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

Restricted access

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.

Article Information

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.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Bar graph showing UPDRS motor scores before surgery, 1 year after surgery, and at the time of the last evaluation. Evaluations were performed in patients during medication-on and medication-off periods with the stimulator turned on and turned off. The bars represent the 25 to 75% interquartile range. Lines in the middle of the bars represent median scores. Whiskers extending from the bars approximate the 95% CI. Circles outside last evaluation bars represent outliers.

References

1.

Bejjani BPGervais DArnulf Iet al: Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry 68:5956002000J Neurol Neurosurg Psychiatry 68:

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 345:9569632001The 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:

3.

Dujardin KDefebvre LKrystkowiak Pet al: Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease. J Neurol 248:6036112001J Neurol 248:

4.

Fahn SElton RL: Unified Parkinson's Disease Rating ScaleFahn SMarsden CDGoldstein M (eds): Recent Developments in Parkinson's Diseaseed 2. New York: Macmillan1987153163

5.

Hauser RAHolford NHG: Quantitative description of loss of clinical benefit following withdrawal of levodopa-carbidopa and bromocriptine in early Parkinson's disease. Mov Disord 17:9619682002Mov Disord 17:

6.

Henderson JMO'Sullivan DJPell Met al: Lesion of thalamic centromedian—parafascicular complex after chronic deep brain stimulation. Neurology 56:157615792001Neurology 56:

7.

Hobson DELang AEMartin WRWet al: Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 287:4554632002JAMA 287:

8.

Houeto JLDamier PBejjani PBet al: Subthalamic stimulation in Parkinson disease: a multidisciplinary approach. Arch Neurol 57:4614652000Arch Neurol 57:

9.

Houeto JLMesnage VMallet Let al: Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 72:7017072002J Neurol Neurosurg Psychiatry 72:

10.

Kleiner-Fisman GSaint-Cyr JAMiyasaki Jet al: Subthalamic DBS replaces levodopa in Parkinson's disease. Neurology 59:129312942002 (Letter)Neurology 59:

11.

Krack PLimousin PBenabid ALet al: Chronic stimulation of subthalamic nucleus improves levodopa-induced dyskinesias in Parkinson's disease. Lancet 350:16761997 (Letter)Lancet 350:

12.

Kumar RLozano AMKim YJet al: Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease. Neurology 51:8508551998Neurology 51:

13.

Langston JWWidner HGoetz CGet al: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 7:2131992Mov Disord 7:

14.

Limousin PKrack PPollak Pet al: Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:110511111998N Engl J Med 339:

15.

Molinuevo JLValldeoriola FTolosa Eet al: Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 57:9839882000Arch Neurol 57:

16.

Moro EScerrati MRomito LMet al: Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson's disease. Neurology 53:85901999Neurology 53:

17.

Morrish PKRakshi JSBailey DLet al: Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F] dopa PET. J Neurol Neurosurg Psychiatry 64:314319199818F] dopa PET. J Neurol Neurosurg Psychiatry 64:

18.

Rodriguez-Oroz MCGorospe AGuridi Jet al: Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease. Neurology 55 (Suppl 6):S45S512000Neurology 55 (Suppl 6):

19.

Romito LMScerrati MContarino MFet al: Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease. Neurology 58:154615502002Neurology 58:

20.

Saint-Cyr JAHoque TPereira LCMet al: Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:115211662002J Neurosurg 97:

21.

Saint-Cyr JATrépanier LLKumar Ret al: Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain 123:209121082000Brain 123:

22.

Simuni TJaggi JLMulholland Het al: Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety. J Neurosurg 96:6666722002J Neurosurg 96:

23.

Thobois SMertens PGuenot Met al: Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients. J Neurol 249:5295342002J Neurol 249:

24.

Trepanier LLKumar RLozano AMet al: Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease. Brain Cogn 42:3243472000Brain Cogn 42:

25.

Valldeoriola FPilleri MTolosa Eet al: Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients. Mov Disord 17:1251322002Mov Disord 17:

26.

Vingerhoets FJGVillemure JGTemperli Pet al: Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up. Neurology 58:3964012002Neurology 58:

27.

Volkmann JAllert NVoges Jet al: Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 56:5485512001Neurology 56:

28.

Welter MLHoueto JLTezenas Du Montcel Set al: Clinical predictive factors of subthalamic stimulation in Parkinson's disease. Brain 125:5755832002Brain 125:

29.

Wenzelburger RZhang BRPoepping Met al: Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus. Ann Neurol 52:2402432002Ann Neurol 52:

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 4 4 2
Full Text Views 78 78 23
PDF Downloads 82 82 30
EPUB Downloads 0 0 0

PubMed

Google Scholar