Neuropsychological Effects of Deep Brain Stimulation in Subjects with Early Stage Parkinson's Disease in a Randomized Clinical Trial

Abstract

Background: Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial.Objective: The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. Methods: Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. Results: Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. Conclusions:The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

Deep-brain stimulation for Parkinson's disease: current perspectives on patient selection with an emphasis on neuropsychology

“…7 In the EARLYSTIM trial, Deuschl et al 1 by Mesnage et al supported the notion that early intervention can prevent motor handicap and adverse reactions to levodopa from interfering with socioprofessional integration and family life. 80 Although early intervention appears to be associated with minimal neuropsychological morbidity, 81 several cautionary points were raised by Mestre et al about DBS early in the disease course. 82 Risks of early treatment include potentially operating on persons with atypical parkinsonism, less benefit to risk ratio for surgery in younger patients, doing DBS despite the fact that mild motor complications could remain stable for several years, potentially higher postsurgical suicide risk in younger patients, and that the long disease course in younger persons raises the risk of potential complications, such as hardware malfunction.…”

Estimulación cerebral profunda en enfermedad de Parkinson

“…En un ensayo clínico aleatorizado pero con una muestra limitada de 30 pacientes se comparó el tratamiento farmacológico solo versus ECP-F y se encontró que en el grupo sometido a ECP-F ocurrieron dos efectos adversos (evento cerebrovascular y hardware infectado) y una disminución en cuanto a la fluidez verbal (p = 0,047), aunque al compararlo con el grupo de solo terapia farmacológica no hay diferencia significativa si se excluyen estos efectos adversos (a los 12 meses de seguimiento: p = 0,066 y a los 24 meses: p = 0,096) (85). Otro estudio con el mismo número de pacientes al anterior y con EP temprana, encontró que al comparar la seguridad de la terapia farmacológica con la ECP-F, este segundo grupo requirió menos medicación antiparkinsoniana durante todo el estudio y que a 24 meses no hubo empeoramiento de la función motora (86).…”

Some Clinically Useful Information that Neuropsychology Provides Patients, Carepartners, Neurologists, and Neurosurgeons About Deep Brain Stimulation for Parkinson's Disease

“…There are now many studies examining neurobehavioral outcomes after DBS: these studies generally compare the pre- and post-operative performance of patients on several neuropsychological tests. Because many studies are either not randomized and/or have small samples, and most use overlapping but not identical test batteries, the focus on this paper is on meta-analyses (characteristics in Table 2 ) that report on outcomes in cognitive and behavioral domains (Table 3 ) or individual tests (Table 4 ) supplemented by recent findings of either large RCTs ( Odekerken et al, 2015 ; Rothlind et al, 2015 ) or well controlled studies not covered by the recent meta-analyses ( Foki et al, 2017 ; Tramontana et al, 2015 ; Tröster et al, 2017 ).…”

“…In addition to these meta-analyses and qualitative reviews, probably the two largest and well-designed RCT comparisons of STN and GPi (VA CSP-468 and NSTAPS) ( Odekerken et al, 2013 , 2015 ; Rothlind et al, 2015 ) and three other controlled studies of STN DBS have recently published detailed neuropsychological follow-up analyses ( Foki et al, 2017 ; Tramontana et al, 2015 ; Tröster et al, 2017 ). The two STN and GPi comparisons are especially useful as they attempt to determine whether reliable changes occur by minimizing multiple comparisons and using multivariate comparisons and/or reliable change methods.…”

“…One small, controlled trial is of importance because it examined the neuropsychological effects of bilateral STN DBS in 15 patients who were “early” in the course of the disease (treated with antiparkinsonian medication for 6 months—4 years) and in a group of 15 early PD patients undergoing BMT ( Tramontana et al, 2015 ). The STN DBS group showed greater declines at 12 months in phonemic fluency, digit span, and on the Stroop task, and lesser gains on the Wisconsin Card Sorting Test (WCST perseverative errors) and some trials of the Paced Auditory Serial Addition test (PASAT).…”