Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-10T08:01:43.762Z Has data issue: false hasContentIssue false

Management of Parkinson's Disease: A Review of Current and New Therapies

Published online by Cambridge University Press:  05 August 2019

Tilak Mendis*
Affiliation:
University of Ottawa, Ottawa Civic Hospital, SCO Hospitals
Oksana Suchowersky
Affiliation:
University of Calgary
Anthony Lang
Affiliation:
Division of Neurology, University of Toronto
Serge Gauthier
Affiliation:
McGill University, McGill Center for Studies in Aging
*
Reprint requests to: Tilak Mendis, Elisabeth Bruyere Health Centre, 75 Bruyere Street, Ottawa, ON K1N 5C8
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The management of Parkinson's disease has undergone recent changes with the advent of new therapies, both pharmacotherapy and surgery. Available interventions are discussed. Levodopa remains the mainstay of therapy. New drugs include the dopamine agonists and COMT inhibitors. New dopamine agonists which may have a levodopa “sparing effect;” it has been suggested that some of the drugs should be considered as first line treatments for newly diagnosed Parkinson's disease patients. We review roles of these drugs. The concept of neuroprotection in neurodegenerative disorders such as Parkinson's disease became popular in the mid 1980s and it is hoped that eventually therapy will be directed at slowing progression of the disease. A great deal more work needs to be done before a suitable agent is identified as being neuroprotective. Potential neuroprotective agents are reviewed. Surgical therapies for Parkinson's disease consisting of various forms of lesion surgery as well as stimulation procedures are reviewed. Complications of drug therapy include motor problems such as motor response fluctuations, as well as psychiatric complications including levodopa-induced psychosis. Atypical neuroleptic agents and ECT for psychiatric syndromes associated with Parkinson's disease are discussed. Algorithms for the management of early disease as well as the management of psychosis in Parkinson's disease are included. Treatment options for advanced disease are tabulated.

Résumé:

Résumé:

Le traitement de la maladie de Parkinson a subi plusieurs changements récemment avec l'arrivée de nouvelles options thérapeutiques tant pharmacologiques que chirurgicales. Dans cet article, nous discutons des modes de traitement qui sont disponibles actuellement. La lévodopa demeure la pierre angulaire du traitement de la maladie de Parkinson. Cependant, plusieurs agents pharmacologiques nouveaux ont été développés, dont les agonistes de la dopamine et les inhibiteurs de la COMT. Avec la venue de nouveaux agonistes de la dopamine qui pourraient avoir un effet d'épargne de la lévodopa, on a suggéré que certains médicaments devraient être considérés comme traitement de première ligne chez les patients dont le diagnostic est récent. Nous revoyons en détail le rôle de ces médicaments. Le concept de la neuroprotection dans les maladies neurodégénératives comme la maladie de Parkinson s'est popularisé au milieu des années 80 et on espère qu'éventuellement le traitement pourra ralentir la progression de la maladie. Il reste beaucoup de travail à faire avant qu'on puisse identifier un agent susceptible d'être neuroprotecteur dans la maladie de Parkinson. Dans cet article, nous revoyons les agents neuroprotecteurs potentiels. Il y a un regain d'intérêt pour les traitements chirurgicaux de la maladie de Parkinson et nous revoyons les différentes formes de traitements chirurgicaux par lésion ainsi que les procédures de stimulation. Les problèmes moteurs, tels les fluctuations de la réponse motrice, et les complications psychiatriques dont la psychose induite par la lévodopa, sont des complications du traitement médicamenteux. Nous revoyons plusieurs interventions utilisées dans ce contexte dont les agents neuroleptiques atypiques et les ETC, dans le contexte des syndromes psychiatriques associés à la maladie de Parkinson. Nous proposons des algorythmes pour le traitement de la maladie de Parkinson au début ainsi que pour la prise en charge de la psychose associée à cette maladie et nous présentons un inventaire des différentes options thérapeutiques dans la maladie de Parkinson en phase avancée. Il y a de plus en plus d'options thérapeutiques dans la maladie de Parkinson et le traitement de ses complications. Il existe des traitements pharmacologiques et chirurgicaux, et, pour la prise en charge des complications psychiatriques, des thérapies psychiatriques. Nous revoyons ces options dans cet article.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 1999

References

1. Charcot, JM. Lectures on the diseases of the nervous system. London: The New Sydenham Society, 1877.Google Scholar
