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Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN‐DBS) and best medical treatment (BMT) was superior to BMT alone. Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN‐DBS and BMT over 2 years, and secondary outcomes included non‐speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician‐ and patient‐reported assessments. Methods: STN‐DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation—for STN‐DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN‐DBS and BMT groups from baseline to 24 months. Results: Over the 2‐year period, changes in speech intelligibility and MPT, as well as patient‐reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN‐DBS and BMT groups, on medication and OFF STN‐DBS, with patients in the STN‐DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN‐DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. Conclusion: At this early stage of the patients' disease, STN‐DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient‐reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is the most common movement disorder. Its pathophysiology is only partially understood. Here, we leveraged graph theoretical analysis on structural covariance patterns quantified from morphometric estimates for cortical thickness, surface area, and mean curvature in patients with ET before and one year after (to account for delayed clinical effect) ventro-intermediate nucleus (Vim) stereotactic radiosurgical thalamotomy. We further contrasted the observed patterns with those from matched healthy controls (HCs). Significant group differences at the level of individual morphometric properties were specific to mean curvature and the post-/pre-thalamotomy contrast, evidencing brain plasticity at the level of the targeted left thalamus, and of low-level visual, high-level visuospatial and attentional areas implicated in the dorsal visual stream. The introduction of cross-correlational analysis across pairs of morphometric properties strengthened the presence of dorsal visual stream readjustments following thalamotomy, as cortical thickness in the right lingual gyrus, bilateral rostral middle frontal gyrus, and left pre-central gyrus was interrelated with mean curvature in the rest of the brain. Overall, our results position mean curvature as the most relevant morphometric feature to understand brain plasticity in drug-resistant ET patients following Vim thalamotomy. They also highlight the importance of examining not only individual features, but also their interactions, to gain insight into the routes of recovery following intervention. [ABSTRACT FROM AUTHOR]

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide., Author(s): Ludwig Kappos [1]; Giancarlo Comi [2]; Hillel Panitch [3]; Joel Oger [4]; Jack Antel [5]; Paul Conlon [6]; Lawrence Steinman (corresponding author) [7]; Giancarlo Comi [8, 24]; Ludwig Kappos [...]

In Parkinson's disease (PD), the effects of both Ldopa and subthalamic deep brain stimulation (STN-DBS) are known to change cost-valuation. However, this was mostly studied through reward-effort task involving distal movements, while axial effort, less responsive to treatments, have been barely studied. Thus, our objective was to compare the influence of both Ldopa and STN-DBS on cost-valuation between two efforts modalities: vowel production (as an example of axial movement) and hand squeezing (as an example of distal movement). Twelve PD patients were recruited to participate in this study. The task consisted in deciding whether to accept or reject trials based on a reward-effort trade-off. Participants performed two blocks with hand squeezing, and two with vowel production, in the four treatment conditions (LdopaOn/Off; STN-DBS On/Off). We found that STN-DBS changed the ratio difference between hand and phonation efforts. Vowel production effort was estimated easier to perform with STN-DBS alone, and harder when associated with Ldopa. The difference between hand and phonation efforts was correlated with quality of life in Off/Off and On Ldopa alone conditions, and with impulsive assessment On STN-DBS alone. We highlighted that STN-DBS could introduce an imbalance between the actual motor impairments and their subjective costs. With this finding, we also suggest paying particular attention to the different treatment effects that should be expected for axial and distal movement dysfunctions. [ABSTRACT FROM AUTHOR]

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot's targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim's circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile. [ABSTRACT FROM AUTHOR]

Objective: We aim to search for predictors of survival among clinical and brain 18F-FDG positron emission tomography (PET) metabolic features in our cohort of patients with multiple system atrophy (MSA).Methods: We included patients with a 'probable' MSA diagnosis for whom a clinical evaluation and a brain PET were performed early in the course of the disease (median 3 years, IQR 2-5). A retrospective analysis was conducted using standardised data collection. Brain PET metabolism was characterised using the Automated Anatomical Labelling Atlas. A Cox model was applied to look for factors influencing survival. Kaplan-Meier method estimated the survival rate. We proposed to develop a predictive 'risk score', categorised into low-risk and high-risk groups, using significant variables entered in multivariate Cox regression analysis.Results: Eighty-five patients were included. The overall median survival was 8 years (CI 6.64 to 9.36). Poor prognostic factors were orthostatic hypotension (HR=6.04 (CI 1.58 to 23.12), p=0.009), stridor (HR=3.41 (CI 1.31 to 8.87), p=0.012) and glucose PET hypometabolism in the left insula (HR=0.78 (CI 0.66 to 0.92), p=0.004). Good prognostic factors were time to diagnosis (HR=0.68 (CI 0.54 to 0.86), p=0.001) and use of selective serotonin reuptake inhibitor (SSRI) (HR=0.17 (CI 0.06 to 0.46), p<0.001). The risk score revealed a 5-year gap separating the median survival of the two groups obtained (5 years vs 10 years; HR=5.82 (CI 2.94 to 11.49), p<0.001).Conclusion: The clinical prognosis factors we have described support published studies. Here, we also suggest that brain PET is of interest for prognosis assessment and in particular in the search for left insula hypometabolism. Moreover, SSRIs are a potential drug candidate to slow the progression of the disease. [ABSTRACT FROM AUTHOR]

Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor Constantin Tuleasca gratefully acknowledges receipt of a "Young Researcher in Clinical Research Award" (Jeune Chercheur en Recherche Clinique) from the University of Lausanne (UNIL), Faculty of Biology and Medicine (FBM) and the Lausanne University Hospital (CHUV). Finally, the right intracalcarine cortex and the left orbitofrontal cortex showed a shorter average path length in ET patients, while the left frontal operculum and the right planum polare showed a higher betweenness centrality in ET patients. In fact, using task-based fMRI, Archer et al. ([2]) provided evidence of a widespread visually sensitive functional network, including extrastriate areas V3 and V5, that relates to tremor severity in patients with essential tremor (ET). [Extracted from the article]

A growing number of studies postulate the use of music to improve motor control in patients with Parkinson's disease (PD). The effects of music are greatly variable from one individual to the other and do not always reach the expected benefits. This study aimed to optimize the use of music in the management of movement disorders inherent to PD in a handwriting task. We developed and tested musical sonification (MS), a method that transforms in real‐time kinematic variables into music. Twelve patients with PD, on medication, and 12 healthy controls were recruited in a pretest/training/posttest design experiment. Three training sessions were compared, for which participants were asked to produce graphomotor exercises: one session with music (unrelated to handwriting), one with MS (controlled by handwriting), and one in silence. Results showed that the performance in training was better under MS than under silence or background music, for both groups. After training, the benefits of MS were still present for both groups, with a higher effect for PD patients than for control group. Our results provide a proof of concept to consider MS as a relevant auditory guidance strategy for movement rehabilitation in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Effects of DBS on freezing of gait and other axial signs in PD patients are unclear.Objective: Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM-trial).Methods: One hundred twenty-four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item-14 of the UPDRS-II at baseline and follow-up. The posture, instability, and gait-difficulty subscore of the UPDRS-III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication-off and medication-on conditions.Results: Fifty-two percent in both groups had freezing of gait at baseline based on UPDRS-II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months (P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group (P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group (P < 0.01) in both medication-off and medication-on conditions.Conclusions: Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication-off condition compared to best medical treatment in these patients. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is frequently associated with behavioral disorders, particularly within the spectrum of motivated behaviors such as apathy or impulsivity. Both pharmacological and neurosurgical treatments have an impact on these impairments. However, there still is controversy as to whether subthalamic nucleus deep brain stimulation (STN-DBS) can cause or reduce impulsive behaviors.Objectives: We aimed to identify the influence of functional surgery on decision-making processes in PD.Methods: We studied 13 PD patients and 13 healthy controls. The experimental task involved squeezing a dynamometer with variable force to obtain rewards of various values under four conditions: without treatment, with l-dopa or subthalamic stimulation alone, and with both l-dopa and subthalamic stimulation. Statistical analyses consisted of generalized linear mixed models including treatment condition, reward value, level of effort, and their interactions. We analyzed acceptance rate (the percentage of accepted trials), decision time, and force applied.Results: Comparatively to controls, patients without treatment exhibited lower acceptance rate and force applied. Patients under l-dopa alone did not exhibit increased acceptance rate. With subthalamic stimulation, either with or without added l-dopa, all measures were improved so that patients' behaviors were undistinguishable from healthy controls'.Conclusions: Our study shows that l-dopa administration does not fully restore cost-benefit decision-making processes, whereas STN-DBS fully normalizes patients' behaviors. These findings suggest that dopamine is partly involved in cost-benefit valuation, and that STN-DBS can have a beneficial effect on motivated behaviors in PD and may improve certain forms of impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Abstract: Impulse control disorders (ICDs) have received increased attention in Parkinson's disease (PD) because of potentially dramatic consequences. Their physiopathology, however, remains incompletely understood. An overstimulation of the mesocorticolimbic system has been reported, while a larger network has recently been suggested. The aim of this study is to specifically describe the metabolic PET substrate and related connectivity changes in PD patients with ICDs. Eighteen PD patients with ICDs and 18 PD patients without ICDs were evaluated using cerebral 18F‐fluorodeoxyglucose positron emission tomography. SPM‐T maps comparisons were performed between groups and metabolic connectivity was evaluated by interregional correlation analysis (IRCA; p < .005, uncorrected; k > 130) and by graph theory (p < .05). PD patients with ICDs had relative increased metabolism in the right middle and inferior temporal gyri compared to those without ICDs. The connectivity of this area was increased mostly with the mesocorticolimbic system, positively with the orbitofrontal region, and negatively with both the right parahippocampus and the left caudate (IRCA). Moreover, the betweenness centrality of this area with the mesocorticolimbic system was lost in patients with ICDs (graph analysis). ICDs are associated in PD with the dysfunction of a network exceeding the mesocorticolimbic system, and especially the caudate, the parahippocampus, and the orbitofrontal cortex, remotely including the right middle and inferior temporal gyri. This latest area loses its central place with the mesocorticolimbic system through a connectivity dysregulation. [ABSTRACT FROM AUTHOR]