Search

Impairments in speech and executive functions are both observed in Parkinson's disease (PD) and might be influenced by subthalamic nucleus deep brain stimulation (STN-DBS). We investigated the effects of STN-DBS on speech and executive functions and their mutual interference in PD.14 PD patients eligible for bilateral STN-DBS (PD-DBS), and 16 PD patients with best medical treatment (PD-BMT) were included. Global cognition, executive functions (inhibition and verbal fluency), speech tasks with acoustic measures, and a dual-task (DT) combining a speech task with a Go or Go/NoGo task were performed at baseline and 12 months follow-up. A normative group of matched healthy participants was included at baseline for the evaluation of speech and DT performance.In both patient groups, global cognition mildly decreased after 12 months (p .001). PD-DBS showed decreased inhibition (p = .016) whereas PD-BMT deteriorated in vowel articulation (p = .011). Using the DT paradigm, PD-DBS showed a slowing of speech rate after 12 months (p = .009) in contrast to PD-BMT (p = .203).STN-DBS does not seem to impair speech and global cognition but might affect certain executive functions (notably inhibition). Speech-cognition interference is relatively preserved in PD patients, even though PD-DBS present larger DT cost on speech rate at 12 months post-DBS compared to PD-BMT. An evaluation with a longer follow-up using a larger sample is needed to confirm long-term effects.

Dopaminergic neurons (DA) of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA in PD have been limited to genomic or transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined multiomic study examining the protein profile of these neurons is currently available. In this exploratory study, we used laser capture microdissection to extract regions from DA in 10 human SNpc obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nanoliquid chromatography–mass spectrometry, respectively, and the differential expression between PD and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This multiomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of laser-dissected neuronal parts from SNpc in PD. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.

Background: Oral microbiota has largely escaped attention in Parkinson’s disease (PD), despite its pivotal role in maintaining oral and systemic health. Objective: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD. Methods: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities. Results: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2–2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant. Conclusion: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson’s disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD. We included 37 SWEDD cases (mean age 60 years, 33 % female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction. PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p 75 %) but not for SWEDD (

Background Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson’s disease (PD). We undertook a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson’s Progression Markers Initiative (PPMI) cohort. Methods We included all PD (n = 154) and Control subjects (n = 62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment. Results Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p p = 0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p = 0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p = 0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p = 0.002 to 0.03). REM sleep behaviour disorder screening questionnaire was associated with lower 123I-FP-CIT binding in caudate nucleus, putamen and pallidum (all p p > 0.45) or excessive daytime sleepiness (all p > 0.29). Conclusions In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.

Parkinson's disease (PD) and other neurodegenerative parkinsonisms are characterised by loss of striatal dopaminergic neurons. Dopamine functional deficits can be measured in vivo using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) ligands assessing either presynaptic (e.g. dopamine synthesis and storage, transporter density) or postsynaptic terminals (i.e. D2 receptors availability). Nuclear medicine imaging thus helps the clinician to separate degenerative forms of parkinsonism with other neurological conditions, e.g. essential tremor or drug-induced parkinsonism. With the present study, we aimed at summarizing the current evidence about dopaminergic molecular imaging in the diagnostic evaluation of PD, atypical parkinsonian syndromes and dementia with Lewy bodies (DLB), as well as its potential to distinguish these conditions and to estimate disease progression. In fact, PET/SPECT methods are clinically validated and have been increasingly integrated into diagnostic guidelines (e.g. for PD and DLB). In addition, there is novel evidence on the classification properties of extrastriatal signal. Finally, dopamine imaging has an outstanding potential to detect neurodegeneration at the premotor stage, including REM-sleep behavior disorder and olfactory loss. Therefore, inclusion of subjects at an early stage for clinical trials can largely benefit from a validated in vivo biomarker such as presynaptic dopamine pathways PET/SPECT assessment.

