Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety

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  • 1 Parkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, and Departments of Neurology and Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; Parkinson's Disease and Movement Disorders Center, Department of Neurology, Northwestern University, Chicago, Illinois; and Quintiles, Inc., Cranford, New Jersey
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Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD.

Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests.

The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods.

Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.

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Contributor Notes

Address reprint requests to: Jurg L. Jaggi, Ph.D., Department of Neurology, University of Pennsylvania, 3 Gates Pavilion, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. email: jaggi@mail.med.upenn.edu.
  • 1.

    Brown RG, , Dowsey PL, & Brown P, et al: Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease. Ann Neurol 45:473488, 1999 Brown RG, Dowsey PL, Brown P, et al: Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease. Ann Neurol 45:473–488, 1999

    • Search Google Scholar
    • Export Citation
  • 2.

    Burchiel KJ, , Anderson VC, & Favre J, et al: Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study. Neurosurgery 45:13751384, 1999 Burchiel KJ, Anderson VC, Favre J, et al: Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study. Neurosurgery 45:1375–1384, 1999

    • Search Google Scholar
    • Export Citation
  • 3.

    Defer GL, , Widner H, & Marie RM, et al: Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord 14:572584, 1999 Defer GL, Widner H, Marie RM, et al: Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord 14:572–584, 1999

    • Search Google Scholar
    • Export Citation
  • 4.

    Fahn S, & Elton RL, members of the UPDRS Development Committee: Unified Parkinson's Disease Rating Scale, in Fahn S, , Marsden CD, & Goldstein M, et al (eds): Recent Developments in Parkinson's Disease, ed 2. New York: Macmillan, 1987, pp 153163 Fahn S, Elton RL, members of the UPDRS Development Committee: Unified Parkinson's Disease Rating Scale, in Fahn S, Marsden CD, Goldstein M, et al (eds): Recent Developments in Parkinson's Disease, ed 2. New York: Macmillan, 1987, pp 153–163

    • Search Google Scholar
    • Export Citation
  • 5.

    Figueiras-Mendez R, , Marin-Zarza F, & Antonio Molina J, et al: Subthalamic nucleus stimulation improves directly levodopa induced dyskinesias in Parkinson's disease. J Neurol Neurosurg Psychiatry 66:549550, 1999 (Letter) Figueiras-Mendez R, Marin-Zarza F, Antonio Molina J, et al: Subthalamic nucleus stimulation improves directly levodopa induced dyskinesias in Parkinson's disease. J Neurol Neurosurg Psychiatry 66:549–550, 1999 (Letter)

    • Search Google Scholar
    • Export Citation
  • 6.

    Freed CR, , Breeze RE, & Fahn S: Placebo surgery in trials of therapy for Parkinson's disease. N Engl J Med 342:353355, 2000 Freed CR, Breeze RE, Fahn S: Placebo surgery in trials of therapy for Parkinson's disease. N Engl J Med 342:353–355, 2000

    • Search Google Scholar
    • Export Citation
  • 7.

    Freedman B: Equipoise and the ethics of clinical research. N Engl J Med 317:141145, 1987 Freedman B: Equipoise and the ethics of clinical research. N Engl J Med 317:141–145, 1987

    • Search Google Scholar
    • Export Citation
  • 8.

    Golden CJ: Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Chicago: Stoelting, 1978 Golden CJ: Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Chicago: Stoelting, 1978

    • Search Google Scholar
    • Export Citation
  • 9.

    Heaton RK: Wisconsin Card Sorting Test: Manual. Odessa, FL: Psychological Assessment Resources, 1981 Heaton RK: Wisconsin Card Sorting Test: Manual. Odessa, FL: Psychological Assessment Resources, 1981

    • Search Google Scholar
    • Export Citation
  • 10.

    Hoehn MM, & Yahr MD: Parkinsonism: onset, progression and mortality. Neurology 17:427442, 1967 Hoehn MM, Yahr MD: Parkinsonism: onset, progression and mortality. Neurology 17:427–442, 1967

    • Search Google Scholar
    • Export Citation
  • 11.

    Houeto JL, , Bejjani PB, & Damier P, et al: Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD. Neurology 55:728730, 2000 Houeto JL, Bejjani PB, Damier P, et al: Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD. Neurology 55:728–730, 2000

    • Search Google Scholar
    • Export Citation
  • 12.

    Kaplan EH, , Goodglass H, & Weintraub S: The Boston Naming Test. Philadelphia: Lea & Febiger, 1983 Kaplan EH, Goodglass H, Weintraub S: The Boston Naming Test. Philadelphia: Lea & Febiger, 1983

    • Search Google Scholar
    • Export Citation
  • 13.

    Krack P, , Limousin P, & Benabid AL, et al: Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease. Lancet 350:1676, 1997 (Letter) Krack P, Limousin P, Benabid AL, et al: Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease. Lancet 350:1676, 1997 (Letter)

    • Search Google Scholar
    • Export Citation
  • 14.

    Krack P, , Pollak P, & Limousin P, et al: Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease. Lancet 350:1675, 1997 (Letter) Krack P, Pollak P, Limousin P, et al: Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease. Lancet 350:1675, 1997 (Letter)

    • Search Google Scholar
    • Export Citation
  • 15.

