Effects of deep brain stimulation frequency on eye movements and cognitive control

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson's Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes

Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.

OBJECTIVE: To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A-ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). METHODS: Cross-modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype-phenotype correlations, 3D-protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. RESULTS: Fifty-nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross-sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild-to-moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: -0.81/year). Explorative sample size calculations indicate that ≥48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. INTERPRETATION: This study provides a deeper understanding of the disease, and paves the way toward large-scale natural history studies and treatment trials in COQ8A-ataxia. ANN NEUROL 2020;88:251-263

Amotivational behavioral syndrome in Parkinson’s disease : clinical correlates and role of dopamine and chronic stimulation of the subthalamic nucleus

La maladie de Parkinson (MP) est une maladie à expression neuropsychiatrique. Le syndrome comportemental amotivationnel incluant l'apathie, l'anxiété et la dépression est fréquent dans la MP et altère de manière significative la qualité de vie des patients. L'objectif de cette thèse était de mieux caractériser le syndrome comportemental amotivationnel, de préciser ses corrélats cliniques et ses relations avec le traitement dopaminerglque et la stimulation chronique bilatérale des noyaux subthalamiques (NST). Notre premier travail a montré que la fatigue était fortement corrélée au syndrome comportemental amotivationnel et qu'elle pouvait être considérée comme un symptôme de cette triade neuropsychiatrique. Notre deuxième travail a étudié l'effet de l'asymétrie des signes moteurs sur la survenue de troubles des comportements motivés. Ce travail a mis en évidence un pattern comportemental distinct selon la latéralisation initiale des signes moteurs. Dans un troisième travail, nous avons montré que la survenue d'une apathie post-opératoire était dépendante du profil préopératoire des patients, de la gestion post-opératoire du traitement dopaminergique et de la stimulation cérébrale profonde. En cas d'apathie motivationnelle, les patients bénéficiaient d'un effet concomitant du traitement dopaminergioue et de la stimulation des portions limbiques du NST gauche. En cas d'apathie cognitive, les patients ne bénéficiaient ni des effets du traitement dopaminergique, ni de ceux de la stimulation cérébrale profonde.Parkinson's disease (PD) is a neuropsychiatrie condition. The amotivational behavioral syndrome, which includes apathy, anxiety and depression is frequently encountered and impairs life quality. Our aim was to better characterize the amotivational behavioral syndrome of PD, to specify its clinical correlates and its association with i) dopaminergic treatment and ii) bilateral deep brain stimulation (DBS) of the subthalamic nucleus (SN). We showed that fatigue was strongly correlated with the amotivational behavioral syndrome and could be considered a symptom of this neuropsychiatrie triad. In a second work we studied relationship between motor signs asymmetry and bahavioral signs. We demonstrated that motor signs asymmetry was associated with an imbalance between approach and avoidance behaviors. In the third part, we showed that postoperative apathy was related to baseline PD profile, but also with postoperative dopaminergic drug and DBS management. In case of motivational apathy, PD patients may benefit from the combined effect of dopaminergic drugs and stimulation within the limbic part of the left STN. In case of cognitive apathy, PD patients did not benefit from either postoperative dopaminergic drug or STN DBS managemen

Bilan de 10 ans de consultations mémoire en région Franche-Comté : description et analyse des données de la base RAPID relatives à la première consultation diagnostique

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Geospatial analysis of individual-based Parkinson's disease data supports a link with air pollution: a case-control study

Background: The etiology of Parkinson’s disease (PD) remains unknown. To approach the issue of PD’s risk factors from a new perspective, we hypothesized that coupling the geographic distribution of PD with spatial statistics may provide new insights into environmental epidemiology research. The aim of this case-control study was to examine the spatial dependence of PD prevalence in the Canton of Geneva, Switzerland (population=474,211). Methods: PD cases were identified through Geneva University Hospitals, private neurologists and nursing homes medical records (n=1,115). Controls derived from a population-based study (n=12,614) and a comprehensive population census dataset (n=237,771). All individuals were geographically localized based on their place of residence. Spatial Getis-Ord Gi* statistics were used to identify clusters of high versus low disease prevalence. Confounder-adjustment was performed for age, sex, nationality and income. Tukey's honestly significant difference was used to determine whether nitrogen dioxide and particulate matters PM10 concentrations were different within PD hotspots, coldspots or neutral areas. Results: Confounder-adjustment greatly reduced greatly the spatial association. Characteristics of the geographic space influenced PD prevalence in 6% of patients. PD hotspots were concentrated in the urban centre. There was a significant difference in mean annual nitrogen dioxide and PM10 levels (+3.6 µg/m3 [p<0.001] and +0.63 µg/m3 [p<0.001] respectively) between PD hotspots and coldspots. Conclusion: PD prevalence exhibited a spatial dependence for a small but significant proportion of patients. A positive association was detected between PD clusters and air pollution. Our data emphasize the multifactorial nature of PD and support a link between PD and air pollution

Diagnostic précoce de la maladie d’Alzheimer : l’arbre qui cache la forêt ?

National audienc

Mouvements anormaux aux urgences

Contrairement à la plupart des affections des ganglions de la base, qui évoluent généralement sur un mode lentement progressif, certains mouvements anormaux peuvent se développer sur un mode aigu ou subaigu, amenant les patients à consulter en urgence. Le diagnostic est souvent délicat. Il repose sur une analyse détaillée de la phénoménologie et une anamnèse médicamenteuse fouillée, dans la mesure où ces situations sont volontiers iatrogènes. Une identification correcte du problème permet souvent une thérapeutique efficace. Le présent article propose une mise au point de trois problématiques de ce type, à savoir la dystonie aiguë, la chorée aiguë et les complications aiguës que l’on peut observer dans la maladie de Parkinson. Chaque sujet est illustré par un cas clinique

Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer’s Disease and Its Impact on Self-Rated Quality of Life and Caregiver’s Burden

International audienceAlzheimer’s disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD

Left Prefrontal Repetitive Transcranial Magnetic Stimulation in a Logopenic Variant of Primary Progressive Aphasia: A Case Report

International audienc

Maladie de Parkinson au stade avancé : indication aux traitements complexes

Advanced Parkinson's disease (PD) is characterized by severe motor and non-motor complications that negatively impact on patients' autonomy and health-related quality of life. In early disease, the therapeutic strategy consists of gradual increase in dopaminergic treatment and levodopa dose fragmentation. In more advanced stages, this approach becomes insufficient and three therapeutic options can be considered: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, and continuous levodopa/carbidopa intestinal gel infusion