Microelectrode recordings (MERs) are often used during deep brain stimulation (DBS) surgeries to confirm the position of electrodes in patients with advanced Parkinson's disease. The present study focused on 32 patients who had undergone DBS surgery for advanced Parkinson's disease. The first objective was to confront the anatomical locations of intraoperative individual MERs as determined electrophysiologically with those determined postoperatively by image reconstructions. The second aim was to search for differences in cell characteristics among the three subthalamic nucleus (STN) subdivisions and between the STN and other identified subcortical structures. Using the DISTAL atlas implemented in the Lead-DBS image reconstruction toolbox, each MER location was determined postoperatively and attributed to specific anatomical structures (sensorimotor, associative or limbic STN; substantia nigra [SN], thalamus, nucleus reticularis polaris, zona incerta [ZI]). The STN dorsal borders determined intraoperatively from electrophysiology were then compared with the STN dorsal borders determined by the reconstructed images. Parameters of spike clusters (firing rates, amplitudes - with minimum amplitude of 60 μV -, spike durations, amplitude spectral density of β-oscillations) were compared between structures (ANOVAs on ranks). Two hundred and thirty one MERs were analyzed (144 in 34 STNs, 7 in 4 thalami, 5 in 4 ZIs, 34 in 10 SNs, 41 others). The average difference in depth of the electrophysiological dorsal STN entry in comparison with the STN entry obtained with Lead-DBS was found to be of 0.1 mm (standard deviation: 0.8 mm). All 12 analyzed MERs recorded above the electrophysiologically-determined STN entry were confirmed to be in the thalamus or zona incerta. All MERs electrophysiologically attributed to the SN were confirmed to belong to this nucleus. However, 6/34 MERs that were electrophysiologically attributed to the ventral STN were postoperatively reattributed to the SN. Furthermore, 44 MERs of 3 trajectories, which were intraoperatively attributed to the STN, were postoperatively reattributed to the pallidum or thalamus. MER parameters seemed to differ across the STN, with higher spike amplitudes (H = 10.64, p 0.01) and less prevalent β-oscillations (H = 9.81, p 0.01) in the limbic STN than in the sensorimotor and associative subdivisions. Some cells, especially in the SN, showed longer spikes with lower firing rates, in agreement with described characteristics of dopamine cells. However, these probabilistic electrophysiological signatures might become clinically less relevant with the development of image reconstruction tools, which deserve to be applied intraoperatively.

Deep-brain stimulation (DBS) programming for dystonia patients is a complex and time-consuming task. To analyze whether programming a programming paradigm based on patient’s self-adjustment is practical, effective and time saving in dystonia. We retrospectively compared dystonia rating scales as well as the time necessary to optimize programming and the number of in-hospital visits in all patients (n = 102) operated at our center who used simple mode (SM) or advanced mode (AM) programming; the latter uses groups of different stimulation parameters and allows the patient and their caregiver to change stimulation groups at home, using the patient remote control. Both AM- and SM-allocated patients improved clinically to the same extent after DBS, as assessed by the Burke–Fahn–Marsden (BFM) and the Toronto Western Spasmodic Torticollis (TWSTRS) dystonia rating scales. All subscores improved after DBS without statistically significant differences in improvement between AM and SM (BFM: − 43% vs. − 53%, p = 0.569; TWSTRS: − 63% vs. − 72%, p = 0.781). AM and SM patients reached optimization within a similar median time [5.5 months (95% CI 4.6–6.3) for AM vs. 6.2 months (4.2–7.6) for SM, p = 0.674) but patients on advanced programming needed fewer in-hospital visits to achieve the same improvement [median of 5 visits (95% CI 4–7) for AM vs. 8 visits (7–9) for SM, p = 0.008]. Advanced DBS programming based on patient’s self-adjustment under the supervision of the treating physician is feasible, practical and significantly reduces consultation time in dystonia patients.

