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International audience; Background and purpose: Studies on long-term nonmotor outcomes of subthalamic nucleus stimulation in Parkinson disease (PD) are scarce. This study reports on very long-term non-motor and motor outcomes in one of the largest cohorts of people with advanced PD, treated for >10 years with subthalamic nucleus stimulation. The main outcome was to document the evolution of independence in activities of daily living. The secondary outcomes were to measure the change in quality of life, as well as non-motor and motor outcomes.Methods: Patients were studied preoperatively, at 1 year, and beyond 10 years after subthalamic stimulation with an established protocol including motor, non-motor, and neuropsychological assessments.Results: Eighty-five people with PD were included. Independence scores in the off-medication condition (measured with the Schwab & England Activities of Daily Living Scale) as well as quality of life (measured with the Parkinson's Disease Questionnaire [PDQ]-37) remained improved at longest follow-up compared to preoperatively (respectively, p < 0.001, p = 0.015). Cognitive scores, measured with the Mattis Dementia Rating Scale, significantly worsened compared to before and 1 year after surgery (p < 0.001), without significant change in depression, measured with the Beck Depression Inventory. Motor fluctuations, dyskinesias, and off dystonia remained improved at longest follow-up (p < 0.001), with a significant reduction in dopaminergic treatment (45%, p < 0.001).Conclusions: This study highlights the long-term improvement of subthalamic stimulation on independence and quality of life, despite the progression of disease and the occurrence of levodopa-resistant symptoms.

Few studies have considered the influence of motor sign asymmetry on motivated behaviors in de novo drug-naïve Parkinson’s disease (PD). We tested whether motor sign asymmetry could be associated with different motivated behaviors patterns in de novo drug naïve PD. We performed a cross-sectional study in 149 de novo drug-naïve Parkinson’s disease patients and used the Ardouin Scale of Behavior in Parkinson’s disease (ASBPD) to assess a set of motivated behaviors. We assessed motor asymmetry based on i) the side of motor onset and ii) the MDS-UPDRS motor score, then we compared right hemibody Parkinson’s disease to left hemibody Parkinson’s disease. Patients with de novo right hemibody onset PD had significantly lower scores on the ASBPD for nocturnal hyperactivity (p = 0.031), eating behavior (p = 0.008), and approach behavior composite scores (p = 0.004) than patients with de novo left hemibody onset PD. Patients with de novo left hemibody onset PD had significantly higher scores on the ASBPD for anxiety (p = 0.025) than patients with de novo right hemibody onset PD. Our findings suggest that motor sign asymmetry may be associated with an imbalance between motivated behaviors in de novo drug-naïve Parkinson’s disease.

The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone.This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments.STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months.Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III.At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

International audience; Background: Verticality perception is frequently altered in Parkinson’s disease (PD) with Pisa syndrome (PS). Is it the cause or the consequence of the PS? Objective: We tested the hypothesis that both scenarios coexist. Methods: We performed a double-blind within-person randomized trial (NCT02704910) in 18 individuals (median age 63.5 years) with PD evolving for a median of 17.5 years and PS for 2.5 years and treated with bilateral stimulation of the subthalamus nuclei (STN-DBS) for 6.5 years. We analyzed whether head and trunk orientations were congruent with the visual (VV) and postural (PV) vertical, and whether switching on one or both sides of the STN-DBS could modulate trunk orientation via verticality representation. Results: The tilted verticality perception could explain the PS in 6/18 (33%) patients, overall in three right-handers (17%) who showed net and congruent leftward trunk and PV tilts. Two of the 18 (11%) had an outstanding clinical picture associating leftward: predominant parkinsonian symptoms, whole-body tilt (head –11°, trunk –8°) and transmodal tilt in verticality perception (PV –10°, VV –8.9°). Trunk orientation or VV were not modulated by STN-DBS, whereas PV tilts were attenuated by unilateral or bilateral stimulations if it was applied on the opposite STN. Conclusion: In most cases of PS, verticality perception is altered by the body deformity. In some cases, PS seems secondary to a biased internal model of verticality, and DBS on the side of the most denervated STN attenuated PV tilts with a quasi-immediate effect. This is an interesting track for further clinical studies.

ObjectivesTo assess the prevalence and the cumulative incidence of dementia at short-, medium- and long-term follow-up after deep brain stimulation (DBS) of the subthalamic nucleus (STN) (at 1, 5, and 10 years) and to evaluate potential risk factors for postoperative dementia.MethodsThe presence of dementia (according to the DSM-V) was retrospectively evaluated at each postoperative follow-up in patients with Parkinson disease (PD) who underwent bilateral STN-DBS. Preoperative and perioperative risk factors of developing postoperative dementia were also investigated. Demographic data, disease features, medications, comorbidities, nonmotor symptoms, PD motor scales, neuropsychological scales at baseline, and perioperative complications were collected for each patient.ResultsA total of 175 patients were included, and 104 were available at 10-year follow-up. Dementia prevalence was 2.3% at 1 year, 8.5% at 5 years, and 29.8% at 10 years. Dementia cumulative incidence at 1, 5, and 10 years was 2.3%, 10.9%, and 25.7%, respectively. The corresponding dementia incidence rate was 35.6 per 1,000 person-years. Male sex, higher age, hallucinations, lower frontal score at baseline, and perioperative cerebral hemorrhage were predictors of dementia.ConclusionsIn patients with PD with longstanding STN-DBS, dementia prevalence and incidence are not higher than those reported in the general PD population. Except for few patients with perioperative cerebral hemorrhage, STN-DBS is cognitively safe, and does not provide dementia risk factors in addition to those reported for PD itself. Identification of dementia predictors in this population may improve patient selection and information concerning the risk of poor cognitive outcome.

