinsons Disease Dogali, M., et al - Neurology 1995; 45:753-761 6. Efforts of Posteroventral Pallidotomy on Parkinsons Disease Dogali, M., et al - Advances in Neurology 1996; 69:585-590 7. Effects of GPi Pallidotomy on Motor Function in Parkinsons Disease Lozano, A.M., et al - Lancet 1995; 346:1383-1387 8. Unilateral Transplantation of Human Fetal Mesencephalic Tissue Into the Camdate Nucleus of Patients with Parkinsons Disease Spencer, D.D., et al - NEJM 1992; 327:1541-1548 9. Survival of Implanted Fetal Dopamine Cells and Neurologic Improvement 12-46 Months After Transplantation for Parkinsons Disease Firod, C.R., et al - NRJM 1992; 327:1541-1555 10. Eighteen Month Course of Two Patients with Grafts of Fetal Dopamine Neurons for Severe parkinsons Disease Hoffer, B.J., et al - Experimental Neurology 1992; 118:243-252 11. Bilateral Fetal Nigral Transplantation into the Post Commissural Putamen in Parkinsons Disease Freeman, T.B., et al - Annals of Neurology 1995; 38:379-388 12. Psychiatric Status After Human Fetal Mesencephalic Tissue Transplantation in Parkinsons Disease Price, L.H., et al - biol. Psychiatry 1995; 38:498-505 13. General Cognitive Ability Following Unilateral and Bilateral Ventgral Mesencephalic Tissue Transplantation for Treatment of Parkinsons Disease Sass, K.J., et al - Arch. Neurology 1995; 52:680-686 [log in to unmask] That man may last, but never lives, Who much receives, but nothing gives; HomeBoy #Parkinsons Whom none can love, whom none can thank,-- Creation's blot, creation's blank. John Cottingham Thomas Gibbons (1720-1785): When Jesus dwelt.