Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson’s Disease: Effects on Cognition, Mood, Anxiety and Personality Traits

Abstract

Objective: To evaluate modifications occurring in cognitive functions and behavioural aspects in a group of 72 consecutive patients with Parkinson’s disease (PD) 15 months after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods: 72 consecutive PD patients bilaterally implanted for DBS of the STN were evaluated before and after surgery with a mean follow-up of 15 months. A neuropsychological assessment was performed to evaluate reasoning (Raven Colour Matrices), memory (Bisyllabic Word Repetition Test, Corsi’s Block-Tapping Test, Paired-Associate Learning) and frontal executive functions (Trail Making Test Part B, Nelson Modified Card Sorting Test, phonemic and category verbal fluency tasks). Mood and suicidal ideation were evaluated using the Beck Depression Inventory (BDI). Anxiety was measured by means of the State-Trait Anxiety Inventory and personality traits were evaluated with the Structured Clinical Interview for the DSM-III-R Axis II Disorders (SCID-II). Assessment of thought disorders and apathy was based on subitems of the Unified Parkinson’s Disease Rating Scale. Results: The comparisons between pre- and postoperative neuropsychological test scores showed a significant worsening only in phonemic and semantic verbal fluency tasks, while fewer errors were found in the Nelson Modified Card Sorting Test. Globally, behavioural assessment evidenced a small improvement in mood, as assessed by the BDI, in obsessive-compulsive and paranoid personality traits (SCID-II). Thought disorders worsened while suicidal ideation, anxiety and apathy showed no postoperative modifications. The analysis of individual outcomes (±1 SD criterion) evidenced a relevant postoperative cognitive decline in 3 patients out of 65 (4.5%). Moreover, following implantation, 1 patients exhibited psychosis (1.5%), 2 patients experienced a clinically relevant worsening of depressive symptoms (3%), 7 patients showed an increase in anxiety (12%) and 3 patients a worsening in depression and anxiety symptoms (3%). On the contrary, 12 patients (20%) showed a relevant improvement in mood and 14 patients (23%) a relevant reduction of anxiety symptoms after the surgery. Conclusions: The present study confirms that STN DBS is cognitively safe since the only relevant change observed was a mild decrease in verbal fluency tasks. Globally, a small postoperative improvement was found in the BDI, and in two SCID-II subscales concerning obsessive-compulsive and paranoid personality traits, even though postoperative behavioural disturbances can occur in individual patients.

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

“…Both STN-and GPi-DBS can have non-motor side effects, especially affecting verbal fluency, cognition and mood (Kumar et al, 1999a, b;Dujardin et al, 2001;Schupbach et al, 2005;Smeding et al, 2005Smeding et al, , 2006Smeding et al, , 2011Castelli et al, 2006;De Gaspari et al, 2006, Merello et al, 2008. 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).…”

“…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). Although almost half patients with DBS experience variable degrees of cognitive changes (Higginson et al, 2009), these deficits become 'relevant' in less than 10% treated patients (Castelli et al, 2006;Tir et al, 2007). However, because DBS is now widely used, even for patients with early PD in some centers, these adverse effects remain a major concern.…”

“…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). Although significant unpleasant mood side effects following STN or GPi DBS are relatively rare (Funkiewiez et al, 2004;Castelli et al, 2006;Tir et al, 2007), their occurrence significantly disrupts patients' quality of life.…”

Different outcomes of phonemic verbal fluency in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation

“…It has been proven that DBS suppresses motor symptoms and reduces the total dose of the antiparkinsonian drugs 2,3 . Among the adverse effects of STN-DBS in patients with PD, the postoperative decline in verbal fluency is well documented 4,5,6,7,8,9,10,11 . However, there are fewer studies about the effect of the stimulation per se, comparing on-and off-stimulation conditions 12,13,14 .…”

“…Also, the majority of previous studies pointed to a negative effect of STN-DBS on verbal fluency when they studied postsurgical patients 22 . Some of the studies on pre-and post-DBS have found a decline in phonemic fluency 5,7,10 , others a decline in semantic fluency 6 and still others in both verbal fluency tasks 4,8,9 .…”