Parkinson’s disease: Surgical options

  • John Hammerstad
  • Penelope Hogarth


The introduction of levodopa revolutionized the treatment of Parkinson’s disease. However, complications of therapy that diminish functional capacity eventually develop in the majority of patients. Studies in animal models have demonstrated that the parkinsonian state is associated with overactivity in the output nuclei of the basal ganglia. This provides a rationale for surgically targeting these nuclei to diminish this overactivity and reestablish a more balanced output (compensatory strategy). Lesioning and high-frequency stimulation of either the pallidum or the subthalamic nuclei are effective, but many questions remain regarding what surgery is best. Even more questions remain regarding the place of a restorative strategy, namely implantation of fetal midbrain tissue to replace the missing dopamine cells and "cure" the disease. Practical, ethical, and legal issues that complicate the use of human tissue have encouraged initial attempts at xenotransplantation using porcine fetal tissue.

References and Recommended Reading

  1. 1.
    Laitinen LV, Bergenheim AT, Hariz MI: Leksell’s posteroventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 1992, 76:53–61.PubMedGoogle Scholar
  2. 2.
    Lang AE: Surgery for Parkinson disease: a critical evaluation of the state of the art. Arch Neurol 2000, 57:1118–1125. This excellent review thoughtfully emphasizes the quality of the evidence and the questions remaining to be answered regarding patient selection and efficacy of the various procedures.PubMedCrossRefGoogle Scholar
  3. 3.
    Krack P, Poepping M, Weinert D, et al.: Thalamic, pallidal, or subthalamic surgery for Parkinson’s disease? J Neurol 2000, 247(suppl 2):II122-II134. Another excellent review, including technical aspects and controversies of the surgical approaches.PubMedGoogle Scholar
  4. 4.
    Hariz MI: Complications of movement disorder surgery and how to avoid them. Prog Neurol Surg 2000, 15:246–265.Google Scholar
  5. 5.
    Hallett M, Litvan I: Evaluation of surgery for Parkinson’s disease: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The Task Force on Surgery for Parkinson’s Disease. Neurology 1999, 53:1910–1921.PubMedGoogle Scholar
  6. 6.
    Benabid AL, Krack P, Benazzouz A, et al.: Deep brain stimulation of the subthalamic nucleus for Parkinson’s disease: methodologic aspects and clinical criteria. Neurology 2000, 55(suppl 6):S40-S44.PubMedGoogle Scholar
  7. 7.
    Burchiel KJ, Anderson VC, Favre J, Hammerstad JP: Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Neurosurgery 1999, 45:1375–1382.PubMedCrossRefGoogle Scholar
  8. 8.
    Schuurman PR, Bosch DA, Bossuyt PM, et al.: A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med 2000, 342:461–468. A well-designed, randomized study showing that thalamotomy and thalamic stimulation are equally effective in suppressing tremor, but thalamic stimulation has fewer adverse effects and results in greater improvement in function.PubMedCrossRefGoogle Scholar
  9. 9.
    Lai EC, Jankovic J, Krauss JK, et al.: Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson’s disease. Neurology 2000, 55:1218–1222.PubMedGoogle Scholar
  10. 10.
    Lang AE, Duff J, Saint-Cyr JA, et al.: Posteroventral medial pallidotomy in Parkinson’s disease. J Neurol 1999, 246(suppl 2):II28-II41.PubMedCrossRefGoogle Scholar
  11. 11.
    Schrag A, Samuel M, Caputo E, et al.: Unilateral pallidotomy for Parkinson’s disease: results after more than 1 year. J Neurol Neurosurg Psychiatry 1999, 67:511–517.PubMedGoogle Scholar
  12. 12.
    de BieRM, de Haan RJ, Nijssen PC, et al.: Unilateral pallidotomy in Parkinson’s disease: a randomised, single-blind, multicentre trial. Lancet 1999, 354:1665–1669.PubMedCrossRefGoogle Scholar
  13. 13.
