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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.

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.

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.

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.

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.

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

ObjectiveTo investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.MethodsWe performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson’s Disease Rating Scale (UPDRS) (UPDRS-III “off” and “on” medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.ResultsPDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.ConclusionImpaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.Clinicaltrials.gov identifierNCT00354133.

Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone.We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only.Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide.In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications.German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic.

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.

Introduction La lateropulsion apres AVC hemispherique a ete decrite empiriquement comme faisant partie du syndrome pusher (SP), qui comprend aussi un pushing actif, une resistance aux corrections posturales et une negligence spatiale. Nous avons analyse l’association de ces symptomes, ainsi que l’existence d’une anosognosie. Materiel et methode L’etude consiste en une analyse des donnees cliniques recueillies prospectivement a J30 chez des personnes admises consecutivement en reeducation neurologique apres un premier AVC hemispherique. Ils etaient classes en 3 groupes selon le Scale for Contraversive Pushing (SCP) : posture symetrique debout, lateropulsion sans ou avec pushing. L’heminegligence et l’anosognosie etaient evaluees par une batterie de tests conventionnels. Resultats Parmi les 178 personnes, la prevalence de lateropulsion etait de 26 % (14 % sans et 12 % avec pushing). Il existait une predominance hemispherique droite (46 % AVC D), ainsi qu’un gradient de lateralite (X2 = 5,6 ; p = 0,018) : tous les individus presentant un AVC D avec lateropulsion etaient droitiers. Heminegligence et lateropulsion etaient etroitement associees (F = 135,6 ; p Discussion/Conclusion Ces resultats montrent que l’heminegligence et l’anosognosie sont fortement associees a la lateropulsion, independamment de l’existence d’un comportement Pusher. Cette etude renforce l’idee que le SP est une forme dramatique de lateropulsion, et non un syndrome idiosyncratique. L’ensemble du spectre Lateropulsion-SP doit etre considere en reeducation.

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.

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.

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.

Recent researches suggested that postural disorders after stroke may be partly caused by a wrong referential of verticality, expressed by a lateropulsion behavior. The role played by lateropulsion in the postural and gait disorders after stroke remained to be investigated, which was the objective of the present study. Retrospective cohort study (2012–2017) of 147 consecutive patients investigated in a neurorehabilitation ward in average at 32.7 days after a first hemispheric stroke: age 62.8 ± 12.6 years, 41 females, 120 with infarction, 57 with right lesion. Trained physiotherapists assessed: lateropulsion with the Scale for Contraversive Pushing (SCP, 0-6), Balance disorders with the Postural Assessment Scale for Stroke (PASS, 0-36) and gait disorders with Lindmark Scale (0–6). Brain imaging was carefully checked (138 MRI, 9 CT). Patients with a malignant stroke, dementia, instable medical status that could interfere with balance and gait recovery, or those who refused the assessments were not included. Descriptive data are given in the form median (first-third quartile). One month poststroke, postural and gait data were: SCP 0 (0–0.25), PASS 32 (25–35) and Gait score 4 (2–6). Fifteen patients were pushers (10%), among them 80% had a right hemisphere stroke. A first result was to confirm that lateropulsion was more severe in right hemisphere stroke than in left (right 46% vs. left 10%, χ2 =47.7; P

Background Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson9s disease, leading to improvement in health-related quality of life (HRQoL). However, an excessive decrease in dopaminergic medication can lead to a withdrawal syndrome with apathy as the predominant feature. The present study aims to assess the impact of postoperative apathy on HRQoL. Methods A cohort of 88 patients who underwent STN-DBS was divided into two groups, those who were apathetic at 1 year and those who were not, as measured by the Starkstein scale. HRQoL was assessed using the Parkinson9s disease questionnaire 39 (PDQ-39) and was compared between the two groups. We also compared activities of daily living, motor improvement and motor complications (Unified Parkinson9s Disease Rating Scale, UPDRS), depression and anxiety, as well as cognition and drug dosages. Baseline characteristics and postoperative complications were recorded. Results One year after surgery, 27.1% of patients suffered from apathy. While motor improvement was significant and equivalent in both the apathy (−40.4% of UPDRS motor score) and non-apathy groups (−48.6%), the PDQ-39 score did not improve in the apathy group (−5.5%; p=0.464), whereas it improved significantly (−36.7%; p≤0.001) in the non-apathy group. Change in apathy scores correlated significantly with change in HRQoL scores (r=0.278, p=0.009). Depression and anxiety scores remained unchanged from baseline in the apathy group (p=0.409, p=0.075), while they improved significantly in patients without apathy (p=0.006, p≤0.001). A significant correlation was found between changes in apathy and depression (r=0.594, p≤0.001). Conclusions The development of apathy after STN-DBS can cancel out the benefits of motor improvement in terms of HRQoL. Systematic evaluation and management of apathy occurring after subthalamic stimulation appears mandatory.

Typical body weight changes are known to occur in Parkinson's disease (PD). Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand, an increasing number of patients show weight gain under dopamine replacement therapy or after surgery. These weight changes are multifactorial and involve changes in energy expenditure, perturbation of homeostatic control, and eating behavior modulated by dopaminergic treatment. Comprehension of the different mechanisms contributing to body weight is a prerequisite for the management of body weight and nutritional state of an individual PD patient. This review summarizes the present knowledge and highlights the necessity of evaluation of body weight and related factors, as eating behavior, energy intake, and expenditure in PD.

Apathy is one of the most common symptoms encountered in Parkinson's disease, and is defined as a lack of motivation accompanied by reduced goal-directed cognition, behaviour and emotional involvement. In a previous study we have described a delayed withdrawal syndrome after successful motor improvement related to subthalamic stimulation allowing for a major decrease in dopaminergic treatment. This withdrawal syndrome correlated with a diffuse mesolimbic dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being related to mesolimbic dopaminergic denervation, we performed a randomized controlled study using piribedil, a relatively selective D2/D3 dopamine agonist to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week prospective, placebo-controlled, randomized, double-blinded trial was conducted in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy Scale score > 14) following subthalamic nucleus stimulation. Patients received either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks. The primary end point was the improvement of apathy under treatment, as assessed by the reduction of the Starkstein Apathy Scale score in both treatment groups. Secondary end points included alleviation in depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints consisted in changes of the Robert Inventory score and Hamilton depression scales. An intention to treat analysis of covariance analysis was performed to compare treatment effects (P < 0.05). The number of premature study dropouts was seven in the placebo and five in the piribedil groups, mostly related to intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With piribedil, modifications in the Beck depression and anxiety scores were -19.8% and -22.8%, respectively versus +1.4% and -8.3% with placebo, without reaching significance level. Piribedil led to a trend towards improvement in quality of life (-16.2% versus +6.7% on placebo; P = 0.08) and anhedonia (-49% versus -5.6% on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score, improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005). Depression, measured by the Hamilton score, improved in the piribedil group (P = 0.05). No significant side effects were observed. The present study provides a class II evidence of the efficacy of the dopamine agonist piribedil in the treatment of apathy in Parkinson's disease.

Addictions to dopaminergic drugs or to pleasant behaviours are frequent and potentially devastating neuropsychiatric disorders observed in Parkinson's disease. They encompass impulse control disorders, punding and dopamine dysregulation syndrome. A relationship with dopaminergic treatment is strongly suggested. Subthalamic stimulation improves motor complications and allows for drastic reductions in medication. This treatment might, therefore, be considered for patients with behavioural addictions, when attempts to reduce dopaminergic medication have failed. However, conflicting data have reported suppression, alleviation, worsening or new onset of behavioural addictions after subthalamic stimulation. Non-motor fluctuations are also a disabling feature of the disease. We prospectively investigated behaviour in a cohort of 63 patients with Parkinson's disease, before and 1 year after subthalamic stimulation using the Ardouin scale, with systematic evaluation of functioning in overall appetitive or apathetic modes, non-motor fluctuations, dopaminergic dysregulation syndrome, as well as behavioural addictions (including impulse control disorders and punding) and compulsive use of dopaminergic medication. Defined drug management included immediate postoperative discontinuation of dopamine agonists and reduction in levodopa. Motor and cognitive statuses were controlled (Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, frontal score). After surgery, the OFF medication motor score improved (-45.2%), allowing for a 73% reduction in dopaminergic treatment, while overall cognitive evaluation was unchanged. Preoperative dopamine dysregulation syndrome had disappeared in 4/4, behavioural addictions in 17/17 and compulsive dopaminergic medication use in 9/9 patients. New onset of levodopa abuse occurred in one patient with surgical failure. Non-motor fluctuations were significantly reduced with improvements in off-dysphoria (P ≤ 0.001) and reduction in on-euphoria (P ≤ 0.001). There was an inversion in the number of patients functioning in an overall appetitive mode (29 before versus 2 after surgery, P ≤ 0.0001) to an overall apathetic mode (3 before versus 13 after surgery, P

International audience; Apathy has been reported to occur after subthalamic nucleus stimulation, a treatment of motor complications in advanced Parkinson's disease. We carried out a prospective study of the occurrence of apathy and associated symptoms, predictors and mechanisms in the year following subthalamic stimulation. Dopamine agonist drugs were discontinued immediately after surgery and levodopa was markedly reduced within 2 weeks. Apathy and depression were assessed monthly, using the Starkstein apathy scale and the Beck Depression Inventory. Dopamine agonists were re-introduced if patients developed apathy or depression. Preoperative non-motor fluctuations were evaluated using the Ardouin Scale. Depression, apathy and anxiety were evaluated both on and off levodopa. Analysis of predictors of apathy was performed using a Cox proportional hazard model. Twelve patients who developed apathy and a control group of 13 patients who did not underwent [11C]-raclopride positron emission tomography scanning before and after oral intake of methylphenidate. In 63 patients with Parkinson's disease treated with subthalamic stimulation, dopaminergic treatment was decreased by 82% after surgery. Apathy occurred after a mean of 4.7 (3.3-8.2) months in 34 patients and was reversible in half of these by the 12-month follow-up. Seventeen patients developed transient depression after 5.7 (4.7-9.3) months and these fell into the apathy group with one single exception. At baseline, fluctuations in depression, apathy and anxiety scores were greater in the group with apathy. Fluctuations in apathy, depression and anxiety ratings during a baseline levodopa challenge were also significant predictors of postoperative apathy in univariate analysis, but not motor and cognitive states or the level of reduction of dopaminergic medication. The multivariate model identified non-motor fluctuations in everyday life and anxiety score during the baseline levodopa challenge as two independent significant predictors of postoperative apathy. Without methylphenidate, [11C]-raclopride binding potential values were greater in apathetic patients bilaterally in the orbitofrontal, dorsolateral prefrontal, posterior cingulate and temporal cortices, left striatum and right amygdala, reflecting greater dopamine D2/D3 receptor density and/or reduced synaptic dopamine level in these areas. The variations of [11C]-raclopride binding potential values induced by methylphenidate were greater in non-apathetic patients in the left orbitofrontal cortex, dorsolateral prefrontal cortex, thalamus and internal globus pallidus and bilaterally in the anterior and posterior cingulate cortices, consistent with a more important capacity to release dopamine. Non-motor fluctuations are related to mesolimbic dopaminergic denervation. Apathy, depression and anxiety can occur after surgery as a delayed dopamine withdrawal syndrome. A varying extent of mesolimbic dopaminergic denervation and differences in dopaminergic treatment largely determine mood, anxiety and motivation in patients with Parkinson's disease, contributing to different non-motor phenotypes.

Resume Introduction Les troubles psychiques de la maladie de Parkinson peuvent etre classes dans deux categories opposees : hypodopaminergiques s’ils sont lies a la denervation dopaminergique et hyperdopaminergiques s’ils sont en rapport avec le traitement dopaminergique. Etat des connaissances L’apathie est le trouble comportemental le plus frequent dans la maladie de Parkinson. Elle fait partie d’un syndrome comportemental hypodopaminergique plus large comprenant, par ailleurs, l’anxiete et la depression. La stimulation subthalamique, autorisant un sevrage en traitement dopaminergique a un stade avance de la maladie de Parkinson, constitue un modele d’etude de certains signes non moteurs dopa-sensibles. Les fluctuations non motrices qui sont essentiellement des fluctuations de l’etat psychique traduisent une denervation mesolimbique mise en evidence en tomographie par emission de positons, la sensibilisation du systeme mesolimbique denerve expliquant les troubles comportementaux hyperdopaminergiques. Les signes psychiques lies a la denervation mesolimbique determinent la qualite de vie plus que les signes moteurs lies a la denervation nigrostriatale. Perspectives et conclusions Ces constatations nous amenent a proposer une nouvelle prise en charge de la maladie en soulignant : (1) l’importance du suivi neuropsychologique pour detecter les signes psychiques hypodopaminergiques appartenant a la maladie et les signes hyperdopaminergiques comportementaux lies au traitement et (2) en redefinissant le role respectif des agonistes dopaminergiques et de la L-dopa dans la prise en charge des signes non moteurs et moteurs.

Elevated plasma levels of numerous low molecular weight proteins (LMWP) in renal insufficiency are likely to contribute to the uremic syndrome. Dialysis-related amyloidosis, caused by the accumulation of beta 2-microglobulin (beta 2M), has highlighted the need for a renal replacement therapy that allows the elimination of LMWP in addition to small solutes. Synthetic membrane materials employed under hemofiltration conditions proved to be most effective in lowering elevated beta 2M plasma levels. In addition to convection, protein adsorption to artificial membrane materials is an important mechanism for beta 2M removal. Using an in vitro setup, 12 commercially available hemofilters representing 11 different membrane materials were perfused with human blood containing 125I-labeled plasma proteins. Under filtration conditions, total protein adsorption ranged from 338-2,098 mg/m2 of membrane surface, and the fraction of adsorbed LMWP varied between 14-70% of total protein adsorption and was negatively correlated to total protein adsorption. beta 2M adsorption showed up to an 8-fold difference between membranes, and was negatively correlated with total protein adsorption and positively correlated with the adsorption of LMWPs.

Protein disulfide isomerase (PDI) was considered to be involved in the hepatic uptake of certain organic anions because the protein is photoaffinity labeled by photolabile derivatives of the bile acid taurocholate. Several lines of evidences including photoaffinity labeling experiments indicated a close relationship between the uptake of bile acids and the organic anion bumetanide. The possible involvement of PDI in hepatic transport processes of these organic anions was tested with polyclonal antibodies raised against a PDI-beta-galactosidase fusion protein. Western blot analysis and immunofluorescence of intact hepatocytes showed that protein disulfide isomerase is located in sinusoidal rat liver plasma membranes. This protein is immunologically identical with microsomal PDI prepared from bovine liver. The plasma membrane form of PDI is, however, not labeled by photoactivated bumetanide as revealed by two-dimensional gel electrophoresis. These results indicate that, although a membrane-bound form of the PDI is present in the sinusoidal plasma membrane of rat hepatocytes, this protein is not involved in the hepatocellular uptake of the organic anion bumetanide.