French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

Validation of a non-motor fluctuations questionnaire in Parkinson's disease.

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.

[Effectiveness of sacral neuromodulation in patients with Parkinson's disease]. / Efficacité de la neuromodulation sacrée chez le patient parkinsonien.

INTRODUCTION: The urinary disorders of the patients with Parkinson's disease are complex and have a negative impact on their quality of life. None of therapy is considered effective ; whether drug or surgical. Sacral neuromodulation, recommended in other neurological pathologies such as multiple sclerosis, has never been studied in the patients with Parkinson's disease. The objective of our study is to assess the efficacy of sacral neuromodulation in the patients with Parkinson's disease. MATERIAL AND METHOD: Multicentric retrospective cohort study, of 22 parkinsonian patients who underwent a sacral neuromodulation test. Epidemiological, clinical and urodynamic data were collected for each patient. A long-term effectiveness telephone survey was conducted. RESULTS: Twenty two patients with Parkinson's disease had a sacral neuromodulation test. 17/22 (77%) had Idiopathic Parkinson's Disease and 5/22 (23%) had Systematized Multi Atrophy. Clinically, the indication for the sacral neuromodulation test was overactive bladder in 68% of the cases. Urodynamically, detrusor hyperactivity is found in 12 patients (8 MPI, 4 AMS). Sacral neuromodulation was effective in only 7 patients (6 MPI and 1 AMS). Rather, the profile of the patient in whom NMS is effective is female, mature, and with PID. The long-term effectiveness of NMS is disappointing. Only 2 permanently implanted patients retained urinary benefit. CONCLUSION: NMS improves urinary symptoms in the patients with Parkinson's disease in 32% of cases. It fluctuates over time and loses its effectiveness in the long term.

Psycho-sensory modalities of visual hallucinations and illusions in Parkinson's disease.

BACKGROUND: Visual illusions (VI) in Parkinson's disease (PD) are generally considered part of the prodrome towards fully formed visual hallucinations (VH), and classified as minor hallucinations. However, this sequential relationship has not been clearly demonstrated and very little is known about the specific phenomenology of VI in regards to VH. We aimed to describe and compare psycho-sensory modalities associated with VI and VH in PD patients. METHODS: PD patients with VI (PD-I, n=26) and VH (PD-H, n=28) were included in this case-controlled study. We compared qualitative and quantitative psycho-sensory modalities of VI and VH using the PsychoSensory hAllucinations Scale (PSAS), and demographical and clinical features of each group. RESULTS: PD-I perceptions were more often colored blots (P=0.05) or objects (P=0.005) compared to PD-H. Conversely, PD-H perceptions were more often described as animals (P<0.001), occurring at night (P=0.03) compared to PD-I. The experienced phenomena were more frequent in PD-H (P=0.02), and lasted longer (P=0.02) than for PD-I, but no between-group difference was observed for other repercussion factors including negative aspect, conviction, impact, controllable nature of the perception. Passage hallucinations and sense of presence were observed in both groups with similar frequencies (respectively P=0.60 and P=0.70). Multivariate analysis adjusting for disease severity or duration confirmed these results. CONCLUSION: VI and VH in PD have different qualitative sensory modalities, with similar quantitative repercussion for patients, and similar association with modalities such as "sense of presence and passage hallucinations", in contrast to the generally accepted classification of VI as minor VH. REGISTRATION NUMBER: clinicaltrials.gov number NCT03454269.

Subacute corticobasal syndrome following internal carotid endarterectomy.

The present report is of two patients who, immediately after internal carotid endarterectomy, presented with unexplained hemiplegia, despite normal findings on repeated MRI scans, which secondarily evolved into homolateral subacute corticobasal syndrome (CBS), with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denervation. This prompted us to propose an hypothesis of transient cerebral hypoxia arising during the surgical clamping period that might have provoked a prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI but only synaptic rearrangement of the neural networks, thereby revealing or exacerbating a potentially preexisting silent impairment.

Impact of localisation of deep brain stimulation electrodes on motor and neurobehavioural outcomes in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents a well-established treatment in advanced Parkinson's disease (PD) for motor signs, but it is still debated concerning psychiatric effects. OBJECTIVE: Exploration of relation between position of active electrode contacts and neuropsychological and motor change after STN DBS procedure for PD. METHODS: A cohort of 34 patients who underwent STN DBS was followed for 6 months. Preoperative and postoperative assessments included mood evaluation (depression and mania) and motor status. Active contact localisation was identified regarding position into the STN (4 groups: IN meant contacts were IN-IN IN-BORDER; OUT: OUT-OUT or OUT-BORDER; BORDER: BORDER-BORDER; IN-OUT: IN-OUT) and compared with clinical outcomes. RESULTS: STN DBS significantly improved motor scores and reduced dopaminergic medication when compared with baseline and active lead groups: the best result was seen with the IN group. At 3 and 6 months postsurgery, depression and manic scores do not significantly differ compared with baseline and between leads groups. Focusing on symptom domains and compared with baseline, a significant loss of appetite was observed for the IN group at M3 and a significant increase in appetite from baseline was observed at M3 for the OUT group. Graphic representations illustrate that postsurgery evolution parameters at M3 or M6 are very good discriminant variables and well differentiate all leading groups. CONCLUSIONS: Stimulation of zona incerta may influence appetite and weight gain. Our clinical results seem to support a personalised DBS-targeted Parkinson therapy including individual motor and non-motor parameters.

French consensus procedure for assessing cognitive function in Parkinson's disease.

INTRODUCTION: One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. METHODS: A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. RESULTS: Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. DISCUSSION AND CONCLUSION: A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease.

Increased risk of impulse control symptoms in Parkinson's disease with REM sleep behaviour disorder.

OBJECTIVE: To assess the frequency of symptoms of impulse control disorders (ICD, namely pathological gambling, compulsive sexual behaviour, compulsive eating and compulsive shopping) and related behaviours (hobbyism, punding, walkabout and dopamine dysregulation syndrome) in patients with Parkinson's disease (PD) with and without probable rapid eye movement, sleep behaviour disorder (pRBD). METHODS: Two hundred and sixteen consecutive PD patients, attending two university-based movement disorders clinics, were screened for p-RBD using the RBD Single Question and the RBD Screening Questionnaire (RBDSQ). Current ICDs and related behaviours symptoms were assessed with the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP)-short form. RESULTS: PD-pRBD patients (n=106/216;49%) had a longer PD duration, a higher Hoehn & Yahr score, a greater levodopa-equivalent daily dose (LEDD), but no difference in dopamine agonist use, compared to PD-without pRBD. A higher proportion of one or more current ICDs and related behaviours symptoms was reported in PD-pRBD compared to PD-without RBD (53% vs28%; p=0.0002). In a multivariate regression analysis accounting for gender, age of onset, PD duration, PD severity, depression score and total and dopaminergic agonist-LEDD, RBD was associated to a relative risk of 1.84 for any ICD or related behaviours symptoms (p=0.01), and to a risk of 2.59 for any ICD symptoms only (p=0.001). Furthermore, PD-pRBD had a more than fourfold risk for symptoms of pathological gambling (relative risk (RR): 4.87; p=0.049) compared to PD-without pRBD. CONCLUSIONS: The present study indicates that RBD is associated with an increased risk of developing symptoms of ICDs in PD. Identifying RBD in PD may help clinicians to choose the best therapeutic strategy. TRIAL REGISTRATION: AU1023 Institutional Ethics Committee.

A case-control study investigating food addiction in Parkinson patients.

Eating disorders (EDs) in patients with Parkinson's disease (PD) are mainly described through impulse control disorders but represent one end of the spectrum of food addiction (FA). Although not formally recognized by DSM-5, FA is well described in the literature on animal models and humans, but data on prevalence and risk factors compared with healthy controls (HCs) are lacking. We conducted a cross-sectional study including 200 patients with PD and 200 age- and gender-matched HCs. Characteristics including clinical data (features of PD/current medication) were collected. FA was rated using DSM-5 criteria and the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R). Patients with PD had more EDs compared to HCs (27.0% vs. 13.0%, respectively, p < 0.001). They mainly had FA (24.5% vs. 12.0%, p = 0.001) and night eating syndrome (7.0% vs. 2.5% p = 0.03). In PD patients, FA was associated with female gender (p = 0.04) and impulsivity (higher attentional non-planning factor) but not with the dose or class of dopaminergic therapy. Vigilance is necessary, especially for PD women and in patients with specific impulsive personality traits. Counterintuitively, agonist dopaminergic treatment should not be used as an indication for screening FA in patients with PD.

[The Idiopathic Parkinson's disease: A metabolic disease?]. / La maladie de Parkinson idiopathique : une maladie métabolique ?

Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.

Parkinson's disease polygenic risk score is not associated with impulse control disorders: A longitudinal study.

OBJECTIVE: To examine the relationship between a Parkinson's disease (PD) polygenic risk score (PRS) and impulse control disorders (ICDs) in PD. BACKGROUND: Genome wide association studies (GWAS) have brought forth a PRS associated with increased risk of PD and younger disease onset. ICDs are frequent adverse effects of dopaminergic drugs and are also more frequent in patients with younger disease onset. It is unknown whether ICDs and PD share genetic susceptibility. METHODS: We used data from a multicenter longitudinal cohort of PD patients with annual visits up to 6 years (DIG-PD). At each visit ICDs, defined as compulsive gambling, buying, eating, or sexual behavior were evaluated by movement disorders specialists. We genotyped DNAs using the Megachip assay (Illumina) and calculated a weighted PRS based on 90 SNPs associated with PD. We estimated the association between PRS and prevalence of ICDs at each visit using Poisson generalized estimating equations, adjusted for dopaminergic treatment and other known risk factors for ICDs. RESULTS: Of 403 patients, 185 developed ICDs. Patients with younger age at onset had a higher prevalence of ICDs (p < 0.001) as well as higher PRS values (p = 0.06). At baseline, there was no association between the PRS and ICDs (overall, p = 0.84). The prevalence of ICDs increased over time similarly across the quartiles of the PRS (overall, p = 0.88; DA users, p = 0.99). CONCLUSION: Despite younger disease onset being associated with both higher PRS and ICD prevalence, our findings are not in favor of common susceptibility genes for PD and ICDs.

Does REM sleep behavior disorder change in the progression of Parkinson's disease?

OBJECTIVES/BACKGROUND: Rapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD. PATIENTS/METHODS: In sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years. RESULTS: At follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = -0.57,p = 0.04). CONCLUSION: Despite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

New electrophysiological mapping combined with MRI in parkinsonian's subthalamic region.

The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson's disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel's field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2-mm anterior track. We calculated off-line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on-line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2-ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.

Overweight after deep brain stimulation of the subthalamic nucleus in Parkinson disease: long term follow-up.

OBJECTIVE: To assess the occurrence of weight gain in patients with Parkinson's disease, with an average 16 months of follow-up after subthalamic nucleus deep brain stimulation. METHODS: We used dual x ray absorptiometry to evaluate changes in body weight and body composition in 22 patients with Parkinson's disease (15 men and seven women) before surgery, 3 months after surgery and on average 16 months after surgery. RESULTS: No patient was underweight before surgery and 50% were overweight. By contrast, 68% were overweight or obese 3 months after surgery and 82% after 16 months (p<0.001). For men, the mean increase in body mass index (BMI) was 1.14 (0.23) kg/m(2) 3 months after surgery and 2.02 (0.36) kg/m(2) 16 months after surgery. For women, the mean increases in BMI at the same evaluation times were 1.04 (0.30) kg/m(2) and 2.11 (0.49) kg/m(2). This weight gain was mainly secondary to an increase in fat mass in both men and women. Three months after surgery, acute subthalamic deep brain stimulation induced an improvement in parkinsonian symptoms (evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III) by 60.7 (2.9)% in the "off" dopa condition and a dramatic improvement of motor complications (dyskinesia duration: 82.8 (12.8)%, p<0.0001; off period duration: 92.7 (18.8)%, p<0.0001). CONCLUSION: Although subthalamic nucleus deep brain stimulation significantly improved parkinsonian symptoms and motor complications, many patients became overweight or obese. This finding highlights the necessity to understand the underlying mechanisms and to provide a diet management with a physical training schedule appropriate for patients with Parkinson's disease.

Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls.

BACKGROUND: Mutations in the parkin gene cause autosomal recessive early-onset parkinsonism. The effect of single heterozygous mutations in parkin is still unclear. The aim of this study was to evaluate the frequency of exonic parkin variants in a case-control study. METHODS: The parkin gene was screened for both point mutations and exon rearrangements in 172 French patients with Parkinson disease (PD) and 170 controls from the same population. Patients with single parkin variants were also screened for PINK1, DJ-1 and LRRK2 exon 41 mutations. RESULTS: 10 exonic sequence variations were identified, including 3 known polymorphisms and 7 rare heterozygous variants, 2 of which were novel. There were significantly more rare heterozygous variants in patients (n = 10) with early-onset PD than in controls (n = 2). Screening of PINK1, DJ-1 and LRRK2 exon 41 in the 10 patients heterozygous for parkin failed to identify a second causative mutation. CONCLUSION: These results suggest that single parkin mutations increase the risk of early-onset PD, but the possibility of a second parkin mutation cannot be excluded.

[Assessment of hyper- and hypodopaminergic behaviors in Parkinson's disease]. / Evaluation des troubles comportementaux hyper- et hypodopaminergiques dans la maladie de Parkinson.

The common perception that Parkinson's disease patients tend to be depressed, anxious, apathetic and harm-avoiding has currently been challenged by the recognition that they can also exhibit a hedonistic, novelty-seeking personality. Thus, Parkinson's disease patients may indulge in their passions in an irresponsible and disinhibited manner, and engage in repetitive, compulsive behaviors that may be harmful and destructive to their social or professional lives. The dopamine dysregulation syndrome includes hypersexuality, pathological gambling, and compulsive shopping; it is associated with addiction to dopaminergic medication. However, not all behavioral changes are necessarily accompanied by a dopaminergic addiction. After antiparkinson treatment is initiated, patients enter a 'honeymoon period' during which changes in mood and behavior reflect a return to the patients' premorbid personality. The increased motivation and higher level of activity in professional as well as leisure activities are considered positive changes by both the patients and their relatives. With prolonged and increased dopaminergic treatment, these positive behavioral changes can become excessive and evolve into nocturnal hyperactivity and stereotyped, repetitive and time consuming behaviors which ultimately disorganize the patient's everyday routine and herald behavioral addictions. These drug-induced behavioral changes are under-appreciated by neurologists and under-reported by the patients who neither complain about the behaviors nor understand the relationship between motivated behavior and dopaminergic medication. For these reasons, we propose a new scale for the assessment of behavior and mood to quantify and track changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This scale is based on the concept of hypo- and hyperdopaminergic mood and behavior. The scale consists of 18 items addressing non-motor symptoms, grouped in four parts: general psychological evaluation, apathy, non-motor fluctuations and hyperdopaminergic behaviors. The rating in five points (0-4 from absent to severe) is carried out during a semi-structured interview. Open-ended questions introduce each item, allowing patients to express themselves as freely as possible. Close-ended questions permit the rating of severity and intensity. This new instrument can be used by psychologists, psychiatrists or neurologists familiar with Parkinson's disease. Designed to detect changes in mood and behavior of Parkinson's disease patients resulting either from the disease or its treatment, this tool can be used in conjunction with the neurocognitive evaluation, to help tailor the treatment of motor and non-motor symptoms to each individual's needs.