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Deep-Brain Stimulation for Parkinson’s Disease 

Deep-Brain Stimulation for Parkinson’s Disease
Chapter:
Deep-Brain Stimulation for Parkinson’s Disease
Author(s):

Sarah E. Buckingham

DOI:
10.1093/med/9780199377527.003.0010
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This trial demonstrated the superior efficacy of neurostimulation over best medical management in patients with advanced Parkinson’s disease and levodopa-related motor complications.

Deuschl et al.1

Research Question:

Is neurostimulation superior to best medical management in patients with advanced Parkinson’s disease?1

Funding:

German Federal Ministry of Education and Research.

Year Study Began:

2001

Year Study Published:

2006

Study Location:

10 academic centers in Germany and Austria.

Who Was Studied:

Patients <75 years of age who received a clinical diagnosis of idiopathic Parkinson’s disease at least 5 years previously and had parkinsonian motor symptoms or dyskinesias that limited their ability to perform activities of daily living (ADL), despite receiving optimal medical therapy.

Who Was Excluded:

Patients with age ≥75 years, dementia, depression or psychosis, or contraindications to surgery.

How Many Patients:

156

Study Overview:

See Figure 10.1 for a summary of the trial’s design.


Figure 10.1 Summary of the Trial’s Design.

Figure 10.1 Summary of the Trial’s Design.

Study Intervention:

Patients were randomly assigned to neurostimulation or to best medical treatment. Patients assigned to the neurostimulation arm underwent bilateral stereotactic surgery under local anesthesia, targeting the subthalamic nucleus. The final implantation point of the microelectrode was the position at which the most significant effect on rigidity and other symptoms of Parkinson’s disease was obtained, at the lowest stimulation intensity and with the largest safety margin during intraoperative testing. Final placement was confirmed with neuroimaging. Postoperatively, the optimal stimulation settings and antiparkinsonian medication were intermittently adjusted according to the patient’s response. “Patients assigned to medical treatment received individualized optimal drug therapy according to the guidelines of the German Society of Neurology. The drugs were adjusted according to the patient’s needs throughout the study.”2

Follow-Up:

All subjects underwent testing at baseline and at 6 months.

Endpoints:

Primary outcome: changes from baseline to 6 months in the quality of life, as assessed by the Parkinson’s Disease Questionnaire (PDQ-39) summary index, and in the severity of motor symptoms while the patient was not taking medication, as assessed by the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III). Secondary outcome: changes in a Dyskinesia Scale and in the activities of daily living as assessed by the UDPRS, part II (UPDRS-II), and the Schwab and England Scale, with and without medication.

The PDQ-39 is used to assess well-being and functioning in Parkinson’s patients and is completed by patients and their families.3 It evaluates eight key dimensions:

  • Mobility

  • ADL

  • Emotional well-being

  • Stigma

  • Social support

  • Cognitions

  • Communication

  • Bodily discomfort

Results

  • Patients treated with neurostimulation had greater improvement in the score on the PDQ-39 summary index than did patients assigned to medical treatment (see Table 10.1).

  • Patients treated with neurostimulation had greater improvement in the score on the UPDRS-III (to assess motor function) administered when the patients were not taking medication (see Table 10.1).

  • ADLs while the patient was not taking medication, as assessed by the UPDRS-II, markedly improved in the neurostimulation group and slightly worsened in the medication group (see Table 10.1).

  • Thirteen severe adverse events were reported in 13 patients (10 in the neurostimulation group and 3 in the medication group, P = 0.04). Three patients died in the deep-brain stimulation group: one from intracerebral hemorrhage during surgery, one from pneumonia 6 weeks after randomization, and one who committed suicide five months after randomization.

