Subthalamic DBS in Advanced Parkinson's Disease
Objectives: Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period.
Methods: In this study, we organised a 'retrospective control group' to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4–11).
Results: Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in 'OFF' and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in 'Medication-OFF' condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients.
Conclusions: To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.
Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) complicated by persistent motor fluctuations.
Several open studies described the medium and long-term effectiveness of STN-DBS on PD cardinal features, while no study investigated the long-term comparative efficacy of surgical and medical treatments. The only comparative data between STN-DBS and medical therapy arise from short-term studies with a follow-up duration comprised between 6 and 18 months. Moreover, any comparison with clinical data arising from PD natural history description could be misleading, as patients undergoing surgery usually represent a selected population of PD subjects, characterised by earlier age at onset, no cognitive impairment and an excellent response to dopaminergic therapies.
Nevertheless, a possible 'neuroprotective' effect of STN-DBS has been hypothesised, even though comparative long-term data versus conventional therapies can only be speculative. In this context, a particular methodological procedure was adopted in this study in order to evaluate STN-DBS and oral medical treatment over a long-term follow-up period: we assessed a series of PD patients selected for STN-DBS who did not undergo surgery for various reasons not closely related to PD (subject's lack of motivation or minor relative contraindications). These patients were assumed to be good candidates for a comparative study with a similar cohort of STN-DBS patients; indeed, both groups satisfied the strict CAPSIT-PD criteria, and all clinical and neuropsychological data were collected with the same methodological procedure.
The two groups, matched for all the main clinical features at baseline, were then compared after a mean follow-up period of 6 years (range 4–11).
Our main aims were: to compare the effects of long-term STN-DBS and oral levodopa treatment over PD main cardinal symptoms and motor fluctuations in order to test whether the reduction of oral levodopa doses and a more stable control of basal ganglia pathological circuitry may lead to a milder long-term outcome of PD symptoms, and to report comparative neuropsychological data between STN-DBS and oral levodopa treated patients, evaluating if a long-term STN-DBS stimulation may result in a different cognitive outcome.
Abstract and Introduction
Abstract
Objectives: Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period.
Methods: In this study, we organised a 'retrospective control group' to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4–11).
Results: Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in 'OFF' and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in 'Medication-OFF' condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients.
Conclusions: To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.
Introduction
Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) complicated by persistent motor fluctuations.
Several open studies described the medium and long-term effectiveness of STN-DBS on PD cardinal features, while no study investigated the long-term comparative efficacy of surgical and medical treatments. The only comparative data between STN-DBS and medical therapy arise from short-term studies with a follow-up duration comprised between 6 and 18 months. Moreover, any comparison with clinical data arising from PD natural history description could be misleading, as patients undergoing surgery usually represent a selected population of PD subjects, characterised by earlier age at onset, no cognitive impairment and an excellent response to dopaminergic therapies.
Nevertheless, a possible 'neuroprotective' effect of STN-DBS has been hypothesised, even though comparative long-term data versus conventional therapies can only be speculative. In this context, a particular methodological procedure was adopted in this study in order to evaluate STN-DBS and oral medical treatment over a long-term follow-up period: we assessed a series of PD patients selected for STN-DBS who did not undergo surgery for various reasons not closely related to PD (subject's lack of motivation or minor relative contraindications). These patients were assumed to be good candidates for a comparative study with a similar cohort of STN-DBS patients; indeed, both groups satisfied the strict CAPSIT-PD criteria, and all clinical and neuropsychological data were collected with the same methodological procedure.
The two groups, matched for all the main clinical features at baseline, were then compared after a mean follow-up period of 6 years (range 4–11).
Our main aims were: to compare the effects of long-term STN-DBS and oral levodopa treatment over PD main cardinal symptoms and motor fluctuations in order to test whether the reduction of oral levodopa doses and a more stable control of basal ganglia pathological circuitry may lead to a milder long-term outcome of PD symptoms, and to report comparative neuropsychological data between STN-DBS and oral levodopa treated patients, evaluating if a long-term STN-DBS stimulation may result in a different cognitive outcome.
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