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International audience; Background: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is usually associated with a poor response to antiseizure medications. We focused on MTLE-HS patients who were seizure free on medication to: (1) determine the clinical factors associated with seizure freedom and (2) develop a machine-learning classifier to better earlier identify those patients.Methods: We performed a retrospective, multicentric study comparing 64 medically treated seizure-free MTLE-HS patients with 200 surgically treated drug-resistant MTLE-HS patients. First, we collected medical history and seizure semiology data. Then, we developed a machine-learning classifier based on clinical data.Results: Medically treated seizure-free MTLE-HS patients were seizure-free for at least 2 years, and for a median time of 7 years at last follow-up. Compared to drug-resistant MTLE-HS patients, they exhibited: an older age at epilepsy onset (22.5 vs 8.0 years, p < 0.001), a lesser rate of: febrile seizures (39.0% vs 57.5%, p = 0.035), focal aware seizures (previously referred to as aura)(56.7% vs 90.0%, p < 0.001), autonomic focal aware seizures in presence of focal aware seizure (17.6% vs 59.4%, p < 0.001), dystonic posturing of the limbs (9.8% vs 47.0%, p < 0.001), gestural (27.4% vs 94.0%, p < 0.001), oro-alimentary (32.3% vs 75.5%, p < 0.001) or verbal automatisms (12.9% vs 36.0%, p = 0.001). The classifier had a positive predictive value of 0.889, a sensitivity of 0.727, a specificity of 0.962, a negative predictive value of 0.893.Conclusions: Medically treated seizure-free MTLE-HS patients exhibit a distinct clinical profile. A classifier built with readily available clinical data can identify them accurately with excellent positive predictive value. This may help to individualize the management of MTLE-HS patients according to their expected pharmacosensitivity.

International audience; Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial.Methods: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events.Results: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed.Conclusions: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Background While transient loss of consciousness is a frequent presenting symptom, differential diagnosis between syncope and epilepsy can be challenging. Misdiagnosis of epilepsy leads to important psychosocial consequences and eliminates the opportunity to treat patient’s true condition. Case summary A 39-year-old woman presenting with recurrent seizures since her childhood was referred to neurological consultation. Electroencephalograms (EEGs) and magnetic resonance imaging previously performed were normal. A sleep-deprived video-EEG was performed and highlighted after 12 h of sleep deprivation a progressive dropping of the heart rate followed by a complete heart block without ventricular escape rhythm and asystole for about 30 s. Her EEG recording later showed diffuse slow waves traducing a global cerebral dysfunction and suffering. The diagnosis of vaso-vagal syncope with predominant cardioinhibitory response was made and a dual-chamber pacemaker with rate-drop response algorithm was implanted. After a 2 years of follow-up, the patient remained free of syncope. Discussion Patients presenting with loss of consciousness and convulsion are often diagnosed with epilepsy despite normal EEGs. In patients presenting with recurrent seizures with unclear diagnosis of epilepsy or in a situation of drug-resistant epilepsy, syncope diagnosis should always be considered and a risk stratification is necessary. The benefit of pacemaker implantation in patients with recurrent vaso-vagal syncope is still very controversial. Only patients presenting with spontaneous asystole should be considered for pacemaker implantation in case of recurrent vaso-vagal syncope.

Objective The aim of this study was to determine the success rate of sEEG in locating the epileptogenic zone (EZ) in patients with pharmaco-resistant epilepsy. Secondary objectives were to analyze sEEG-related morbidity and outcomes for post-sEEG thermocoagulation and cortical resection. Methods Data were collected on 49 sEEGs from 46 consecutive patients between 2010 and 2018. Following sEEG, either resective or palliative surgery with vagus nerve stimulation was performed. In 8 patients, EZ thermocoagulation was performed before EEG leads were withdrawn. Outcomes were collected based on the Engel and ILAE outcome scales. Results sEEG was contributive in 45 of 49 recordings, with a success rate of 92% in locating the EZ. Minor complications, such as transient neurologic deficit and electrode implantation failures, occurred in 6%. One major complication occurred, with death due to atypical late hematoma. Thermocoagulation was performed in 8 patients and stopped or significantly reduced seizure frequency in 7 (88%). Outcome of surgical resection (n = 33) was good, with 20 (61%) seizure-free patients and 32 (97%) with definite improvement. Conclusions Our findings suggest that sEEG is an effective technique for EZ location in patients with drug-resistant epilepsy. sEEG was contributive in up to 92% of patients, allowing thermocoagulation and/or surgical resection that resulted in seizure-freedom in two-thirds and seizure-reduction in one-third of cases. This study highlights the need for strict selection of implantation candidates, with strong initial hypothesis as to EZ location.

