Project description:In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments "but not higher-level exploration patterns" are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits.
Project description:BackgroundSubthalamic nucleus deep brain stimulation improves motor symptoms and fluctuations in advanced Parkinson's disease, but the degree of clinical improvement depends on accurate anatomical electrode placement. Methods used to localize the sensory-motor part of the nucleus vary substantially. Using microelectrode recordings, at least three inserted microelectrodes are needed to obtain a three-dimensional map. Therefore, multiple simultaneously inserted microelectrodes should provide better guidance than single sequential microelectrodes. We aimed to compare the use of multiple simultaneous versus single sequential microelectrode recordings on efficacy and safety of subthalamic nucleus stimulation.MethodsSixty patients were included in this double-blind, randomized study, 30 in each group. Primary outcome measures were the difference from baseline to 12 months in the MDS-UPDRS motor score (part III) in the off-medication state and quality of life using the Parkinson's Disease Questionnaire-39 (PDQ-39) scores.ResultsThe mean reduction of the MDS-UPDRS III off score was 35 (SD 12) in the group investigated with multiple simultaneous microelectrodes compared to 26 (SD 10) in the single sequential microelectrode group (p = 0.004). The PDQ-39 Summary Index did not differ between the groups, but the domain scores activities of daily living and bodily discomfort improved significantly more in the multiple microelectrodes group. The frequency of serious adverse events did not differ significantly.ConclusionsAfter 12 months of subthalamic nucleus stimulation, the multiple microelectrodes group had a significantly greater improvement both in MDS-UPDRS III off score and in two PDQ-39 domains. Our results may support the use of multiple simultaneous microelectrode recordings.Trial registrationhttp://ClinicalTrials.gov Identifier: NCT00855621 (first received March 3, 2009).
Project description:The aims of this study were to assess the incidence rate and risk factors for sialorrhea in the long-term follow-up in a cohort of 132 patients with advanced Parkinson's disease [88 with deep brain stimulation (DBS) and 44 on medical treatment]. The incidence rate of sialorrhea did not differ between the two groups; male sex, Hoehn and Yahr stage and dysphagia resulted risk factors for sialorrhea. These findings indicate that DBS does not increase the risk of developing sialorrhea.
Project description:IntroductionDeep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism.MethodsPET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67 ± 7).ResultsThe patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism.ConclusionsThe present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.
Project description:PurposeTo study the effect of STN-DBS on balance performance of Parkinson's disease.Method16 idiopathic PD patients treated with bilateral STN-DBS (DBS Group) and 20 PD patients treated with Levodopa (Medicine group) were included in the study. Clinical material including Levodopa Equivalent Daily Dose (LEDD, mg/day), life quality (PDQ-39) were collected. For DBS group and Medicine group, The motor disability (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale Ⅲ, MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS) and the Limits of Stability (LoS) (target acquisition percentage, trunk swing angle standard deviation, time) in state of Med-Off/Med-On at preoperation, postoperation, 6 months postoperation and 12 months postoperation were evaluated. Repeated ANOVA was used to analyze the effect of STN-DBS on balance performance.ResultThe Clinical material (age, gender, duration, LEDD preoperation, PDQ39), motor disability (Med-on/Med-Off), balance performance (Med-on/Med-Off) and LoS preoperation had no differences in DBS-group and Medical-group (P>0.05). During the follow up, LEDD, PDQ39, Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) in Medicine-group had no significant changes in both Med-Off and Med-On. For DBS-group, immediately improvement of motor disability (MDS-UPDRSIII), LoS (target acquisition percentage, trunk swing angle standard deviation, time) and LEDD were observed postoperation (P<0.05); PDQ39, balance performance (MDS-UPDRS 3.12, BBS) began to improve at 6 months and 12 months postoperation. Repeated ANOVA showed that DBS could significantly improve the motor disability, balance performance and LoS in PD.ConclusionSTN-DBS could improve the balance performance of PD patients in H&Y3.
Project description:Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD.
Project description:ObjectiveDeep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment option in Parkinson's disease with motor and non-motor fluctuations allowing for postoperative reduction of dopaminergic medication. However, evidence is scarce on optimal medication adjustments following STN-DBS implantation. Opicapone allows for long-lasting inhibition of the catechol-O-methyltransferase (COMT) thereby enabling more constant dopaminergic stimulation compared to levodopa alone. However, especially COMT inhibitors are regularly discontinued after STN-DBS surgery. In this single-centre retrospective analysis, we aimed to analyse the clinical phenotype of patients selected for opicapone treatment following STN-DBS implantation and to define clinical determinants of patients requiring more intense dopamine-stabilising strategies after STN-DBS implantation.MethodsA patient cohort treated with STN-DBS + levodopa + opicapone (n = 16) was compared to an age-matched control cohort without opicapone treatment at baseline before and ≥ 5 months post-surgery. As main outcomes we assessed the MDS-UPDRS III and IV scores and reduction of the cumulative dopaminergic medication quantified by the levodopa equivalent dosages (LED).ResultsWhilst the MDS-UPDRS III (median [min - max]) in patients with STN-DBS as well as anatomical electrode positions did not differ significantly between the opicapone 20 [4-40] and control cohort 14 [1-44], the patients selected for opicapone treatment showed a significantly higher degree of dyskinesias already preoperatively as reflected by a UPDRS-IV A subscore of 2 [0-4] compared to controls 0 [0-4]. Postoperatively, the opicapone cohort showed stronger motor fluctuations MDS-UPDRS IV 6 [0-14] compared to the controls 0 [0-10], albeit without statistical significance. Moreover, the opicapone cohort showed significantly less reduction of dopaminergic medication (-36.4 % vs. -46.2 % in the control cohort) following STN-DBS implantation independent from the intake of dopamine agonists.ConclusionThese results indicate a clinical phenotype characterised by more motor fluctuations requiring a more stable dopamine replacement therapy to address the patients' disease biology. In these cases, levodopa + COMT inhibition by opicapone represents a therapeutic approach but determination of the potential clinical benefit requires further prospective studies.
Project description:ObjectivesTo study whether 60-Hz stimulation, compared with routine 130 Hz, improves swallowing function and freezing of gait (FOG) in patients with Parkinson disease (PD) who undergo bilateral subthalamic nucleus (STN) deep brain stimulation (DBS).MethodsWe studied 7 patients with PD who experienced FOG that persisted despite routine 130-Hz stimulation and dopaminergic medication. Each patient received 3 modified barium swallow (MBS) studies in a single day under 3 DBS conditions in the medication-on state: 130 Hz, 60 Hz, or DBS off, in a randomized double-blind manner. The laryngeal penetration and aspiration events were cautiously assessed, and a swallowing questionnaire was completed. The Unified Parkinson's Disease Rating Scale, Part III motor score, axial subscore, tremor subscore, and FOG by a questionnaire and stand-walk-sit test were also assessed. The best DBS condition (60 Hz here) producing the least FOG was maintained for 3 to 8 weeks, and patients were assessed again. Changes in measurements between the 60 Hz and 130 Hz were analyzed using paired t test, with swallowing function as primary and the remainder as secondary outcomes. Changes between other DBS conditions were further explored with Bonferroni correction.ResultsCompared with the routine 130 Hz, 60-Hz stimulation significantly reduced aspiration frequency by 57% on MBS study and perceived swallowing difficulty by 80% on questionnaire. It also significantly reduced FOG, and axial and parkinsonian symptoms. The benefits at 60-Hz stimulation persisted over the average 6-week assessment.ConclusionsCompared with the routine 130 Hz, the 60-Hz stimulation significantly improved swallowing function, FOG, and axial and parkinsonian symptoms in patients with PD treated with bilateral STN-DBS, which persisted over the 6-week study period.Classification of evidenceThis study provides Class IV evidence that for patients with PD who experience FOG, STN-DBS at 60 Hz decreases aspiration events observed during MBS compared with DBS at 130 Hz.