Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation.

OBJECTIVE To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS). METHODS Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms "off" and "on" levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality. RESULTS Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery ("on" dopamine/"on" STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score). CONCLUSIONS We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Stimulation bilatérale du noyau sous-thalamique (prédictibilité clinique et mécanismes neurophysiologiques dans la maladie de Parkinson)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Effets de la stimulation cérébrale profonde sur l’équilibre et la marche chez les patients atteints de la maladie de Parkinson : une revue systématique neurophysiologique

International audienceDeep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control.La stimulation cérébrale profonde du noyau sous-thalamique (NST) ou du globus pallidum interne (GPi) représente un traitement efficace des troubles moteurs de la maladie de Parkinson. Les effets de la stimulation cérébrale profonde (SCP) sur les troubles de la marche et de l’équilibre sont moins probants avec parfois une aggravation postopératoire du freezing de la marche et/ou des chutes. L’identification du circuit substantia nigra pas reticulata (SNr) – région locomotrice mésencéphalique (RLM), qui comprend le noyau pédunculopontin (NPP) comme ayant un rôle majeur dans le contrôle postural et la locomotion et de leur dysfonctionnement/lésion chez les patients parkinsoniens souffrant de troubles de la marche et de l’équilibre a permis d’envisager la SCP de ces régions cérébrales pour améliorer ces signes moteurs invalidants. Toutefois, les résultats cliniques ont été assez décevants. Dans cette revue, nous rapportons les effets de la SCP des ganglions de la base et du NPP sur les paramètres neurophysiologiques de la marche et du contrôle postural chez les patients parkinsoniens. En moyenne, la SCP du NST et du GPi améliore les paramètres locomoteurs et le contrôle postural en position statique, mais semble avoir peu ou pas d’effet sur le contrôle postural dynamique avec peut-être une aggravation, en particulier avec la SCP-NST. Inversement, la SCP de la SNr ou du PPN ne modifie pas les paramètres locomoteurs mais pourrait améliorer les ajustements posturaux anticipatoires et le contrôle postural dynamique

Does Bilateral Deep Brain Stimulation of the Subthalamic Nucleus Modify Ano‐Rectal Motility in Parkinson's Disease? Results of a Randomized Cross‐Over Study

International audienc

Age-related changes in the center of mass velocity control during walking.

International audienceDuring walking, the body center of mass oscillates along the vertical plane. Its displacement is highest at mid-swing and lowest at terminal swing during the transition to double support. Its vertical velocity (CoMv) has been observed to increase as the center of mass falls between mid- and late swing but is reduced just before double support. This suggests that braking of the center of mass is achieved with active neural control. We tested whether this active control deteriorates with aging (Experiment 1) and during a concurrent cognitive task (Experiment 2). At short steps of 0.4m but older subjects did so to a lesser extent. During the cognitive task, young subjects increased CoMv control (i.e. increase in CoMv braking) while maintaining step length and walking speed. Older subjects on the other hand, did not increase CoMv control but rather maintain it by reducing both step length and walking speed. These results suggest that active braking of the CoM during the transition to double support predominates in steps >0.4m. It could be a manifestation of the balance control system, since the braking occurs at late stance where body weight is being shifted to the contralateral side. The active braking mechanism also appears to require some attentional resource. In aging, reducing step length and speed are strategic to maintaining effective center of mass control during the transition to double support. However, the lesser degree of control in older adults indicates a true age-related deficit

Studying falls in real situations: Coupling subjective experience and biomarkers in the design of innovative methods

International audienc