Anterior sagittal imbalance (ASI) is a severity factor in spinal pathology. Stabilometric study of the dynamic position of the center of pressure (CoP) assesses orthostatic control. These analyses provide the energy expenditure used for this control.Stabilometric signs are associated with ASI indicate increased energy expenditure.Healthy male volunteers were subjected to reversible ASI induced by wearing a kyphotic thermoformed thoracolumbar corset. The deformation was assessed by C7 tilt on EOS whole-spine views. Static and dynamic posturographic force platform study was performed under conditions of anteroposterior and mediolateral instability. Mean CoP position (XThe corset significantly increased C7 tilt (p0.0001). This did not significantly change mean CoP positions (XPosturographic parameters were impacted by inducing ASI in healthy subjects. Significant differences were seen in stabilography, CE and LAS, were greater on dynamic testing, and correlated with radiologic sagittal balance. Force platforms can reveal increased energy expenditure in maintaining posture.II; Single-center prospective study involving healthy volunteers.

Degenerative processes induce loss of lumbar lordosis and anterior sagittal imbalance (ASI). Optoelectronic study provides kinematic analysis of movement and can also detect ASI. The aim of the present study was to assess gait kinematic modifications induced by ASI.Thirty-five healthy male volunteers were subjected to reversible ASI induced by wearing a kyphotic thermoformed thoracolumbar corset. The deformation was assessed by C7 tilt on EOS (EOS Imaging, Paris, France) full-spine views. Ten optoelectronic gait recordings were made with corset and 10 without. Gait kinematic parameters (stride length, walking speed, rhythm), gait balance parameters (center of mass braking index, stride width, double support time) and spinal sagittal balance parameters (C7T10S1, C7´S1' and spinal angles) were averaged. Adjusted analysis distinguished direct ASI impact from locomotor factors.The corset-induced ASI produced +15° change in C7 tilt (P0.0001), -7.4° in C7T10S1 (P0.0001), +66.2 mm in C7´S1' (P0.0001), and +13.1° in spinal angle (P0.0001). Radiographic and optoelectronic data correlated significantly. Stride length (P0.0001) and rhythm (P = 0.0003) were significantly reduced, contributing to a reduction in walking speed (P0.0001), and strongly influencing double support time (β = -0.38; 95% confidence interval [CI]: -0.69; -0.06). Center of mass braking index was significantly reduced (P0.0001) and significantly influenced by ASI (β = -0.51; 95% CI: -0.78; -0.28). Stride width was significantly increased by ASI (P0.0001), independently of rhythm and stride length.ASI induced by a kyphotic corset was detectable on the optoelectronic system, leading to significant changes in gait kinematics. Locomotor parameters were significantly reduced. Balance parameters were significantly and directly altered by ASI.

Objectives Given the need to detect subclinical changes in brain health that sometimes occur with aging in apparently healthy older adults, we assessed whether bimanual gesture imitation performance, simple to assess clinically, can detect age effects and alterations in cognition, olfaction, and movement. Design Cross-sectional study. Setting Baltimore Longitudinal Study of Aging. Participants Men and women, aged 22 to 101 years, without cognitive impairment, dementia, stroke, Parkinson disease, resting tremor, abnormal muscle tone, or abnormal coordination (N = 507). Measurements Bimanual gesture imitation was measured using a test validated in older adults. We assessed (1) cognition, including verbal memory, executive function, attention, visuospatial ability, visuoperceptual speed, and language; (2) manual dexterity with the Purdue Pegboard Test; (3) olfaction, using the 16-item Sniffin' Sticks Identification Test; (4) upper extremity motor function, using a computer-based finger tapping test; and (5) lower extremity motor function, including 6-meter usual and rapid gait speeds, 400-meter walk time, Health ABC Physical Performance Battery, and total standing balance time. Cross-sectional associations between bimanual gesture imitation performance and each measure were examined using linear regression after adjustment for age, sex, race, education, and body mass index. Models with mobility measures also adjusted for height. Results Higher gesture imitation performance was associated with younger age. After adjustment, a worse score was associated with worse olfaction, executive function, and visuospatial ability. Gesture imitation score was not associated with other cognitive measures or motor function. Conclusion In persons without clinically detectable neurological conditions, poor bimanual gesture imitation is associated with other indicators of brain health, including olfaction and selected cognitive function domains. Bimanual gesture imitation may be useful clinically to detect subtle brain changes in apparently healthy older adults. J Am Geriatr Soc 67:2581-2586, 2019.

Background While ankle muscles, highly affected by aging, are highly implicated in the changes in gait kinematics and involved in the limitation of seniors' mobility, whether neuromuscular electrical stimulation (NMES) training of these muscles could impact gait kinematics in older adults has not been investigated yet. Research question What are the effects of 12 weeks of ankle plantar and dorsiflexors NMES training on strength and gait kinematics in healthy older adults? Methods Fourteen older adults (73.6 ± 4.9 years) performed a three-time per week, three months long NMES training of both ankle plantar and dorsiflexors. Before and after training, neuromuscular parameters, gait kinematic parameters, and daily physical activity were measured. Results The participants significantly increased their lower limb muscle mass and their plantar and dorsiflexors isometric strength after training. They reduced the hip abduction/adduction and the pelvic anterior tilt range of motion and variability during gait. However, the participants became less active after the training. Significance NMES training of ankle muscles, by increasing ankle muscle mass and strength,modified gait kinematics. NMES training of ankle muscles is feasible and effective to lower the hip implication and increment foot progression angle during gait. Further study should determine if this could lower the risk of falling.