Objective Deep brain stimulation (DBS) has become a well-established treatment that significantly improves the motor symptoms of Parkinson's disease (PD). Patients may nevertheless experience psychosocial maladjustment after surgery, as reported by an increasing body of research. Yet, no comprehensive theoretical approach has been proposed to account for this. Initially conceptualized for postsurgical epilepsy, the burden of normality (BoN) may be viewed as a model that is potentially applicable to psychosocial maladjustment after PD-DBS. Method We systematically examined the literature to verify this assumption by scrutinizing the 3 theoretical levels of the BoN, specifically, precursory conditions for the applicability of the model, clinical manifestations of psychosocial maladjustment, and 2 mediating variables: expectations and discarding the roles associated with the pretreatment condition. Results The applicability of the BoN to PD-DBS found support for the first 2 of these 3 levels in 88 scientific articles included in the review. The number of studies that addressed the mediating variables was nevertheless insufficient to draw any definitive conclusion. The degenerative condition of PD further limits the distinction between symptoms pertaining to psychosocial maladjustment and disease progression. Conclusions Considering psychosocial maladjustment through the lens of the BoN is complementary to the traditional medical perspective of PD-DBS and illuminates the potential contribution of specialists from multiple disciplines in clinical rehabilitation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Patients with Parkinson's disease (PD) may benefit from deep brain stimulation (DBS) to improve motor and medication-induced symptoms. Yet mixed evidence regarding the outcome of successful DBS on couple satisfaction has been highlighted in the literature. Thirty patients diagnosed with PD were included in a study investigating couple satisfaction (MSS-14), depression (HAD-D) and anxiety (HAD-A) at four measurement times: before DBS and 6, 12, and 18 months post-surgically. Sixteen spouses/partners were included as well. Couple satisfaction from the patient perspective was never associated with depression or anxiety. However, poor marital adjustment (i.e., difference and absolute difference between patients and spouses/partners MSS-14 scores) predicted patients' pre-operative depressive mood. Longitudinal analyses showed that couple satisfaction (n = 9) worsened at 12 months and 18 months compared to pre-DBS scores, F(2.047, 16.378) = 8.723, p = .003, and despite concomitant motor improvement. Growth curve analyses showed that couple satisfaction worsening occurred between 6 and 12 months post-operatively (b = 2.938, p < .001). Thus, couple satisfaction did not increase along with motor improvement and deteriorated after the adjustment period following DBS.

Background Despite successful functional neurosurgery, patients suffering from epilepsy or Parkinson’s disease may experience postoperative psychological distress and social maladjustments. Difficulties in coping with postoperative changes, even positive ones, have shown to be related to patients’ presurgery cognitive representations (i.e., expectations, hope). The aim of this study was to develop an instrument assessing various key features of surgery outcomes’ representations, namely the Preoperative Hope and Expectations Questionnaire (PHEQ). Methods Participants were patients (n = 50) diagnosed with Parkinson’s disease (n = 25) or epilepsy (n = 25), candidates for functional neurosurgery (i.e., Deep brain stimulation, anterior temporal lobectomy). Two to three weeks before the planned surgery, they were administrated items assessing their actual state, preoperative expectations, and hope regarding surgery outcomes. They also completed measures assessing optimism, quality of life and mood. Results Exploratory analysis resulted in a 14-item version of the PHEQ composed of two factors (abstract representations, including psychological well-being and concrete representations, such as direct surgery outcomes). The PHEQ demonstrated high internal consistency and good convergent validity. Patients were more prone to express postoperative improvements in terms of hope rather than expectations. They generally focused on concrete rather than abstract features, although patients with Parkinson’s disease had higher abstract future-oriented representations. Conclusions The PHEQ presents satisfactory psychometric properties and may be considered as a reliable instrument for research and clinical practice.

Background Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA neurons in PD have been limited to genomic and transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined polyomic study examining the protein profile of these neurons, is currently available. Methods In this exploratory study, we used laser microdissection to extract DA neurons from 10 human SNpc samples obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nano-LC-MS/MS, respectively, and the differential expression between the PD and control group was assessed. Results Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This polyomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. Conclusion This is the first exploratory study analyzing both gene and protein expression of LMD-dissected DA neurons from SNpc in PD. Although correlation between RNA and protein expressions was limited, this polyomic study provides an extensive and integrated overview of molecular changes identified in the PD SNpc and may offer novel insights into specific pathological processes at work in PD degeneration.

BACKGROUND The etiology of Parkinson's disease (PD) remains unknown. To approach the issue of PD's risk factors from a new perspective, we hypothesized that coupling the geographic distribution of PD with spatial statistics may provide new insights into environmental epidemiology research. The aim of this case-control study was to examine the spatial dependence of PD prevalence in the Canton of Geneva, Switzerland (population = 474,211). METHODS PD cases were identified through Geneva University Hospitals, private neurologists and nursing homes medical records (n = 1115). Controls derived from a population-based study (n = 12,614) and a comprehensive population census dataset (n = 237,771). All individuals were geographically localized based on their place of residence. Spatial Getis-Ord Gi* statistics were used to identify clusters of high versus low disease prevalence. Confounder-adjustment was performed for age, sex, nationality and income. Tukey's honestly significant difference was used to determine whether nitrogen dioxide and particulate matters PM10 concentrations were different within PD hotspots, coldspots or neutral areas. RESULTS Confounder-adjustment greatly reduced greatly the spatial association. Characteristics of the geographic space influenced PD prevalence in 6% of patients. PD hotspots were concentrated in the urban centre. There was a significant difference in mean annual nitrogen dioxide and PM10 levels (+3.6 μg/m3 [p

To respond to the need of objective screening tools for motor speech disorders (MSD), we present the screening version of a speech assessment protocol (MonPaGe-2.0.s), which is based on semi-automated acoustic and perceptual measures on several speech dimensions in French. We validate the screening tool by testing its sensitivity and specificity and comparing its outcome with external standard assessment tools. The data from 80 patients diagnosed with different types of mild to moderate MSD and 62 healthy test controls were assessed against the normative data obtained on 404 neurotypical speakers, with Deviance Scores computed on seven speech dimensions (voice, speech rate, articulation, prosody, pneumophonatory control, diadochokinetic rate, intelligibility) based on acoustic and perceptual measures. A cut-off of the MonPaGe total deviance score (TotDevS) >2 allowed MSD to be diagnosed with specificity of 95% and an overall sensitivity of 83.8% on all patients pulled, reaching 91% when very mildly impaired patients were excluded. A strong correlation was found between the MonPaGe TotDevS and an external composite perceptual score of MSD provided by six experts. The MonPaGe screening protocol has proven its sensitivity and specificity for diagnosing presence and severity of MSD. Further implementations are needed to complement the characterization of impaired dimensions in order to distinguish subtypes of MSD.

International audience; Hallucinations in Parkinson’s disease (PD) are disturbing and frequent non-motor symptoms and constitute a major risk factor for psychosis and dementia. We report a robotics-based approach applying conflicting sensorimotor stimulation, enabling the induction of presence hallucinations (PHs) and the characterization of a subgroup of patients with PD with enhanced sensitivity for conflicting sensorimotor stimulation and robot-induced PH. We next identify the fronto-temporal network of PH by combining MR-compatible robotics (and sensorimotor stimulation in healthy participants) and lesion network mapping (neurological patients without PD). This PH-network was selectively disrupted in an additional and independent cohort of patients with PD, predicted the presence of symptomatic PH, and associated with cognitive decline. These robotics-neuroimaging findings extend existing sensorimotor hallucination models to PD and reveal the pathological cortical sensorimotor processes of PH in PD, potentially indicating a more severe form of PD that has been associated with psychosis and cognitive decline.

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson's disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson's Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD.We included 37 SWEDD cases (mean age 60 years, 33 % female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction.PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p 0.0001). PD group also showed lower binding in the thalamus relative to controls (p = 0.007). Receiver operating characteristics (ROC) area under the curve (AUC) did not show a significant difference when using extrastriatal region in addition to striatal ROIs for the separation of SWEDD and PD (95 % ROC-AUC for both methods, p = 0.52). In addition, striatal [123I]FP-CIT binding contralateral to the clinically more affected side was usually lower for PD ( 75 %) but not for SWEDD ( 49 %, p 0.002). No significant difference regarding [123I]FP-CIT binding was observed between SWEDD and controls.These findings corroborate the view that SWEDD cases represent a heterogeneous group of conditions not involving dopaminergic and serotonergic terminals. Further studies are warranted to be assessed whether using extrastriatal [123I]FP-CIT evaluation can be of help in the assessment of degenerative parkinsonism.

SummaryHallucinations in Parkinson’s disease (PD) are one of the most disturbing non-motor symptoms, affect half of the patients, and constitute a major risk factor for adverse clinical outcomes such as psychosis and dementia. Here we report a robotics-based approach, enabling the induction of a specific clinically-relevant hallucination (presence hallucination, PH) under controlled experimental conditions and the characterization of a PD subgroup with enhanced sensorimotor sensitivity for such robot-induced PH. Using MR-compatible robotics in healthy participants and lesion network mapping analysis in neurological non-PD patients, we identify a fronto-temporal network that was associated with PH. This common PH-network was selectively disrupted in a new and independent sample of PD patients and predicted the presence of symptomatic PH. These robotics-neuroimaging findings determine the behavioral and neural mechanisms of PH and reveal pathological cortical sensorimotor processes of PH in PD, identifying a more severe form of PD associated with psychosis and cognitive decline.

There is a debate on possible alterations of self-identity following deep brain stimulation for neurological disorders including Parkinson&rsquo, s disease. Among the psychological variables likely to undergo changes throughout such a medical procedure, illness representations and coping strategies have not been the target of much research to this day. In order to remedy this, we investigated the dynamics of illness representations and coping strategies in an 18-month longitudinal study involving 45 patients undergoing deep brain stimulation for idiopathic Parkinson&rsquo, s disease. Two research hypotheses were formulated and investigated through repeated measures of ANOVAs and structural equation modelling with full information maximum likelihood and Bayesian estimations. Representations of Parkinson&rsquo, s disease as a cyclical condition and perception of control over the disease diminished after surgery. Use of instrumental coping strategies was not modified after deep brain stimulation. These changes were identified by SEM but not ANOVAs, their magnitude was nevertheless relatively small, implying general stability in representations. These findings suggest that psychological variables do not undergo major changes after deep brain stimulation for Parkinson&rsquo, s disease.

Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis ofWe included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants.Relative to controls, all forms of degenerative parkinsonism showed decreasedThis study provides evidence of a major extrastriatal

Introduction:Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of 123I–N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) images to measure extrastriatal regional deficits in PD and APS, and assess their added diagnostic value in discriminating degenerative parkinsonisms from other conditions. Methods: We included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants. 123I-FP-CIT SPECT images were processed with statistical parametric mapping 12 (SPM12)-based PETPVE12 software and subjected to partial volume effect correction for ROI-based group comparisons. Results: Relative to controls, all forms of degenerative parkinsonism showed decreased 123I-FP-CIT uptake in caudate nucleus, putamen but also pallidum and insula. In addition, a significant uptake reduction was observed in thalamus for MSA-P and PSP, in midbrain for PD and PSP, and in the amygdala for PSP (ANCOVA controlling for age, sex and antidepressant medication, all Bonferroni-corrected p

Background Functional parkinsonism (FP) is considered rare but no studies have looked at its frequency. Case series have described high rates of comorbidity with Parkinson's disease (PD), suggesting a possible association between these conditions. Objectives To study the prevalence, epidemiology and clinical features of FP and its association with PD. Methods We conducted a cross-sectional population-based prevalence study as well as a chart review of cases who received a diagnosis of FP over a 10-year-period in two movement disorder clinics in Switzerland. Epidemiological data regarding FP features were collected. The co-occurrence of PD, psychiatric disorders and other functional disorders were recorded. Clinical differences between FP and FP + PD groups are presented and discussed in light of a literature review. Results The crude prevalence of FP was 0.64 per 100,000 in our population. FP represented 0.24% of patients with parkinsonism. Among 12 FP cases, female gender predominance (87%), mean age of onset of 45.5(± 13.3 Standard deviation SD) years and prolonged diagnostic delay (mean 59 ± 75 SD months) was found. Six patients had an additional diagnosis of PD, 83% of depression and 66% of other functional neurological disorder. In four patients with FP + PD, FP preceded PD by 6 to 56 months. Conclusions These results suggest that FP should be considered in the differential diagnosis of patients presenting with parkinsonism. The high rate of co-occurrence with PD emphasizes the importance of long-term follow up of these patients. The observation that FP often precedes PD should be verified in prospective studies.

