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: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: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:ObjectivesThe aim of this study was to report a case of levodopa-induced ocular dyskinesia in an early-onset Parkinson disease patient and to investigate the pathogenic gene.MethodsWe report the case of a 49-year-old male patient with a 13-year history of Parkinson disease. Involuntary eye movements were noticed after treatment with amantadine for limb dyskinesias. Levodopa-induced ocular dyskinesias involving repetitive, transient, and stereotyped rightward deviations of gaze appeared after intake of an antiparkinsonian drug. Limb dyskinesias also occurred simultaneously. We used a next-generation sequencing targeted gene panel and found a heterozygous missense mutation (p.R535H) in GBA. Direct Sanger sequencing verified the missense mutation.ConclusionsWe report the case of an uncommon early-onset PD patient carrying a GBA mutation presenting ocular dyskinesia. Genetic screening may provide a better mechanistic insight into dyskinesias.
Project description:INTRODUCTION:Deep 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. METHODS:PET 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). RESULTS:The 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. CONCLUSIONS:The 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: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: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:BackgroundGait disturbances have emerged as some of the main therapeutic concerns in late-stage Parkinson's disease (PD) treated with dopaminergic therapy and deep brain stimulation (DBS). External cues may help to overcome freezing of gait (FOG) and improve some of the gait parameters.AimTo evaluate the effect of 3D visual cues and STN-DBS on gait in PD group.MethodsWe enrolled 35 PD patients treated with DBS of nucleus subthalamicus (STN-DBS). Twenty-five patients (5 females; mean age 58.9 ±6.3) and 25 sex- and age-matched controls completed the gait examination. The gait in 10 patients deteriorated in OFF state. The severity of PD was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY). The PD group filled the Falls Efficacy Scale-International (FES) and Freezing of Gait Questionnaire (FOGQ). Gait was examined using the GaitRite Analysis System, placed in the middle of the 10m marked path. The PD group was tested without dopaminergic medication with and without visual cueing together with the DBS switched ON and OFF. The setting of DBS was double-blind and performed in random order.ResultsThe UPDRS was 21.9 ±9.5 in DBS ON state and 41.3 ±13.7 in DBS OFF state. HY was 2.5 ±0.6, FES 12.4 ±4.1 and FOGQ 9.4 ±5.7. In the DBS OFF state, PD group walked more slowly with shorter steps, had greater step length variability and longer duration of the double support phase compared to healthy controls. The walking speed and step length increased in the DBS ON state. The double support phase was reduced with 3D visual cueing and DBS; the combination of both cueing and DBS was even more effective.ConclusionCueing with 3D visual stimuli shortens the double support phase in PD patients treated with DBS-STN. The DBS is more effective in prolonging step length and increasing gait speed. We conclude that 3D visual cueing can improve walking in patients with DBS.
Project description:Classic antiglomerular basement membrane (anti-GBM) disease is an exceedingly rare but extremely aggressive form of glomerulonephritis, typically caused by autoantibodies directed against cryptic, conformational epitopes within the noncollagenous domain of the type IV collagen alpha-3 subunit. Pathologic diagnosis is established by the presence of strong, diffuse, linear staining for immunoglobulin on immunofluorescence microscopy. Recently, patients with atypical clinical and pathologic findings of anti-GBM disease have been described. These patients tend to have an indolent clinical course, without pulmonary involvement, and laboratory testing rarely reveals the presence of anti-GBM antibodies. Specific guidelines for the treatment and management of these patients are unclear. Here, we describe a case of atypical anti-GBM disease in a young child who presented with hematuria and prominent proteinuria. Throughout the course of his illness, creatinine remained normal. He was conservatively treated with steroids and rituximab, resulting in resolution of his clinical symptoms and normalization of laboratory findings.