Deep Brain Stimulation Of The Globus Pallidus Interna

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Surgery targeting the internal segment of the globus pallidus has been shown to improve all of the cardinal features of PD including bradykinesia, rigidity, and tremor as well as levodopa-induced dyskinesia. Due to concerns of complications related to speech, balance, and cognition with bilateral pallidal lesions, bilateral DBS of the GPi is preferred to pallidotomy. Multiple studies have reported the efficacy of GPi stimulation for PD (15-20) (Table 1). Many of these studies have a small number of patients and/or a relatively short follow-up period.

Kumar et al. (19) reported 22 PD patients who were treated with either unilateral (n = 5) or bilateral (n = 17) GPi stimulation. Evaluations performed in the medication off/stimulation on state at six months reported a 32% improvement in UPDRS motor scores and a 40% improvement in UPDRS activities of daily living (ADL) scores compared to baseline medication off scores. There was also a 68% reduction in dyskinesia. The Deep Brain Stimulation for Parkinson's Disease Study Group (16) reported a multinational, prospective study of bilateral GPi stimulation in PD. Forty-one patients were enrolled and electrodes were implanted in 38 patients. Two patients had cerebral hemorrhages and one patient had intraoperative confusion. In comparison to baseline, there was a significant improvement of 33% in UPDRS motor scores in the medication off/stimulation on state. More specifically, tremor was reduced by 59%, rigidity was reduced 31%, bradykinesia was reduced 26%, gait improved by 35%, and postural instability improved by 36%. Patient diaries revealed that the percentage of on time without dyskinesia increased from 28% to 64% and daily off time was reduced from 37% to 24%. The mean daily dose of levodopa equivalents was unchanged between baseline and six months.

Several studies have examined the long-term benefits of DBS of the GPi (Table 1). Anderson et al. (21) reported 10 PD patients one year after bilateral GPi DBS.

TABLE 1 Selected Studies of Deep Brain Stimulation of the Globus Pallidus Interna

Number of

Follow-up

UPDRS improvement3

Dyskinesiab

Author

patients

(mo)

ADL (%)

Motor (%)

(%)

Kumar et al. (19)

17 bilateral/

5 unilateral

6

40

32

68

DBSPDSG (16)

38 bilateral

6

36

33

67

Volkmann et al. (44)

11 bilateral

12

42

68

80

Loher et al. (17)

9 unilateral

12

33

38

55

Loher et al. (17)

10 bilateral

12

34

41

71

Anderson et al. (21)

10 bilateral

12

18

39

89

Ghika et al. (18)

6 bilateral

24-30

68

50

65

Lyons et al. (22)

6 bilateral/

25-81

21

37

64

3 unilateral

Rodriguez-Oroz

20 bilateral

12

32

43

72

et al. (23)

Rodriguez-Oroz

20 bilateral

36-48

28

39

76

et al. (23)

Volkmann et al. (20)

10 bilateral

12

49

56

58

Volkmann et al. (20)

9 bilateral

36

26

49

63

Volkmann et al. (20)

6 bilateral

60

-1.5

23

64

aPercentage improvement from baseline medication off state to medication off/stimulation on at follow-up. bPercentage reduction in dyskinesia.

Abbreviations: ADL, activities of daily living; DBSPDSG, Deep Brain Stimulation for Parkinson's Disease Study Group; UPDRS, Unified Parkinson's Disease Rating Scale.

aPercentage improvement from baseline medication off state to medication off/stimulation on at follow-up. bPercentage reduction in dyskinesia.

Abbreviations: ADL, activities of daily living; DBSPDSG, Deep Brain Stimulation for Parkinson's Disease Study Group; UPDRS, Unified Parkinson's Disease Rating Scale.

In the medication off state they showed an 18% improvement in UPDRS ADL scores and a 39% improvement in UPDRS motor scores with stimulation compared to baseline medication off scores. There was also an 89% reduction in dyskinesia and a 3% reduction in antiparkinsonian medications. Lyons et al. (22) reported nine patients (three unilateral and six bilateral) with a mean follow-up of 48.5 months (range 25-81 months) after GPi DBS. There was a significant improvement in UPDRS ADL scores of 21% and a 37% improvement in UPDRS motor scores. Dyskinesia was reduced by 64% and there were no reductions in antiparkinsonian medications. Rodriguez-Oroz et al. (23) reported results of a multicenter study of 20 PD patients who received bilateral GPi DBS. After three to four years of follow-up, significant improvements in UPDRS ADL and motor scores in the medication off/stimulation on condition compared with the baseline medication off state were maintained. More specifically, at the three-to-four-year visit, there were significant improvements in tremor, rigidity, bradykinesia, gait, and dyskinesia compared to baseline and there was no significant worsening compared to the one-year visit.

In contrast, some studies have shown a loss of effect of GPi DBS over time (18,20). Ghika et al. (18) reported six PD patients with a minimum follow-up of 24 months after GPi DBS. The mean improvement in UPDRS motor scores in the medication off/stimulation on state compared to the baseline medication off condition was 50% and for UPDRS ADL scores it was 68%. Mean daily off time decreased from 40% to 10% and dyskinesia was reduced by 65%. Although the improvements persisted beyond two years after surgery, signs of decreased efficacy were seen after 12 months. Volkmann et al. (20) reported long-term outcomes of bilateral GPi DBS 12, 36, and 60 months after surgery (Table 1). UPDRS motor scores were significantly improved in the medication off/stimulation on condition compared to baseline by 56% at 12 months and 43% at 36 months. However, at 60 months there was a nonsignificant improvement of 24% compared to baseline. Similarly, for UPDRS ADL scores, at 12 months, there was a significant improvement of 49% compared to baseline; however, a 26% improvement at 36 months was not significantly different from baseline and at 60 months there was a worsening of 1.5%. More specifically, at 12 months, there was a significant improvement in bradykinesia, rigidity, tremor, and postural instability/gait, at 36 months there were significant improvements only in bradykinesia and postural instability/gait, and by 60 months, there was a significant improvement only in rigidity. In contrast, dyskinesia continued to be significantly improved throughout the five-year follow-up.

In summary, multiple studies have demonstrated the short-term benefits of GPi DBS in controlling the cardinal symptoms of PD and reducing dyskinesia. Results have been inconsistent regarding the long-term benefits in the cardinal symptoms of PD with GPi DBS; however, there is consensus regarding a significant and sustained reduction in levodopa-induced dyskinesia despite minimal if any reductions in antiparkinsonian medications. Further research is necessary to confirm the long-term benefits of GPi DBS.

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