Parkinson's disease (PD) affects 1 percent of the population over the age of 65. The number of people with this disorder is steadily rising. Therapy for PD remains primarily pharmacologic, with medications that target the depleted dopaminergic system being the mainstay of therapy. Surgical therapies, both ablative and stimulatory, are in creasingly being used for patients with more advanced disease and/or complications of drug therapy. Experimental therapies aimed at restoring dopaminergic function and protecting dopaminergic cells are being studied. Alternate neurotransmitter systems are being evaluated as potential targets for therapy. Complete treatment of patients with PD utilizes education, physical therapy, support groups, and medication. When a comprehensive approach is used, PD is treatable and manageable.
References
1.
Cotzias GC, VanWoert MH, Schiffer LMAromatic amino acids and modification of parkinsonismN Engl J Med1967, 276:374-379
2.
Bernheimer H. , Birkmayer W., Hornykiewicz O., Jellinger K., Seitelberger F.Brain dopamine and the syndromes of Parkinson and HuntingtonJ Neurol Sci1973; 20:415-455
3.
. Hornykiewicz O.Parkinson's disease and the adaptive capacity of the nigrostriatal dopamine system: Possible neurochemical mechanismsAdv Neurol1993, 60:140-147
4.
. Lee T., Seeman P., Rajput A., Farley IJ, Hornykiewicz O.Receptor basis for dopaminergic supersensitivity in Parkinson's diseaseNature1978; 273:59-61
5.
. Hornykiewicz O.Biochemical aspects of Parkinson's diseaseNeurology1998, 51 (2):2-9
6.
. Wichmann T., Delong MRFunctional and pathophysiological models of the basal gangliaCurr Opin Neurobiol1996; 6:751-758
7.
. Jenner P.The rationale for the use of dopamine agonists in Parkinson's diseaseNeurology1995, 45(Suppl 3):S6-S12
8.
. Engber TM, Susel Z., Kuo S. et al.Levodopa replacement alters enzyme activities in stnatum and neuropeptide content in stnatal output regions of 6-hydroxydopamine lesioned ratsBrain Res1991, 552:113-118
9.
Juncos JLLevodopa: Pharmacology, pharmacokinetics, and pharmacodynamicsNeurol Clin1992; 10:487-509
10.
. Block G.Liss C., Reines S., Irr J., Nibbelink D.Comparison of immediate-release and controlled-release carbidopa/levodopa in Parkinson's disease: A multicenter 5-year studyEur Neurol1997; 37:23-27
11.
. Montgomery EBPharmacokinetics and pharmacodynamics of levodopaNeurology1992; 42 (Suppl 1):17-22
12.
. Golbe LIYoung-onset Parkinson's disease: A clincial reviewNeurology1991; 41:168-173
13.
. Fabbrini G. , Mouradian MM, Juncos JL, et al.Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, Part IAnn Neurol1988; 24366-371
14.
. Mouradian MM , Juncos JL, Fabbrini G., et al.Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, Part IIAnn Neurol1988; 24.372-378
15.
. Chase TN, Baronti F., Fabbrini G., et al.Rationale for continuous dopaminomimetic therapy of Parkinson's diseaseNeurology1989; 39(Suppl 2):7-10
16.
. Lieberman A. , Kupersmith M., Estey E., Goldstem M.Treatment of Parkinson's disease with bromocriptineN Engl J Med1976, 295:1400-1404
17.
. Olanow CW, Koller WC (eds.). An algonthm (decision tree) for the management of Parkinson's disease treatment guidelinesNeurology1998; 30(3 Suppl 3):S1-S57.
18.
Montastruc JL, Rascol O., Senard JMCurrent status of dopamine agonists in Parkinson's disease managementDrugs1993; 46:384-393
19.
. Rajput AHAdverse effects of ergot-derived dopamine agonists In: Olanow CW, Obeso JA (eds.). Dopamine agonists m early Parkinson's diseaseKent, UK: Wells Medical, 1997209-216
20.
Michel PP, Hefti F.Toxicity of 6-hydroxydopamine and dopamme for dopaminergic neurons in cultureJ Neurosci Res1990, 26:428-435
21.
. Basma AN, Morris EJ, Nicklas WJ, Geller HML-Dopa cytotoxicity to PC12 cells in culture is via its autoxidationJ Neurochem1995; 64:825-832
22.
. Mena MA, Casarejos MJ, Carazo A., Paino CL, DeYebenes JGGlia conditioned medium protects fetal rat midbrain neurones in culture from L-dopa toxicityNeuroReport1996; 7:441-445
23.
. Clarke CEDoes levodopa therapy delay death in Parkinson's disease? A review of the evidenceMov Disord1995; 10:250-256.
24.
Quinn N.Parkes D., Janota I.Marsden CDPreservation of the substantia nigra and locus coeruleus in a patient recieving levodopa (2 kg) plus decarboxylase inhibitor over a 4-year periodMov Disord1986; 1:65-68
25.
. Ogawa N.Neuroprotection with dopamine agonists In: Olanow CW, Obeso JA (eds.). Dopamine agonists in early Parkinson's disease.Kent, UK: Wells Medical, 1997:195-200.
26.
Yoshikawa T. , Minnamiyama Y., Naito Y., Kondo M.Antioxidant properties of bromocriptine, a dopamine agonistJ Neurochem1994; 62:1034-1038
27.
. Cassarino DS , Fall CP, Smith TS, Bennett JPPramipexole reduces reactive oxygen species production in vivo and in vitro and inhibits the mitochondrial permeability transition produced by the parkinsonian neurotoxin methylpyridinium ionJ Neurochem1998; 71(1):295-301
28.
. Sawada H., Ibi M., Kihara T., et alDopamine 132-type agonists protect mesencephalic neurons for glutamate neurotoxicity: Mechanisms of neuroprotective treatment against oxidative stressAnn Neurol1998; 44(1):110-119
29.
. Parkinson Study Group.Effect of deprenyl on the progression of disability in early Parkinson's diseaseN Engl J Med1989; 321. 1364-1371
30.
. Parkinson Study Group.Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's diseaseN Engl J Med1993; 328:176-183
31.
. Parkinson Study Group.Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopaAnn Neurol1996 ; 39:37-45
32.
. Mytilineou C., Radcliffe PM, Olanow CWL-(-)-desmethylselegiline, a metabolite of selegiline [L-(-)-deprenyl], protects mesencephalic dopamine neurons from excitotoxicity in vitroJ Neurochem1997; 68:434-436
33.
. Kurth MC, Adler CHCOMT inhibition: A new treatment strategy for Parkinson's diseaseNeurology1998; 50(Suppl 5):S3-S14
34.
. Waters CH, Kurth M., Bailey P., et al. and the Tolcapone Stable Study Group.Tolcapone in stable Parkinson's disease: Efficacy and safety of long term treatmentNeurology1997; 49.665-671
35.
Baas H., Beiske AG, Ghika M, et al.Catechol-O-methyltransferase inhibition with tolcapone reduces the "weanng off' phenomenon and levodopa requirements in fluctuating parkinsonian patientsJ Neurol Neurosurg Psychiatry1997 ; 63:421-428
Mann DC, Pearce LA, Waterbury LDAmantadine for Parkinson's diseaseNeurology1971; 21:958-962
38.
. Butzer JF, Silver DE, Sahs ALArnantadine in Parkinson's diseaseNeurology1975; 25:603-606
39.
. Verhagen Metman L, DelDotto P., Blanchet PJ, van den Munckhof P., Chase TNBlockade of glutaminergic transmission as treatment for dyskinesias and motor fluctuations in parkinson's diseaseAmino Acids1998; 14(1-3).75-82.
40.
Komhuber J.Weller M.Schoppmeyer K., Riederer P.Amantadine and memantme are NMDA receptor antagonists with neuroprotective propertiesJ Neural Transm1994; 43(Suppl).91-104
41.
Koller WCPharmacologic treatment of parkinsonian tremorArch Neurol1986; 43126-127
42.