2. Barbeau, A. The pathogenesis of Parkinson’s disease: a new hypoth-esis. Can Med Assoc J 1962; 87: 802807.Google Scholar
3. Comella, C, Tanner, CM. Anticholinergic drugs in the treatment of Parkinson’s disease. In: Koller, WC, Paulson, G, eds. Therapy of Parkinson’s disease. New York: Marcel Dekker, 1990; 123160.Google Scholar
4. Schwab, RS, England, ECJ, Poskanzer, DC, Young, KR. Amantadine in the treatment of Parkinson’s disease. JAMA 1969; 208: 11681170.Google Scholar
5. Parkes, JD, Zilkha, KH, Marsden, D, Baxter, RC, Knill-Jones, RP. Amantadine dosage in treatment of Parkinson’s disease. Lancet 1970;1: 11301133.Google Scholar
6. Walker, JE, Albers, JW, Tourtelotte, WW, Henderson, WG, Potvin, AR, Smith, A. A qualitative and quantitive evaluation of amantadine in the treatment of Parkinson’s disease. J Chron Dis 1972;25: 149182.Google Scholar
7. Parkes, JD, Calver, DM, Zilkha, KH, Knill-Jones, RP. Controlled trial of amantadine hydrochloride in Parkinson’s disease. Lancet 1970; 1: 259262.Google Scholar
8. Grelak, RP, Clark, R, Stump, JM, Vernier, VG. Amantadine-dopamine interaction: possible mode of action in parkinsonism. Science 1970; 169: 203204.Google Scholar
9. Von Voightlander, PF, Moore, KE. Dopamine: release from the brain in vivo by amantadine. Science 1971; 174: 408409.Google Scholar
10. Merrick, EM, Schmitt, PP. A controlled study of the clinical effects of amantadine in hydrochloride (Symmetrel). Cur Thera Res 1973; 15: 552558.Google Scholar
11. Farnebo, LO, Fuxe, K, Goldstein, M, Hamberger, B, Ungerstedt, U. Dopamine an noradrenaline releasing action of amantadine in the central and peripheral nervous system: a possible mode of action in Parkinson’s disease. Eur J Pharm 1971; 16: 2738.Google Scholar
12. Bormann, J. Memantine is a potent blocker of NMDA receptor chan-nels. Eur J Pharm 1989; 166: 591592.Google Scholar
13. Uitti, RJ, Rajput, AH, Ahlskog, JE, et al. Amantadine treatment is an independent predictor of improved survival in Parkinson’s disease. Neurology 1996; 46: 15511556.Google Scholar
14. Koller, WC, Silver, DE, Lieberman, A. An algorithim for the manage-ment of Parkinson’s disease. Neurology 1994; 33 (12 Suppl 10): S1–S52.Google Scholar
15. Hoehn, M. Parkinson’s disease: progression and mortality. Adv Neurol 1986; 45: 457461.Google Scholar
16. Birkmayer, W, Hornykiewicz, O. Der L-3, 4-diphenylalanin(=DOPA) Effekt bei der Parkinson-Akinese. Wien Klin Wochenschr 1961; 73: 787788.Google Scholar
17. Cotzias, GC, Papvasilou, PS. Therapeutic studies of parkinsonian patients: long term effects of D,L- and L-Dopa. Presented at the Second International Congress of Neuro-ophthalmology; Sept 19, 1967; Montreal, Canada.Google Scholar
18. Yeh, KC, August, TF, Bush, DF, et al. Pharmacokinetics and bioavail-ability of Sinemet CR: a summary of human studies. Neurology 1989; 39: 2538.Google Scholar
19. Gauthier, S, Rajput, A, Suchowersky, O, et al. Canadian multicenter study of initiating Sinemet CR treatment in patients with idio-pathic Parkinson’s disease. 11th International Symposium on Parkinson’s disease 1994; Rome,March,(Abstract).Google Scholar
20. Marsden, CD, Parkes, JD. Success and problems of long-term lev-odopa therapy in Parkinson’s disease. Lancet 1977; 1: 349.Google Scholar
21. Poewe, WH, Lees, AJ, Stern, GM. Low dose L-dopa therapy in Parkinson’s disease: A 6–year follow-up study. Neurology 1986; 36: 15281530.Google Scholar
22. Muenter, MD, Sharpless, NS, Tyce, SM, Darley, FL. Patterns of dysto-nia (“I-D-I” and “D-I-D”) in response to L-dopa therapy for Parkinson’s disease. Mayo Clin Proc 1977; 52: 163174.Google Scholar
23. Lhermitte, F, Agid, Y, Signoret, JL. Onset and end of dose levodopa-induced dyskinesias. Possible treatment by increasing the daily doses of levodopa. Arch Neurol 1978; 35: 261263.Google Scholar
24. Chase, TN, Engber, TM, Mouradian, MM. Palliative and prophylactic benefits of continously administered dopaminomimetics in Parkinson’s disease. Neurology 1994; 44: S15–S18.Google Scholar
25. Koller, WC, Pahwa, R. Treating motor fluctuations with controlled release levodopa preparations. Neurology 1994; 44: S23–S28.Google Scholar
26. Block, G, Liss, C, Reines, S, et al. Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson’s disease. Eur J Neurol 1997; 37: 2327.Google Scholar
27. Caplideo, R. Implications of the 5-year CR FIRST trial. Neurology 50 (Suppl 6) June 1998 S11–S14.Google Scholar
28. Juncos, JL, Mouradian, MM, Fabbrini, G, Chase, TN. Levodopa infu-sion therapy. In: Koller, WC, Paulson, G, eds. Therapy of Parkinson’s disease. New York: Marcel Dekker Inc. 1990.Google Scholar
29. Kurlan, R, Nutt, JG, Woodward, WR, et al. Duodenal and gastric deliv-ery of levodopa in parkinsonism. Ann Neurol 1988; 23: 589595.Google Scholar
