Long‐term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease

Abstract

We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group.

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…Mood problems are more common in patients treated with STN-DBS than those treated with GPi-DBS Follett et al, 2010;Moro et al, 2010;Bronstein et al, 2011). Although the underlying substrate of these side effects remains to be characterized, it has been suggested that they may be induced by stimulation in non-motor areas of STN or GPi, inadvertent involvement of limbic structures outside of the target regions (Bejjani et al, 1999;Krack and Vercueil, 2001;Kulisevsky et al, 2002;Romito et al, 2002;Herzog et al, 2003a;Okun et al, 2003;Stefurak et al, 2003), and preexisting psychiatric conditions (Lilleeng and Dietrichs, 2008).…”

“…Most neurosurgeons currently prefer the STN over the GPi as a target for DBS in PD, because of the perceived greater antiparkinsonian benefit of STN-DBS (Anderson et al, 2005;Moro et al, 2010). However, there is no clear evidence that the STN is, in fact, a better target than GPi.…”

Combining functional imaging with brain stimulation in Parkinson's disease

“…DBS of the GPi is also effective in improving motor function in PD patients (Follett et al, 2010;Moro et al, 2010). 18 F-FDG and positron emission tomography (PET) have revealed that the neural correlates of GPi-DBS in PD, as for the STN-DBS, are consistent with a stimulation-specifi c reduced expression of the PDRP, which was shown to correlate with clinical improvement (Fukuda et al, 2001b).…”

“…A few studies have suggested that this invasive stimulation may be effective in treating the symptoms of some motor disorders (Nguyen et al, 1998) and possibly to be effective for PD as well (Canavero et al, 2002(Canavero et al, , 2003Woolsey et al, 1979). However, other studies found no improvement (Moro et al, 2010). Cilia et al (2008) also observed only limited clinical benefi t using this stimulation technique, but using single photon emission tomography (SPECT), found signifi cant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, as well as left prefrontal areas and right thalamus.…”

“…This kind of stimulation has also been shown to alter the levels of the neurotransmitters involved in such neuronal defi cits (Strafella et al, 2001(Strafella et al, , 2004. To reach and stimulate subcortical areas that show an abnormal fi ring activity in PD, a surgical approach uses deep brain stimulation (DBS) to continuously apply electrical pulses that relieve PD motor symptoms (Krack et al, 2002;Moro et al, 2010), with variable effects on cognitive symptoms (Campbell et al, 2008). DBS can be applied in different subcortical targets, each with different effi cacy for symptom relief.…”