Long-term follow up of bilateral deep brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease

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  • 1 Division of Neurology and Neurosurgery, Toronto Western Hospital, University of Toronto; and the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
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Object. The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator.

Methods. Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time.

In this cohort the median duration of follow-up review was 24 months (range 12–52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35–50%], p < 0.001) and the motor score decreased by 48% (95% CI 42–55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31–50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27–48%, p < 0.001) at 1 year and 36% (95% CI 25–48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2–72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa.

Conclusions. In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.

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Contributor Notes

Address reprint requests to: Anthony E. Lang, M.D., Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, 399 Bathurst Street, MP11–306, Toronto, Ontario M5T 2S8, Canada. email: lang@uhnres.utoronto.ca.
  • 1.

    Bejjani BP, , Gervais D, & Arnulf I, et al: Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 68:595600, 2000 Bejjani BP, Gervais D, Arnulf I, et al: Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 68:595–600, 2000

    • Search Google Scholar
    • Export Citation
  • 2.

    The Deep-Brain Stimulation for Parkinson's Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med 345:956963, 2001 The Deep-Brain Stimulation for Parkinson's Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med 345:956–963, 2001

    • Search Google Scholar
    • Export Citation
  • 3.

    Dujardin K, , Defebvre L, & Krystkowiak P, et al: Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease. J Neurol 248:603611, 2001 Dujardin K, Defebvre L, Krystkowiak P, et al: Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease. J Neurol 248:603–611, 2001

    • Search Google Scholar
    • Export Citation
  • 4.

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

    • Search Google Scholar
    • Export Citation
  • 5.

    Hauser RA, & Holford NHG: Quantitative description of loss of clinical benefit following withdrawal of levodopa-carbidopa and bromocriptine in early Parkinson's disease. Mov Disord 17:961968, 2002 Hauser RA, Holford NHG: Quantitative description of loss of clinical benefit following withdrawal of levodopa-carbidopa and bromocriptine in early Parkinson's disease. Mov Disord 17:961–968, 2002

    • Search Google Scholar
    • Export Citation
  • 6.

    Henderson JM, , O'Sullivan DJ, & Pell M, et al: Lesion of thalamic centromedian—parafascicular complex after chronic deep brain stimulation. Neurology 56:15761579, 2001 Henderson JM, O'Sullivan DJ, Pell M, et al: Lesion of thalamic centromedian—parafascicular complex after chronic deep brain stimulation. Neurology 56:1576–1579, 2001

    • Search Google Scholar
    • Export Citation
  • 7.

    Hobson DE, , Lang AE, & Martin WRW, et al: Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 287:455463, 2002 Hobson DE, Lang AE, Martin WRW, et al: Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 287:455–463, 2002

    • Search Google Scholar
    • Export Citation
  • 8.

    Houeto JL, , Damier P, & Bejjani PB, et al: Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. Arch Neurol 57:461465, 2000 Houeto JL, Damier P, Bejjani PB, et al: Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. Arch Neurol 57:461–465, 2000

    • Search Google Scholar
    • Export Citation
  • 9.

    Houeto JL, , Mesnage V, & Mallet L, et al: Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 72:701707, 2002 Houeto JL, Mesnage V, Mallet L, et al: Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 72:701–707, 2002

    • Search Google Scholar
    • Export Citation
  • 10.

    Kleiner-Fisman G, , Saint-Cyr JA, & Miyasaki J, et al: Subthalamic DBS replaces levodopa in Parkinson's disease. Neurology 59:12931294, 2002 (Letter) Kleiner-Fisman G, Saint-Cyr JA, Miyasaki J, et al: Subthalamic DBS replaces levodopa in Parkinson's disease. Neurology 59:1293–1294, 2002 (Letter)

    • Search Google Scholar
    • Export Citation
  • 11.

    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
  • 12.

    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
  • 13.

    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
  • 14.

    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
  • 15.

    Molinuevo JL, , Valldeoriola F, & Tolosa E, et al: Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 57:983988, 2000 Molinuevo JL, Valldeoriola F, Tolosa E, et al: Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 57:983–988, 2000

    • Search Google Scholar
    • Export Citation
  • 16.

    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
  • 17.

    Morrish PK, , Rakshi JS, & Bailey DL, et al: Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F] dopa PET. J Neurol Neurosurg Psychiatry 64:314319, 1998 Morrish PK, Rakshi JS, Bailey DL, et al: Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F] dopa PET. J Neurol Neurosurg Psychiatry 64:314–319, 1998

    • Search Google Scholar
    • Export Citation
  • 18.

    Rodriguez-Oroz MC, , Gorospe A, & Guridi J, et al: Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease. Neurology 55 (Suppl 6):S45S51, 2000 Rodriguez-Oroz MC, Gorospe A, Guridi J, et al: Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease. Neurology 55 (Suppl 6):S45–S51, 2000

    • Search Google Scholar
    • Export Citation
  • 19.

    Romito LM, , Scerrati M, & Contarino MF, et al: Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease. Neurology 58:15461550, 2002 Romito LM, Scerrati M, Contarino MF, et al: Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease. Neurology 58:1546–1550, 2002

    • Search Google Scholar
    • Export Citation
  • 20.

    Saint-Cyr JA, , Hoque T, & Pereira LCM, et al: Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:11521166, 2002 Saint-Cyr JA, Hoque T, Pereira LCM, et al: Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:1152–1166, 2002

    • Search Google Scholar
    • Export Citation
  • 21.

    Saint-Cyr JA, , Trépanier LL, & Kumar R, et al: Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain 123:20912108, 2000 Saint-Cyr JA, Trépanier LL, Kumar R, et al: Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain 123:2091–2108, 2000

    • Search Google Scholar
    • Export Citation
  • 22.

    Simuni T, , Jaggi JL, & Mulholland H, et al: Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety. J Neurosurg 96:666672, 2002 Simuni T, Jaggi JL, Mulholland H, et al: Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety. J Neurosurg 96:666–672, 2002

    • Search Google Scholar
    • Export Citation
  • 23.

    Thobois S, , Mertens P, & Guenot M, et al: Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients. J Neurol 249:529534, 2002 Thobois S, Mertens P, Guenot M, et al: Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients. J Neurol 249:529–534, 2002

    • Search Google Scholar
    • Export Citation
  • 24.

    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 42:324347, 2000 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 42:324–347, 2000

    • Search Google Scholar
    • Export Citation
  • 25.

    Valldeoriola F, , Pilleri M, & Tolosa E, et al: Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients. Mov Disord 17:125132, 2002 Valldeoriola F, Pilleri M, Tolosa E, et al: Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients. Mov Disord 17:125–132, 2002

    • Search Google Scholar
    • Export Citation
  • 26.

    Vingerhoets FJG, , Villemure JG, & Temperli P, et al: Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up. Neurology 58:396401, 2002 Vingerhoets FJG, Villemure JG, Temperli P, et al: Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up. Neurology 58:396–401, 2002

    • Search Google Scholar
    • Export Citation
  • 27.

    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
  • 28.

    Welter ML, , Houeto JL, & Tezenas Du Montcel S, et al: Clinical predictive factors of subthalamic stimulation in Parkinson's disease. Brain 125:575583, 2002 Welter ML, Houeto JL, Tezenas Du Montcel S, et al: Clinical predictive factors of subthalamic stimulation in Parkinson's disease. Brain 125:575–583, 2002

    • Search Google Scholar
    • Export Citation
  • 29.

    Wenzelburger R, , Zhang BR, & Poepping M, et al: Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus. Ann Neurol 52:240243, 2002 Wenzelburger R, Zhang BR, Poepping M, et al: Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus. Ann Neurol 52:240–243, 2002

    • Search Google Scholar
    • Export Citation

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