Resume Objectifs Evaluer l’efficacite de la rTMS « a large champ » dans la fibromyalgie. Une evaluation multidimensionnelle a ete realisee avec pour critere de jugement principal l’echelle numerique de la douleur et criteres secondaires les scores FIQ, MFI-20, HAD et WPI - SSS. Methodologie Essai clinique monocentrique ouvert, realise en neurophysiologie chez des patients atteints de fibromyalgie consultant au Centre d’evaluation et traitement de la douleur du CHU de Rouen entre novembre 2014 et juin 2016. Les patients etaient inclus sur la base du FIRST, des criteres ACR 1990 et ACR 2010. Les donnees etaient recueillies sur autoquestionnaires a j1, j7, j15 et j30 (EN douleur, scores FIQ, HAD, MFI-20 et WPI–SSS). Un examen clinique avec recherche des points de Yunus etait realise a j1 et j30. Trois seances de stimulations magnetiques transcrâniennes, espacees sur 5 a 8 jours, ont ete realisees pour chaque patient. Les seances comprenaient 30 stimulations, renouvelees 3 fois, soit 90 stimulations par seances. Resultats Vingt-et-un patients ont ete inclus. L’EN douleur, le FIQ et le HAD anxiete etaient significativement ameliores a j7 (respectivement p = 0,004, p = 0,007 et p = 0,049) et cette efficacite persistait jusqu’a j30. L’amelioration de la douleur portait a la fois sur les caracteristiques affectives et sensorielles au QDSA evalue a j30 ( p = 0,02). Le WPI etait significativement ameliore a j7 ( p = 0,049) mais cette efficacite disparaissait au cours du suivi. L’amelioration du MFI etait retardee par rapport aux stimulations (j30, p = 0,04) ainsi que l’amelioration du score HAD depression (j15, p = 0,007 et j30, p = 0,049). Conclusion La rTMS « a large champ » permet une amelioration des patients fibromyalgiques dans les multiples dimensions etudiees. Un essai clinique randomise controle devrait etre realise pour confirmer les resultats preliminaires.

Background Idiopathic Parkinson’s disease (IPD) has a long preclinical phase. Research question This study assesses data on prediagnostic markers of IPD from a longitudinal, natural history study of aging. Methods Participants were selected from the database of the Baltimore Longitudinal Study of Aging, and included 10 prediagnosed IPD cases (eight men and two women) and 30 age and sex matched healthy controls. Patients with prediagnosed IPD had already had an assessment for IPD 2.6 ± 1.3 years (range 1.0–5.3 years) before the actual diagnosis, including: gait speed (six-meter corridor walk), spatio-temporal gait parameters using Vicon motion capture, balance, upper-limb motor skills, neuropsychological profile, and non-motor symptoms. Results Prediagnosed IPD cases compared to controls had slower gait speed (Δ=-0.13 m.s−1, p = 0.03) due to shorter step length (Δ=−5 cm, p = 0.004), worse visuospatial ability (card rotation test, Δ=-42, p = 0.0001) and worse executive function (category fluency test, Δ=-2.6, p = 0.04). Significance Our findings identify dimensions that merit further study as prediagnostic markers of Idiopathic Parkinson’s disease to identify patients who might benefit from future neuroprotective therapy in order to delay, or prevent, clinical manifestations.

Parkinson's disease (PD) is known to have a long prodromal stage due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta over the course of many years without clinical manifestations of PD. When the diagnosis is made, the neuropathological process is already well entrenched. Consequently, identifying individuals during this prodromal period could be very helpful for future trials of neuroprotective or disease-modifying therapies, which might slow or prevent the degeneration of dopaminergic neurons. Thus, efforts are needed to determine appropriate early markers of PD. Gait and balance disorders are frequent during the early stages of PD. This systematic review aims to determine if gait and balance disorders occur before the diagnosis of PD and if so, whether they could be used as markers of preclinical PD. Findings reveal that, at the presymptomatic stage of PD, impaired basal ganglia function leads to disorders in gait and balance. Both clinical and instrumental assessments allow early detection of these disorders, particularly when performed under challenging conditions (e.g. dual-task). Among all studied parameters, temporal gait variability and arm kinematics appear to be promising markers of preclinical PD.

Background Ano-rectal motility impairment is often observed during Parkinson's disease (PD), generating symptoms as constipation and/or incontinence with impaired quality of life. Subthalamic nuclei (STN) deep brain stimulation (DBS) improves motor symptoms of PD, but its effects on anorectal motility are unknown. This study aimed to assess the effects of STN-DBS on the anorectal motility in PD patients, in a randomized cross-over study. Methods Sixteen PD patients with bilateral STN-DBS for at least 6 months were included. The anal resting pressure, duration and maximal amplitude of squeeze effort, recto-anal inhibitory reflex, maximal tolerable rectal volume, and anal pressure during defecation effort were measured and compared after STN-DBS was switched OFF and then ON for 2 hours, or vice-versa, in a randomized order. Key results STN-DBS increased maximal amplitude of anal squeezing pressure (OFF: 85.7 ± 14.5 vs ON: 108.4 ± 21.0 cmH2 O; P = 0.02), with no significant difference in the duration (P = 0.10). No other significant difference was found between stimulation conditions (OFF vs ON) for anal resting pressure (OFF: 72.5 ± 8.6 cmH2 O vs ON: 71.7 ± 9.0 cmH2 O; P = 0.24), recto-anal inhibitory reflex, maximal tolerable rectal volume (OFF: 231 ± 24 mL vs ON: 241 ± 26 mL; P = 0.68), or anal pressure during defecation effort with a similar rate of ano-rectal dyssynergia (7/16 and 8/16 with and without STN-DBS, respectively). No order effect (ON-OFF vs OFF-ON) was observed. Conclusion and inferences STN-DBS increased anal squeezing pressure, but did not modify anorectal dyssynergia in PD patients, This study demonstrated the involvement of STN in the voluntary control of anorectal motility in PD patients.

