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In this retrospective study, we longitudinally analyzed axial impairment and falls in people with Parkinson’s disease (PD) and subthalamic nucleus deep brain stimulation (STN-DBS). Axial scores and falling frequency were examined at baseline, and 1, 10, and 15 years after surgery. Preoperative demographic and clinical data, including PD duration and severity, phenotype, motor and cognitive scales, medications, and vascular changes on neuroimaging were examined as possible risk factors through Kaplan–Meier and Cox regression analyses. Of 302 individuals examined before and at 1 year after surgery, 102 and 57 were available also at 10 and 15 years of follow-up, respectively. Axial scores were similar at baseline and at 1 year but worsened at 10 and 15 years. The prevalence rate of frequent fallers progressively increased from baseline to 15 years. Preoperative axial scores, frontal dysfunction and age at PD onset were risk factors for axial impairment progression after surgery. Axial scores, akinetic/rigid phenotype, age at disease onset and disease duration at surgery predicted frequent falls. Overall, axial signs progressively worsened over the long-term period following STN-DBS, likely related to the progression of PD, especially in a subgroup of subjects with specific risk factors.

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.

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

Background Mood symptoms negatively affect quality of life of Parkinson's disease (PD); however little is known about the impact of behavioral disorders such as impulse control disorders, and non-motor fluctuations on quality of life. Objective To assess the impact of mood and behavioral disorders on quality of life in PD. Methods 136 (84% male) PD were included (mean age: 61 ± 8y; mean duration of disease: 8.8 ± 5.4y). Mood symptoms, behavioral disorders and non-motor fluctuations were detected and quantified using the recently validated "Ardouin Scale of Behavior in Parkinson's Disease". Motor symptoms were assessed using UPDRS and quality of life with the "39-item Parkinson's Disease Questionnaire". Results Both motor and non-motor factors significantly affected the quality of life of PD patients. Multivariate regression of the relationship between items of the quality of life questionnaire and the Ardouin Scale showed that alteration of patients' quality of life was strongly correlated with the presence of mood symptoms (such as depression, anxiety ...) and with non-motor fluctuations (especially in the OFF period). A significant correlation was also found between the number of symptoms and their severity, and the quality of life deterioration. Some behavioral disorders (compulsive buying / eating behavior) also negatively affected patient's quality of life to a lesser extent. Alternatively, excess in motivation and hobbyism behaviors had a positive impact on mobility and emotional well-being dimensions respectively of quality of life. Conclusions This study shows the main impact of mood symptoms and non-motor fluctuations on worsening quality of life in PD.

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

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.

Neuropsychiatric symptoms are common non-motor symptoms in Parkinson's disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states. Apathy belongs to the spectrum of hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy is a key symptom of PD which worsens with disease progression. Animal models, imaging and pharmacological studies concur in pointing out dopaminergic denervation in the aetiology of parkinsonian apathy with a cardinal role of decreased tonic D2/D3 receptor stimulation. ICDs are part of the hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine dysregulation syndrome (DDS), which are all related to non-physiological dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical observations in drug addiction and PD as well as data from studies in dopamine depleted rodents provide hints allowing to argue that both pulsatile D1 and D2 receptor stimulation and the severity of dopaminergic denervation are risk factors to develop punding behavior and DDS. Imaging studies have shown that the brain structures involved in drug addiction are also involved in hyperdopaminergic behaviours with increase of bottom-up appetitive drive and decrease in prefrontal top down behavioural control.

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