Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial.

BACKGROUND AND PURPOSE: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD. METHODS: A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores. RESULTS: Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported. CONCLUSIONS: STN or GPi DBS are ineffective on dystonia related to WD.

Limbic Stimulation Drives Mania in STN-DBS in Parkinson Disease: A Prospective Study.

In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low-dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411-417.

Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.

BACKGROUND: Several surgical methods are used for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). This study aimed to compare clinical outcomes and electrode placement accuracy after robot-assisted (RAS) versus frame-based stereotactic (FSS) STN DBS in Parkinson's disease. METHODS: In this single-center open-label study, we prospectively collected data from 48 consecutive PD patients who underwent RAS (Neuromate®; n = 20) or FSS (n = 28) STN DBS with the same MRI-based STN targeting between October 2016 and December 2018 in the university neurological hospital of Lyon, France. Clinical variables were assessed before and 1 year after surgery. The number of electrode contacts within the STN was determined by merging post-operative CT and pre-operative MRI using Brainlab® GUIDE™XT software. RESULTS: One year after surgery, the improvement of motor manifestations (p = 0.18), motor complications (p = 0.80), and quality of life (p= 0.30) and the reduction of dopaminergic treatment (p = 0.94) and the rate of complications (p = 0.99) were similar in the two groups. Surgery duration was longer in the RAS group (p = 0.0001). There was no difference in the number of electrode contacts within the STN. CONCLUSION: This study demonstrates that RAS and FSS STN DBS for PD provide similar clinical outcomes and accuracy of electrode placement.

[Parkinson's disease treatment: from honey moon to motor fluctuations]. / Prise en charge de la maladie de Parkinson : de la lune de miel aux fluctuations.

Parkinson's disease treatment: from honey moon to motor fluctuations. The treatment of Parkinson's disease remains symptomatic but allows, for many years, a good control of motor and non-motor signs. This treatment is complex and has to deal with very heterogeneous motor and non-motor presentation. Initial treatment is started once disability occurs and is mainly based either on levodopa or dopamine agonists. When motor fluctuations start, the principle of treatment is to optimize levodopa intake and combine various drugs depending on the clinical presentation. Third line strategies of treatment such as pumps or deep brain stimulation may be proposed at this stage. Later on, when doparesistant signs appear, treatment has often to be simplified, cognitive decline to be taken in charge and physiotherapy is crucial even if physical exercise is of great importance whatever the stage of the disease. Finally, non-motor manifestations have to be carefully addressed throughout the course of the disease because their impact on quality of life is sometimes greater than the one of motor signs.

Prise en charge de la maladie de parkinson : de la lune de miel aux fluctuations Le traitement de la maladie de Parkinson reste à ce jour symptomatique mais permet le contrôle des signes moteurs et non moteurs de la maladie pendant de nombreuses années. Il est complexe du fait de la variété des signes à la fois moteurs et non moteurs. Le traitement initial est décidé lorsqu'une gêne apparaît, et la discussion principale est celle du choix entre L-dopa et agonistes dopaminergiques. Au stade des fluctuations motrices, les options sont nombreuses et reposent sur l'optimisation de la dopathérapie et la combinaison avec d'autres traitements selon les manifestations observées. Les thérapies de recours telles que les pompes ou la stimulation cérébrale profonde peuvent être proposées à ce stade. La phase de déclin se caractérise par la présence de signes dopa-résistants et, à ce stade, il est souvent nécessaire de simplifier le traitement, de prendre en charge le déclin cognitif et de renforcer la physiothérapie. L'exercice physique est important à tous les stades, de même que la prise en compte des troubles neuropsychiques liés à la maladie ou induits par les traitements car ils contribuent dans une grande mesure à la détérioration de la qualité de vie des patients.

Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.

BACKGROUND: Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD). OBJECTIVES: We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs. METHODS: We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 µg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success. RESULTS: Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6). DISCUSSION: Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted. TRIAL REGISTRATION: The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018.

Depression in Patients with Parkinson's Disease: Current Understanding of its Neurobiology and Implications for Treatment.

Depression is one of the most frequent and burdensome non-motor symptoms in Parkinson's disease (PD), across all stages. Even when its severity is mild, PD depression has a great impact on quality of life for these patients and their caregivers. Accordingly, accurate diagnosis, supported by validated scales, identification of risk factors, and recognition of motor and non-motor symptoms comorbid to depression are critical to understanding the neurobiology of depression, which in turn determines the effectiveness of dopaminergic drugs, antidepressants and non-pharmacological interventions. Recent advances using in vivo functional and structural imaging demonstrate that PD depression is underpinned by dysfunction of limbic networks and monoaminergic systems, depending on the stage of PD and its associated symptoms, including apathy, anxiety, rapid eye movement sleep behavior disorder (RBD), cognitive impairment and dementia. In particular, the evolution of serotonergic, noradrenergic, and dopaminergic dysfunction and abnormalities of limbic circuits across time, involving the anterior cingulate and orbitofrontal cortices, amygdala, thalamus and ventral striatum, help to delineate the variable expression of depression in patients with prodromal, early and advanced PD. Evidence is accumulating to support the use of dual serotonin and noradrenaline reuptake inhibitors (desipramine, nortriptyline, venlafaxine) in patients with PD and moderate to severe depression, while selective serotonin reuptake inhibitors, repetitive transcranial magnetic stimulation and cognitive behavioral therapy may also be considered. In all patients, recent findings advocate that optimization of dopamine replacement therapy and evaluation of deep brain stimulation of the subthalamic nucleus to improve motor symptoms represents an important first step, in addition to physical activity. Overall, this review indicates that increasing understanding of neurobiological changes help to implement a roadmap of tailored interventions for patients with PD and depression, depending on the stage and comorbid symptoms underlying PD subtypes and their prognosis.

Nucleus Basalis of Meynert Stimulation for Lewy Body Dementia: A Phase I Randomized Clinical Trial.

OBJECTIVES: Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) has been proposed for patients with dementia. Here, we aim to assess the safety and effects of NBM-DBS in patients with Lewy body dementia (LBD), in a randomized, double-blind, crossover clinical trial. METHODS: Six patients with mild to moderate LBD (mean [SD] age, 62.2 [7.8] years) were included, operated on for bilateral NBM-DBS, and assigned to receive either active or sham NBM-DBS followed by the opposite condition for 3 months. The primary outcome was the difference in the total free recalls of the Free and Cued Selective Reminding Test (FCSRT) between active and sham NBM-DBS. Secondary outcomes were assessments of the safety and effects of NBM-DBS on cognition, motor disability, sleep, and PET imaging. RESULTS: There was no significant difference in the FCSRT score with active vs sham NBM-DBS. The surgical procedures were well tolerated in all patients, but we observed significant decreases in Stroop and Benton scores after electrode implantation. We observed no significant difference in other scales between active and sham NBM-DBS. With active NBM-DBS relative to baseline, phonemic fluency and motor disability significantly decreased. Lastly, the superior lingual gyrus metabolic activity significantly increased with active NBM-DBS. CONCLUSIONS: NBM-DBS does not appear to be totally safe for patients with LBD with no evidence of cognitive benefit. CLINICALTRIALSGOV IDENTIFIER: NCT01340001. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients with LBD operated on for bilateral NBM-DBS, active NBM-DBS stimulation compared to sham stimulation did not significantly change selective recall scores.

Changes in Prefrontal Cortical Activity During Walking and Cognitive Functions Among Patients With Parkinson's Disease.

Background: Walking becomes more and more degraded as Parkinson's Disease (PD) progresses. Previous research examined factors contributing to this deterioration. Among them, changes in brain cortical activity during walking have been less studied in this clinical population. Objectives: This study aimed to: (1) investigate changes in dorsolateral prefrontal cortex (DLPFC) activation during usual walking and dual-task walking conditions in patients with PD; (2) examine the association between cortical activity and behavioral/cognitive outcomes; and (3) explore which factors best predict increased activation of the DLPFC during usual walking. Methods: Eighteen patients with early stage PD and 18 controls performed 4 conditions: (1) standing while subtracting, (2) usual walking, (3) walking while counting forward, and (4) walking while subtracting. Cortical activity in DLPFC, assessed by changes in oxy-hemoglobin (ΔHbO2) and deoxy-hemoglobin (ΔHbR), was measured using functional near infrared spectroscopy (fNIRS). Gait performance was recorded using wearables sensors. Cognition was also assessed using neuropsychological tests, including the Trail Making Test (TMT). Results: DLPFC activity was higher in patients compared to controls during both usual walking and walking while subtracting conditions. Patients had impaired walking performance compared to controls only during walking while subtracting task. Moderate-to-strong correlations between ΔHbO2 and coefficients of variation of all gait parameters were found for usual walking and during walking while counting forward conditions. Part-B of TMT predicted 21% of the variance of ΔHbO2 during usual walking after adjustment for group status. Conclusions: The increased DLPFC activity in patients during usual walking suggests a potential compensation for executive deficits. Understanding changes in DLPFC activity during walking may have implications for rehabilitation of gait in patients with PD.

Personality Dimensions Are Associated with Quality of Life in Fluctuating Parkinson's Disease Patients (PSYCHO-STIM).

BACKGROUND: Parkinson's disease (PD) negatively affects patients' Quality of Life (QoL) which depends on both objective criteria such as physical health and subjective ones such as worries and norms according to personal believes. Therefore, QoL could be also associated to personality dimensions in chronic neurological diseases such as PD. OBJECTIVE: Our objective was thus to study the potential association between personality dimensions and QoL in PD patients with motor fluctuations before Deep Brain Stimulation of the Sub-Thalamic Nucleus (DBS-STN). METHODS: Data were obtained from the French multicentric cohort study Predi-Stim. All PD patients awaiting DBS-STN and responding to the inclusion criteria at the time of the study were included. All participants answered the "Temperament and Character Inventory" (TCI) and the PDQ-39 before surgery. Analyses were made using adjusted univariate generalized linear regression models to evaluate a potential association between TCI dimensions and PDQ-39 scores. RESULTS: Three hundred thirty-three consecutive patients were included. The temperament Harm Avoidance was negatively associated with QoL (p = 1e-4, R2= 0.33), whereas the character Self-Directedness was positively associated with mental component of QoL (p = 2e-4, R2= 0.33) in PD patients with motor fluctuations awaiting DBS-STN. CONCLUSIONS: PD patients with motor fluctuations, with lower Harm Avoidance and higher Self-Directedness scores have the best QoL mainly at an emotional and social level. Therapeutic education of these PD patients focusing on their personal resources may thus be important to improve their well-being.

Age and time course of long-term motor and nonmotor complications in Parkinson disease.

OBJECTIVE: To determine the time course of hazard for motor and nonmotor milestones of Parkinson disease (PD) in the long term and to investigate whether risk scales nonlinearly with time is instrumental in identifying changes in pathological processes and evaluating disease-modifying therapies in PD. METHODS: Outpatients with PD at the Lyon University Movement Disorders Center were evaluated for 7 clinical milestones in this retrospective cohort study, encompassing 4 domains of PD progression: (1) motor (motor fluctuations, dyskinesias); (2) axial (postural instability and falls, freezing of gait); (3) neuropsychiatric (impulse control disorders, hallucinations); and (4) cognitive (dementia) complications. For each complication, we estimated the outcome-specific hazard using parsimonious smooth parametric Poisson regression models allowing for nonlinear scaling over disease duration, age at diagnosis, current age, and their interaction. RESULTS: A total of 1,232 patients with PD experienced 1,527 disease-related complications in up to 12 years of follow-up. Specific to each complication, hazard rates increased dramatically starting from diagnosis and were highest for motor fluctuations and lowest for dementia up to 6 years after diagnosis in patients aged 65 years at diagnosis. Nonlinear patterns indicated dramatic changes in the course of PD after 5 years and predicted more severe axial prognosis after 70 years and for motor fluctuations, dyskinesias, and impulse control disorders before 60 years at diagnosis. CONCLUSION: Time course of motor and nonmotor milestones in PD is determined by disease duration and age at diagnosis in nonlinear patterns and their interaction. This indicates disease- and age-specific thresholds across the multiple neurodegenerative processes accumulating in PD at different paces.

Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies. OBJECTIVE: Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics. METHODS: In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies. RESULTS: Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found. CONCLUSIONS: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies.

Toe dystonia in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation.

BACKGROUND: Off state toe dystonia (TD) is a symptom frequently encountered in Parkinson's disease (PD), but little is known about its evolution after subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVE: To analyze the prevalence and the evolution of TD in PD patients candidate to STN-DBS. METHODS: Individual data of consecutive 130 PD patients who underwent STN-DBS between 2010 and 2015 were collected. RESULTS: Data were successfully collected in 95 patients. TD affect 45.3% of the patients in our cohort. TD was present in 32.7% of patients before surgery and was alleviated by STN-DBS in 48% of the cases. Motor improvement provided by STN-DBS, levodopa-equivalent treatment diminution after surgery, disease duration or age at the time of surgery were not predictive of TD evolution. A younger age at PD diagnosis was significantly associated with TD resolution. CONCLUSION: STN-DBS is partially efficient for TD but its evolution seems independent of significant predictive factors.

Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2.

OBJECTIVE: To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. METHODS: In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). RESULTS: 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). CONCLUSIONS: Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing.

Imagerie cérébrale dans les syndromes parkinsoniens.

Role of brain imaging for Parkinsonism T brain MRI is normal in Pakinson's disease. Brain MRI is useless when clinical presentation is typical of idiopathic Parkinson's disease. Brain MRI is the exam of choice for differentiating idiopathic Parkinson's disease and atypical parkinsonism. DATscan* confirms or rules out dopaminergic degeneration but does not separate idiopathic Parkinson's disease from Parkinson "plus" syndromes. FDG PET is helpful to separate idiopathic Parkinson's disease from Parkinson "plus" syndromes.

High incidence of carpal tunnel syndrome after deep brain stimulation in Parkinson's disease.

We observed several cases of carpal tunnel syndrome (CTS) revealed after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). 115 consecutive PD patients who underwent STN-DBS between 2010 and 2014 at the Neurological Hospital in Lyon were retrospectively included. CTS was accepted as the diagnosis only if clinical examination and ENMG both confirmed it. Nine patients (7.8 %) developed CTS in the 2 years following surgery, which is far beyond the 2.7/1000 incidence in the general population. The present study shows an overrepresentation of CTS occurrence after STN-DBS in PD.

Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia.

BACKGROUND: Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. RESULTS: In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called "simple mannerisms, childish behaviour or fake pathological movements" was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud's pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim's 1911 seminal description of dystonia musculorum deformans in Berlin. DISCUSSION: Brissaud-Meige's misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970-1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society's classification of dystonia.

History of physical and 'moral' treatment of hysteria.

This historical review presents the advances made mostly during the last 200 years on the description, concepts, theories, and (more specifically) cure of patients suffering from hysteria, a still obscure entity. The denomination of the syndrome has changed over time, from hysteria (reinvestigated by Paul Briquet and Jean-Martin Charcot) to pithiatism (Joseph Babinski), then to conversion neurosis (Sigmund Freud), and today functional neurological disorders according to the 2013 American Neurological Association DSM-5 classification. The treatment was renewed in the second half of the 19th century in Paris by Paul Briquet and then by Jean-Martin Charcot. Hysterical women, who represented the great majority of cases, were cured by physical therapy (notably physio-, hydro-, and electrotherapy, and in some cases ovary compression) and 'moral' therapies (general, causal therapy, rest, isolation, hypnosis, and suggestion). At the turn of the 19th and 20th centuries, psychotherapy, psychoanalysis, and persuasion were established respectively by Pierre Janet, Sigmund Freud, and Joseph Babinski. During World War I, military forces faced a large number of posttrauma neurosis cases among soldiers (named the 'Babinski-Froment war neurosis' and Myers 'shell shock', in the French and English literature, respectively). This led to the use of more brutal therapies in military hospitals, combining electrical shock and persuasion, particularly in France with Clovis Vincent and Gustave Roussy, but also in Great Britain and Germany. After World War I, this method was abandoned and there was a marked decrease in interest in hysteria for a long period of time. Today, the current treatment comprises (if possible intensive) physiotherapy, together with psychotherapy, and in some cases psychoanalysis. Antidepressants and anxiolytics may be required, and more recently cognitive and behavioral therapy. Repetitive transcranial magnetic stimulation is a new technique under investigation which may be promising in patients presenting with motor conversion syndrome (motor deficit or movement disorder). Functional neurological disorders remain a difficult problem to manage with frequent failures and chronic handicapping evolution. This emphasizes the need for therapeutic innovations in the future.