International audience; Introduction: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. Methods: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). Results: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. Discussion: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Introduction Les premieres etudes de vie reelle concernant la tolerance du perampanel (PER) alertent sur des effets indesirables psychiatriques. Objectifs L’objectif principal de l’etude est d’identifier des facteurs de risque de developper des effets indesirables psychiatriques sous PER. Les objectifs secondaires sont d’evaluer l’efficacite et la tolerance globale du traitement. Patients et Methodes Cette etude retrospective, monocentrique au CHU de Rouen, inclut les patients adultes traites par perampanel entre mars 2014 et mars 2018. Nous avons separe la population en 2 groupes : ceux ayant presente des effets indesirables psychiatriques et les autres. Nous avons compare ces groupes a 9 variables : sexe, âge, âge de debut d’epilepsie, antecedents psychiatriques, effets indesirables psychiatriques sous un autre antiepileptique, trouble cognitif, epilepsie focale, nombre de traitements associes, posologie du PER. Resultats Soixante-dix-huit patients ont ete inclus, dont 85,9 % de pharmacoresistants. Le taux de retention du PER etait de 48,7 %. Au total, 11,5 % etaient libres de crise et 33,3 % repondeurs. Cinquante-neuf pour cent ont eu des effets indesirables dont 42 % psychiatriques. Les antecedents psychiatriques existent chez 17 patients (51,5 %) dans le groupe « effets indesirables psychiatriques » vs 8 (17,7 %) dans l’autre p = 0,003 ; les effets indesirables psychiatriques sous un autre antiepileptique sont presents respectivement chez 13 patients (39,4 %) vs 8 (17,7 %) p = 0,041. Discussion Dans notre etude, les taux de retention du PER et d’efficacite sont comparables aux donnees des autres etudes. Dans ces dernieres, la frequence de survenue d’effets indesirables psychiatriques varie entre 1,4 % et 54,5 %, vs 42 % dans notre etude. Un antecedent psychiatrique ou d’effet indesirable psychiatrique sous un autre antiepileptique augmente le risque de developper un effet indesirable psychiatrique sous PER. Conclusion Les antecedents psychiatriques et les antecedents d’effets indesirables psychiatriques sous un autre antiepileptique sont des potentiels facteurs de risque de mauvaise tolerance psychiatrique du perampanel.

Background Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. Methods Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. Key Results During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p

International audience; Alzheimer’s and Parkinson’s diseases are age-related progressive neurodegenerative diseases of increasing prevalence worldwide. In the absence of curative therapy, current research is interested in prevention, by identifying subtle signs of early-stage neurodegeneration. Today, the field of behavioral neuroscience has emerged as one of the most promising areas of research on this topic. Recently, it has been shown that the exacerbation of gait disorders under dual-task conditions (i.e., simultaneous performance of cognitive and motor tasks) could be a characteristic feature of Alzheimer’s and Parkinson’s diseases. The cognitive-motor dual-task paradigm during walking allows to assess whether (i) executive attention is abnormally impaired in prodromal Alzheimer’s disease or (ii) compensation strategies are used in order to preserve gait function when the basal ganglia system is altered in prodromal Parkinson’s disease. This review aims at (i) identifying patterns of dual-task-related gait changes that are specific to Alzheimer’s and Parkinson’s diseases, respectively, (ii) demonstrating that these changes could potentially be used as prediagnostic markers for disease onset, (iii) reviewing pros and cons of existing dual-task studies, and (iv) proposing future directions for clinical research.

Spinal diseases often induce gait disorders with multifactorial origins such as lumbar pain, radicular pain, neurologic complications, or spinal deformities. However, radiography does not permit an analysis of spinal dynamics; therefore, sagittal balance dynamics during gait remain largely unexplored. This prospective and controlled pilot study assessed the Vicon system for detecting sagittal spinopelvic imbalance, to determine the correlations between optoelectronic and radiographic parameters.Reversible anterior sagittal imbalance was induced in 24 healthy men using a thoracolumbar corset. Radiographic, optoelectronic, and comparative analyses were conducted.Corset wearing induced significant variations in radiographic parameters indicative of imbalance; the mean C7-tilt and d/D ratio increased by 15° ± 7.4° and 359%, respectively, whereas the mean spinosacral angle decreased by 16.8° ± 8° (all P0.001). The Vicon system detected the imbalance; the mean spinal angle increased by 15.4° ± 5.6° (P 0.01), the mean floor projection of the C7S1 vector (C7'S1') increased by 126.3 ± 51.9 mm (P 0.001), and the mean C7-T10-S1 angle decreased by 9.8° ± 3° (P0.001). Variations in C7'S1' were significantly correlated with d/D ratio (ρ = 0.58; P0.05) and C7-tilt (ρ = 0.636; P0.05) variations.Corset wearing induced radiographically confirmed anterior sagittal imbalance detected using the Vicon system. Optoelectronic C7'S1' correlated with radiographic C7-tilt and d/D ratio.

International audience; While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia.We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia.In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed.

Backgrounds Worsening of verbal fluency is reported after subthalamic nucleus deep brain stimulation in Parkinson's disease. It is postulated that these changes could reflect microlesion consecutive to the surgical procedure itself. Methods We evaluated verbal fluency, in 26 patients (mean age, 57.9 ± 8.5 years; mean disease duration, 11.4 ± 3.5 years) both before surgery (baseline) and, after surgery respectively the third day (T3), the tenth day (T10) just after STN implantation before turning on the stimulation and at six months (T180). Results Number of total words and switches was significantly reduced at T3 and T10, while average cluster size was unchanged. Repeated post-operative neuropsychological testing demonstrated reliable improvement from T3 to T180 on verbal fluency. Conclusion This study provides evidence of transient verbal fluency decline consecutive to a microlesion effect. Further studies needed to determine a putative relationship between early and long-term verbal fluency impairment.

Resume Une formation medicale continue necessite un travail de preparation dont le but est de stimuler les processus cognitifs favorisant l’apprentissage : la motivation, la perception, l’attention, la memoire, les representations et les connaissances anterieures, le statut de l’erreur et l’effet enseignant. Il faut une planification systematique des apprentissages surtout si l’on se place dans la perspective de faciliter l’apprentissage des participants. Les etapes de cette planification sont : la determination des besoins educatifs, la formulation des objectifs d’apprentissage, la determination de la methode pedagogique, la mesure de l’atteinte des objectifs par les apprenants et enfin l’evaluation de l’activite.

Objective To analyse postoperative pain due to osteoarthritis in patients with Parkinson's disease submitted to bilateral subthalamic nucleus stimulation. Methods Fifty-three parkinsonian patients (mean age, 59.9±8.3 years; mean disease duration, 11.5±4.2 years) referred for subthalamic nucleus stimulation were enrolled. Patients were prospectively asked to refer and describe any pain due to osteoarthritis they experienced at any time during the preoperative period and within the 6 postoperative months. Pre-existing pain due to osteoarthritis, therapeutic changes, parkinsonian motor disability and weight gain were assessed as explanatory factors for occurrence pain due to osteoarthritis after surgery. Results After surgery, thirty patients (57%) complained of pain due to osteoarthritis whereas all demonstrated great functional improvement. Twenty (67%) among the 30 experienced similar pain sensation before surgery. Symptoms occurred rapidly, between 4 and 26 postoperative weeks. Multiple stepwise regression analysis showed that pre-existing pain due to osteoarthritis, 6-month postoperative UPDRS III motor score and axial sub-score improvements in the off -drug/ on -stimulation condition were accurate independent predictors of pain due to osteoarthritis after surgery ( F (8,41)=2.20, p Conclusion Our results highlight the high prevalence of pain due to osteoarthritis arising shortly after subthalamic implantation. An accurate pain and osteo-articular assessment should be performed preoperatively in parkinsonian candidates for subthalamic nucleus stimulation in order to limit occurrence of complications in the early postoperative period.

Object A collision/implantation or microlesion effect is commonly described after subthalamic nucleus (STN) implantation for high-frequency stimulation, and this is presumed to reflect disruption of cells and/or fibers. Off-period dystonia, a frequent cause of disability in patients with advanced Parkinson disease, can lead to the need for surgical treatment. The authors assessed the early effect of this microlesion on off-period dystonia. Methods The authors assessed 30 consecutive patients with the advanced levodopa-responsive form of Parkinson disease. The patients' symptoms were Hoehn and Yahr Scale score ≥ 3, the mean duration of their disease was 11.4 ± 3.5 years, and they had undergone bilateral implantation of electrodes within the STN for high-frequency stimulation between February 2004 and December 2006. The microlesion effect was defined by the clinical improvement (Unified Parkinson's Disease Rating Scale [UPDRS] Part III score, UPDRS Part IV, item 35) assessed the morning of the 3rd day following STN implantation, after at least a 12-hour withdrawal of dopaminergic treatment and before the programmable pulse generator was switched on (off-drug/off-stimulation mode). Results Compared with baseline (off state), the microlesion effect improved the motor score (UPDRS Part III) by 27%. Subscores for tremor, rigidity, and bradykinesia respectively improved by 42, 37, and 25%. Nineteen patients (63%) suffered from off-period dystonia before surgery. Twelve (41%) reported complete relief of their symptoms in the immediate postoperative period and remained free of painful off-period dystonia throughout the 6-month follow-up period. Conclusions The author postulated that off-period dystonia alleviation may reflect both a microsubthalamotomy and micropallidotomy effect. They hypothesize, moreover, that the microlesion could play a role in the 6-month postoperative outcome.

A microsubthalamotomy (mSTN) effect has been frequently reported after implantation that improves Parkinson's motor disability. It is usually believed that mSTN effect reflects the post-traumatic tissue reaction within the STN. However, it has never, to our knowledge, been reported whether pre and intraoperative factors could predict this mSTN effect. Preoperative clinical characteristics, that is, age, disease duration, Mattis Dementia Rating Scale score, levodopa responsiveness, severity of motor fluctuations and dyskinesia, and intraoperative parameters, that is, the number of tracks, distance of typical STN neuronal activity recorded along all microelectrodes, and along the definitive electrodes, were assessed in 40 consecutive PD patients submitted for STN stimulation. Multiple stepwise regression analysis showed that only the number of tracks used for microelectrodes recordings was predictor of the contralateral mSTN effect (F (4,73) = 1.83, P = 0.02). This result suggests that the contralateral mSTN depends on the tissue changes along the entirety of surgical trajectories affecting both STN and its adjacent structures. © 2008 Movement Disorder Society

A microsubthalamotomy (mSTN) effect is commonly described after implantation that improves Parkinson's motor disability and is considered to be an obvious sign of good placement of the definitive electrode within the subthalamic nucleus (STN). There has been no formal study, however, demonstrating whether this mSTN effect can predict the long-term efficacy of STN stimulation in Parkinson Disease. The mSTN effect was defined by the percentage improvement of unified parkinson's disease rating scale (UPDRS III) baseline score assessed the third day morning following STN implantation, after at least a 12 hour withdrawal of dopaminergic treatment and before the programmable pulse generator was switched on. It was assessed in 30 consecutive patients with PD submitted for STN stimulation. Multiple stepwise regression analysis showed that mSTN effect (P = 0.005) and global mean intensity of stimulation (P = 0.004) were accurate independent predictors of the 6-month postoperative UPDRS III motor score improvement in the off-drug/on-stimulation condition.

We compared postural performances in early stage Parkinson's disease (PD) patients and healthy subjects, and to determine if PD patients have infraclinical postural instability. Nine PD patients and 18 age- and sex-matched control subjects were recorded with open eyes (OE) and closed eyes (CE) using a force platform in static and dynamic conditions with a mobile platform allowing antero posterior and medio lateral oscillations. Oscillations of the mobile platform and balance strategy were quantified using both a force platform and the Vicon system. Under static conditions with both OE and CE, PD patients had a larger center foot pressure sway area than the control subjects (P = 0.007 and P = 0.04, respectively). Under dynamic conditions, the PD patients' sway area was greater than that of the control subjects in the CE antero posterior position (P = 0.04). Oscillations of the mobile platform were not different between the two groups. Lastly, all subjects used an ankle strategy, but PD patients had larger head oscillations than the control subjects. Early stage PD patients have an infraclinical postural instability which is compensated when it is more difficult to maintain good balance, suggesting that the neurological mechanisms of balance are partially still operating at this stage of the disease.

Background: In our stereotactic procedure, intraoperative radiological documentation of electrode localization is performed using the Stereoplan. The aim of the study was to evaluate its accuracy. Patients and Methods: Data of 20 consecutive patients, treated for Parkinson’s disease by implantation of deep brain stimulators into the subthalamic nucleus, were collected prospectively. During surgery, Stereoplan coordinates of the tip of the central macroelectrodes were compared with intended coordinates along the central trajectory at 4 levels: (1) 10 mm above the anatomical target, (2) in the target, (3) in the substantia nigra pars reticulata, and (4) at the depth of contact 1. Before the frame’s removal, Stereoplan coordinates of the contacts of the definitive electrode were compared with postoperative MRI coordinates. The mean of the differences was calculated in the x-, y-, and z-axis. Clinical results at 6 months were recorded.Results: The mean of the differences between Stereoplan coordinates and intended coordinates for the macroelectrodes was lower than 1 mm. A submillimeter difference was also found for the definitive contacts. At 6 months, the Unified Parkinson‘s Disease Rating Scale III score improved by 70.6% compared with the baseline score. Dyskinesia and motor fluctuations decreased by 85.7 and 87%, respectively (p < 0.0001). Conclusion: Stereoplan could be considered an accurate intraoperative radiological system which assures the correct position of the electrode in the anatomical target.

Familial amyloidosis of the Finnish type (FAF) is a rare autosomal-dominant disorder caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin, an actin-modulating protein. The main symptoms include corneal lattice dystrophy, progressive cranial and peripheral neuropathy, and skin changes. To date, only two mutations in the GSN gene have been described: the p.Asp187Asn mutation in most patients and the p.Asp187Tyr mutation in a Danish and Czech family. We report on the third family with the p.Asp187Tyr mutation and the first French FAF family. Severe cardiac conduction alterations in three patients were mainly caused by cardiac sympathetic denervation. These findings demonstrate the cardiological involvement of the FAF phenotype and suggest that cardiological follow-up is required in FAF patients.

Idiopathic Parkinson's disease (PD) has a long preclinical phase during which non-motor symptoms exist but are not specific. The aim of the study is to determine whether subtle gait disorders are prediagnostic markers of PD. Participants were selected from the Baltimore Longitudinal Study of Aging, including 10 prediagnostic PD (8M/2W) and thirty age-matched healthy controls. Prediagnostic PD were assessed for an average of 2.6 ± 1.3 years (range 1.0–5.3 years) before PD diagnosis with: clinical gait and balance assessment (i.e., 6-meter corridor walk at usual and maximal gait speed, semi-tandem stand, tandem stand, and one-leg stand), instrumental gait analysis (VICON®), upper-limb motor skills (i.e., Hand Rapid Alternating Movement Test, Finger Tapping Test, and Purdue Pegboard Test), neuropsychological assessment (i.e., processing speed, attention, executive functions, memory, language, and visuo-spatial skills), and non-motor symptoms (orthostatic hypotension, depression, sleep disorders, and urinary symptoms). Prediagnostic IPD showed slower gait speed due to shorter step length compared to controls. They also showed greater gait speed variability, which was correlated with falls. No statistically significant differences were found between the two groups for balance, upper-limb motor skills and non-motor symptoms. Prediagnostic PD showed lower visuospatial ability (Card Rotation Test) than controls. The set of variables that best discriminate between the two groups were age, clinical gait speed, Trail-Making Test Part B, and Card Rotation Test with 100% sensibility and 95.8% specificity. This is the first prospective longitudinal study demonstrating gait changes in prediagnostic idiopathic Parkinson's disease. Previous published studies have recruited high-risk population for PD, as asymptomatic carriers of LRRK2 mutation [1] or patients with rapid eye movement sleep behavior disorder [2] , [3] . Our findings could potentially be used as prediagnostic markers of IPD to identify those who could benefit from future neuroprotective therapy in order to delay, or even prevent, clinical manifestations.

Introduction Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative diseases of increasing prevalence worldwide. In the absence of effective therapy, current research is focused on identifying individuals at high risk, who could be targeted in intervention trials. Today, the field of behavioral neuroscience has emerged as one of the most promising areas of research on this topic. Recently, it has been shown that the exacerbation of gait disorders in dual-task conditions, which involve the concurrent performance of a cognitive task while walking, is a characteristic feature of AD and PD. Objectives This review aims: – to summarize evidence supporting or refuting that the dual-task walking paradigm have added value for early detection of older people at risk for progression to AD or PD; – to propose new dual-task paradigms and markers for more accurate and earlier diagnosis of these diseases. Study selection The following inclusion criteria were used in this review: – used self-paced (comfortable) walking as the primary motor task; – reported gait parameters during both single- and dual-task performance, or dual-tasking effects on gait; – employed secondary cognitive tasks during dual-task walking. Results Dual-task-related gait changes precede the traditional clinical symptoms of AD and PD. Inhibition and flexibility are mostly impaired in preclinical AD and PD, respectively. Strategies in dual-task conditions may differentiate between preclinical AD and PD. A number of issues related to the application of dual-task methodology in gait (e.g., effect of type of cognitive task, choice of gait parameters, complementary use of linear and nonlinear measures) are discussed. Conclusion and perspectives We propose novel dual-task paradigms and markers based on the pathophysiological mechanisms that underlie gait disorders in each disease to advance our knowledge in this innovative area of research.

A significant proportion of patients with Parkinson's disease suffers from digestive symptoms. Bilateral deep brain stimulation of the subthalamic nucleus has become a reliable therapeutic option for parkinsonian patients, but its effects on digestive motility remain poorly investigated. The aim of our study was to assess whether subthalamic stimulation could induce changes in gastric, colonic, and rectal motility and modulate brain centers involved in gut motility.In anesthetized rats, unilateral subthalamic nucleus stereotactic implantation was performed while intra-gastric, -colonic, and -rectal pressures were recorded during the ON and OFF periods of the stimulation. c-Fos protein expression was quantified by immunostaining in the nucleus of the solitary tract, the dorsal motor nucleus of the vagus nerve, the locus coeruleus, and the Barrington's nucleus.Compared to baseline, sham stimulation did not change phasic gastric, colonic or rectal motor activity. Unilateral subthalamic stimulation increased colonic phasic motility (P0.05) compared to baseline and the OFF period with no change in gastric and rectal motility. Pre-treatment with atropine, or specific D1 and D2 receptors antagonists prevented the rise in colonic motor activity. An increase in c-Fos protein-positive cells within all the studied nuclei was observed in the stimulated group compared to the sham group.Unilateral subthalamic stimulation impacts on gut motility in anesthetized rats with a significant increase in colonic motility probably via the modulation of several brain centers. These findings warrant further confirmation in parkinsonian rat models before being transposed to clinical conditions.

Psychogenic paralysis presents a real treatment challenge. Despite psychotherapy, physiotherapy, antidepressants, acupuncture, or hypnosis, the outcome is not always satisfactory with persistent symptoms after long-term follow-up. We conducted a retrospective study to assess clinical features and to propose an alternative treatment based on repetitive transcranial magnetic stimulation (rTMS). Seventy patients (44 F/26 M, mean age: 24.7 +/- 16.6 years) experienced paraparesis (57%), monoparesis (37%), tetraparesis (3%), or hemiparesis (3%). A precipitating event was observed in 42 patients, primarily as a psychosocial event or a physical injury. An average of 30 stimuli over the motor cortex contralateral to the corresponding paralysis was delivered at low frequency with a circular coil. The rTMS was effective in 89% of cases, with a significantly better outcome for acute rather than chronic symptoms. In conclusion, motor cortex rTMS seem to be very effective in patients with psychogenic paralysis and could be considered a useful therapeutic option.

A collision/implantation or microlesion effect is commonly described after subthalamic nucleus (STN) implantation for high-frequency stimulation, and this is presumed to reflect disruption of cells and/or fibers. Off-period dystonia, a frequent cause of disability in patients with advanced Parkinson disease, can lead to the need for surgical treatment. The authors assessed the early effect of this microlesion on off-period dystonia.The authors assessed 30 consecutive patients with the advanced levodopa-responsive form of Parkinson disease. The patients' symptoms were Hoehn and Yahr Scale scoreor = 3, the mean duration of their disease was 11.4 +/- 3.5 years, and they had undergone bilateral implantation of electrodes within the STN for high-frequency stimulation between February 2004 and December 2006. The microlesion effect was defined by the clinical improvement (Unified Parkinson's Disease Rating Scale [UPDRS] Part III score, UPDRS Part IV, item 35) assessed the morning of the 3rd day following STN implantation, after at least a 12-hour withdrawal of dopaminergic treatment and before the programmable pulse generator was switched on (off-drug/off-stimulation mode).Compared with baseline (off state), the microlesion effect improved the motor score (UPDRS Part III) by 27%. Subscores for tremor, rigidity, and bradykinesia respectively improved by 42, 37, and 25%. Nineteen patients (63%) suffered from off-period dystonia before surgery. Twelve (41%) reported complete relief of their symptoms in the immediate postoperative period and remained free of painful off-period dystonia throughout the 6-month follow-up period.The author postulated that off-period dystonia alleviation may reflect both a microsubthalamotomy and micropallidotomy effect. They hypothesize, moreover, that the microlesion could play a role in the 6-month postoperative outcome.

Introduction.Study of sagittal spinal balance is based on radiographs which are by definition static, providing a snapshot of an intrinsically mobile structure. In reality, a non-architectural functional component may affect the patient’s position at the moment of imaging.The dynamic aspect of posture can be considered using optoelectronic motion detectors; for example, Vicon stereophotogrammetry is available in the gait laboratory of the university hospital of Rouen, France.The aim of the present study was to confirm this system’s ability to detect anterior tilt on the relevant assessment criteria. A graphic illustration of sagittal spinal kinetics was undertaken. The posturographic impact of the deformity was measured on a barodynamic platform. Finally, the study assessed the impact of posture on gait kinematics, and notably on vertical braking of the center of mass.Methods.35 healthy male volunteers were recruited by the clinical investigation center (CIC) INSERM 1404 of the university hospital of Rouen, France. Anterior sagittal deformity (ASD) was created by means of a kyphotic corset. Full-spine EOS® views were taken with and without corset, to quantify the induced deformity.A posturographic study on a Satel® barodynamic platform assessed the individual kinetics of the center of mass with and without corset-induced ASD.Subjects were then fitted with 38 reflectors and moved around in a room equipped with the Vicon® system, with 9 infra-red video-cameras. This optoelectronic study assessed spinal posture and gait kinematics.Results.Gait tests were formed without any adverse events occurring. Radiologic ASD was confirmed by a significant increase in C7 sacral tilt (p, Introduction.L’étude de l’équilibre sagittal rachidien s’appuie sur des analyses radiographiques nécessairement statiques, reflet postural ponctuel d’une structure intrinsèquement mobile. Cependant, une part fonctionnelle peut influencer la position d’un patient au moment du cliché.Pour considérer la part dynamique de la posture, il est apparu pertinent d’employer des outils de capture optoélectronique du mouvement tels que la stéréophotogrammétrie Vicon.Les objectifs étaient de confirmer la capacité du système à percevoir la gite antérieure selon des critères pertinents et d’illustrer graphiquement la cinétique rachidienne sagittale. Le retentissement posturographique de la déformation a été mesuré sur plateforme barodynamique. Enfin, l’influence de la posture sur la cinématique de la marche et notamment sur le freinage vertical du centre de masse a été évaluée.Méthodes.35 sujets volontaires sains masculins ont été recrutés. Une déformation sagittale antérieure (DSA) a été artificiellement créée par le port de corsets cyphosants. Des clichés de télérachis EOS® avec et sans corset ont quantifié la déformation induite.Une étude posturographique sur plateforme barodynamique Satel® a étudié la cinétique du centre de pression des individus avec et sans DSA.Ces-derniers ont ensuite été équipés de 38 marqueurs pour se déplacer dans une salle équipée du système Vicon®. L’étude optoélectronique a évalué la posture rachidienne et la cinématique de la marche.Résultats.La DSA radiologique a été confirmée par l’augmentation significative de la GSC7 (p