    Merello M, Nouzeilles MI, Cammarota A, et al.: Comparison of 1-year follow-up evaluations of patients with indication for pallidotomy who did not undergo surgery versus patients with Parkinson’s disease who did undergo pallidotomy: a case control study. Neurosurgery 1999, 44:461–467.PubMedCrossRefGoogle Scholar
  14. 14.
    Baron MS, Vitek JL, Bakay RA, et al.: Treatment of advanced Parkinson’s disease by unilateral posterior GPi pallidotomy: 4-year results of a pilot study. Mov Disord 2000, 15:230–237.PubMedCrossRefGoogle Scholar
  15. 15.
    Fine J, Duff J, Chen R, et al.: Long-term follow-up of unilateral pallidotomy in advanced Parkinson’s disease. N Engl J Med 2000, 342:1708–1714. The largest group of patients with long-term follow-up, illustrating the enduring benefit of pallidotomy, but also the limitations of a unilateral lesion.PubMedCrossRefGoogle Scholar
  16. 16.
    Pal PK, Samii A, Kishore A, et al.: Long term outcome of unilateral pallidotomy: follow up of 15 patients for 3 years. J Neurol Neurosurg Psychiatry 2000, 69:337–344.PubMedCrossRefGoogle Scholar
  17. 17.
    Eskandar EN, Shinobu LA, Penney JB Jr, et al.: Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson’s disease: surgical technique and 2-year results. J Neurosurg 2000, 92:375–383.PubMedGoogle Scholar
  18. 18.
    Kishore A, Panikar D, Balakrishnan S, et al.: Evidence of functional somatotopy in GPi from results of pallidotomy. Brain 2000, 123:2491–2500.PubMedCrossRefGoogle Scholar
  19. 19.
    Lombardi WJ, Gross RE, Trepanier LL, et al.: Relationship of lesion location to cognitive outcome following microelectrode-guided pallidotomy for Parkinson’s disease: support for the existence of cognitive circuits in the human pallidum. Brain 2000, 123(Pt. 4):746–758.PubMedCrossRefGoogle Scholar
  20. 20.
    Guridi J, Rodriquez-Oroz M, Lozano AM, et al.: Targeting the basal ganglia for deep brain stimulation in Parkinson’s disease. Neurology 2000, 55(suppl 6):S21-S28.PubMedGoogle Scholar
  21. 21.
    Hariz MI, Fodstad H: Do microelectrode techniques increase accuracy or decrease risks in pallidotomy and deep brain stimulation? A critical review of the literature. Stereotact Funct Neurosurg 1999, 72:157–169.PubMedCrossRefGoogle Scholar
  22. 22.
    Green J, Barnhart H: The impact of lesion laterality on neuropsychological change following posterior pallidotomy: a review of current findings. Brain Cogn 2000, 42:379–398.PubMedCrossRefGoogle Scholar
  23. 23.
    Junque C, Alegret M, Nobbe FA, et al.: Cognitive and behavioral changes after unilateral posteroventral pallidotomy: relationship with lesional data from MRI. Mov Disord 1999, 14:780–789.PubMedCrossRefGoogle Scholar
  24. 24.
    Kubu CS, Grace GM, Parrent AG: Cognitive outcome following pallidotomy: the influence of side of surgery and age of patient at disease onset. J Neurosurg 2000, 92:384–389.PubMedCrossRefGoogle Scholar
  25. 25.
    Lacritz LH, Cullum CM, Frol AB, et al.: Neuropsychological outcome following unilateral stereotactic pallidotomy in intractable Parkinson’s disease. Brain Cogn 2000, 42:364–378.PubMedCrossRefGoogle Scholar
  26. 26.
    Rettig GM, York MK, Lai EC, et al.: Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2000, 69:326–336.PubMedCrossRefGoogle Scholar
  27. 27.
    Stebbins GT, Gabrieli JD, Shannon KM, et al.: Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson’s disease. Brain Cogn 2000, 42:348–363.PubMedCrossRefGoogle Scholar
  28. 28.
    Trepanier LL, Kumar R, Lozano AM, et al.: Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson’s disease. Brain Cogn 2000, 42:324–347.PubMedCrossRefGoogle Scholar
  29. 29.
    Saint-Cyr JA, Trepanier LL: Neuropsychologic assessment of patients for movement disorder surgery. Mov Disord 2000, 15:771–783.PubMedCrossRefGoogle Scholar
  30. 30.
    Ghika J, Ghika-Schmid F, Fankhauser H, et al.: Bilateral contemporaneous posteroventral pallidotomy for the treatment of Parkinson’s disease: neuropsychological and neurological side effects. Report of four cases and review of the literature. J Neurosurg 1999, 91:313–321.PubMedGoogle Scholar
  31. 31.
    Tronnier VM, Fogel W, Kronenbueger M, et al.: Is the medial globus pallidus a site for stimulation or lesioning in the treatment of Parkinson’s disease? Stereotact Funct Neurosurg 1997, 69:62–68.PubMedCrossRefGoogle Scholar
  32. 32.
    Gross CE: Stimulation of the globus pallidus internus. Prog Neurol Surg 2000, 15:148–155.CrossRefGoogle Scholar
  33. 33.
    Pahwa R, Wilkinson S, Smith D, et al.: High frequency stimulation of the globus pallidus for the treatment of Parkinson’s disease. Neurology 1997, 49:249–253.PubMedGoogle Scholar
  34. 34.
    Gross C, Rougier A, Guehi D, et al.: High frequency stimulation of the globus pallidus internalis in Parkisnon’s disease: a study of seven cases. J Neurosurg 1997, 87:491–497.PubMedGoogle Scholar
  35. 35.
    Volkmann J, Weiss SV, Kappler J: Bilateral high frequency stimulation of the internal globus pallidus in advanced Parkinson’s disease. Ann Neurol 1998, 44:953–961.PubMedCrossRefGoogle Scholar
  36. 36.
    Ghika J, Villemure JG, Fankhauser H, et al.: Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa responsive patients with Parkinson’s disease with severe motor fluctuations: a 2 year follow up review. J Neurosurg 1998, 89:713–718.PubMedCrossRefGoogle Scholar
  37. 37.
    Kumar R, Lang AE, Rodriguez-Oroz MC, et al.: Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson’s disease. Neurology 2000, 55:S34-S39. Multicenter trial of the largest series of patients reported to date. As with similar series, the patients were not randomized, the assessments were not blinded, and only short-term results were reported.PubMedGoogle Scholar
  38. 38.
    Bejjani B, Damier P, Bonnet AM, et al.: Pallidal stimulation for Parkinson’s disease: two targets? Neurology 1997, 49:1564–1569.PubMedGoogle Scholar
  39. 39.
    Kumar R, Sime E, Lozano A, Lang AE: Abnormal involuntary movements induced by globus pallidus internus stimulation in parkinsonian patients [abstract]. Mov Disord 1997, 12(S1):131.Google Scholar
  40. 40.
    Merello M, Nouzeilles MI, Kuzis G, et al.: Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: a prosepctive randomized comparison. Mov Disord 1999, 14:50–56.PubMedCrossRefGoogle Scholar
  41. 41.
    Guridi J, Obeso JA: The role of the subthalamic nucleus in the origin of hemiballism and parkinsonism: new surgical perspectives. Adv Neurol 1997, 74:235–247.PubMedGoogle Scholar
  42. 42.
    Alvarez L, Macias R, Guridi J, et al.: Dorsal subthalamotomy for Parkinson’s disease. Mov Disord 2001, in press.Google Scholar
  43. 43.