. Vitek JLStereotaxic surgery and deep brain stimulation for Parkinson's disease and movement disorders In: Watts RL, Koller WC (eds.). Movement disorders neurologic principles and practiceNew York . McGraw-Hill,1997:237-255
43.
Gross RE, Lombardi WJ, Lang AE, et al.Relationship of lesion location to clinical outcome following microelectrodeguided pallidotomy for Parkinson's diseaseBrain1999; 122:381-382
44.
. Vitek JL, Hashimoto T., Baron MS, et al.Lesion location related to outcome in microelectrode-guided pallidotomyAnn Neurol1994; 36(2):279
45.
. Gross RE, Lombardi WJ, Hutchinson WD, et al.Variability in lesion location after microelectrode-guided pallidotomy for Parkinson's disease: Anatomical, physiological and technical factors that determine lesion distributionJ Neurosurg1999; 90(3):468-417
46.
. Baron MS, Vitek JL, Bakay Rae, et alTreatment of advanced Parkinson's disease by posterior GP1 pallidotomy 1 year results of a pilot studyAnn Neurol1996, 40:355-366
47.
. Galvez-Jimenez N., Lang AE, Lozano AM, et al.Deep brain stimulation in Parkinson's disease: New methods of tailoring functional surgery to patient needs and responseNeurology1996; 48:A402
48.
. Lang AE, Lozano AM, Montgomery E., et al.Posteroventral medial pallidotomy in advanced Parkinson's disease: Two-year expenenceN Engl J Med1997 ; 337:1036-1042
49.
. Samii A., Turnbull IM, Kishore A., et al.Reassessment of unilateral pallidotomy in Parkinson's disease. A 2-year follow-up studyBrain1999; 122:417-425
50.
. Merello M., Nouzeilles MI, Kuzis G., et al.Unilateral radiofrequency lesion versus electrostimulation of the posteroventral pallidum : A prospective randomized comparisonMov Disord 199; 14(1):50-56
51.
. Volkmann J. , Sturm V., Weiss P., et al.Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's diseaseAnn Neurol1998; 44(6):953-961
52.
. Siegel J., Lippitz B.Bilateral chronic electrostimulation of ventroposterolateral pallidum: A new therapeutic approach for alleviating all parkinsonian symptomsNeurosurgery1994; 35:1126-1130
53.
. Galvez-Jimenez N., Lozano A., Tasker R., et alPallidal stimulation in Parkinson's disease patients with a prior unilateral pallidotomyCan J Neurologic Sci1998; 25(4):300-305
54.
. Pollak P., Benabid AL, Limousin P., et al.Subthalamic nucleus stimulation alleviates akinesia and rigidity in parkinsonian patients. Adv Neurol1996; 69:591-594
55.
. Benazzouz A. , Boraud T., Feger J., et al.Alleviation of experimental herniparkinsonism by high frequency stimulation of the subthalamic nucleus in pnmates. A comparison with L-dopa treatmentMov Disord1996; 11(6):627-632
56.
. Limousin P. , Pollak P., Benazzouz A., et al.Bilateral subthalamic nucleus stimulation for severe Parkinson's diseaseMov Disord1995; 10:672-674
57.
. Kumar R., Lozano AM, Kim YJ, et alDouble-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's diseaseNeurology1998 ; 51(3):850-855
58.
. Krack P., Benazzouz A., Pollak P., et al.Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulationMov Disord1998; 13(6):907-914
59.
. Hauser RA, Freeman TB, Snow BJ, et al.Long term evaluation of bilateral fetal nigral transplantation in Parkinson's diseaseArch Neurol1999; 56:179-187
60.
Edwards LL, Quigley Emm, Hamed KK, Hofinan R., Pfeiffer RFDefacatory function in Parkinson's disease Response to apomorphme . Ann Neurol1993; 33:490-493
61.
Naumann M., Hofmann U., Bergmann I., et al.Focal hyperhydrosis: Effective treatment with intracutaneous botulinum toxinArch Derm1998; 134(3):301-304
62.
. Stolman LPTreatment of hyperhydrosisDerm Clin1998; 16(4):863-869.
63.
Edwards LLQuigley Emm, Hamed RF, Hotman R., Pfeiffer RFCharacterization of swallowing and defication in Parkinson's diseaseAm J Gastroenterol1994; 89:15-25
64.
Mayeux R., Chen J., Mirabello E., et al.An estimate of the incidence of dementia in idiopathic Parkinson's diseaseNeurology1990; 40:1513-1517
65.
. Liberman A. , Dziatolowski M., Kupersmith M., et alDementia in Parkinson's diseaseAnn Neurol1977; 6:355-359
66.
. Shea C., MacKnight C., Rockwood K.Donepezil for treatment of dementia with Lewy bodies: A case series of nine patientsInternational Psychogeriatrics1998 ; 10(3):229-238
67.
Kuroda K., Tatara K., Takatorige T., Shinsho F.Effect of physical exercise on mortality in patients with Parkinson's diseaseActa Neurol Scand1992; 86:55-59
68.
. Comella CL, Stebbins GT, Brown-Toms N., Goetz CGPhysical therapy and Parkinson's disease: A controlled clinical trialNeurology1994, 44.376-378
69.
. Gash DM, Zhang Z., Gerhardt G.Neuroprotective and neurorestorative properties of GDNFAnn Neurol1998; 44(3 Suppl 1):S121-S125
70.
. Lapchak PAA preclinical development strategy designed to optimize the use of glial cell line-derived neurotrophic factor in the treatment of Parkinson's diseaseMov Disord1998; 13(Suppl 1).49-54
71.
. Grondin R., Gash DMGlial cell line-derived neurotrophic factor (GDNF): A drug candidate for the treatment of Parkinson's diseaseJ Neurol1998; 245(11 Suppl 3):P35-42
72.
. Hunot S.Bernard V., Faucheux B., et al.Glial cell-line derived neurotrophic factor (GDNF) gene expression in the human brain. A post mortern in situ hybridization study with special reference to Parkinson's diseaseJ Neural Transm1996; 103(8-9):1043-52
73.
Wang Y., Tien LT, Lapchak PA, Hoffer BJGDNF triggers fiber outgrowth of fetal mesencephalic grafts from nigra to striatum in 6-OHDA-lesioned ratsCell Tissue Res1996; 286(2):225-33
74.
Winkler C., Sauer H., Lee CS, Bjorklund A.Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's diseaseJ Neurosci1996; 16(22):7206-7215
75.
. Date I., Shingo T., Ohmoto T., Emench DFLong-term enhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian rats with co-grafted polymer-encapsulated human NGFsecreting cellsExp Neurol1997; 147(1) 10-17
76.
. Parsian A., Racette B., Zhang ZH, et al.Mutation, sequence analysis, and association studies of alpha-synuclein in Parkinson's diseaseNeurology1998, 51(6):1757-1759
77.
Wang WW, Khajavi M., Patel BJ, et al.The G209A mutation in the alpha-synuclein gene is not detected in familial cases of Parkinson's disease in non-Greek and/or Italian populationsArch Neurol1998; 55(12):1521-1523
Gasser T.Genetics of Parkinson's diseaseClin Genet1998, 54(4):259-265
80.
Horellou P. , Brundm P., Kalen P., Mallet J., Bjorklund A.In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striaturnNeuron1990, 5:393-402.
81.
Kang UJPotential of gene therapy for Parkinson's disease Neurobiologic issues and new developments in gene transfer methodologiesMov Disord1998; 13(Suppl 1):59-72
82.
. Freese A., Stern M., Kaplitt MG, et alProspects for gene therapy in Parkinson's diseaseMov Disord1996, 5.469-488
83.
During MJ, Naegele JP, O'Malley KL, Geller AILong-term behavioral recovery in parkinsonian rats by an HSV vector expressing tyrosine hydroxylaseScience1994 , 266:1399-1403
84.
. Kaplitt MG, Leone P., Samulski RJ, et alLong-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brainNat Genet1994, 8:148-154.