Table 10.1. Summary of Key Findings

Outcome Measures

Group

P Value

Baseline

Δ‎ Baseline to 6 Mo

Neurostimulation

Medication

Neurostimulation

Medication

PDQ-39 Summary Indexa

41.8 ± 13.9

39.6 ± 16.0

9.5 ± 15.3

–0.2 ± 11.2

0.02

UPDRS-III

Without medication

48.0 ± 12.3

46.8 ± 12.1

19.6 ± 15.1

0.4 ± 9.5

<0.001

With medication

18.9 ± 9.3

17.3 ± 9.6

4.0 ± 10.1

–0.4 ± 7.7

0.01

UPDRS-II

Without medication

22.5 ± 7.2

21.9 ± 6.4

8.8 ± 8.6

–0.8 ± 6.4

<0.001

With medication

9.0 ± 5.5

7.9 ± 5.8

1.5 ± 5.4

–1.1 ± 5.2

0.005

Dyskinesia Scale

Without medication

0.5 ± 2.0

0.5 ± 1.7

0.2 ± 2.2

0.2 ± 1.7

0.78

With medication

6.7 ± 5.3

8.4 ± 5.9

3.4 ± 4.5

–0.4 ± 4.6

<0.001

Schwab and England Scaleb

Without medication

47 ± 19

48 ± 19

–23 ± 22

1 ± 16

<0.001

With medication

80 ± 19

82 ± 17

–4 ± 16

3 ± 16

0.02

a Scores for PDQ-39 can range from 0–100. Scores for UPDRS-III can range from 0–108. Scores for UPDRS-II can range from 0–52. Scores for the Dyskinesia Scale can range from 0–28. For all of these scales, lower scores indicate better function or quality of life.

b Scores for Schwab and England scale can range from 0–100. Higher scores indicate better function or quality of life.

Criticisms and Limitations:

There was no sham-surgery or placebo control in this study. Multiple studies to date have demonstrated that neurostimulation of the subthalamic nucleus in Parkinson’s disease is associated with a placebo effect. The implementation of a sham-surgery arm is controversial, however, because of its potential adverse effects. The best medical treatment group did not receive standardized therapy; rather, the choice of medication regimen was determined on an individual basis in accordance with national guidelines for the treatment of advanced Parkinson’s disease, as published by the German Society of Neurology.

Other Relevant Studies and Information:

  • This study primarily focused on quality of life measures, in contrast to previous studies, which used motor scales as the primary outcome measure.4,5 These 2 studies demonstrated that subthalamic stimulation improved fluctuating motor symptoms; however, they were not prospective trials.

  • The current guidelines on treating Parkinson’s disease with motor fluctuations and dyskinesia were published by the American Academy of Neurology in 2006. They are compatible with this study and state, “DBS of the STN is possibly effective in improving motor function and reducing motor fluctuations, dyskinesia, and antiparkinsonian medication usage in [Parkinson’s disease] patients.”6

Summary and Implications:

Subthalamic neurostimulation resulted in a signficant and clinically meaningful improvement in the quality of life of patients <75 years of age who had advanced Parkinson’s disease with parkinsonian motor symptoms or dyskinesias. Patients who received neurostimulation had longer periods and better quality of mobility with less dyskinesia, compared to those patients who received best medical therapy alone.

Clinical Case: Management of Advanced Parkinson’s Disease

Case History:

A 71-year-old woman with idiopathic Parkinson’s disease diagnosed 10 years ago presents to clinic complaining of worsening mobility. She states that throughout the day she fluctuates between feeling stiff and slow just prior to her next dose of carbidopa-levodopa and experiencing uncontrollable dyskinesias. These symptoms interfere with her ability to perform many tasks, and her husband now helps with most of her ADL. Her parkinsonian symptoms have worsened despite escalation of medical therapy. She otherwise is healthy and takes one antihypertensive medication for high blood pressure. Both she and her husband report worsening quality of life and wonder if any other treatment options exist.

Suggested Answer:

This study demonstrated that deep-brain stimulation of the subthalamic nucleus in patients with advanced Parkinson’s disease results in greater improvement in motor function and quality of life compared to best medical management.

The patient in this vignette has advanced Parkinson’s disease, with severe motor fluctuations, despite optimal medical therapy. She has no evidence of dementia or major psychiatric illness and is otherwise healthy with no contraindications to surgery. Therefore, neurostimulation targeting the subthalamic nucleus should be recommended. Based on this study, neurostimulation is expected to improve her motor fluctuations, help her become more independent with her ADL, and improve her overall quality of life. Surgery is not without risks; however, for this patient the benefits of neurostimulation likely outweigh those risks, and DBS should be offered.

References

1. Deuschl G, Schade-Britinger C, Krack P, et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355:896–908.Find this resource:

2. Oertel W, Deuschl G, Eggert K, et al. Parkinson-Syndrome. In: Diener HC, ed. Leitlinien für Diagnostik und Therapie in der Neurologie: Stuttgart: Thieme-Verlag, 2003:38–57.Find this resource:

    3. Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The Parkinson’s Disease Questionnaire (PDQ-39): development and validation of a Parkinson’s disease summary index score. Age Ageing. 1997;26(5):353–357.Find this resource:

    4. 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. 2001;345:956–63.Find this resource:

    5. Krack P, Batir A, Van Blercom N, et al. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med. 2003;349:1925–1934.Find this resource:

    6. Pahwa R, Factor SA, Lyons KE, et al. Practice parameter: Treatment of Parkinson disease with motor fluctuation and dyskinesia (an evidence-based review). Neurology. 2006;6:983–995.Find this resource: