Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: The COMPARE Trial

Abstract

Objective There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD). Methods Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off ) at 7 months. Results Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre- to post-DBS in the optimal setting (Hotelling's T2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less “happy”, less “energetic” and more “confused” when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets. Interpretations There were no significant differences in in the co-primary outcome measures of mood and cognition between STN and GPi in the optimal DBS state.. However, adverse mood effects were noted when stimulating ventrally to the optimal site in both targets. Furthermore, a worsening for letter verbal fluency was noted in the 3 non-optimal post-DBS states in the STN target only. The persistence of deterioration in verbal fluency in the off DBS state at 7 months is, suggestive of a surgical rather than a stimulation-induced effect at the STN target. STN and GPi DBS resulted in similar motor improvement.

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Stimulation of the sensorimotor STN or GPi between 30 and 100 Hz is relatively ineffective for parkinsonian features, while benefit is seen around 100 Hz and above, using stimulation amplitudes of 2-4 V and pulse widths of 60-90 μs. The available data indicate that both STN and GPi DBS in patients with PD relieve tremor, rigidity, and bradykinesia [216][217][218][219][220][221], and may improve gait and postural control in some patients [222].…”

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

“…Verbal fluency and cognition problems are more often seen in old patients (Hariz et al, 2000;Saint-Cyr et al, 2000;Funkiewiez et al, 2004;Smeding et al, 2011), or in those with poor cognition or depression at baseline (De Gaspari et al, 2006). Specific cognition deficits include impairments of working memory (Saint-Cyr et al, 2000;Higginson et al, 2009;Okun et al, 2009), cognitive processing, visuo-spatial skills and setshifting (Saint-Cyr et al, 2000;Alegret et al, 2001), response inhibition (Witt et al, 2004), or the decoding of facial expressions (Dujardin et al, 2004;Schroeder et al, 2004;Biseul et al, 2005;Drapier et al, 2008). Even when present, the impact of changes in verbal fluency on the quality of life appears to be relatively small (Alegret et al, 2004;Morrison et al, 2004;Montel and Bungener, 2009;Zahodne et al, 2009).…”

“…There is evidence that DBS may also worsen depression and mania, increase apathy, affect emotional lability, and increase the risk of suicide (Berney et al, 2002;Doshi et al, 2002;Okun et al, 2003Okun et al, , 2009Funkiewiez et al, 2004;Smeding et al, 2005Smeding et al, , 2006Drapier et al, 2008;Voon et al, 2008). 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).…”

Depression and Anxiety Following Deep Brain Stimulation in Parkinson’s Disease: Systematic Review and Meta-Analysis

“…[6][7][8] On the other hand, several studies found no significant adverse psychiatric outcomes following DBS in PD. [9][10][11] Accurate knowledge on this theme is paramount, as several authors have demonstrated that non-motor symptoms (NMS), namely depression and anxiety, impact significantly on the quality of life and illness-related distress of PD patients. [12][13][14] In fact, the importance of NMS in PD led to the recent proposal of an integrated assessment approach as part of the clinical routine.…”