Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants

Abstract

Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinson's disease. Prospective studies have shown that although the beneficial effects of this procedure are maintained at 5 years, axial motor features and cognitive decline may occur in the long term after the implants. In order to address some unsolved questions raised by previous studies, we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years. The overall motor improvement reported at 5 years (55.5% at Unified Parkinson's Disease Rating Scale-motor part, P < 0.001 compared with baseline) was only partly retained 3 years later (39%, P < 0.001, compared with baseline; -16.5%, P < 0.01, compared with 5 years), with differential effects on motor features: speech did not improve and postural stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle worsening of motor features, a dramatic impairment in functional state (-56.6% at Unified Parkinson's Disease Rating Scale-Activities of Daily Living, P < 0.01) emerged after the fifth year of stimulation. The present study did not reveal a predictive value of preoperative levodopa response, whereas few single features at baseline (such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose) could predict long-term motor outcome. A decline in verbal fluency (slightly more pronounced than after 5 years) was detected after 8 years. A significant but slight decline in tasks of abstract reasoning, episodic memory and executive function was also found. One patient had developed dementia at 5 years with further progression at 8 years. Executive dysfunction correlated significantly with postural stability, suggesting interplay between axial motor deterioration and cognition. Eight years after surgery, no significant change was observed on scales assessing depression or anxiety when compared with baseline. At 8 years, there was no significant increase of side-effects when compared with 5-year follow-up. In conclusion, deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up. However, the global benefit partly decreases later in the course of the disease, due to progression of Parkinson's disease and the appearance of medication- and stimulation-resistant symptoms.

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

“…Our findings agree with what observed in other studies [6], [7] and [8], and could be chiefly explained by the progression of the disease over time [16]. While the cardinal PD symptoms keep on improving with stimulation, there is a progressive emerging of poorly levodopa-responsive symptoms, mainly axial symptoms, speech problems and postural instability.…”

“…STN-DBS efficacy on PD motor symptoms is well documented in the short-and medium-term, up to 5-6 years [4] and [5], while a few papers with a small number of examined patients addressed the long-term efficacy of this procedure [6], [7] and [8].…”

“…Recently, three series have further expanded the time-length of the follow-up, showing that the effect of STN-DBS on motor symptoms persists after 8-10 years of continuous stimulation [6], [7] and [8]; however, the patients showed a progressive decline in activities of daily living (ADL), consistent with the progression of disease.…”

Subthalamic deep brain stimulation: clinical and neuropsychological outcomes in mild cognitive impaired parkinsonian patients

“…In fact, longterm follow-up studies on STN-DBS treated patients [5,7] demonstrated that stimulation efficacy could be limited by the progressive development of neuropsychological alterations, even though few data have been reported on the long-term STN-DBS outcomes in relation to the baseline cognitive performances. The majority of follow-up studies focused only on patients reaching the long-term evaluation, without considering subjects who developed dementia or died after a variable period of time after DBS.…”

Neurostimulation for Parkinson's Disease with Early Motor Complications

“…[2][3][4] Because levodopa-responsive parkinsonian symptoms are improved by high-frequency stimulation of the subthalamic nucleus, 5,6 neurostimulation has become an established treatment for advanced Parkinson's disease with medically intractable fluctuations and dyskinesia [7][8][9][10] and has shown long-term efficacy. [11][12][13] It is typically used after the disease has been present for 11 to 13 years, 7-10 when quality of life, social adjustment (psychosocial competence), 14 and professional activity are already severely impaired. Neurostimulation improves quality of life, [7][8][9][10] in addition to motor symptoms.…”