Acute and Chronic Mood and Apathy Outcomes from a Randomized Study of Unilateral STN and GPi DBS

Abstract

ObjectiveTo study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD).BackgroundThere are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.MethodsA standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed.ResultsThirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases.ConclusionsThere were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates

“…However there was steady worsening in mood and anxiety at 2, 4, 6 and 12 months compared to baseline when combining the STN and GPi groups. Furthermore, the changes in LEDD did not correlate with changes in mood or UPDRS II scores in both groups [43] or with QOL at 1 year post STN DBS in another study [44]. Similarly we did not find a correlation between LEDD and Q-LES in our cohort, but we observed significant positive correlation between the change in LEDD and change in BDI scores in all patients but not in TNM(+) subgroup.…”

“…Taken together, these observations suggest that the aggressive medication reduction after STN DBS can lead to levodopa agonist withdrawal which could unmask an underlying mesolimbic hypodopaminergic vulnerability state [40] and manifest as psychiatric symptoms (reviewed in [41, 42]. To test this intriguing concept, Okun et al [43] compared the effect of slow reduction in LEDD on psychiatric side effects following unilateral STN (n=16) and GPi DBS (n=14). No significant differences were found between the two targets in mood, anxiety or motor outcomes.…”

La Enfermedad de Parkinson: Etiología, Tratamientos y Factores Preventivos

“…Esta última recibe el nombre de estimulación cerebral profunda (ECP o DBS, por sus iniciales en inglés). Los criterios de inclusión y los parámetros de estimulación para pacientes parkinsonianos que reciben ECP varían ampliamente de acuerdo a cada valoración neurológica en particular, pero se ha utilizado exitosamente para cuadros de trastorno obsesivo compulsivo (Benabid & Torres, 2012;Kopell & Greenberg, 2008;Rezai, 2009), epilepsia (Jaseja, Gupta, Jain, & Gupta, 2014;Van et al, 2015;Mottonen et al, 2016), depresión (Cusin & Dougherty, 2013;Okun et al, 2014;Berlim, McGirr, Van den Eynde, Fleck, & Giacobbe, 2014;Quraan et al, 2014;Lilleeng, Gjerstad, Baardsen, Dalen, & Larsen, 2015;Williams et al, 2016) & Beuls, 2004;Sakas et al, 2007;Larson, 2008;Marks, Honeycutt, Acosta, & Reed, 2009).…”

“…Si se desea subir o mantener estable la dosis diaria de L-Dopa, ECP-GPi es una mejor opción (Okun & Foote, 2010). Por otro lado, ECP-NST parece tener mayor efectividad en el control de síntomas motores en Parkinson mientras ECP-GPi tiene mayor efectividad en la reducción de disquinesia (Okun et al, 2014;Nowacki et al, 2015;Murchison, Fletcher, & Cheeran, 2016). Sin embargo, efectos secundarios, tales como déficits cognoscitivos, dificultades de habla, desequilibrio y depresión, se presentan en mayor proporción en ECP-NST comparado con ECP-GPi (Lezcano et al, 2003;O'Sullivan & Pell, 2009).…”

Comments on the paper “Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson’s disease: a meta-analysis of randomized controlled trials”

“…Second, in their analysis (eg, Figure 3, the subgroup of 6 months), the authors pooled Zahodne et al’s3 and Okun et al’s4 studies that describe data from the COMPARE NIH trial 5. Therefore, the pooling of these studies in the same meta-analysis model will double the weight of patients of the COMPARE trial, leading to imprecise effect estimates.…”