Deep Brain Stimulation Of The Subthalamic Nucleus

Multiple reports have demonstrated the short-term benefits of STN DBS in controlling the cardinal features of PD and reducing dyskinesia and antiparkinsonian medications (16,24-31). One of the largest studies was conducted by the Deep Brain Stimulation for Parkinson's Disease Study Group (16). This was a multicenter study in which 96 PD patients received bilateral STN DBS and 91 completed the six-month follow-up visit. In the medication off/stimulation on condition at six months compared to the baseline medication off condition there was a mean improvement of 44% in the UPDRS ADL scores and a 51% improvement in UPDRS motor scores. More specifically, tremor was improved by 79%, rigidity by 58%, bradykinesia by 42%, gait by 56%, and postural instability by 50%, all of which were significant improvements compared to baseline. According to patient diaries, there was a significant decrease in daily off time from 49% to 19%, a significant increase in on time without dyskinesia from 27% to 74% and a decrease in on time with dysk-inesia from 23% to 7%. The Rush Dyskinesia Scale demonstrated a significant improvement in dyskinesia of 58% and antiparkinsonian medications were reduced an average of 37%.

Several studies have demonstrated the long-term benefits of STN DBS (23,32-37) (Table 2). Rodriguez-Oroz et al. (23) examined 49 PD patients who received bilateral STN DBS as part of the original Deep Brain Stimulation for Parkinson's Disease Study Group trial (16), three to four years after initial implant. They demonstrated a 43% improvement in UPDRS ADL scores and a 50% improvement in UPDRS motor scores in the medication off/stimulation on condition compared to the baseline medication off state. More specifically, there was an 87% improvement in tremor, a 59% improvement in rigidity, a 42% improvement in bradykinesia, a 41% improvement in gait, a 31% improvement in postural instability, a 59% reduction in dyskinesia, and a 34% reduction in levodopa compared to baseline. Compared with

TABLE 2 Selected Studies of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus

Number of

Follow-up

UPDRSa

Dyskinesiab

Medicationb

Author

patients

(mo)

ADL (%)

Motor (%)

(%)

(%)

DBSPDSG (16)

96

6

44

51

58

37

Ostergaard

et al. (31)

26

12

66

64

86

19

Vesper et al. (27)

38

12

52

72

53

Anderson

et al. (21)

10

12

28

48

62

38

Pahwa et al. (36)

19

28

27

28

Significant

57

Kleiner-Fisman,

et al. (35)

25

30

24

41

80

36

Krause et al. (33)

27

30

17

44

70

30

Romito et al.(34)

15

24

68

50

Significant

64

Romito et al.(34)

13

36

65

49

Significant

52

Rodriguez-Oroz

et al. (23)

49

12

50

57

51

41

Rodriguez-Oroz

et al. (23)

49

36-48

43

50

59

34

Schupbach

et al. (32)

32

24

68

69

86

63

Schupbach

et al. (32)

30

60

40

54

79

58

Krack et al. (37)

43

12

66

66

71

59

Krack et al. (37)

42

36

51

59

71

63

Krack et al. (37)

42

60

49

54

71

63

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

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.

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

the one-year visit, at three to four years after implant, there was a worsening in UPDRS ADL and motor scores, gait, postural instability, and speech in the medication off/stimulation on condition although other than speech which was never improved, they were all still significantly improved compared to the baseline medication off state.

Two studies have reported five-year post-STN DBS outcomes (32,37). Schupbach et al. (32) examined 30 PD patients five years after STN DBS. They found that UPDRS ADL (40%) and motor scores (54%) as well as axial symptoms (43%) were significantly improved at five years in the medication off/stimulation on condition compared to the baseline medication off state. However, there was a significant worsening in each of these scores compared to the two-year assessment. Dyskinesia (79%) and levodopa equivalent dose (58%) were significantly reduced at five years and there were no significant changes in these variables throughout the five-year period. On the other hand, there was a significant worsening at five years in UPDRS mentation scores, Mattis Dementia Rating Scale scores, and frontal scores compared to baseline. Similarly, Krack et al. (37) examined 42 PD patients 60 months after bilateral STN DBS. In the medication off/stimulation on condition compared to baseline, there was a 54% improvement in UPDRS motor scores and a 49% improvement in UPDRS ADL scores. Significant improvements were seen for tremor (75%), rigidity (71%), akinesia (49%), postural instability (44%), gait (52%), writing (37%), and freezing (46%). Although significantly better than baseline, compared to the one-year visit, there was significant worsening in UPDRS motor and ADL scores, akinesia, gait, and freezing. However, there were sustained reductions in dyskinesia of 71% and daily levodopa equivalence dose of 63%.

In summary, STN DBS has been shown to control tremor, rigidity, bradykine-sia, and dyskinesia up to five years after surgery while allowing a significant reduction in antiparkinsonian medications. Although there is some deterioration over time, this appears to be related to the natural progression of the disease and the majority of symptoms remain improved compared to before surgery.

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