Clinical and neurophysiological assessment of DBS frequency

Deep brain stimulation is a surgical treatment for patients with advanced Parkin son’s disease whose symptoms have become challenging to control with available drug therapy. It involves implanting electrodes bilaterally into the subthalamic nu clei and then connecting them to a stimulator placed under the skin in the thoracic area. Several stimulation parameters can be adjusted to produce the best clinical effect, namely: frequency, pulse width, and voltage. After several years of DBS, many patients develop postural instability, gait, and speech disorders. Those prob lems have been attributed to disease progression. Nevertheless, recent studies have shown that they might improve using a lower frequency of stimulation than the one commonly used. We have decided to conduct this thesis to try to understand better the role of the DBS frequency. We looked at the effect of 80Hz vs. 130Hz. We have per formed four studies exploring different domains. Fifteen patients were randomized in a cross-over trial to receive 3 weeks of stimulation at 80 Hz and 130 Hz. Study 1 was dedicated to assessing the motor outcome, which showed that: a) overall clinical scores were unchanged and stable throughout the trial, b) proximal and complex movements were slightly improved at 80Hz, but more distal movements were improved at 130 Hz. Study 2 analyzed the cognitive aspects and showed an improvement of 80 Hz on phonetic fluency but not on semantic fluency. Study 3: looked at the neurophysiological aspects: various paradigms assessed cortical ex citability by transcranial magnetic stimulation (TMS): short intracortical inhibition ended up being more physiological at 130Hz. Study 4 was performed to compare saccades and antisaccades’ performances at 80 and 130Hz, respectively. 21 patients and 16 matched healthy controls (HC) were enrolled: saccades were facilitated at 80Hz instead of 130Hz; however, more errors were seen

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

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Evaluation précoce de la maturation cérébrale chez des enfants prématurés et des enfants nés à terme à l'aide de l'imagerie par résonance magnétique

Nous avons étudié, par imagerie par résonance magnétique, l'impact d'une naissance prématurée sur la maturation cérébrale. Nous avons comparé, à la naissance puis à 40 semaines, 15 enfants prématurés en bonne santé, nés entre 29 et 34 semaines de gestation. Nous les avons ensuite comparés à un groupe contrôle de 12 enfants nés à 40 semaines. Nous avons mesuré le volume des compartiments cérébraux par segmentation : matière grise, blanche myélinisée et non-myélinisée et les ganglions de la base (globaux et relatifs). Le volume cérébral global, la matière grise et la matière blanche myélinisée augmentent de taille, en revanche la matière blanche non-myélinisée diminue entre les deux examens dans le groupe prématuré. Il n'y pas de différence significative entre les enfants prématurés à l'âge du terme et le groupe contrôle. En conclusion, les prématurés nés entre 29 et 34 semaines n'ont pas de retard radiologique de la maturation cérébrale

Stimulation cérébrale profonde : trajectoire du patient

An eligibility assessment for deep brain stimulation is performed in order to select patients who are likely to benefit from it. Parkinson's patients have to stop dopaminergic drugs the day before surgery. During the operation, the patient must remain awake for recording of neuronal activity and for test stimulations to optimize the position of the electrodes. Postoperatively, the stimulation is increased progressively in parallel with a decrease of dopaminergic treatments. After about ten days, the patient can return to home and controls continue as an outpatient. Three months postoperatively, a complete testing of the neurostimulator is performed and at the one year follow-up visit, the effectiveness of the DBS is assessed

Modeling of Electric Fields in Individual Imaging Atlas for Capsular Threshold Prediction of Deep Brain Stimulation in Parkinson's Disease: A Pilot Study.

Background: Modeling of deep brain stimulation electric fields and anatomy-based software might improve post-operative management of patients with Parkinson's disease (PD) who have benefitted from subthalamic nucleus deep brain stimulation (STN-DBS). Objective: We compared clinical and software-guided determination of the thresholds for current diffusion to the pyramidal tract, the most frequent limiting side effect in post-operative management of STN-DBS PD patients. Methods: We assessed monopolar reviews in 16 consecutive STN-DBS PD patients and retrospectively compared clinical capsular thresholds, which had been assessed according to standard clinical practice, to those predicted by volume of tissue activated (VTA) model software. All the modeling steps were performed blinded from patients' clinical evaluations. Results: At the group level, we found a significant correlation (p = 0.0001) when performing statistical analysis on the z-scored capsular thresholds, but with a low regression coefficient (r = 0.2445). When considering intra-patient analysis, we found significant correlations (p < 0.05) between capsular threshold as modeled with the software and capsular threshold as determined clinically in five patients (31.2%). Conclusions: In this pilot study, the VTA model software was of limited assistance in identifying capsular thresholds for the whole cohort due to a large inter-patient variability. Clinical testing remains the gold standard in selecting stimulation parameters for STN-DBS in PD

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