STN-DBS ameliorates the cardinal symptoms of PD, including bradykinesia, rigidity, and tremors, and activities of daily living (ADL). It primarily ameliorates motor symptoms and ADL during drug off-periods, shortens drug off-periods, allows dose tapering, and ameliorates dyskinesia, and improves QOL (Limousin et al. 1998; Kumar et al. 1998, 1999; Burchiel et al. 1999; Moro et al. 1999; Molinuevo et al. 2000; Deep-Brain Stimulation for Parkinson’s Disease Study Group 2001; Pinter et al. 1999; Houeto et al. 2000; Katayama et al. 2001; Simuni et al. 2002; Herzog et al. 2003; Kleiner-Fisman et al. 2003; Krack et al. 2003; Rodriguez-Oroz et al. 2004). Kleiner-Fisman et al. (2006) performed a systematic review of 37 cohort studies including 921 cases and reported that UPDRS ADL scores (UPDRS-II) and motor scores (UPDRS-III) improved by 50 and 52 %, respectively, when comparing postoperative off-periods and stimulation on-periods and preoperative drug off-periods. Levodopa dosage, dyskinesia, and daytime off-periods decreased by 55.9, 69.1, and 68.2 %, respectively. A 34.5 % improvement was observed in the PD questionnaire (PDQ-39).

Till date, three randomized controlled trials have compared drug therapy alone with STN-DBS for advanced PD. Deuschl et al. (2006) divided 156 PD patients aged ≥75 years into an STN-DBS group (n = 78) and a drug therapy alone group (n = 78) and compared their prognoses after 6 months using PDQ-39 and UPDRS-III. These outcomes significantly improved in the STN-DBS group compared with those in the drug therapy alone group. Weaver et al. (2009) divided 255 PD patients into a DBS group [STN (n = 60) or GPi (n = 61)] and a drug therapy alone group (n = 134) and compared symptoms during the on-period after 6 months. Their results revealed improved on-periods without dyskinesia or motor function problems and improved QOL in the DBS group. However, adverse effects associated with the surgical procedure were observed, with serious adverse effects being more common in the DBS group. These studies observed STN-DBS over short 6-month periods, whereas the PD-SURG trial, a large randomized trial evaluating the role of surgery as therapy for PD, compared treatment outcomes and complications after 1 year. Williams et al. (2010) allocated 366 PD patients to surgery (n = 183; STN-DBS group: 174 patients) or drug therapy alone (n = 183) and assessed their PDQ-39 scores after 1 year (PD-SURG trial). Improvements in the PDQ-39 summary index, mobility domain, ADL domain, and bodily discomfort domain were significantly greater in the STN-DBS group than in the drug therapy alone group. Complications associated with surgery were observed in 36 patients, with one procedure-related death. Twenty patients in the STN-DBS group and 13 in the drug therapy group experienced serious adverse effects associated with PD. The results indicated that STN-DBS was more effective than drug therapy alone.

The primary effect of STN-DBS is a significant decrease in the off-period duration. The treatment also affects the on-period, although less significantly. In patients with marked motor fluctuations with a good preoperative on-period state, the good state can be maintained after DBS (see Fig. 7.3, Case A). Conversely, in patients with advanced PD who already exhibit a poor response to levodopa, good outcomes are unlikely despite a slightly improved response to DBS (see Fig. 7.3, Case B). This applies equally to the long-term, where off-period improvements are maintained for a comparatively long period. However, even if an improvement is seen in the on-period, levels quickly return to their preoperative state, and there is often a subsequent exacerbation (Deuschl et al. 2006; Rodriguez-Oroz et al. 2005; Moro et al. 2010).

Levodopa dosage or the levodopa-equivalent dosage can be decreased after STN-DBS (Tavella et al. 2002; Thobois et al. 2002; Vingerhoets et al. 2002). While the extent of dose reduction varies among reports, most state that STN-DBS can decrease the dosage of anti-PD drugs. However, this effect is not significant for GPi-DBS (Scotto di Luzio et al. 2001; Volkmann et al. 2001; Anderson et al. 2005; Minguez-Castellanos et al. 2005; Weaver et al. 2005; Valldeoriola et al. 2002). In addition, amelioration of levodopa-induced dyskinesia can be expected, which is thought to be due to decreased dyskinesia resulting from anti-PD dose reductions (Deuschl et al. 2006; Anderson et al. 2005; Weaver et al. 2005; Valldeoriola et al. 2002). A direct effect has also been reported (Katayama et al. 2006).

Several prospective studies with 3- to 5-year follow-up periods have examined the long-term effects of STN-DBS. Sustained improvements are observed in ADL, motor symptoms, rigidity, bradykinesia, and dose reductions (see Fig. 7.4) (Krack et al. 2003; Rodriguez-Oroz et al. 2005; Schüpbach et al. 2005; Østergaard and Aa Sunde 2006; Volkmann et al. 2009; Moro et al. 2010). The results of 8- or 10-year follow-ups have also been reported, and while tremors remain controlled in the long-term, there appears to be a decline in the effect on axial symptoms (Fasano et al. 2010; Castrioto et al. 2011).

DBS tends to be inadequate in patients with levodopa-resistant symptoms such as weakness, dysarthria, freezing of gait, and postural instability. Axial symptoms (particularly in the on-period) can be difficult to control. STN-DBS mainly ameliorates motor symptoms during the off-period (Deuschl et al. 2006; Anderson et al. 2005; Weaver et al. 2005), and axial symptoms such as postural instability and freezing of gait observed in the preoperative on-period often fail to ameliorate after surgery and appear during long-term follow-up of STN-DBS therapy (Welter et al. 2002; Tsai et al. 2009; Davis et al. 2006).

In a meta-analysis by St George at al. that was based on 11 articles, postural instability and gait disturbance deteriorated within 2 years, regardless of postoperative improvement, and tended to fall below preoperative levels (St George et al. 2010). In a 7-year follow-up reported by Muniz et al. (2010), freezing of gait (on initiation of walking) occurred more readily in the STN-DBS group than in the drug therapy alone group. In a study that examined the long-term effects of STN-DBS over 8–10 years, axial symptoms were the first to deteriorate (Fasano et al. 2010; Castrioto et al. 2011). Axial symptoms such as freezing and postural instability and related gait disturbance are motor symptoms that are difficult to control with STN-DBS, and their management is a topic for future study.