    Obeso J: Subthalamotomy for Parkinson’s Disease [abstract]. Mov Disord 2000, 15:8.Google Scholar
  44. 44.
    Benazzouz A, Gross C, Ferger J, et al.: Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 1993, 5:382–389.PubMedCrossRefGoogle Scholar
  45. 45.
    Benazzouz A, Boraud T, Ferger J, et al.: Alleviation of experimental hemiparkinsonism by high-frequency stimulation of the subthalamic nucleus in primates: a comparison with L-dopa treatment. Mov Disord 1996, 11:627–632.PubMedCrossRefGoogle Scholar
  46. 46.
    Limousin P, Krack P, Pollak P, et al.: Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 1998, 339:1105–1111. Largest series of patients described thus far, reported by the group that pioneered subthalamic nucleus stimulation.PubMedCrossRefGoogle Scholar
  47. 47.
    Rodriguez-Oroz MC, Gorospe A, Guridi J, et al.: Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Neurology 2000, 55:S45-S51. Second largest series reported to date, confirming the experience of Limousin et al. [46].PubMedGoogle Scholar
  48. 48.
    Krack P, Pollak P, Limousin P, et al.: Subthalamic nucleus or internal pallidal stimulation in young-onset Parkinson’s disease. Brain 1998, 121:106–112.CrossRefGoogle Scholar
  49. 49.
    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 (suppl 1):73–82.PubMedGoogle Scholar
  50. 50.
    Volkmann J, Allert N, Voges J, et al.: Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 2001, 56:548–551.PubMedGoogle Scholar
  51. 51.
    Bejjani BP, Damier P, Arnulf I, et al.: Transient acute depression induced by high-frequency deep brain stimulation. N Engl J Med 1999, 340:1476–1480.PubMedCrossRefGoogle Scholar
  52. 52.
    Caparros-Lefebvre D, Ruchoux MM, Blond S, et al.: Long-term thalamic stimulation in Parkinson’s disease: postmoretem anatomoclinical study. Neurology 1994, 44:1856–1860.PubMedGoogle Scholar
  53. 53.
    Freeman TB, Olanow CW, Hauser RA, et al.: Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann Neurol 1995, 38:379–388.PubMedCrossRefGoogle Scholar
  54. 54.
    Kordower JH, Freeman TB, Olanow CW: Neuropathology of fetal nigral grafts in patients with Parkinson’s disease. Mov Disord 1998, 13(suppl 1):88–95.PubMedGoogle Scholar
  55. 55.
    Lindvall O: Update on fetal transplantation: the Swedish experience. Mov Disord 1998, 13(suppl_1):83–87.PubMedGoogle Scholar
  56. 56.
    Hagell P, Schrag A, Piccini P, et al.: Sequential bilateral transplantation in Parkinson’s disease: effects of the second graft. Brain 1999, 122(Pt 6):1121–1132. Excellent account of the Swedish approach to fetal cell transplantation.PubMedCrossRefGoogle Scholar
  57. 57.
    Freed CR, Greene PE, Breeze RE, et al.: Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001, 344:710–719. First randomized, double-blind study of fetal cell transplantation using sham surgery as control. This study has generated considerable controversy, which is alluded to in accompanying editorials.PubMedCrossRefGoogle Scholar
  58. 58.
    Brundin P, Pogarell O, Hagell P, et al.: Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson’s disease. Brain 2000, 123(Pt 7):1380–1390.PubMedCrossRefGoogle Scholar
  59. 59.
    Larsson LC, Widner H: Neural tissue xenografting. Scand J Immunol 2000, 52:249–256.PubMedCrossRefGoogle Scholar
  60. 60.
    Schumacher JM, Ellias SA, Palmer EP, et al.: Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology 2000, 54:1042–1050.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • John Hammerstad
    • 1
  • Penelope Hogarth
    • 1
  1. 1.Parkinson Center of Oregon, Department of NeurologyOregon Health Sciences UniversityPortlandUSA

Personalised recommendations