Long-Term Follow-Up of Deep Brain Stimulation in Parkinson’s Disease

ABSTRACT & COMMENTARY

By Claire Henchcliffe, MD

Synopsis: Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson’s disease after some 6-12 months of treatment.
Source: Rodriguez-Oroz MC, et al. Bilateral Deep Brain Stimulation in Parkinson’s Disease: A Multicentre Study With 4 Years Follow-Up. Brain. June 23, 2005; (Epub ahead of print).
Rodriguez and colleagues prospectively studied 69 patients with advanced Parkinson’s disease (PD) over a 3- to 4-year period, after bilateral deep brain stimulation (DBS) at 8 centers in Europe and Canada. Stimulation site depended on investigator judgment, rather than randomization, with the subthalamic nucleus (STN) targeted in 49 subjects and the globus pallidus internus (GPi) in 20. Mean age in the STN group was similar (STN: 59.8; range, 38-75 years; GPi: 55.8; range, 43-70 years), and mean disease duration was 15.4 years in each group. Baseline motor scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor subscale were similar, but baseline scores for dyskinesias on medication were higher in the GPi group (2.83 ± 1.18 on a UPDRS subscale 1-4) than the STN group (1.95 ± 1.07). The STN group took more levodopa equivalents (1336 ± 619 mg/day) than the GPi group (1074 ± 462 mg/day) prior to surgery. Primary outcome measure was change in UPDRS motor subscale off medication, on stimulation at 3 to 4 years postoperatively, compared to baseline. Both groups maintained substantial improvements (STN: 56.7 ± 15.7 to 28.6 ± 15.7, P < 0.001; GPi: 51.7 ± 13.6 to 31.7 ± 12.8, P < 0.001). However, gait, postural stability, and speech subscales significantly declined at 3 to 4 years in the STN group, despite improvement at 1 year. In contrast, changes in the GPi group were not statistically significant. Dyskinesias on medication improved in both groups (STN: 1.95 ± 1.07 to 0.80 ± 0.78; GPi: 2.83 ± 1.18 to 0.68 ± 0.75). Levodopa equivalent intake was reduced from mean 1309 ± 649 to 859 ± 659 mg/day in the STN group at one year, with no further significant change at the end of the study. However, GPi patients’ daily levodopa equivalents did not significantly change. Persistent adverse effects were reported in 53% and 35% of the STN and GPi groups, respectively. Twelve STN patients suffered cognitive decline (8 rated moderate-severe), compared to 1 GPi patient (mild), and 3 STN patients had mood disturbances not reported in GPi patients. Nine STN patients suffered dysphonia or dysarthria, compared to 1 GPi patient. Six from the STN group and 1 from the GPi group required repeat surgery for lead fracture, skin erosion, or infection, and 2 patients discontinued DBS therapy due to infection.

Commentary

This important article demonstrates maintenance of benefit for DBS of both STN and GPi targets at 3 to 4 years post-procedure in the UPDRS motor subscale for a highly selected group of PD patients with advanced disease. Off periods and dyskinesias were dramatically reduced, as in previous short-term studies. Krack and colleagues recently published their experience with STN stimulation at 5 years follow up.1 They similarly demonstrated that, despite maintenance of benefit for classic levodopa-responsive features of PD, speech deficits and postural instability gradually accrued in patients treated with STN DBS. In the present study, Rodriguez-Oroz and colleagues found that GPi-stimulated patients fared better for speech, postural stability, and gait, and additionally had a better adverse event profile than STN patients. Unfortunately, with lack of randomization, it is likely that particular subpopulations of PD patients were selected for the 2 target sites. Moreover, GPi patients required more levodopa after surgery (possibly as dyskinesias ameliorated, allowing correction of prior under-medication): therefore, off scores at 12 hours after medication withdrawal could appear better because of long-term medication effects. Although not designed as a head-to-head comparison of STN and GPi as targets for DBS, these findings clearly require further study to clarify their potential clinical significance regarding target choice in individual PD patients. Finally, despite careful patient screening, significant cognitive decline and mood disturbances were noted in a subset of patients. These non-motor symptoms are common in elderly patients, and it is imperative we better understand their relationship to DBS.

References

1. Krack P, 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.

2. Oxman MN, et al. A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. N Eng J Med. 2005;352:2271-2284.