Background: Previous studies described a parkinsonian personality characterized as rigid, introverted, and cautious; however, little is known about personality traits in de novo Parkinson’s disease (PD) patients and their relationships with motor and neuropsychiatric symptoms. Objective: To investigate personality in de novo PD and explore its relationship with PD symptoms. Methods: Using Cloninger’s biosocial model, we assessed personality in 193 de novo PD patients. Motor and non-motor symptoms were measured using several validated scales. Cluster analysis was conducted to investigate the interrelationship of personality traits, motor, and non-motor symptoms. Results: PD patients showed low novelty seeking, high harm avoidance, and normal reward dependence and persistence scores. Harm avoidance was positively correlated with the severity of depression, anxiety, and apathy (rs = [0.435, 0.676], p

Background: Fatigue is a frequent and troublesome symptom present from the early stages of Parkinson’s disease (PD). Objective: To examine the relationship between fatigue and the neuropsychiatric triad, which includes apathy, depression, and anxiety, in de novo PD. Methods: We performed a cross-sectional study including 197 patients with de novo PD and assessed fatigue using the Parkinson’s Disease Fatigue Scale (PDFS-16). We evaluated motor status using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III score and evaluated neuropsychiatric status using the Ardouin Scale of Behavior in Parkinson’s Disease (ASBPD). We carried out univariate and multivariate analyses to model association between motor signs, non-motor signs, and fatigue risk. Results: Frequency of fatigue (28.9%) was of the same order of magnitude as that of apathy. PD patients with fatigue reported a lower quality of life than patients without fatigue (p

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Background Effects of DBS on freezing of gait and other axial signs in PD patients are unclear. Objective Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM-trial). Methods One hundred twenty-four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item-14 of the UPDRS-II at baseline and follow-up. The posture, instability, and gait-difficulty subscore of the UPDRS-III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication-off and medication-on conditions. Results Fifty-two percent in both groups had freezing of gait at baseline based on UPDRS-II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months (P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group (P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group (P < 0.01) in both medication-off and medication-on conditions. Conclusions Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication-off condition compared to best medical treatment in these patients. (c) 2019 International Parkinson and Movement Disorder Society

STUDY OBJECTIVES: ADCY5 mutations cause early-onset hyperkinetic movement disorders comprising diurnal and nocturnal paroxysmal dyskinesia, and patient-reported sleep fragmentation. We aimed to characterize all movements occurring during sleep and in the transition from sleep to awakening, to ascertain if there is a primary sleep disorder, or if the sleep disturbance is rather a consequence of the dyskinesia. METHODS: Using video polysomnography, we evaluated the nocturnal motor events and abnormal movements in 7 patients with ADCY5-related dyskinesia and compared their sleep measures with those of 14 age- and sex-matched healthy controls. RESULTS: We observed an increased occurrence of abnormal movements during wake periods compared to sleep in patients with ADCY5-related dyskinesia. While asleep, abnormal movements occurred more frequently during stage N2 and REM sleep, in contrast with stage N3 sleep. Abnormal movements were also more frequent during morning awakenings compared to wake periods before falling asleep. The pattern of the nocturnal abnormal movements mirrored those observed during waking hours. Compared to controls, patients with ADCY5-related dyskinesia had lower sleep efficiencies due to prolonged awakenings secondary to the abnormal movements, but no other differences in sleep measures. Notably, sleep onset latency was short and devoid of violent abnormal movements. CONCLUSIONS: In this series of patients with ADCY5-related dyskinesia, nocturnal paroxysmal dyskinesia were not associated with drowsiness or delayed sleep onset, but emerged during nighttime awakenings with subsequent delayed sleep, whereas sleep architecture was normal.

ObjectiveTo evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on motor complications in patients with Parkinson disease (PD) beyond 15 years after surgery.MethodsData on motor complications, quality of life (QoL), activities of daily living, Unified Parkinson’s Disease Rating Scale motor scores, dopaminergic treatment, stimulation measures, and side effects of STN-DBS were retrospectively retrieved and compared before surgery, at 1 year, and beyond 15 years after bilateral STN-DBS.ResultsFifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the “off” state were reduced by 75% (p < 0.001) and by 58.7% (p < 0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p < 0.001). Parkinson's Disease Quality of Life Questionnaire total score and the emotional function and social function domains improved 13.8% (p = 0.005), 13.6% (p = 0.01), and 29.9% (p < 0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up.ConclusionsSTN-DBS is effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and nonmotor symptoms over the years, patients undergoing STN-DBS could maintain an improvement in QoL.Classification of EvidenceThis study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.

OBJECTIVE This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). METHODS All consecutive PD patients who underwent bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short-term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long-term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores compared to the baseline off-medication scores. As a secondary objective, potential predictors of short-term motor outcome after STN-DBS were assessed by performing univariate and multivariate linear regression analyses. RESULTS In the long-term analyses (mean follow-up = 8.4 ± 6.26 years, median = 10 years, range = 1-17 years), 138 patients were included. Preoperative higher frontal score and off-medication MDS-UPDRS part III scores predicted a better long-term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1-year follow-up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off-medication MDS-UPDRS part III scores predicted the short-term motor outcome. INTERPRETATION Frontal lobe dysfunction, disease severity in the off-medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long-term motor STN-DBS effects. ANN NEUROL 2021.

Background Non-motor fluctuations represent a main source of disability in Parkinson's disease (PD). Among them, neuropsychiatric fluctuations are the most frequent and are often under-recognized by patients and physicians, partly because specific tools for assessment of neuropsychiatric fluctuations are lacking. Objective To develop a scale for detecting and evaluating the presence and the severity of neuropsychological symptoms during the ON and OFF phases of non-motor fluctuations. Methods Neuropsychiatric symptoms reported by PD patients in the OFF- and the ON-medication conditions were collected using different neuropsychiatric scales (BDI-II, BAI, Young, VAS, etc.). Subsequently, tree phases of a pilot study was performed for cognitive pretesting, identification of ambiguous or redundant items (item reduction), and to obtain preliminary data of acceptability of the new scale. In all the three phases, the scale was applied in both the OFF and ON condition during a levodopa challenge. Results Twenty items were selected for the final version of the neuropsychiatric fluctuation scale (NFS): ten items measured the ON neuropsychological symptoms and ten items the OFF neuropsychological manifestations. Each item rated from 0-3, providing respective subscores from 0 to 30. Conclusions Once validated, our NFS can be used to identify and quantify neuropsychiatric fluctuations during motor fluctuations. The main novelty is that it could be used in acute settings. As such, the NFS can assess the neuropsychiatric state of the patient at the time of examination. The next step will be to validate the NFS to be used in current practice.

BackgroundReports on behavioural outcomes after subthalamic nucleus deep brain stimulation in Parkinson’s disease are controversial and limited to short-term data. Long-term observation in a large cohort allows a better counselling and management.MethodsTo determine whether a long-term treatment with subthalamic stimulation induces or reduces impulse control behaviours, neuropsychiatric fluctuations and apathy, 69 patients treated with subthalamic stimulation are prospectively and retrospectively assessed using Ardouin Scale of Behavior in Parkinson’s Disease before and after 3–10 years of stimulation.ResultsAt a mean follow-up of 6 years, all impulse control disorders and dopaminergic addiction were significantly decreased, apart from eating behaviour and hypersexuality. Neuropsychiatric fluctuations also significantly improved (ON euphoria: 38% of the patients before surgery and 1% after surgery, PConclusionsBilateral subthalamic nucleus stimulation was overall very effective in improving impulse control disorders and neuropsychiatric fluctuations in parkinsonian patients in the long term despite a counteracting frequent apathy. Transient episodes of impulse control disorders still occurred within the follow-up. These findings recommend a close follow-up in parkinsonian patients presenting with neuropsychiatric symptoms before deep brain stimulation surgery.Clinical trial registrationNCT01705418;Post-results.

Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

Objective:To report on the long-term outcomes of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD), essential tremor (ET), and dystonic tremor.Methods:One hundred fifty-nine patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at the Grenoble University Hospital. The primary outcome was a change in the tremor scores at 1 year after surgery and at the latest follow-up (21 years). Secondary outcomes included the relationship between tremor score reduction over time and the active contact position. Tremor scores (Unified Parkinson's Disease Rating Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the coordinates of the active contacts were recorded.Results:Ninety-eight patients were included. Patients with PD and ET had sustained improvement in tremor with VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10 years, respectively; p < 0.05). There was no significant loss of stimulation benefit over time (p > 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not sustained after 5 years (30% improvement, p = 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery (p = 0.029). During the whole follow-up, forty-eight patients (49%) experienced minor side effects, whereas 2 (2.0%) had serious events (brain hemorrhage and infection).Conclusions:VIM DBS is an effective long-term (beyond 10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were modest and transient.Classification of evidence:This provides Class IV evidence. It is an observational study.

Background: Subthalamic stimulation improves the motor and neuropsychiatric symptoms of Parkinson's disease. However, the impact of this treatment on impulse control and personality is the subject of heavy debate. The objective of this study was to investigate personality changes after subthalamic stimulation. Methods: Using Cloninger's biosocial model, we assessed personality in 73 Parkinson's disease patients before and 12 months after subthalamic stimulation accompanied by a drastic reduction in dopaminergic medication. Changes in psychobehavioral symptoms were measured using a battery of validated clinical scales (apathy, depression, anxiety, hyperemotionality, mania, psychosis, punding, and impulse control behaviors). Results: One year after surgery, the harm avoidance personality domain total score increased compared with the baseline (+2.8; 34 patients; P

The subthalamic nucleus (STN) plays a critical role during action inhibition, perhaps by acting like a fast brake on the motor system when inappropriate responses have to be rapidly suppressed. However, the mechanisms involving the STN during motor inhibition are still unclear, particularly because of a relative lack of single-cell responses reported in this structure in humans. In this study, we used extracellular microelectrode recordings during deep brain stimulation surgery in patients with Parkinson's disease (PD) to study STN neurophysiological correlates of inhibitory control during a stop signal task. We found two neuronal subpopulations responding either during motor execution (GO units) or during motor inhibition (STOP units). GO units fired selectively before patients' motor responses whereas STOP units fired selectively when patients successfully withheld their move at a latency preceding the duration of the inhibition process. These results provide electrophysiological evidence for the hypothesized role of the STN in current models of response inhibition.

STUDY OBJECTIVES: ADCY5 mutations cause early-onset hyperkinetic movement disorders comprising diurnal and nocturnal paroxysmal dyskinesia, and patient-reported sleep fragmentation. We aimed to characterize all movements occurring during sleep and in the transition from sleep to awakening, to ascertain if there is a primary sleep disorder, or if the sleep disturbance is rather a consequence of the dyskinesia. METHODS: Using video polysomnography, we evaluated the nocturnal motor events and abnormal movements in 7 patients with ADCY5-related dyskinesia and compared their sleep measures with those of 14 age- and sex-matched healthy controls. RESULTS: We observed an increased occurrence of abnormal movements during wake periods compared to sleep in patients with ADCY5-related dyskinesia. While asleep, abnormal movements occurred more frequently during stage N2 and REM sleep, in contrast with stage N3 sleep. Abnormal movements were also more frequent during morning awakenings compared to wake periods before falling asleep. The pattern of the nocturnal abnormal movements mirrored those observed during waking hours. Compared to controls, patients with ADCY5-related dyskinesia had lower sleep efficiencies due to prolonged awakenings secondary to the abnormal movements, but no other differences in sleep measures. Notably, sleep onset latency was short and devoid of violent abnormal movements. CONCLUSIONS: In this series of patients with ADCY5-related dyskinesia, nocturnal paroxysmal dyskinesia were not associated with drowsiness or delayed sleep onset, but emerged during nighttime awakenings with subsequent delayed sleep, whereas sleep architecture was normal. CITATION: Méneret A, Roze E, Maranci JB, Dodet P, Doummar D, Riant F, Tranchant C, Fraix V, Anheim M, Ekmen A, McGovern E, Vidailhet M, Arnulf I, Leu-Semenescu S. Sleep in ADCY5-related dyskinesia: prolonged awakenings caused by abnormal movements. J Clin Sleep Med. 2019;15(7):1021–1029.

ObjectiveTo determine the postoperative attempted and completed suicide rates after subthalamic nucleus deep brain stimulation (STN-DBS) in a single-center cohort and to determine factors associated with attempted and completed suicide.MethodsWe retrospectively included all patients with Parkinson disease (PD) who underwent bilateral STN-DBS surgery at the Grenoble University Hospital between 1993 and 2016. For each patient who committed or attempted suicide, 2 patients with PD with STN-DBS without any suicidal behaviors were matched for age (±1 year), sex, and year of surgery (±2 years). Clinical data were collected from medical records. Detailed preoperative and postoperative neuropsychological evaluations, including frontal and Beck Depression Inventory (BDI) scores, were gathered.ResultsA total of 534 patients with PD were included. Completed and attempted suicide percentages were 0.75% (4 of 534) and 4.11% (22 of 534), respectively. The observed suicide rate in the first postoperative year (187.20 of 100,000 per year, 1 of 534) was higher than the expected National Observatory on Suicide Risks rate adjusted for age and sex (standardized mortality ratio 8.1). This rate remained similar over the second and third postoperative years. In a comparison of the 26 patients completing/attempting suicide and the 52 controls, the first group showed more frequent history of suicidal ideation/suicide attempts and psychotic symptoms, higher percentage of family psychiatric history, higher psychiatric medication use, and higher preoperative frontal and BDI scores on neuropsychological evaluations.ConclusionsSuicide behaviors can occur after STN-DBS, especially during the first 3 years. A careful multidisciplinary assessment and long-term follow-up are recommended to recognize and treat this potentially preventable risk for mortality.

Resume La stimulation cerebrale profonde (SCP) est un traitement reconnu des formes severes de la maladie de Parkinson (MP). Actuellement, la SCP du noyau subthalamique (NST) est consideree comme le traitement chirurgical de reference dans la MP. Les principales indications de ce traitement chirurgical sont les complications motrices et le tremblement dopa-resistant. La prise en charge du parkinsonien stimule est multidisciplinaire, impliquant neurologues, neurochirurgiens, neurophysiologistes, neuropsychologues, psychiatres, neuroradiologues, medecin generaliste referent, kinesitherapeutes et soignants. Celle-ci est fondamentale pour une selection optimale du malade, sa gestion peroperatoire et le suivi postoperatoire pour assurer des resultats de qualite. Nous proposons dans cet article les points essentiels de la gestion pratique postoperatoire initiale et a long terme du parkinsonien stimule. La prise en charge postoperatoire initiale a pour objectifs de detecter et prevenir les complications liees a la procedure chirurgicale et au materiel implante et d’obtenir un equilibre therapeutique avant le retour a domicile. Au long cours les objectifs therapeutiques comprennent la detection et la prise en charge des complications liees a la stimulation et a l’evolution de la maladie. Le role du neurologue traitant dans la prise en charge du patient neurostimule est fondamental pour optimiser le traitement, depister les complications liees a la stimulation, au materiel implante et a l’evolution de la maladie.

Item does not contain fulltext BACKGROUND: Impulse control disorders (ICD), including pathological gambling, are common in Parkinson's disease (PD) and tend to improve after subthalamic (STN) stimulation after a marked reduction of dopaminergic medication. In order to investigate the effect of STN stimulation on impulsive decision making, we used the Iowa Gambling task (IGT). METHODS: We investigated IGT performance in 20 patients with PD before STN surgery with and without dopaminergic treatment and in 24 age-matched controls. All patients underwent an extensive neuropsychological interview screening for behavioural disorders. Assessment in patients was repeated 3 months after surgery without dopaminergic treatment with and without stimulation. RESULTS: Chronic antiparkinsonian treatment was drastically reduced after surgery (-74%). At baseline, on high chronic dopaminergic treatment 8/20 patients with PD presented with pathological hyperdopaminergic behaviours, which had resolved in 7/8 patients 3 months after surgery on low chronic dopaminergic treatment. Preoperative performance on the IGT was significantly impaired compared to after surgery. CONCLUSIONS: Dopaminergic medication likely contributes to the impairment in decision making underlying ICDs. Deep brain stimulation allows drastic reduction of dopaminergic medication and, thus, concomitant remediation of medication-induced impairment in decision making.

Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown. Specifically, the influence of levodopa on the networks involved in motor imagery (MI) of parkinsonian gait has not been directly studied, comparing the off and on medication states in the same patients. We therefore conducted an [H2 (15) 0] Positron emission tomography study in eight advanced parkinsonian patients (mean disease duration: 12.3 ± 3.8 years) presenting with levodopa-responsive gait disorders and FoG, and eight age-matched healthy subjects. All participants performed three tasks (MI of gait, visual imagery and a control task). Patients were tested off, after an overnight withdrawal of all antiparkinsonian treatment, and on medication, during consecutive mornings. The order of conditions was counterbalanced between subjects and sessions. Results showed that imagined gait elicited activations within motor and frontal associative areas, thalamus, basal ganglia and cerebellum in controls. Off medication, patients mainly activated premotor-parietal and pontomesencephalic regions. Levodopa increased activation in motor regions, putamen, thalamus, and cerebellum, and reduced premotor-parietal and brainstem involvement. Areas activated when patients are off medication may represent compensatory mechanisms. The recruitment of these accessory circuits has also been reported for upper-limb movements in Parkinson's disease, suggesting a partly overlapping pathophysiology between imagined levodopa-responsive gait disorders and appendicular signs. Our results also highlight a possible cerebellar contribution in the pathophysiology of parkinsonian gait disorders through kinesthetic imagery.

Subthalamic stimulation improves the motor and neuropsychiatric symptoms of Parkinson's disease. However, the impact of this treatment on impulse control and personality is the subject of heavy debate. The objective of this study was to investigate personality changes after subthalamic stimulation.Using Cloninger's biosocial model, we assessed personality in 73 Parkinson's disease patients before and 12 months after subthalamic stimulation accompanied by a drastic reduction in dopaminergic medication. Changes in psychobehavioral symptoms were measured using a battery of validated clinical scales (apathy, depression, anxiety, hyperemotionality, mania, psychosis, punding, and impulse control behaviors).One year after surgery, the harm avoidance personality domain total score increased compared with the baseline (+2.8; 34 patients; P 0.001), as did 3 of its 4 subdomains: anticipatory worry (+0.7; 10 patients; P = 0.005), shyness (+0.6; 7 patients; P = 0.03), and fatigability (+1.1; 10 patients; P = 0.0014). Evolution of the shyness personality trait correlated with the decrease in dopaminergic medication. Total scores in the other personality domains remained unchanged, except for extravagance, a subdomain of novelty seeking, and persistence, a subdomain of reward dependence, which both decreased following surgery (-0.3; 7 patients; and -0.6; 9 patients; P = 0.03 and P = 0.0019, respectively). Although apathy increased, other psychobehavioral symptoms, including impulse control behaviors and neuropsychiatric nonmotor fluctuations, improved. Depression and anhedonia remained stable. Scores in hypodopaminergia and neuropsychiatric nonmotor OFF correlated with harm avoidance. Scores in hyperdopaminergia and neuropsychiatric nonmotor ON correlated with novelty seeking.When subthalamic stimulation is applied in Parkinson's disease, significant changes in personality traits are observed, which may be related to postoperative tapering of dopaminergic treatment. © 2017 International Parkinson and Movement Disorder Society.

Imagerie kinesthesique de la marche chez des patients parkinsoniensDe nombreux travaux associent l’imagerie motrice aux techniques d’imagerie cerebrale pour explorer les bases neurales du mouvement. Cependant, l’engagement reel des participants dans la tâche d’interet, ainsi que la modalite de representation mentale utilisee, ne sont pas systematiquement controles. Or, la pratique d’une imagerie kinesthesique, durant laquelle le sujet doit ressentir les consequences sensorielles de l’action, est preconisee pour examiner les circuits cerebraux du controle moteur. La presente etude avait ainsi pour objectif d’evaluer l’aptitude de dix-huit patients parkinsoniens souffrant de troubles locomoteurs a imaginer leur marche selon cette perspective, mais aussi l’effet du traitement dopaminergique sur cette faculte. Nous rapportons une capacite d’imagerie kinesthesique preservee chez ces derniers, independamment de la prise du medicament. Il a aussi ete constate, chez certains patients sous traitement, une dissociation entre les durees de marche reelle et imaginee. Ces resultats attestent donc de la possibilite d’utiliser un protocole controle d’imagerie motrice pour etudier les correlats neuronaux des troubles de la marche de la maladie de Parkinson, mais aussi de l’interet de cette methode en tant qu’outil de reeducation therapeutique.

Dopamine replacement therapy in PD has been associated with both behavioral addictions and dopamine addiction.To investigate potential association between l-dopa induced neuropsychiatric fluctuations and addictions in PD.A cohort of 102 patients with PD suffering from motor complications of l-dopa treatment was prospectively analyzed. We evaluated dopamine addiction, behavioral addictions, and neuropsychiatric fluctuations using the Ardouin scale of behavior in PD.Patients with (n = 51) or without (n = 51) neuropsychiatric fluctuations did not differ in age, disease duration, medication, or UPDRS III motor score during on and off drug condition. Patients with neuropsychiatric fluctuations had a higher HY stage in off-drug condition. A multivariate model showed that dopamine addiction (odds ratio: 8.9; P = 0.02) and behavioral addictions (odds ratio: 3.76; P = 0.033) were more frequent in the presence of neuropsychiatric fluctuations. Behavioral addictions and dopamine addiction were more frequent in the presence than in the absence of on-drug euphoria (46% vs. 13.9%; P 0.001 and 27% vs 6.2 %; P = 0.003), while conversely, no association emerged between dopamine or behavioral addictions and presence of off-drug dysphoria. Patients with neuropsychiatric fluctuations had a poorer quality of life and a more frequent history of anxiety disorder.The psychostimulant effects of dopamine treatment during on-drug euphoria, rather than avoidance of off-drug dysphoria, appear to drive both behavioral addictions and abuse of medication. © 2017 International Parkinson and Movement Disorder Society.

The aim of this work was to study cerebral vasoreactivity to hypercapnia in Parkinson's disease (PD) before and after levodopa administration. The prospective study was conducted in 20 patients presenting with PD, using 3T blood oxygenation level-dependent (BOLD) functional MRI (fMRI) covering the whole brain. The hypercapnic stimulus was block-designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L-dopa dose (ON). Ten age-matched controls were enrolled for between-group comparisons. Analyses were conducted with a random effects model and corrected for multiple comparisons. No adverse reaction to the hypercapnic stimulus was reported. However, 10 patients and 2 controls were excluded because of incomplete protocol realization, inappropriate hypercapnic stimulus, or excessive movements, leaving 10 patients and 8 controls for further analyses. The hypercapnic stimulus increased whole-brain BOLD signal of 1.48% ± 0.06% (mean ± standard error) in controls, 1.59% ± 0.05% in patients OFF, and 1.62% ± 0.09% in patients ON. Regions of interest analyses showed a signal increase in gray matter of 2.60% ± 0.16% in controls, 2.89% ± 0.21% in patients OFF, and 2.87% ± 0.12% in patients ON. No global or regional significant difference was detected, when comparing patients OFF and ON L-dopa, or between patients and controls. Contrary to Alzheimer's disease, the vasoreactivity to hypercapnia was normal in PD before and after L-dopa administration, compared to controls. This negative result is an important finding, especially for neuroscientists using fMRI to investigate motricity and cognition, discarding a significant confounding effect.

Background Levodopa therapy in Parkinson9s disease (PD) is associated with non-motor complications resulting from sensitisation of the ventral striatum system. Recent studies showed an improvement in non-motor complications in PD patients with subthalamic stimulation. We hypothesised that ventral striatum desensitisation might contribute to this improvement. Methods Psychostimulant effects of levodopa were prospectively assessed in 36 PD patients with an acute levodopa challenge, before and 1 year after chronic subthalamic stimulation, using the Addiction Research Centre Inventory euphoria subscale. Postoperative evaluation was performed with the same dose of levodopa used in the preoperative assessment and after switching off stimulation. Preoperative and postoperative non-motor fluctuations in everyday life were investigated with the Ardouin Scale. Furthermore, in order to artificially reproduce non-motor fluctuations, a levodopa challenge keeping subthalamic stimulation on was performed to assess depression, anxiety and motivation before and after surgery under the different medication conditions. Results After 1 year of chronic subthalamic stimulation with 60.3% reduction in dopaminergic medication, the acute psychostimulant effects of levodopa were significantly reduced compared with preoperatively, as measured by the euphoria subscale (7.22±4.75 vs 4.75±5.68; p=0.0110). On chronic subthalamic stimulation and with markedly reduced dopaminergic medication, non-motor fluctuations were significantly improved. While off medication/on stimulation scores of depression and anxiety were improved, in the on medication/on stimulation condition the motivation score worsened. Conclusions Acute psychostimulant effects of levodopa (off stimulation) were significantly reduced 1 year after surgery. These findings are likely due to desensitisation of the ventral striatum, allowed by the reduction of dopaminergic treatment, and the replacement of pulsatile treatment with continuous subthalamic stimulation.

Object The aim of this study was to study the effects of MR imaging on the electrical settings of deep brain stimulation (DBS) systems and their clinical consequences. Methods The authors studied the effects of 1.5-T MR imaging on the electrical settings of implanted DBS systems, including 1 or more monopolar or quadripolar leads, extension leads, and single- or dual-channel implantable pulse generators (IPGs). The IPG was switched off during the procedure and the voltage was set to 0. The impedances were checked before and after MR imaging. Results Five hundred seventy patients were treated with DBS for movement disorders and underwent brain MR imaging after lead implantation and before IPG implantation. None of the patients experienced any adverse events. Thirty-one of these patients underwent 61 additional MR imaging sessions after the entire DBS system had been implanted. The authors report neither local cutaneous nor neurological disorders during or after the MR imaging session. No change in the IPG settings occurred when the magnet reed switch function remained disabled during the procedure. Conclusions This study demonstrates that 1.5-T MR imaging can be performed safely with continuous monitoring in patients with a DBS system. The ability to disable the magnet reed switch function of the IPG prevents any change in the electrical settings and thus any side effects. The increasing number of DBS indications and the widespread use of MR imaging indicates the need for defining safety guidelines for the use of MR imaging in patients with implanted neurostimulators.

Introduction/Background The pathophysiology of Pisa Syndrome (PS), lateral trunk tilt occurring in the advanced stages of Parkinson's disease (PD), remains to be solved. It might be the consequence of biased spatial referentials. We comprehensively investigated the representation of the vertical (visual-VV and postural-PV), together with that of the long body axis (LBA) in PD patients with PS. Material and method Double-blind controlled trial in 18 PD patients showing PS and treated with bilateral deep brain stimulation (DBS) of the subthalamic nuclei (STN): 63.5 [5.5] years, 11 females, disease duration 17.5 [5.2] years. Spatial estimates were tested off medication under four conditions of stimulation (bilateral on, bilateral off, unilateral on/off, unilateral off/on). Motor state (UPDRS), scoliosis and lateral trunk tilt were also assessed. Twenty healthy age- and gender-matched participants were also included. Results The median lateral trunk tilt was 7.5° (IQD = 5) under the instruction to stand upright. Scoliosis was frequent (67%) reaching 82% in participants with severe PS, of moderate magnitude (16° [12.5]), and side congruent with that of the PS (67%). The correlation between PS and scoliosis (Cobb) magnitude was strong (r = 0.71, P = 0.008). In contrast no concordance was found between the side of the PS and disease sides (10/18 tilted to the side of the most denervated striatum; 11/18 tilted toward the most affected hemibody). Spatial perceptions were more frequently biased in patients than in controls (P 0.05). No statistical rule was found between any of biased referential (side or magnitude) and the trunk tilt (side or magnitude). No spatial referential was modulated by DBS. Conclusion Spatial biases are frequently in PS but are not the cause of the lateral trunk tilt. In contrast scoliosis was not only strongly associated to severe PS. We found a troubling concordance in sides and magnitude.

We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-live STN patients and 16 GPi patienis were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN. P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with of regardless of the sequence of stimulation. In open assessment. both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN. P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS advanced PD. Although the surgical targets were not randomized, there was a trend to 1 better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group. (C) 2010 Movement Disorder Society

Stimulation (DBS) of the globus pallidus (GP) is effective to treat generalized dystonia. Little is known about the evolution of dystonia in case of arrest after a long period of stimulation. This study describes the course of dystonia during a 48 hours period without stimulation followed by a 24 hours period after turning ON the stimulator. 14 patients with generalized dystonia treated with bilateral GP DBS for 3 years or more were recruited. Blinded video-based analysis was performed using Burke-Fahn-Marsden scale at (1) baseline (ON stimulation), (2) up to 48 hours after the stimulator was turned OFF, and (3) 24 hours after the stimulator was turned ON. 13 patients completed the 48 hours OFF-stimulation period. The dystonia movement score progressively worsened from 24.3 +/- 13.9 at baseline to 48.9 +/- 19.8 after 48 hours (P < 0.00001). The disability score also worsened from 4.4 +/- 1.2 at baseline to 5.7 +/- 1.5 after 48 hours without stimulation (P < 0.001). When the neurostimulator was turned ON, the dystonia scores returned to baseline level after 10 hours. The interruption of GP DBS in dystonia results in a progressive worsening which is rapidly reversible once the neurostimulator is turned ON.

We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time.

Les syndromes parkinsoniens sont une cause importante de handicap, en particulier chez les sujets âges. L’IRM a une place importante dans la prise en charge diagnostique et therapeutique de ces patients. Orientee par l’anamnese et l’examen clinique, l’IRM conventionnelle est habituellement normale dans la maladie de Parkinson alors que des anomalies evocatrices de pathologies neurodegeneratives (atrophie multi-systematisee, paralysie supra nucleaire progressive…) ou de diverses pathologies (hypoxiques, toxiques, familiales…) doivent etre recherchees. En recherche clinique, les techniques avancees (spectroscopie, diffusion, IRM fonctionnelle) offrent une etude anatomo-fonctionnelle et metabolique de la physiopathologie de ces affections.

See Schrag and Politis (doi:[10.1093/aww190][1]) for a scientific commentary on this article . Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson’s disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson’s disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ −21) and 15 non-apathetic (−36 ≤ Lille Apathy Rating Scale scores ≤ −22) drug-naive de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [11C- N -(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane (PE2I)] ( n = 29) and serotonergic [11C- N , N -dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine (DASB)] ( n = 27) presynaptic transporter radioligands. Apathetic parkinsonian patients presented higher depression ( P = 0.0004) and anxiety ( P = 0.004) scores – as assessed using the Beck Depression Inventory and the part B of the State-Trait Anxiety Inventory, respectively – compared to the non-apathetic ones – who were not different from the age-matched healthy subjects ( n = 15). Relative to the controls, the non-apathetic parkinsonian patients mainly showed dopaminergic denervation ( n = 14) within the right caudate nucleus, bilateral putamen, thalamus and pallidum, while serotonergic innervation ( n = 15) was fairly preserved. Apathetic parkinsonian patients exhibited, compared to controls, combined and widespread dopaminergic ( n = 15) and serotonergic ( n = 12) degeneration within the bilateral caudate nuclei, putamen, ventral striatum, pallidum and thalamus, but also a specific bilateral dopaminergic disruption within the substantia nigra–ventral tegmental area complex, as well as a specific serotonergic alteration within the insula, the orbitofrontal and the subgenual anterior cingulate cortices. When comparing the two parkinsonian groups, the apathetic patients mainly displayed greater serotonergic alteration in the ventral striatum, the dorsal and the subgenual parts of the anterior cingulate cortices, bilaterally, as well as in the right-sided caudate nucleus and the right-sided orbitofrontal cortex. Regression analyses also revealed that the severity of apathy was moreover mainly related to specific serotonergic lesions within the right-sided anterior caudate nucleus and the orbitofrontal cortex, while the degree of both depression and anxiety was primarily linked to serotonergic disruption within the bilateral subgenual parts and/or the right dorsal part of the anterior cingulate cortex, without prominent role of the dopaminergic degeneration in the pathogenesis of these three non-motor signs. Altogether, these findings highlight a prominent role of the serotonergic degeneration in the expression of the neuropsychiatric symptoms occurring at the onset of Parkinson’s disease. * Abbreviations : ACC : anterior cingulate cortex BDI : Beck Depression Inventory BPND : non-displaceable binding potential DASB : N , N -dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine DAT : dopaminergic transporter GPe : globus pallidus pars externa or external pallidum LARS : Lille Apathy Rating Scale MDS-UPDRS : Movement Disorders Society Unified Parkinson’s Disease Rating Scale OFC : orbitofrontal cortex PE2I : N -(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane SERT : serotonergic transporter SN-VTA : substantia nigra–ventral tegmental area STAI-YB : State-Trait Anxiety Inventory part B [1]: /lookup/doi/10.1093/brain/aww190

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Item does not contain fulltext BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson's disease (PD) and motor complications of dopaminergic treatment. Whether STN-DBS should be considered when PD patients experience neuropsychiatric symptoms is controversial. Lack of systematic behavioral evaluation at baseline hampers the understanding of postoperative neuropsychiatric outcomes. OBJECTIVE: This study compares the behavioral profile of a surgical population to that in general PD. METHODS: Single center data from 234 PD surgical candidates were compared to data from 260 non-demented PD patients consulting in 13 PD expert centers at different stages of disease. The latter were considered representative of the general PD population. Neuropsychiatric symptoms were assessed using the Ardouin Scale of Behavior in PD, a guided interview quantifying changes in severity of 21 neuropsychiatric symptoms, classified into psychic non-motor fluctuations, hypo- and hyperdopaminergic behaviors. Multivariate analyses were performed to study differences in behavioral items between the two groups. RESULTS: Surgical candidates were younger, had longer disease duration and used significantly higher doses of dopaminergic drugs. After adjustment for covariates, dopaminergic addiction (OR 10.83; p = 0.002), nocturnal hyperactivity (OR 1.87; p = 0.04), excessive hobbyism (OR 2.37; p = 0.008), "excess in motivation" (OR 4.02; p < 0.001), psychic OFF (2.87; p < 0.001) and psychic ON (2.10; p = 0.001) fluctuations were more frequent in the surgical candidates. Depressed mood prevailed in the general PD population (OR 0.53; p = 0.045). CONCLUSION: Behavioral complications of dopaminergic treatment are frequent in PD patients candidates for STN-DBS. They cannot be considered as contraindications for STN-DBS but must be taken into account in postoperative management.

Action tremor has been described in cerebellar, task-specific, dystonic, or Holmes tremor. We report 2 patients who developed unilateral kinetic or isometric action tremor of the upper extremity, following cervical spondylotic myelopathy and capsular ischemic stroke. Slight motor weakness and spasticity with exaggerated tendon jerks and passive stretch-induced clonus were present on the same limb. The central motor pathways lesions might have been responsible for a hyperexcitability of the stretch-reflex arc and an enhancement of the coactivation of skeletal muscles through a loss of the descending or segmental control of the spinal reflexes. The unusual topography of the symptoms, their occurrence during motion, and the similar frequency of the passive clonus and the action tremor, led us to hypothesize that both patients had prolonged action-induced clonus, mimicking action tremor. Lesions of the central motor pathways lesions might be responsible for action tremor under certain conditions.

International audience; The electrical effects on the nervous system have been known for long. The excitatory effect has been used for diagnostic purposes or even for therapeutic applications, like in pain using low-frequency stimulation of the spinal cord or of the thalamus. The discovery that High-Frequency Stimulation (HFS) mimics the effect of lesioning has opened a new field of therapeutic application of electrical stimulation in all places where lesion of neuronal structures, such as nuclei of the basal ganglia, had proven some therapeutic efficiency. This was first applied to the thalamus to mimic thalamotomy for the treatment of tremor, then to the subthalamic nucleus and the pallidum to treat some advanced forms of Parkinson's disease and control not only the tremor but also akinesia, rigidity and dyskinesias. The field of application is increasingly growing, currently encompassing dystonias, epilepsy, obsessive compulsive disease, cluster headaches, and experimental approaches are being made in the field of obesity and food intake control. Although the effects of stimulation are clear-cut and the therapeutic benefit is clearly recognized, the mechanism of action of HFS is not yet understood. The similarity between HFS and the effect of lesions in several places of the brain suggests that this might induce an inhibition-like process, which is difficult to explain with the classical concept of physiology where electrical stimulation means excitation of neural elements. The current data coming from either clinical or experimental observations are providing elements to shape a beginning of an understanding. Intra-cerebral recordings in human patients with artefact suppression tend to show the arrest of electrical firing in the recorded places. Animal experiments, either in vitro or in vivo, show complex patterns mixing inhibitory effects and frequency stimulation induced bursting activity, which would suggest that the mechanism is based upon the jamming of the neuronal message, which is by this way functionally suppressed. More recent data from in vitro biological studies show that HFS profoundly affects the cellular functioning and particularly the protein synthesis, suggesting that it could alter the synaptic transmission by reducing the production of neurotransmitters. It is now clear that this method has a larger field of application than currently known and that its therapeutical applications will benefit to several diseases of the nervous system. The understanding of the mechanism has opened a new field of research, which will call for reappraisal of the basic effects of electricity on the living tissues.

Resume Le traitement neurochirurgical de la maladie de Parkinson (MP) par stimulation cerebrale profonde (SCP) a ete introduit pour la premiere fois en 1987. Il a depuis lors connu un developpement considerable lie non seulement aux limites du traitement medicamenteux mais egalement a l’amelioration des techniques d’imagerie cerebrale et aux progres realises dans la connaissance du fonctionnement des ganglions de la base. Le tremblement resistant au traitement medicamenteux et les complications motrices liees a la levodopa constituent les principales indications de SCP dans la MP. Le noyau ventral intermediaire du thalamus (Vim) fut la premiere cible utilisee pour le traitement des tremblements severes. L’inconstance des effets observes sur la rigidite et l’akinesie parkinsoniennes ainsi que sur les dyskinesies liees a la levodopa limite les indications de la stimulation du Vim au traitement du tremblement essentiel invalidant. Le pallidum interne et le noyau subthalamique sont les deux autres cibles indiquees dans le traitement des formes severes de MP. La stimulation du pallidum interne est indiquee chez des patients presentant des dyskinesies invalidantes. Elle a l’avantage de pouvoir etre realisee de facon bilaterale, sans complication arthrique, posturale ou neuropsychologique majeure par rapport aux pallidotomies. La taille et la complexite de fonctionnement de la structure pallidale sont vraisemblablement a l’origine de la variabilite des effets observes et des resultats obtenus par differentes equipes. Le noyau subthalamique constitue la cible de reference pour le traitement neurochirurgical de la MP. Sa stimulation chronique permet de controler l’ensemble des symptomes de la triade parkinsonienne. L’amelioration de l’etat moteur permet de reduire considerablement le traitement medicamenteux et, par ce mecanisme, les dyskinesies liees a la levodopa. Des complications severes peuvent survenir dans 2 a 4 p. 100 des cas. Il s’agit d’infections sur materiel implante et de contusions hemorragiques. Ces techniques neurochirurgicales ne peuvent etre mises en œuvre que par des equipes pluridisciplinaires regroupant des neurochirurgiens experts en stereotaxie fonctionnelle, des neurologues specialises dans les troubles du mouvement, des neuroradiologues, des neuropsychologues et des kinesitherapeutes. Ce sont des techniques sophistiquees dont l’indication doit etre posee avec discernement.

background Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson’s disease have been well documented, the long-term outcomes of the procedure are unknown. methods We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson’s Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. results As compared with base line, the patients’ scores at five years for motor function while off medication improved by 54 percent (P

Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported. To determine in Parkinson’s disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release. Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping. For PD patients, the mean [11C]-Raclopride BP (± SD) were, in Off stimulation condition: 1.7 ± 0.3 for the right caudate nucleus, 1.8 ± 0.4 for the left caudate nucleus, 2.6 ± 0.5 for the right putamenand 2.6 ± 0.5 for the left putamen. In On stimulation condition: 1.7 ± 0.4 for the right caudate nucleus, 1.9 ± 0.5 for the left caudate nucleus, 2.8 ± 0.7 for the right putamen and 2.7 ± 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted. STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.

Parkin gene mutations are reported to be a major cause of early-onset parkinsonism (age at onset < or = 45 years) in families with autosomal recessive inheritance and in isolated juvenile-onset parkinsonism (age at onset

To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations.