Parkinson's disease progression at 30 years: a study of subthalamic deep brain-stimulated patients

Abstract

Clinical findings in Parkinson's disease suggest that most patients progressively develop disabling non-levodopa-responsive symptoms during the course of the disease. Nevertheless, several heterogeneous factors, such as clinical phenotype, age at onset and genetic aspects may influence the long-term clinical picture. In order to investigate the main features of long-term Parkinson's disease progression, we studied a cohort of 19 subjects treated with subthalamic nucleus deep brain stimulation after >20 years of disease, reporting clinical and neuropsychological data up to a mean of 30 years from disease onset. This group of patients was characterized by an early onset of disease, with a mean age of 38.63 years at Parkinson's disease onset, which was significantly lower than in the other long-term subthalamic nucleus deep brain stimulation follow-up cohorts reported in the literature. All subjects were regularly evaluated by a complete Unified Parkinson's Disease Rating Scale, a battery of neuropsychological tests and a clinical interview, intended to assess the rate of non-levodopa-responsive symptom progression. Clinical data were available for all patients at presurgical baseline and at 1, 3 and 5 years from the subthalamic nucleus deep brain stimulation surgical procedure, while follow-up data after >7 years were additionally reported in a subgroup of 14 patients. The clinical and neuropsychological performance progressively worsened during the course of follow-up; 64% of patients gradually developed falls, 86% dysphagia, 57% urinary incontinence and 43% dementia. A progressive worsening of motor symptoms was observed both in 'medication-ON' condition and in 'stimulation-ON' condition, with a parallel reduction in the synergistic effect of 'medication-ON/stimulation-ON' condition. Neuropsychological data also showed a gradual decline in the performances of all main cognitive domains, with an initial involvement of executive functions, followed by the impairment of language, reasoning and memory. Thirty years after the disease onset, most patients presented non-levodopa-responsive symptoms, although the effect of both subthalamic nucleus deep brain stimulation and dopaminergic therapies still showed significant efficacy on the main disease cardinal features. Nevertheless, compared with other subthalamic nucleus deep brain stimulation follow-up studies, which included patients with a shorter disease duration at the time of surgery, a higher prevalence of axial and non-levodopa-responsive symptoms was observed in the long-term evaluations, confirming that several complex aspects underlie the development of non-motor symptoms and other features of Parkinson's disease progression, even in patients with an early disease onset and a prior long-lasting response to dopaminergic therapies.

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

“…Contrasting neuropsychological data have been reported on PD patients treated with STN-DBS: some studies suggested that cognitive outcomes might follow the natural history of the disease [5,28] , whereas others reported an increased risk of dementia early after surgery [29,30] .…”

l‐Dopa/carbidopa intestinal gel and subthalamic nucleus stimulation: Effects on cognition and behavior

“…Long‐term studies have shown that the proportion of STN‐DBS patients who converted to dementia was not different compared to those receiving medication at 2 years follow‐up (Zibetti et al., 2011). Overall, STN‐DBS does not seem to modify the cognitive evolution along the course of the disease (Rodriguez‐Oroz, Obeso, & Lang, 2005; Merola et al, 2011). …”

An International Survey of Deep Brain Stimulation Procedural Steps

“…The outcome of DBS for the treatment of these disorders has been reported. Specifically, results of DBS for PD have been published for randomized, controlled trials conducted in the USA [1], the UK [2], and Germany [3], demonstrating superiority in the improvement of quality of life as compared to best medical treatment [1], as well as long-term sustained efficacy of stimulation on most PD motor symptoms [4,5,6], for generalized and segmental dystonia [7,8,9] as well as for ET [10,11,12]. These clinically impressive outcomes have resulted in the procedure now being performed at many centers in a variety of countries.…”