    Kumar R, , Lozano AM, & Kim YJ, et al: Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology 51:850855, 1998 Kumar R, Lozano AM, Kim YJ, et al: Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology 51:850–855, 1998

    • Search Google Scholar
    • Export Citation
  • 16.

    Langston JW, , Widner H, & Goetz CG, et al: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 7:213, 1992 Langston JW, Widner H, Goetz CG, et al: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 7:2–13, 1992

    • Search Google Scholar
    • Export Citation
  • 17.

    Limousin P, , Krack P, & Pollak P, et al: Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:11051111, 1998 Limousin P, Krack P, Pollak P, et al: Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:1105–1111, 1998

    • Search Google Scholar
    • Export Citation
  • 18.

    Macklin R: The ethical problems with sham surgery in clinical research. N Engl J Med 341:992996, 1999 Macklin R: The ethical problems with sham surgery in clinical research. N Engl J Med 341:992–996, 1999

    • Search Google Scholar
    • Export Citation
  • 19.

    Mattis S: Dementia Rating Scale: Professional Manual. Odessa, FL: Psychological Assessment Resources, 1988 Mattis S: Dementia Rating Scale: Professional Manual. Odessa, FL: Psychological Assessment Resources, 1988

    • Search Google Scholar
    • Export Citation
  • 20.

    Molinuevo JL, , Valls-Sole J, & Valldeoriola F: The effect of transcranial magnetic stimulation on reaction time in progressive supranuclear palsy. Clin Neurophysiol 111:20082013, 2000 Molinuevo JL, Valls-Sole J, Valldeoriola F: The effect of transcranial magnetic stimulation on reaction time in progressive supranuclear palsy. Clin Neurophysiol 111:2008–2013, 2000

    • Search Google Scholar
    • Export Citation
  • 21.

    Moro E, , Scerrati M, & Romito LM, et al: Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease. Neurology 53:8590, 1999 Moro E, Scerrati M, Romito LM, et al: Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease. Neurology 53:85–90, 1999

    • Search Google Scholar
    • Export Citation
  • 22.

    Obeso JA, , Guridi J, & Obeso JA, et al: Surgery for Parkinson's disease. J Neurol Neurosurg Psychiatry 62:28, 1997 Obeso JA, Guridi J, Obeso JA, et al: Surgery for Parkinson's disease. J Neurol Neurosurg Psychiatry 62:2–8, 1997

    • Search Google Scholar
    • Export Citation
  • 23.

    Olanow CW, , Jenner P, & Brooks D: Dopamine agonists and neuroprotection in Parkinson's disease. Ann Neurol 44 (Suppl 3):S167S174, 1998 Olanow CW, Jenner P, Brooks D: Dopamine agonists and neuroprotection in Parkinson's disease. Ann Neurol 44 (Suppl 3):S167–S174, 1998

    • Search Google Scholar
    • Export Citation
  • 24.

    Pahwa R, , Wilkinson S, & Smith D, et al: High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease. Neurology 49:249253, 1997 Pahwa R, Wilkinson S, Smith D, et al: High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease. Neurology 49:249–253, 1997

    • Search Google Scholar
    • Export Citation
  • 25.

    Pillon B, , Ardouin C, & Damier P, et al: Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson's disease. Neurology 55:411418, 2000 Pillon B, Ardouin C, Damier P, et al: Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson's disease. Neurology 55:411–418, 2000

    • Search Google Scholar
    • Export Citation
  • 26.

    Rodriguez MC, , Obeso JA, & Olanow CW: Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann Neurol 44 (Suppl 3):S175S188, 1998 Rodriguez MC, Obeso JA, Olanow CW: Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann Neurol 44 (Suppl 3):S175–S188, 1998

    • Search Google Scholar
    • Export Citation
  • 27.

    Schaltenbrand G, & Wahren W: Atlas for Stereotaxy of the Human Brain, ed 2. Stuttgart: Georg Thieme, 1977 Schaltenbrand G, Wahren W: Atlas for Stereotaxy of the Human Brain, ed 2. Stuttgart: Georg Thieme, 1977

    • Search Google Scholar
    • Export Citation
  • 28.

    Schwab R, & England AC Jr: Projection technique for evaluating surgery in Parkinson's disease, in Gillingham FJ, & Donaldson IML (eds): Third Symposium on Parkinson's Disease. Edinburgh: E & S Livingstone, 1969, pp 152157 Schwab R, England AC Jr: Projection technique for evaluating surgery in Parkinson's disease, in Gillingham FJ, Donaldson IML (eds): Third Symposium on Parkinson's Disease. Edinburgh: E & S Livingstone, 1969, pp 152–157

    • Search Google Scholar
    • Export Citation
  • 29.

    Volkmann J, , Allert N, & Voges J, et al: Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 56:548551, 2001 Volkmann J, Allert N, Voges J, et al: Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 56:548–551, 2001

    • Search Google Scholar
    • Export Citation
  • 30.

    Wechsler D: WAIS-R Manual: Wechsler Adult Intelligence Scale-Revised. New York: Psychological Corp., 1981 Wechsler D: WAIS-R Manual: Wechsler Adult Intelligence Scale-Revised. New York: Psychological Corp., 1981

    • Search Google Scholar
    • Export Citation
  • 31.

    Yesavage JA, , Brink TL, & Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:3749, 1983 Yesavage JA, Brink TL, Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:37–49, 1983

    • Search Google Scholar
    • Export Citation

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