BACKGROUND We investigated the acute effect of short pulse widths on the therapeutic window in subthalamic nucleus deep brain stimulation in Parkinson's disease. METHODS We assessed 10 PD patients with STN-DBS at a 60-µs pulse width. We randomly and double-blindedly applied 10- to 50-µs pulse widths. The principal outcome was the therapeutic window (difference between the amplitude thresholds for visible muscle contraction and for best rigidity control). The secondary outcome was the charge per pulse (which reflects the efficiency of the stimulation) needed to control rigidity. Two-way analysis of variance and pairwise t tests were applied. RESULTS The therapeutic window widened when the pulse width shortened (r = -0.45; P

BACKGROUND Acute dyskinesias elicited by STN-DBS, here referred to as stimulation-induced dyskinesias, predict optimal clinical outcome in PD. However, it remains elusive whether stimulation-induced dyskinesias can guide DBS programming. OBJECTIVES Here, we characterized stimulation-induced dyskinesias clinically and anatomically. We then tested whether dyskinesia-inducing contacts could be effectively programmed using independent current source technology. METHODS We characterized stimulation-induced dyskinesias with directional and ring stimulation retrospectively in 20 patients. We then localized dyskinesia-inducing contacts by imaging coregistration and eventually programmed those contacts. RESULTS We elicited dyskinesias in half of our patients. Dyskinesia-inducing contacts were mainly directional and were all located ventrally within the dorsolateral motor STN. When these dyskinesia-inducing contacts were programmed using independent current source technology, dyskinesia disappeared and robust antibradykinetic effects were obtained. CONCLUSION We confirm that stimulation-induced dyskinesias are helpful clinical observations, which may guide programming of directional STN-DBS in PD. © 2019 International Parkinson and Movement Disorder Society.

Psychosocial maladjustment frequently occurs following deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). This paper aimed at investigating, for the first time with first-hand data, whether the burden of normality model (BoN) could adequately describe the manifestations and underlying dynamics of psychosocial maladjustment after DBS for PD. In a mixed experimental design including quantitative and qualitative data, 19 patients treated with DBS for PD were interviewed on their post-DBS lived experience with the Austin CEP Interview, a semi-structured instrument addressing all elements of the BoN. In addition, health-related quality of life was measured before surgery and at the time of interview with the Medical Outcome Study 36-Item Short Form Health Survey. All patients experienced clinical manifestations of psychosocial maladjustment as described in the BoN. Yet, there was a great interindividual heterogeneity in descriptions of the perceived course of the post-DBS life. Experiencing various types of symptoms was nevertheless associated with the perception of a less satisfying life after surgery. In addition, most patients had realistic expectations on the surgical outcome, and those with unrealistic or mixed expectations did not differ from other patients in terms of psychosocial maladjustment. The BoN accurately conceptualizes psychosocial maladjustment experienced by DBS patients with PD. However, no relationship was established between the nature of pre-operative expectations and BoN symptoms.

Introduction High cognitive reserve is associated with milder cognitive and motor deficits in Parkinson's disease (PD). We investigated whether educational status (as a proxy for cognitive reserve) could modulate dual-task (DT) related gait changes after subthalamic nucleus deep brain stimulation (STN-DBS) in PD. Methods DT-related gait changes were assessed in 34 PD patients (age: 60.5 ± 8.7; % female: 44%), before and one year after STN-DBS. Based on walking speed change after DBS, patients were classified into responders (improvement) and non-responders (deterioration) using automated k-means clustering for four DT (i.e. forward and backward counting; semantic and phonemic fluency). Results Patients with high education level improved DT gait performance compared to lower educated patients (p = 0.03). Baseline cognitive performance, disease progression and stimulation efficiency were similar between groups (i.e. responders versus non-responders). Logistic regression showed an association between responders and high level of education for verbal fluency (semantic/phonemic fluency, beta = 3.9/3.4, p = 0.03). No significant changes for any gait parameter were found using all-group analyses. Conclusion Education level is associated with DT-related gait changes in PD one year post-DBS. Subgroup analyses should be considered for highly variable gait outcomes after STN-DBS. With regard to the predominance of motor-cognitive DT performance in everyday life, a high CR could be considered as a favourable inclusion criterion for future DBS candidates.

