Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.

Pattern of encounters to emergency departments for suicidal attempts in France: Identification of high-risk days, months and holiday periods.

INTRODUCTION: Seasonal change in patterns of suicidal attempts is not well known in France and may differ from other western countries. We aimed to determine the peak times (days, months and holiday periods) of suicidal attempts in France. METHODS: We carried out a multicentre retrospective epidemiological study, using data from the Organization for Coordinated Monitoring of Emergencies (OSCOUR®) network. We aggregated daily data from January 1, 2010, to December 31, 2019. Variations in suicidal attempts on specific days were investigated by comparing their frequencies (ad hoc Z-scores). RESULTS: 114,805,488 ED encounters were recorded including 233,242 ED encounters regarding suicidal attempts. Men accounted for 45.7%. A significantly higher frequency of ED encounters for suicidal acts were found on Sundays in the months of May-June for both sexes and on New Year's Day for all genders and age groups. An increased risk was also noted on July 14th (National Day) and June 22nd (Summer Solstice). A protective effect was noted on the day after Valentine's Day, on Christmas Day and Christmas time (in particular December 24 and 26). CONCLUSION: Sundays, June, New Year's Day were at increased risk of suicidal attempts in France requiring a strengthening of prevention.

Dealing with the diagnosis of Parkinson's disease and its implications for couple functioning in the early stage: An interpretative phenomenological analysis.

BACKGROUND: For couples facing Parkinson's disease, marital relationships are significantly impacted, even at the early stages of the disease. However, very few studies have explicitly explored the functioning of the couple and how both partners deal with Parkinson's disease. The aim of this study was to explore the experiences and strategies of couples facing Parkinson's disease in the early stage using dyadic interpretative phenomenological analysis. METHODS: Fifteen couples agreed to participate in the study. Semistructured interviews were conducted with each partner separately regarding his or her individual experience with Parkinson's disease, the couple's history, the impact of the diagnosis on the functioning of the couple, and his or her projections for the future. RESULTS: Three higher-order themes emerged from the analyses. The first theme, "Being tested by the diagnosis", highlights 4 dyadic configurations according to the individual's and the couple's capacity for adjustment following the diagnosis: "noncongruent", "collapsed", "relieved" and "avoidant". The second theme, "Talking about everything except the disease", underlines that communication about the disease is often avoided both within the couple and with relatives to protect the persons with Parkinson's disease or respect their wishes. The third theme, "Supporting each other", describes the different levels of harmony between the two partners in the management of daily life and symptoms and their relational impacts. CONCLUSION: These results allow us to better understand the experiences of both partners and to highlight the importance of promoting better acceptance of the diagnosis by persons with Parkinson's disease to allow better communication between partners and with relatives. Such support prevents disease-specific distress and facilitates better adjustment in the later stages of the disease.

A Double-Blind, Randomized, Placebo-Controlled Trial of Bumetanide in Parkinson's Disease.

BACKGROUND: Acting on the main target of dopaminergic cells, the striatal γ-aminobutyric acid (GABA)-ergic cells, might be a new way to treat persons with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD. METHODS: This was a 4-month double-blind, randomized, parallel-group, placebo-controlled trial of 1.75 to 3 mg/day bumetanide as an adjunct to levodopa in 44 participants with PD and motor fluctuations. RESULTS: Compared to the baseline, the mean change in OFF Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score after 4 months of treatment (primary endpoint) did not improve significantly compared with placebo. No changes between participants treated with bumetanide and those treated with placebo were observed for most other outcome measures. Despite no relevant safety signals, bumetanide was poorly tolerated. CONCLUSIONS: There was no evidence in this study that bumetanide has efficacy in improving motor symptoms of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Use of Image Guided Programming to Improve Deep Brain Stimulation Workflows with Directional Leads in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation specificity in this challenging area but also requires more precise stimulation parameters. OBJECTIVE: We investigated whether commercially available software for image guided programming (IGP) could maximize the benefits of DBS by informing the clinical standard care (CSC) and improving programming workflows. METHODS: We prospectively analyzed 32 consecutive parkinsonian patients implanted with bilateral directional leads in the STN. Double blind stimulation parameters determined by CSC and IGP were assessed and compared at three months post-surgery. IGP was used to adjust stimulation parameters if further clinical refinement was required. Overall clinical efficacy was evaluated one-year post-surgery. RESULTS: We observed 78% concordance between the two electrode levels selected by the blinded IGP prediction and CSC assessments. In 64% of cases requiring refinement, IGP improved clinical efficacy or reduced mild side effects, predominantly by facilitating the use of directional stimulation (93% of refinements). CONCLUSIONS: The use of image guided programming saves time and assists clinical refinement, which may be beneficial to the clinical standard care for STN-DBS and further improve the outcomes of DBS for PD patients.

Prognosis of impulse control disorders in Parkinson's disease: a prospective controlled study.

BACKGROUND: The long-term prognosis of impulsive compulsive disorders (ICD) remains poorly studied in Parkinson's disease (PD). OBJECTIVE: Evaluating the natural history of ICD and its impact on PD symptoms including cognition and treatment adjustments. MATERIALS AND METHODS: We assessed PD patients at baseline (BL) with (BL-ICD+) or without (BL-ICD-) ICD despite dopamine agonist (DA) exposure of > 300 mg levodopa-equivalent daily dose for > 12 months at baseline and after more than two years of follow-up. ICD were assessed using the Ardouin's Scale of Behaviors in PD (ASBPD), cognition using the Mattis scale, and PD symptoms using the UPDRS score. Treatment adjustments, DA withdrawal-associated symptoms, and ICDs social consequences were recorded. RESULTS: 149 patients were included (78 cases and 71 controls), mean duration of follow-up was 4.4 ± 1 years. At baseline, psychiatric disorders were more common among BL-ICD + (42.3 vs 12.3% among BL-ICD-, p < 0.01). At follow-up, 53.8% of BL-ICD + were not ICD-free while 21.1% of BL-ICD- had developed ICD. BL-ICD + more frequently experienced akinesia (21.8 vs 8.5%, p = 0.043) and rigidity worsening (11.5 vs 1.4%, p = 0.019) following therapeutic modifications. Decision to decrease > 50% DA doses (12.8 vs 1.4%, p = 0.019) or to withdraw DA (19.2 vs 5.6%, p = 0.025) was more frequently considered among BL-ICD+ . At follow-up, the prevalence of cognitive decline was lower among BL-ICD + (19.2 vs 37.1%, p = 0.025). CONCLUSION: ICDs were associated with increased psychiatric burden at baseline and better cognitive prognosis. Most patients were still showing ICDs at the follow-up visit, suggesting ICD to be considered as a chronic, neuropsychiatric disorder.

Characterization of theory of mind performance in patients with myotonic dystrophy type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is associated with motor dysfunction as well as psychological and cognitive impairments, including altered social cognition. Theory of mind (ToM) impairments have been reported in this disease but their nature and their cognitive/cerebral correlates have yet to be determined. METHODS: Fifty DM1 patients and 50 healthy controls were assessed using the Movie for the Assessment of Social Cognition, which quantifies impairments in affective and cognitive components of ToM through the depiction of everyday situations. We also measured the study participants' cognitive, behavioral and social abilities, quality of life, and brain MRI characteristics. RESULTS: DM1 patients presented a significant impairment in ToM performance compared to controls (p < .001). The patients' errors were related to hypomentalizations (p < .001 vs controls) but not to hypermentalizations (p = .95). The affective component was affected (p < .001 vs controls) but not the cognitive component (p = .09). The ToM impairment was associated with demographic variables (older age and a lower educational level), genetic findings (a larger CTG triplets repeat expansion) and cognitive scores (slower information processing speed). Associations were also found with brain MRI variables (lower white matter and supratentorial volumes) but not with behavioral or social variables. DISCUSSION: DM1 patients display a ToM impairment, characterized by predominant hypomentalizations concerning the affective component. This impairment might result from structural brain abnormalities observed in DM1.

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

BACKGROUND: Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. OBJECTIVE: The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). METHODS: 108 non-demented PD patients with (n = 31) and without (n = 77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. RESULTS: Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. CONCLUSIONS: Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.

Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.

BACKGROUND: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms. OBJECTIVE: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients. METHODS: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up. RESULTS: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center. CONCLUSION: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline.

The contribution of executive control dysfunction to freezing of gait in Parkinson's disease.

OBJECTIVE: An executive dysfunction is supposed to contribute to freezing of gait (FoG) in Parkinson's disease. We aimed to investigate at a behavioral and cortical levels whether an attentional load (particularly, a conflicting situation) can specifically impact preparation and execution phases of step initiation in parkinsonian patients with FoG. METHODS: Fifteen patients with FoG, 16 without and 15 controls performed an adapted version of the Attention Network Test, with step initiation as response instead of the standard manual keypress. Kinetic and kinematic features of gait initiation as well as high-resolution electroencephalography were recorded during the task. RESULTS: Patients with FoG presented an impaired executive control. Step execution time was longer in parkinsonian patients. However, the executive control effect on step execution time was not different between all groups. Compared to patients, controls showed a shorter step initiation-locked alpha desynchronization, and an earlier, more intense and shorter beta desynchronization over the sensorimotor cortex. Even though controls were faster, the induced alpha and beta activity associated with the effect of executive control didn't differ between patients and controls. CONCLUSIONS: Tasks of conflict resolution lead to a comparable alteration of step initiation and its underlying brain activity in all groups. Links between executive control, gait initiation and FoG seem more complex than expected. SIGNIFICANCE: This study questions the cognitive hypothesis in the pathophysiology of freezing of gait. Executive dysfunction is associated with FoG but is not the main causal mechanism since the interaction between attention and motor preparation didn't provoke FoG.

Alterations in the LRRK2-Rab pathway in urinary extracellular vesicles as Parkinson's disease and pharmacodynamic biomarkers.

Expression or phosphorylation levels of leucine-rich repeat kinase 2 (LRRK2) and its Rab substrates have strong potential as disease or pharmacodynamic biomarkers. The main objective of this study is therefore to assess the LRRK2-Rab pathway for use as biomarkers in human, non-human primate (NHP) and rat urine. With urine collected from human subjects and animals, we applied an ultracentrifugation based fractionation protocol to isolate small urinary extracellular vesicles (uEVs). We used western blot with antibodies directed against total and phosphorylated LRRK2, Rab8, and Rab10 to measure these LRRK2 and Rab epitopes in uEVs. We confirm the presence of LRRK2 and Rab8/10 in human and NHP uEVs, including total LRRK2 as well as phospho-LRRK2, phospho-Rab8 and phospho-Rab10. We also confirm LRRK2 and Rab expression in rodent uEVs. We quantified LRRK2 and Rab epitopes in human cohorts and found in a first cohort that pS1292-LRRK2 levels were elevated in individuals carrying the LRRK2 G2019S mutation, without significant differences between healthy and PD groups, whether for LRRK2 G2019S carriers or not. In a second cohort, we found that PD was associated to increased Rab8 levels and decreased pS910-LRRK2 and pS935-LRRK2. In animals, acute treatment with LRRK2 kinase inhibitors led to decreased pT73-Rab10. The identification of changes in Rab8 and LRRK2 phosphorylation at S910 and S935 heterologous phosphosites in uEVs of PD patients and pT73-Rab10 in inhibitor-dosed animals further reinforces the potential of the LRRK2-Rab pathway as a source of PD and pharmacodynamic biomarkers in uEVs.

Pain and Parkinson's disease: Current mechanism and management updates.

The aim of this comprehensive review was to provide an overview of pain in Parkinson's disease (PD) by identifying different clinical features and potential mechanisms, and presenting some data on the evaluation and management of pain in PD. PD is a multifocal degenerative and progressive disease, which could affect the pain process at multiple levels. Pain in PD has a multifactorial aetiology, with a dynamic process based on pain intensity, complexity of symptoms, pain pathophysiology and presence of comorbidities. In fact, pain in PD responds to the concept of multimorphic pain, which can evolve, in relation to the different factors, whether they are linked to disease and its management. Understanding the underlying mechanisms will help in guiding of treatment choices. Providing scientific support useful for clinicians and health professionals involved in management of PD, the aim of this review was to bringing practical suggestions and clinical perspectives on the development of a multimodal approach guided by a multidisciplinary clinical intervention through a combination of pharmacological and rehabilitative approaches, to manage pain to improve the quality of life on individuals with PD.

Cognitive Behavioral Therapy for Anxiety in Parkinson's Disease Induces Functional Brain Changes.

BACKGROUND: Cognitive behavioral therapy (CBT) reduces anxiety symptoms in patients with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to identify changes in functional connectivity in the brain after CBT for anxiety in patients with PD. METHODS: Thirty-five patients with PD and clinically significant anxiety were randomized over two groups: CBT plus clinical monitoring (10 CBT sessions) or clinical monitoring only (CMO). Changes in severity of anxiety symptoms were assessed with the Parkinson Anxiety Scale (PAS). Resting-state functional brain MRI was performed at baseline and after the intervention. Functional networks were extracted by an Independent Component Analysis (ICA). Functional connectivity (FC) changes between structures involved in the PD-related anxiety circuits, such as the fear circuit (involving limbic, frontal, and cingulate structures) and the cortico-striato-thalamo-cortical limbic circuit, and both within and between functional networks were compared between groups and regressed with anxiety symptoms changes. RESULTS: Compared to CMO, CBT reduced the FC between the right thalamus and the bilateral orbitofrontal cortices and increased the striato-frontal FC. CBT also increased the fronto-parietal FC within the central executive network (CEN) and between the CEN and the salience network. After CBT, improvement of PAS-score was associated with an increased striato-cingulate and parieto-temporal FC, and a decreased FC within the default-mode network and between the dorsal attentional network and the language network. CONCLUSION: CBT in PD-patients improves anxiety symptoms and is associated with functional changes reversing the imbalance between PD-related anxiety circuits and reinforcing cognitive control on emotional processing.

Couples facing the "honeymoon period" of Parkinson's disease: A qualitative study of dyadic functioning.

INTRODUCTION: The public health issue of the Parkinson's disease (PD) has led to a great deal of research that has highlighted the individual challenges faced by the person with the Parkinson's disease (PwPD) and the caregiving spouse. Few studies, however, have sought to understand the functioning of couples facing PD, by differentiating each stage, each of which has its own issues. In particular, the "honeymoon period", characterized by a symptomatic respite allowed by the effectiveness of treatments for motor symptoms, has been poorly documented, especially at the dyadic level. DESIGN AND METHOD: This qualitative study, based on Interpretative Phenomenological Analysis, aimed to understand the experience of couples and their functioning at this stage. Fifteen couples participated in separate semi-structured interviews for each partner. The analyses highlighted four dyadic dynamics, which call into question the relevance of the term "honeymoon" to describe the experience of couples. RESULTS: While some couples appear to adjust by means of flexible functioning and a positive reinterpretation of this experience, other dyads oscillate between rigid hyperprotection in the face of perceived distress or a vicious circle of control/avoidance and, in some cases, gradually slipping towards the erosion of the relationship. DISCUSSION: These results show that the relational difficulties suffered by partners at this stage should be taken into account as soon as possible after the diagnosis. Strengthening the communication and the togetherness between partners, as well as working on dyadic emotional regulation, are particularly relevant options for these couples.

Brain network characteristics and cognitive performance in motor subtypes of Parkinson's disease: A resting state fMRI study.

INTRODUCTION: Parkinson's disease (PD) is a heterogeneous disorder with great variability in motor and non-motor manifestations. It is hypothesized that different motor subtypes are characterized by different neuropsychiatric and cognitive symptoms, but the underlying correlates in cerebral connectivity remain unknown. Our aim is to compare brain network connectivity between the postural instability and gait disorder (PIGD) and tremor-dominant (TD) subtypes, using both a within- and between-network analysis. METHODS: This cross-sectional resting-state fMRI study includes 81 PD patients, 54 belonging to the PIGD and 27 to the TD subgroup. Group-level spatial maps were created using independent component analysis. Differences in functional connectivity were investigated using dual regression analysis and inter-network connectivity analysis. An additional voxel-based morphometry analysis was performed to examine if results were influenced by grey matter atrophy. RESULTS: The PIGD subgroup scored worse than the TD subgroup on all cognitive domains. Resting-state fMRI network analyses suggested that the connection between the visual and sensorimotor network is a potential differentiator between PIGD and TD subgroups. However, after correcting for dopaminergic medication use these results were not significant anymore. There was no between-group difference in grey matter volume. CONCLUSION: Despite clear motor and cognitive differences between the PIGD and TD subtypes, no significant differences were found in network connectivity. Methodological challenges, substantial symptom heterogeneity and many involved variables make analyses and hypothesis building around PD subtypes highly complex. More sensitive visualisation methods combined with machine learning approaches may be required in the search for characteristic underpinnings of PD subtypes.

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease.

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(ISQR)∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.

Conservative Iron Chelation for Neuroferritinopathy.

BACKGROUND: Neuroferritinopathy is a rare inherited neurodegenerative disease with brain iron accumulation characterized by brain iron overload resulting in progressive movement disorders. No treatment is currently available. OBJECTIVE: We assessed conservative iron chelation with deferiprone at 30 mg/kg/day on the disease progression with controlled periods of discontinuation. METHODS: Four patients with confirmed molecular diagnosis of neuroferritinopathy were given deferiprone at different stages of disease progression and with clinical and biological monitoring to control benefit and risk. RESULTS: The four patients showed slight to high improvement. In one case, we managed to stabilize disease progression for more than 11 years. In another case, we were able to reverse symptoms after a few months of treatment. The earliest the treatment was started, the most efficient it was on disease progression. CONCLUSIONS: Conservative iron chelation should be further assessed in neuroferritinopathy. © 2022 International Parkinson and Movement Disorder Society.

Lived experience of domestic violence among men with Parkinson's disease: A qualitative study.

OBJECTIVES: To explore possible forms of domestic violence suffered by men with Parkinson's disease (PD). METHODS: A qualitative study was conducted through face-to face interviews, followed by a conceptual content analysis. Forms of violence were predetermined as code categories according to a classification of mistreatment and a lack within Maslow's hierarchy of needs. Data triangulation was performed by two researchers using the "long table" method according to Krueger & Casey. RESULTS: Eleven men with PD were interviewed to identify experienced forms of domestic violence. Since PD, the men felt neglected by their partners, lived in the fear of the partner's reactions, described a mutual sexual and physical distance, suffered from mockeries, humiliations, physical violence, and had a feeling of abandon while facing and managing PD. CONCLUSIONS: Domestic violence against men with PD exists and should be screened during communication with healthcare professionals. PRACTICE IMPLICATIONS: Domestic violence has different faces and is not always identified by the victims themselves. Spouses with profiles at risk for domestic violence against men with PD should be identified. Domestic violence can be triggered by female gender, alcoholism, anxiety and depression, a low educational level, low interest in and low knowledge about PD.

Can Dopamine Responsiveness Be Predicted in Parkinson's Disease Without an Acute Administration Test?

BACKGROUND: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. OBJECTIVE: Our objective was to develop a predictive model combining clinical scores and imaging. METHODS: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001). CONCLUSION: These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.