30. Sage, JI, Trooskin, S, Sonsalla, PK, Heikkila, R, Duvoisin, RC. Long-term duodenal infusion of levodopa for motor fluctuations in parkinsonism. Ann Neurol 1988; 24: 8789.Google Scholar
31. Cohen, G. Oxidative stress in the nervous system. In: Sies, H; emer-gency department. Oxidative stress. New York: Academic Press; 1985: 383402.Google Scholar
32. Adams, JD, Odunze, N. Oxygen Free Radicals and Parkinson’s dis-ease. Free Radical Biology and Medicine, 1991; 10: 161169.Google Scholar
33. Agid, Y. Levodopa: is toxicity a myth? Neurology 1998 Apr; 50(4): 858–63.Google Scholar
34. Rajput, AH, Uitti, RJ, Rajput, AH, Offord, KP. Timely Levodopa (LD) Administration prolongs survival in Parkinson’s disease. Parkinsonism and Related Disorders 1997; 3(3): 159165.Google Scholar
35. Wolters, EC, Tissingh, G, Bergmans, PLM, Kuiper, MA. Dopamine agonists in Parkinson’s disease. Neurology 1995; 43: S28–S34.Google Scholar
36. Pezzoli, G, Martignoni, E, Pacchetti, C, et al. A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson’s disease. Neurology 1995; 43: S22–S27.Google Scholar
37. Demonet, JF, Rostin, M, Dueymes, JM, Iovalalen, A, Montastruc, JL, Rascol, A. Retroperitoneal fibrosis and treatment of Parkinson’s disease with high doses of bromocriptine. Clin Neuropharmacol 1986; 9: 200201.Google Scholar
38. Jimenez-Jimemez, FJ, Lopez-Alvarez, J, Sanchez-Chapado, M, et al. Retroperitoneal fibrosis in a patient with Parkinson’s disease treated with pergolide. Clin Neuropharmacol 1995; 18: 277279.Google Scholar
39. Adler, C, Sethi, KD, Hauser, RA, et al. Ropinirole for the treatment of early Parkinson’s disease. Neurology 1997; 49: 393399.Google Scholar
40. Brooks, DJ, Torjanski, N, Burn, DJ. Ropinirole in the symptomatic treatment of Parkinson’s disease. J Neural Transm 1995; 45(suppl): 231238.Google Scholar
41. Rascol, O, Lees, AJ, Senard, JM, et al. Ropinirole in the treatment of levodopa induced motor fluctuation in patients with Parkinson’s disease. Clin Neuropharmacol 1996; 19: 234245.Google Scholar
42. Boothman, BR, Spokes, EGS. Pharmacokinetic data for ropinirole. Lancet 1990; 336: 814.Google Scholar
43. Hubble, JP, Koller, WC, Cutler, NR, et al. Pramipexole in patients with early Parkinson’s disease. Clin Neuropharmacol 1995; 18: 338347.Google Scholar
44. Lieberman, A, Ranhosky, A, Korts, D. Clinical evaluation of pramipexole in advance Parkinson’s disease: results of a double-blind, placebo controlled, parallel-group study. Neurology 1997; 49: 162168.Google Scholar
45. Guttman, M and the International Pramipexole-Bromocriptine Study Group. Double-blind comparison of pramipexole and bromocrip-tine treatment with placebo in advanced Parkinson’s disease. Neurology 1997; 49: 10601065.Google Scholar
46. Christian Shilling, J, Adamus, WS, Palluk, R. Neuroendrocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans. Clin Pharmacoly and Therapeutics 1992; 51: 541548.Google Scholar
47. Korczyn, M, Brooks, DJ, Brunt, ER et al. Ropinirole vs. bromocriptine in the treatment of early Parkinson’s disease: a 6 month interim report of a 3-year study. Mov Dis 1998; 13: 4651.Google Scholar
48. Geminiani, G, Fetoni, V, Genitrini, S, Giovannine, P, Tamma, F, Caraceni, T. Cabergoline in Parkinson’s disease complicated by motor fluctuations. Mov Dis 1996; 11: 495500.Google Scholar
49. Carvey, PM, Pieri, S, Ling, ZD. Attenuation of levodopa induced tox-icity in mesencephalic cultures by pramipexole. J Neural Trasm 1997; 104: 209228.Google Scholar
50. Yoshikawa, T, Minamiyama, Y, Naito, Y, Kondo, M. Antioxidant properities of bromocriptine, a dopamine agonist. J Neurochem 1994; 62: 01341038.Google Scholar
51. Olanow, CW. A rationale for using dopamine agonists as primary symptomatic therapy in Parkinson’s disease. In: Olanow, CW, Obeso, JA eds. Dopamine agonists in early Parkinson’s disease.Kent, UK: Wells Medical, 1997; 3752.Google Scholar
52. Goetz, C. Dopaminergic agonists in the treatment of Parkinson’s dis-ease. Neurology 1990; 40: 5054.Google Scholar
53. Poewe, W, Kleedorfer, B, Gerstenbrand, F. Subcutaneous apomor-phine in Parkinson’s disease. Lancet 1988; 23: 943.Google Scholar
54. Poewe, W, Kleedorfer, B, Wagner, M, Bosch, S, Schelosky, L. Continuous apomorphine infusions for fluctuating Parkinson’s disease: Long-term follow-up in 18 patients. Adv Neurol 1993; 60: 656659.Google Scholar
55. Hughes, AJ, Bishop, S, Kleedorfer, B, et al. Subcutaneous apomor-phine in Parkinson’s disease: response to chronic administration for up to five years. Mov Disord 1993; 8: 165170.Google Scholar
56. Kapoor, R, Turjanski, N, Frankel, J, Kleedorfer, B, Lees, A, Stern, G. Intranasal apomorphine: a new treatment in Parkinson’s disease (letter). J Neurol Neurosurg Psychiatry 1990; 1: 1015.Google Scholar
57. Van Laar, T, Jansen, EN, Essink, AW, Neef, C. Intranasal apomorphine in parkinsonian on-off fluctuations. Arch Neurol 1992; 49: 482484.Google Scholar
58. Galvez-Jimenez, N, Lang, AE. Perioperative problems in Parkinson’s disease and their management: Apomorphine with rectal domperidone. Can J Neurol Sci 1996; 23: 198203.Google Scholar
59. Parkinson Study Group. Effect of lazabemide on the progression of disability in early Parkinson’s disease. Ann Neurol, 1996; 40: 99107.Google Scholar
60. Parkinson Study Group. Effect of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Eng J Med 1993; 328: 176183.Google Scholar
61. Schulzer, M, Mak, E, Calne, DB. The antiparkinsonian effiacy of deprenyl derives from transient improvement that is likely to be symptomatic. Ann Neurol 1992; 32: 795798.Google Scholar
62. Parkinson Study Group. Impact of deprenyl and tocopherol treat- ment of Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol, 1996; 39: 2936.Google Scholar
63. Parkinson Study Group. Impact of deprenyl and tocopherol treat- ment of Parkinson’s disease in DATATOP patients requiring lev-odopa. Ann Neurol, 1996; 39: 3745.Google Scholar
64. Olanow, CW, Hauser, RA, Gauger, L, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1995; 38: 771777.Google Scholar
65. Lees, AJ, Parkinson’s Disease Research Group of the United Kingdom. Comparisonof therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early mild Parkinson’s disease. Br Med J 1995; 311: 16021607.Google Scholar
66. Parkinson Study Group. Mortality in DATATOP: a multicenter trial in early Parkinson’s disease. Ann Neurol 1998; 43: 318325.Google Scholar
67. DaPrada, M, Borgulya, J, Napolitano, A, Zurcher, G. Improved ther-apy of Parkinson’s disease with tolcapone, a central and peripheral COMT inhibitor with an S-adenosyl-l-methionine-sparing effect. Clin Neuropharmacol 1994; 17: S26–S37.Google Scholar
68. Davis, TL, Roznoski, M, Burns, RS. Acute effects of COMT inhibi-tion on L-Dopa pharmacokinetics in patients treated with car-bidopa and selegiline. Clin Neuropharmacol 1995; 18: 333337.Google Scholar
69. Limousin, P, Pollack, P, Pfefen, JP, et al. Acute administration of lev-odopa-benserazide and tolcapone, a COMT inhibitor in Parkinson’s disease. Clin Neuropharmacol 1995; 18: 258265.Google Scholar
70. Waters, CH, Kurth, H, Baily, P et al. Tolcapone in stable Parkinson’s disease: efficacy and safety in long term treatment. Neurology 1997; 49: 665671.Google Scholar
71. Rajput, A, Martin, WRW, Sainte-Hillaire, MH et al. Tolcapone improves motor function in Parkinsonian patients with the ‘wearing off’ phenomenon: a double-blind placebo controlled multi-center trial. Neurology 1997; 49: 10661071.Google Scholar
72. Assal, F, Spahr, L, Hadengue, A et al. Tolcapone and fuminant hep-atitis. Lancet 1998; 352: 9132.Google Scholar
73. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa treated Parkinson's disease patients. Annals of Neurology 1997; 42: 747755.Google Scholar
74. Shoulson, I. Protective therapy for Parkinson’s disease. In: Marsden, CD, Fahn, S, eds. Movement Disorders. 3rd Emergency Department. Butterworth-Heinemann Ltd. 1994: 165179.Google Scholar
75. Chase, TN, Engler, TM, Maral Mouradin, M. Contributions of dopaminergic and glutaminergic mechanisms to the pathgenisis of motor response complications in PD. Adv Neurology 1996; 69: 497501.Google Scholar
76. Greenmayre, JT, Eller, RV, Zhang, Z et al. Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist in rodent and primate models. Ann Neurol 1994; 35: 655661.Google Scholar
77. Selby, G. Stereotactic surgery for the relief of Parkinson’s disease. J Neurol Sci 1967; 5: 315342.Google Scholar
78. DeLong, MR. Primate models of movement disorders of basal gan-glia origin. TINS 1990; 13: 281285.Google Scholar
79. Miller, WC, DeLong, MR. Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter, MB, Jayaraman, A, editors. The basal ganglia II. New York: Plenum Press, 1987: 15–427.Google Scholar
80. Alexander, GE, Crutcher, MD, DeLong, MR. Basal ganglia-thalamo-cortical circuits: Parallel substrates for motor, oculomotor, “pre-frontal” and “limbic” functions. Prog Brain Res 1990; 85: 119146.Google Scholar
81. Rand, RW, Jacques, DB, Melbye, RW, Copcutt, BG, Fisher, MR, Levenick, MN. Gamma knife thalamotomy and pallidotomy in patients with movement disorders: preliminary results. Stereotact Funct Neurosurg 1993; 61(suppl 1): 6592.Google Scholar
82. Fox, MW, Ahlskog, JE, Kelly, PJ. Stereotactic ventrolateralis thala-motomy of medically refractory tremor in post-levodopa era Parkinson’s disease patients. J Neurosurg 1991; 75: 723730.Google Scholar
83. Diederich, N, Goetz, CG, Stebbins, GT, Klawans, HL, Nittner, K, Koulosakis, A, et al. Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson’s disease. Neurology 1992; 42: 13111314.Google Scholar
84. Matsumoto, K, Shichijo, F, Fukami, T. Long-term follow-up review of cases of Parkinson’s disease after unilateral or bilateral thala-motomy. J Neurosurg 1984; 60: 10331044.Google Scholar
85. Page, RD. The use of thalamotomy in the treatment of levodopa-induced dyskinesia. Acta Neurochir (Wien) 1992; 114: 77117.Google Scholar
86. Benabid, AL, Pollack, P, Gervason, C, Hoffman, D, Gao, DM, Hommel, M, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 1991; 337: 403406.Google Scholar
87. Caparros-Lefebvre, D, Blond, S, Vermersch, P, Pecheux, N, Guieu, J-D, Petit, H. Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1993; 56: 268273.Google Scholar
88. Strafella, A, Ashby, P, Munz, M, Dostrovsky, JO, Lozano, AM, Lang, AE. Inhibition of voluntary activity by thalamic stimulation in humans: Relevance for the control of tremor. Mov Disord 1997; 12: 727737.Google Scholar
89. Caparros-Lesebvre, D, Ruchoux, MM, Blond, S, Petit, H, Percheron, G. Long-term thalamic stimulation in Parkinson’s disease: postmortem anatomoclinical study. Neurology 1994; 44: 18561860.Google Scholar
90. Svennilson, E, Torvik, A, Lowe, R, Leksell, L. Treatment of parkin-sonism by stereotactic thermo lesions in the pallidal region. A clinical evaluation of 81 cases. Acta Psychiatr Neurol Scand 1960; 35: 358377.Google Scholar
91. Goetz, CG, De Long, MR, Penn, RD, Bakay, RAE. Neurosurgical horizons in Parkinson’s disease. Neurology 1993; 43: 17.Google Scholar
92. Ceballos-Baumann, AO, Obeso, JA, Vitek, JL, DeLong, MR, Bakay, R, Linazasoro, G, et al. Restoration of thalamocortical activity after posteroventral pallidotomy in Parkinson’s disease. Lancet 1994; 344: 814 Google Scholar
93. Grafton, ST, Waters, C, Sutton, J, Lew, MF, Couldwell, W. Pallidotomy increases activity of motor association cortex in Parkinson’s disease: A positron emission tomographic study. Ann Neurol 1995; 37: 776783.Google Scholar
94. Laitinen, LV, Bergenheim, AT, Hariz, MI. Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 1992; 76: 5361.Google Scholar
95. Dogali, M, Fazzini, E, Kolodny, E, Eidelberg, D, Sterio, D, Devinsky, O, et al. Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 1995; 45: 753761.Google Scholar
96. Sutton, JP, Couldwell, W, Lew, MF, Mallory, L, Grafton, S, DeGiorgio, C, et al. Ventroposterior medial pallidotomy in patients with advanced Parkinson’s disease. Neurosurgery 1995; 36: 11121117.Google Scholar
97. Iacono, RP, Shima, F, Lonser, RR, Kuniyoshi, S, Maeda, G, Yamada, S. The results, indications, and physiology of posteroventral pal-lidotomy for patients with Parkinson’s disease. Neurosurgery 1995; 36: 11181127.Google Scholar
98. Baron, MS, Vitek, JL, Bakay, RAE, Green, J, Kaneoke, Y, Hashimoto, T, et al. Treatment of Advanced Parkinson’s Disease by Posterior GPi Pallidotomy: 1-Year Results of a Pilot Study. Ann Neurol 1996; 40: 355366.Google Scholar
99. Johansson, F, Malm, J, Nordh, E, Hariz, M. Usefulness of pallidoto-my in advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 62: 125132.Google Scholar
100. Kishore, A, Turnbull, IM, Snow, BJ, R, De la Fuente-Fernandez, Schulzer, M, Mak, E, et al. Efficacy, stability and predictors of outcome of pallidotomy for Parkinson’s disease – Six-month follow-up with additional 1-year observations. Brain 1997; 120: 729737.Google Scholar
101. Kopyov, O, Jacques, D, Duma, C, Buckwalter, G, Kopyov, A, Lieberman, A, et al. Microelectrode-guided posteroventral medial radiofrequency pallidotomy for Parkinson’s disease. J Neurosurg 1997; 87: 5259.Google Scholar
102. Uitti, RJ, Wharen, RE, Turk, MF, Lucas, JA, Finton, MJ, Graff-Radford, NR, et al. Unilateral pallidotomy for Parkinson’s disease: Comparison of outcome in younger versus elderly patients. Neurology 1997; 49: 10721077.Google Scholar
103. Samuel, M, Caputo, E, Brooks, DJ, Schrag, A, Scaravilli, T, Branston, NM, et al. A study of medial pallidotomy for Parkinson’s disease: clinical outcome, MRI location and complications. Brain 1998; 121: 5975.Google Scholar
104. Ondo, WG, Jankovic, J, Lai, EC, Sankhla, C, Khan, M, Ben-Arie, L, et al. Assessment of motor function after stereotactic pallidotomy. Neurology 1998; 50: 266270.Google Scholar
105. Shannon, KM, Penn, RD, Kroin, JS, Adler, CH, Janko, KA, York, M, et al. Stereotactic pallidotomy for the treatment of Parkinson’s disease – Efficacy and adverse effects at 6 months in 26 patients. Neurology 1998; 50: 434438.Google Scholar
106. Scott, R, Gregory, R, Hines, N, Carroll, C, Hyman, N, Papanasstasiou, V, et al. Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson’s disease – A consecutive series of eight simultaneous bilateral and twelve unilateral procedures. Brain 1998; 121: 659675.Google Scholar
107. Lozano, AM, Lang, AE, Galvez-Jimenez, N, Miyasaki, J, Duff, J, Hutchison, WD, et al. Effect of GPi pallidotomy on motor function in Parkinson’s disease. Lancet 1995; 346: 13831387.Google Scholar
108. Lang, AE, Lozano, AM, Montgomery, E, Duff, J, Tasker, R, Hutchison, W. Posteroventral Medial Pallidotomy in Advanced Parkinson’s Disease. N Engl J Med 1997; 337: 10361042.Google Scholar
109. Giller, CA, Dewey, RB, Ginsburg, MI, Mendelsohn, DB, Berk, AM. Stereotactic pallidotomy and thalamotomy using individual variations of anatomic landmarks for localization. Neurosurgery 1998; 42: 5662.Google Scholar
110. Schuurman, PR, De Bie, RMA, Speelman, JD, Bosch, DA. Bilateral posteroventral pallidotomy in advanced Parkinson’s disease in three patients. Mov Disord 1997; 12: 752755.Google Scholar
111. Baron, MS, Vitek, JL, Bakay, RAE, Green, J, Kaneoke, Y, Hashimoto, T, et al. Neuropsychological and behavioral changes and weight gain after medial pallidotomy – Reply. Ann Neurol 1997; 41: 835836.Google Scholar
112. Soukup, VM, Ingram, F, Schiess, MC, Bonnen, JG, Nauta, HJW, Calverley, JR. Cognitive sequelae of unilateral posteroventral pal-lidotomy. Arch Neurol 1997; 54: 947950.Google Scholar
113. Perrine, K, Dogali, M, Fazzini, E, Sterio, D, Kolodny, E, Eidelberg, D, et al. Cognitive functioning after pallidotomy for refractory Parkinson’s disease. J Neurol Neurosurg Psychiatry 1998; 65: 150154.Google Scholar
114. Trépanier, LL, Saint-Cyr, JA, Lozano, AM, Lang, AE. Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson’s disease. Neurology 1998; 51: 207215.Google Scholar
115. Lozano, A, Hutchison, W, Kiss, Z, Tasker, R, Davis, K, Dostrovsky, J. Methods for microelectrode-guided posteroventral pallidotomy. J Neurosurg 1996; 84: 194202.Google Scholar
116. Siegfried, J, Lippitz, B. Bilateral chronic electrostimulation of ven-troposterolateral pallidum: A new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery 1994; 35: 11261130.Google Scholar
117. Krack, P, Pollak, P, Limousin, P, Hoffmann, D, Xie, J, Benazzouz, A, et al. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 1998; 121: 451457.Google Scholar
118. Pahwa, R, Wilkinson, S, Smith, D, Lyons, K, Miyawaki, E, Koller, WC. High-frequency stimulation of the globus pallidus for the treatment of Parkinson’s disease. Neurology 1997; 49: 249253.Google Scholar
119. Kumar, R, Lozano, AM, Montgomery, E, Lang, AE. Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson’s disease. Mov Disord 1998; 13: 7382.Google Scholar
120. Galvez-Jimenez, N, Lang, AE, Lozano, A, Tasker, R, Duff, J, Hutchinson, WD, et al. Deep brain stimulation in Parkinson’s disease: new methods of tailoring functional surgery to patient needs and response. Neurology 1996; 46: A402Google Scholar
121. Krack, P, Pollak, P, Limousin, P, Hoffmann, D, Benazzouz, A, Benabid, AL. Inhibition of levodopa effects by internal pallidal stimulation. Mov Disord 1998; 13: 648652.Google Scholar
122. Krack, P, Pollak, P, Limousin, P, Hoffman, D, Benazzouz, A, Le Bas, JF, et al. Opposite motor effects of pallidal stimulation in Parkinson’s disease. Ann Neurol 1998; 43: 180192.Google Scholar
123. Bejjani, B, Damier, P, Arnulf, I, Bonnet, AM, Vidailhet, M, Dormont, D, et al. Pallidal stimulation for Parkinson’s disease – Two targets? Neurology 1997; 49: 15641569.Google Scholar
124. Bergman, H, Wichmann, T, DeLong, MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 1990; 249: 14361438.Google Scholar
125. Sellal, F, Hirsch, E, Lisovoski, F, Mutschler, V, Collard, M, Marescaux, C. Contralateral disappearance of parkinsonian signs after subthalamic hematoma. Neurology 1992; 42: 255256.Google Scholar
126. Gill, SS, Heywood, P. Bilateral dorsolateral subthalamotomy for advanced Parkinson’s disease. Lancet 1997; 350: 12241224.Google Scholar
127. Limousin, P, Pollak, P, Benazzouz, A, Hoffmann, D, Le Bas, J-F, Broussolle, E, et al. Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 1995; 345: 9195.Google Scholar
128. Limousin, P, Pollak, P, Benazzouz, A, Hoffmann, D, Broussolle, E, Perret, JE, et al. Bilateral subthalamic nucleus stimulation for severe Parkinson’s disease. Mov Disord 1995; 10: 672674.Google Scholar
129. Kumar, R, Lozano, AM, Kim, YJ, Hutchison WD, SE, Halket, E, Lang, AE. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced PD. Neurology 1998; 51: 850855.Google Scholar
130. Krack, P, Pollak, P, Limousin, P, Benazzouz, A, Benabid, AL. Stimulation of subthalamic nucleus alleviates tremor in Parkinson’s disease. Lancet 1997; 350: 1675–1675.Google Scholar
131. Krack, P, Limousin, P, Benabid, AL, Pollak, P. Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson’s disease. Lancet 1997; 350: 1676–1676.Google Scholar
132. Madrazo, I, Drucker-Colin, R, Diaz, V, Martinez-Mata, J, Torres, C, Becerril, JJ. Open Microsurgical Autograft of Adrenal Medulla to the Right Caudate Nucleus in Two Patients with Intractable Parkinson’s Disease. N Engl J Med 1987; 316: 831873.Google Scholar
133. Goetz, GC, Olanow, WC, Koller, W. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson’s disease. N Engl J Med 1989; 320: 337341.Google Scholar
134. Ahlskog, JE, Kelly, PJ, van Heerden, JA, Stoddard, SL, Tyce, GM, Windebank, AJ, et al. Adrenal Medullary Transplantation Into the Brain for Treatment of Parkinson’s Disease: Clinical OUtcome and Neurochemical Studies. Mayo Clin Proc 1990; 65: 305328.Google Scholar
135. Allen, GS, Burns, S, Tulipan, NB, Parker, RA. Adrenal Medullary Transplantation to the Caudate Nucleus in Parkinson’s Disease. Arch Neurol 1989; 46: 487491.Google Scholar
136. Diamond, SG, Markham, CH, Rand, RW, Becker, DP, Treciokas, LJ.Four-year follow-up of adrenal-to-brain transplants in Parkinson’s disease. Arch Neurol 1994; 51: 559563.Google Scholar
137. Olanow, CW, Koller, W, Goetz, CG, Stebbins, GT, Cahill, DW, Gauger, LL, et al. Autologous Transplantation of Adrenal Medulla in Parkinson’s Disease. Arch Neurol 1990; 47: 12861289.Google Scholar
138. Watts, RL, Freeman, A, Goetz, C, Graham, S, Zakers, GO, Bakay, AE, et al. Autologous Intrastriatal Adrenal Medulla/Nerve Cografts in Parkinson’s Disease (PD): Early Results. Neurology 1993; 43: A222Google Scholar
139. Widner, H, Tetrud, J, Rehncrona, S, Snow, B, Brundin, P, Gustavii, B, etal. Bilateral Fetal Mesencephalic Grafting in Two Patients with Parkinsonism Induced by 1-methyl-4-Phenyl-a,2,3,6-Tetrahydropyridine (MPTP). N Engl J Med 1992; 327: 15561563.Google Scholar
140. Lindvall, O, Widner, H, Rehncrona, S, Brudin, P, Odin, P, gustavii, J, et al. Transplantation of Fetal Dopamine Neurons in Parkinson’s Disease: One-hear Clinical and Neurophysiological Observations in Two Patients with Putaminal Implants. Arch Neurol 1992; 31: 155173.Google Scholar
141. Spencer, DD, Robbins, RJ, Naftolin, F, Marek, KL, Vollmer, T, Leranth, C, et al. Unilateral Transplantation of Human Fetal Mesencephalic Tissue into the Caudate Nucleus of Patients with Parkinson’s Disease. N Engl J Med 1992; 327: 15411548.Google Scholar
142. Freed, CR, Breeze, RE, Rosenberg, NL, Schneck, SA, Kriek, E, Qi, J-X, et al. Survival of Implanted Fetal Dopamine Cells and Neurologic Improvement 12 to 46 months after Transplantation for Parkinson’s Disease. N Engl J Med 1992; 327: 15491555.Google Scholar
143. Freeman, TB, Olanow, CW, Hauser, RA, Nauert, GM, Smith, DA, Borlongan, CV, et al. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann Neurol 1995; 38: 379388.Google Scholar
144. Lindvall, O, Sawle, G, Widner, H, Rothwell, JC, Björklund, A, Brooks, D, et al. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 1994; 35: 172180.Google Scholar
145. Kordower, JH, Freeman, TB, Snow, BJ, Vingerhoets, FJG, Mufson, EJ, Sanberg, PR, et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med 1995; 332: 11181124.Google Scholar
146. Dooneief, G, Mirabello, E, Bell, K et al. An estimate of the incidence of depression in idiopathic Parkinson’s disease. Archives of Neurology 1992, 49,305307.Google Scholar
147. Huber, SJ, Friedenberg, DL, Paulson, GW, Shuttleworth, EC and Christy, JA. The pattern of depressive symptoms varies with progression of Parkinson’s disease. J Neurol Neurosurg Psychiatry, 1990; 53; 527278.Google Scholar
148. Depression in Parkinson’s disease. J Psychology 1996; 130(6) 659667.Google Scholar
149. Brown, R, Jahanshahi, M. Behavioural Neurology of Movement Disorders. Advances in Neurology 1995; 6: 6184.Google Scholar
150. Rao, SM, Huber, SJ & Bornstein, RA. Emotional changes with mul-tiple sclerosis and Parkinson’s disease. J Consult Clin Psychology 1992: 60: 369378.Google Scholar
151. Sano, M, Stern, Y, Williams, J, Cote, L, Rosenstein, R, Mayeux, R: Coexisting Dementia and Depression in Parkinson’s Disease. Arch Neurol 1989; 46: 12841286.Google Scholar
152. Tom, T, Cummings, JL. Jan 1998. Drugs-Aging; 12(1): 5574.Google Scholar
153. Richard, IH, Kurlan, R: A survery of antidepressant use in PD. PSG Neurology 1997 Oct; 49(4): 1168–70.Google Scholar
154. Ritter, JL, Alexander, B: Retrospective study of selegiline-antide-pressant drug interactions and a review of the literature. Ann Clin Psychiatry. 1997 Mar; 9(1): 713.Google Scholar
155. Lieberman, A. Depression in PD. BNI Quarterly 1997; 13: 2733.Google Scholar
156. Stein, MB, Heuser, IJ, Vade, TW. Anxiety disorders in patients with PD. Am. J. Psychiatry 1990; 147: 217220.Google Scholar
157. Lieberman, A. Managing the neuropsychiatric symptoms of PD. Neurology. June 1998; 50 Suppl 6: S27–S32.Google Scholar
158. Balldin, J, Eden, S, Granerus, AK, et al. Electroconvulsive therapy in Parkinson's syndrome with “on-off” phenonenon. J Neural Transm 1980; 47: 1121.Google Scholar
159. Andersen, K, Balldin, J, Gottfries, CG, et al. A double-blind evalua-tion of electroconvulsive therapy in Parkinson’s disease with “on-off” phenomenona. Acta Neurol Scand 1987; 76: 191199.Google Scholar
160. Baruch, P, Jouvent, R, Vincreau, R, Drouillon, C, Widlocher, D, Agid, Y. Improvement of parkinsonism in ECT-treated depressed patients: Parkinson’s disease or depression-related extrapyradmi-dal disorder? World Congress Biological Psychiatry 1985; 452.2(Abstract).Google Scholar
161. Editorial. ECT for Parkinson’s disease? Convulsive Ther 1988; 4: 189191.Google Scholar
162. Abrams, R, Swartz, CM. Electroconvulsive therapy and prolactin release: Relation to treatment response in melancholia. Convulsive Ther 1985; 1: 3842.Google Scholar
163. Bolwig, TG, Hertz, MM, Paulson, OB, Spotoft, H, Rafaelson, OJ. The permeability of the blood brain barrier during electrically induced seizures in man. Eur J Clin Investigation 1977; 7: 8793.Google Scholar
164. Sandyk, R. Mechanisms of action of ECT in Parkinson’s disease:possible role of pineal melantonin. Int J Neurosci 1990; 50: 8394.Google Scholar
165. Saint-Cyr, JA, Taylor, AE, Lang, AE. Neuropsychological and psy-chiatric side effects in the treatment of Parkinson’s disease. Neurology 1993; 43 Suppl.6.S47–S52.Google Scholar
166. Goetz, CG, Stebbins, GT. Risk factors for nursing home placement in advanced Parkinson’s disease. Neurology 1993; 43: 22272229.Google Scholar
167. Goetz, CG, Tanner, CM, Klawans, HL. Pharmacology of hallucina-tions induced by long-term drug therapy. Am J Psychiatry 1982; 139: 494497.Google Scholar
168. Lloyd, KG, Kornykiewicz, O. Occurrence and distribution of aro-matic acid (L-dopa) decarboxylase in human brain. J Neurochem 1972; 19: 15491559.Google Scholar
169. Kalat, JW. Biological psychology. 3rd ed. Belmont, California: Wadsworth Publishing Co. 1988.Google Scholar
170. Moskovitz, C, Moses, H, Klawans, HL. Levodopa-induced psy-chosis: a kindling phenomenon. Am J Psychiatry 1978; 135: 669675.Google Scholar
171. Klawans, HL. Psychiatric side effects during the treatment of Parkinson’s disease. J Neurol Transm Suppl 1988; 27: 117122.Google Scholar
172. Marsden, CD, Fahn, S. Problems in Parkinson’s disease. In: Marsden, CD, Fahn, S, eds. Movement Disorders. London: Butterworth Scientific, 1981: 17.Google Scholar
173. Friedman, JH, Lannon, MC. Clozapine in the treatment of psychosis in PD. Neurology 1989; 39: 12191221.Google Scholar
174. Pakkenberg, H, Pakkenberg, B. Clozapine in the treatment of tremor. Acta Neurol Scand 1986; 73: 295297.Google Scholar
175. Bennett, JP Jr., Landow, ER, Schuh, LA. Suppression of dyskinesias in advanced Parkinson’s disease. II. Increasing daily clozapine doses suppress dyskinesias and improve parkinsonism symptoms. Neurology 1993; 43: 15511555.Google Scholar
176. Mendis, T, Barclay, CL, Mohr, E. Drug-induced psychosis in Parkinson’s disease: a review of management. CNS Drugs 1996; 5: 166174.Google Scholar
177. Ford, B, Lynch, T, Greene, P. Risperidone in Parkinson’s disease. Lancet 1994; 344: 681.Google Scholar
178. Zoldan, J, Friedberg, G, Goldberg-Stern, H, Melamed, E. Ondansetron for hallucinosis in advanced Parkinson’s disease. Lancet 1993; 341: 562563.Google Scholar
179. Zoldan, J, Friedberg, G, Livneh, M, Melamed, E. Psychosis in advanced Parkinson’s disease: treatment with odansetron, a 5-HT3 receptor antagonist. Neurology 1995; 45: 13051308.Google Scholar
180. Pars, MA, Bastani, B. Quetiapine (Seroquel) in the treatment of psy-chosis in patients with PD. J Neuropsychiatry Clin Neurosci 1998 Spring; 10(2): 216–9.Google Scholar
181. Mohr, E, Mendis, T, Grimes, Jd. Late cognitive changes in Parkinson’s disease with an emphasis on dementia. Behavioural Neurology of Movement Disorders. Emergency department. WJ Werner and AE Lang. Advances in Neurology, Vol 65. Raven Press Ltd. New York 1995: 97113.Google Scholar
182. Levin, BE, Katzen, HL. Early cognitive changes and non-dementing behavioural abnormalities in Parkinson’s disease. Behavioural Neurology of Movement Disorders Emergency department. WJ Weiner and AE Lang. Advances in Neurology Vol 65. Raven Press Ltd. New York 1995: 8595.Google Scholar
183. Rho, JP, Lipson, LG. Focus on donezepil: a reversible acethyl-cholinesterace inhibitor for the treatment of Alzheimer’s disease. Formulary 1997; 32: 677684.Google Scholar
184. Tanner, CM, Goetz, CG, Klawans, HL. Autonomic nervous system in Parkinson’s disease. In: Koller, WC, ed. Handbook of Parkinson’s disease. New York: Marcel Dekker, 1992: 185215.Google Scholar
185. Suchowersky, O, Furtado, S, Rohs, G. Beneficial effect of intranasal desmopressin for nocturnal polyuria in patients with Parkinson’s disease. Mov Dis 1995; 10: 337340.Google Scholar
186. Carter, JH, Stewart, BJ, Archbold, PG et al. Living with a person who has Parkinson’s disease; the spouse’s perspective by stage of disease. Mov Dis 1998; 13: 2028 Google Scholar