Drug-induced parkinsonism (DIP) is a common movement disorder characterized by the rapid development of a most commonly symmetrical and akinetic-rigid syndrome weeks after initiation of a causative medication that resolves completely within months after withdrawal. Besides neuroleptics, the list of medications known to induce parkinsonism is long and includes, among many others, calcium channel blockers, antidepressants, and antiepileptics. Most have in common to alter dopaminergic transmission, more specifically D2 receptor-mediated motor modulation in the striatum. DIP and Parkinson’s disease (PD) may be virtually indistinguishable, yet some particular features may help to separate them. However, in a quarter of suspected DIP cases, the offending agent seems to have unmasked, rather than induced, a preexisting neurodegenerative condition. There is no specific treatment for DIP besides stopping the incriminated medication which, in the majority of patients, is curative.

AIMS OF THE STUDY Currently, the characterisation of advanced Parkinson’s disease (APD) does not follow standardised diagnostic criteria, which complicates the evaluation of ongoing care and treatment strategies, such as eligibility for device-aided treatment (DAT). Therefore, this study aimed to determine the proportion of APD and non-advanced Parkinson’s disease (non-APD) patients treated at specialised movement disorder centres in Switzerland, to compare clinical characteristics of APD versus non-APD patients and to assess eligibility for and use of DAT. Furthermore, potential differences between the Swiss and international situation should be uncovered. METHODS OBSERVE-PD was a cross-sectional, international, observational study including 2615 patients from 128 movement disorder centres in 18 countries. For the Swiss subgroup of the study analysed here, which included 134 patients from 5 movement disorder centres, motor and non-motor symptoms, activities of daily living and quality of life were assessed as endpoints. The correlation between physician’s judgement of APD and the Delphi criteria for APD, which were developed by an international expert group, as well as the clinical burden in APD and non-APD patients and eligibility for and use of DAT were evaluated. The results for the Swiss subgroup were subsequently compared with the international full analysis set of the OBSERVE-PD study. RESULTS Based on physician’s judgement, 69.4% of patients included in the Swiss study suffered from APD. A moderate correlation between physician’s judgement and the Delphi criteria for APD was observed (Κ = 0.480, 95% confidence interval 0.317–0.642). Clinical burden was higher for APD patients, as shown by worse scores for activities of daily living, motor symptom severity, dyskinesia duration/disability, duration of “off” time, non-motor symptoms and quality of life as compared with non-APD patients (p

Introduction 123 I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1–15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue. Methods We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis. Results Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome. Conclusion SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned.

A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and inappropriately managed. In particular, second generation antipsychotics, like first generation agents, are associated with potentially debilitating side-effects, most notably tardive syndromes and parkinsonism, as well as potentially fatal acute syndromes. Appropriate, evidence-based management is essential as these drugs are being prescribed to a growing population vulnerable to these side-effects, including children and elderly people. Prevention of the development of drug-induced movement disorders is an important consideration when prescribing medications that can induce movement disorders. Recent developments in diagnosis, such as the use of dopamine transporter imaging for drug-induced parkinsonism, and treatment, with the approval of valbenazine and deutetrabenazine, the first drugs indicated for tardive syndromes, have improved outcomes for many patients with drug-induced movement disorders. Future research should focus on development of safer antipsychotics and specific therapies for the different tardive syndromes and the treatment of drug-induced parkinsonism.

Unlike most basal ganglia disorders, which usually progress slowly and relentlessly, a number of movement disorders may develop as acute or subacute conditions. Their occurrence commonly prompts patients to rush into the emergency room. A proper diagnosis is not always straightforward and requires a detailed analysis of the movement disorder phenomenology and a thorough medication screening, as many of these acute situations may be iatrogenic and drug-related. An accurate identification of the problem may enable an effective management and an appropriate therapy. This article is an overview of three distinct movement disorder emergencies, namely acute dystonia, acute chorea, and acute complications that can be observed in Parkinson's disease. Each topic is illustrated with a case report.Contrairement à la plupart des affections des ganglions de la base, qui évoluent généralement sur un mode lentement progressif, certains mouvements anormaux peuvent se développer sur un mode aigu ou subaigu, amenant les patients à consulter en urgence. Le diagnostic est souvent délicat. Il repose sur une analyse détaillée de la phénoménologie et une anamnèse médicamenteuse fouillée, dans la mesure où ces situations sont volontiers iatrogènes. Une identification correcte du problème permet souvent une thérapeutique efficace. Le présent article propose une mise au point de trois problématiques de ce type, à savoir la dystonie aiguë, la chorée aiguë et les complications aiguës que l’on peut observer dans la maladie de Parkinson. Chaque sujet est illustré par un cas clinique.

Objective Deep brain stimulation of the subthalamic nucleus (STN) is advocated in patients with advanced Parkinson disease. Intraoperative microelectrode recordings (MER) and stimulation or imaging are applied to confirm electrode targeting. The study objective was to evaluate which intraoperative electrophysiologic marker, MER, stimulation, or local field potentials (LFP) was the most predictive of the clinical efficacy. Methods Efficacy was determined with lateralized motor scores of Movement Disorders Society–Unified Parkinson's Disease Rating Scale in 36 patients (OFF-drug/ON-stimulation 1 year after surgery vs. OFF-drug before surgery). Trajectory lengths in STN were determined from MER. Stimulation was increased up to the thresholds of first decrease, of complete suppression of rigidity, and of excitation of pyramidal motor tract. β oscillations (11–31 Hz) were computed from LFP of the electrode macrocontact. Univariate and multivariate analyses were computed. Results Motor improvements were linked to trajectory lengths in STN (R2 = 0.17; P > 0.005). No significant relationship was found for thresholds of first decrease or suppression in rigidity or for motor tract excitation (R2 0.05). Motor improvements were most linked to β oscillation increases (R2 = 0.57, P Conclusions Motor improvements emerged as most related to β oscillations, before trajectory length within the STN, whereas stimulation thresholds of rigidity or of motor tract excitation failed to show any relationship. The study encourages LFP measurement to confirm STN electrode location.

Purpose Dopamine transporter SPECT imaging is a valuable tool to estimate the integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms. Evidence about SPECT differential pattern between parkinsonian and cerebellar forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at assessing whether MSA-P and MSA-C variants have a distinct semiquantitative I-FP-CIT SPECT pattern. Methods We studied a unicentric 13-year (2003-2016) retrospective cohort of subjects with possible or probable MSA and scanned with the same acquisition and reconstruction SPECT protocol. Age-dependent semiquantitative reference limits for striatal volumes of interest, asymmetry indices, and caudate/putamen ratio were previously established with a percentile approach on a cohort of subjects with nondegenerative conditions and normal visual scan. Results Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA-C) were identified (mean age, 68.2 ± 10.1 years; male/female ratio 1.00; disease duration, 2.5 ± 2.2 years; Movement Disorders Society Unified Parkinson's Disease Rating Scale III score, 33.8 ± 12.4). The MSA-P subjects exhibited lower uptake values for all volumes of interest, for example, striatal uptake on the more affected side (1.10 ± 0.51) compared with MSA-C (2.30 ± 0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 ± 24.8 vs 6.3 ± 4.5, P = 0.028) and caudate/putamen ratio (2.26 ± 1.23 vs 1.13 ± 0.17, P = 0.00148). Conclusions The MSA-P and MSA-C subjects exhibited significantly distinct semiquantitative SPECT pattern with severe uptake impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C. Clinical distinction of these 2 phenotypical entities is necessary in order to evaluate SPECT potential to discriminate between degenerative parkinsonisms.

To overcome the issue of reference values for DaTSCAN® requiring healthy controls, we propose an original approach using scans from individuals with non- degenerative conditions performed at one single center following the same acquisition protocol. Procedures: From a cohort of 970 consecutive patients, we identified 182 patients with a clinical diagnosis of non-degenerative parkinsonism or tremor and a visually normal DATSCAN®. Caudate nucleus (C), putamen (P), and striatum (S) uptake values, C/P ratios, and asymmetry indexes (AI) were calculated using semi-quantitative methods. Outcomes were assessed according to age and gender, and reference limits were established using the percentile approach. Results: A significant negative linear effect of age was found upon striatal nuclei uptake of 0.21–0.22 per decade (6.8 %/decade for striatum), whereas a potential gender influence proved unclear. Inferior reference limits were established at the 5th percentile. C/P ratios and AIs were not influenced by age or gender, and superior reference limits were set at the 95th percentile. Conclusions: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects.