No evidence for an association of voxel-based morphometry with short-term non-motor outcomes in deep brain stimulation for Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson's disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.

Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.

BACKGROUND: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. METHODS: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. RESULTS: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. CONCLUSIONS: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.

The PD-Ballet study: study protocol for a randomised controlled single-blind hybrid type 2 clinical trial evaluating the effects of ballet dancing on motor and non-motor symptoms in Parkinson's disease.

BACKGROUND: To date, beneficial effects of multimodal exercise programmes on Parkinson's disease (PD) have focused on motor symptoms and little attention has been paid to the potential effects of such programmes on the non-motor symptoms of PD, which are now universally known as one of the key drivers of quality of life and a key unmet need. We aim to explore clinical effectiveness of a ballet-based dance programme in addressing non-motor and motor symptoms of Parkinson's disease across all stages of progression. METHODS: A randomised, single-blind, controlled trial of 160 people with Parkinson's across all motor stages (Participants will be stratified into three groups of motor advancement: Hoehn and Yahr (HY) stages I and II being Mild Group, HY Stage III being Moderate Group and HY Stages IV and V being Severe Group) will be randomly allocated to either an intervention or a control group using an independent randomisation body. The primary outcome is an improvement in non-motor symptoms as measured by the Movement Disorders Society Non-Motor Scale (MDS-NMS). The intervention protocol consists of 12 one-weekly dance sessions led by English National Ballet. Each session is followed by a 'tea and biscuit' social time. Control group follows standard clinical pathway and joins the 'tea and biscuit' to control for any positive effects of social interactions. All participants are assessed at baseline, immediately after completion of the intervention and 3-6 months later to explore any potential longitudinal effects. DISCUSSION: To our knowledge, no adequately powered study has explored the effects of a dance-based intervention on non-motor symptoms of Parkinson's disease, assessing these on both holistic and granular levels. We also aim to stratify participants in accordance with their motor state as assessed by. HY staging to explore specific effects on the symptoms at the initial, moderate and complex stages of the disease. If successful, this trial provides first evidence on clinical effectiveness of a ballet-based dance intervention for symptoms of Parkinson's disease, assessed in a robust, rigorous manner. TRIAL REGISTRATION: NCT04719468.

Stratifying quality of life outcome in subthalamic stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves quality of life (QoL), motor and non-motor symptoms (NMS). However, in previous studies, 43%-49% of patients did not experience clinically relevant postoperative QoL improvement. To inform individualised prediction of postoperative QoL improvement, we developed a stratification analysis of QoL outcomes based on preoperative non-motor total burden, severity of motor progression and motor response in levodopa challenge tests. METHODS: This was a prospective, open-label, multicentre, international study with a 6-month follow-up. A distribution-based threshold identified 'QoL responders' in the PDQuestionnaire-8 Summary Index (PDQ-8 SI). After baseline stratification based on the NMS Scale, Hoehn and Yahr Scale and levodopa response assessed with the Unified PD Rating Scale-III, we compared postoperative QoL response between these strata. To assess the clinical usefulness and statistical feasibility of stratifications, we compared cumulative distribution function curves, respectively PDQ-8 within-stratum variation. RESULTS: All main outcomes improved postoperatively. Based on the 8.1 points threshold for clinically meaningful PDQ-8 SI improvement, only 80/161 patients were classified as 'QoL responders'. The absolute risk reductions for QoL non-response among respective non-motor, motor progression and levodopa response strata were 23%, 8% and 3%, respectively. Only non-motor stratification reduced PDQ-8 within-stratum variation compared with the overall cohort. CONCLUSIONS: Non-motor stratification, but not motor progression or levodopa response stratification, is clinically useful and statistically feasible for personalised preoperative prediction of postoperative QoL outcome of STN-DBS for PD. Our findings highlight that non-motor assessments are necessary components of a case-based, holistic approach of DBS indication evaluations geared towards optimising postoperative QoL outcomes. TRIAL REGISTRATION NUMBER: GermanClinicalTrialsRegister: #6735.

Addressing the gap for racially diverse research involvement: The King's Model for minority ethnic research participant recruitment.

Objectives: Ethnic minorities (EM) are still underrepresented in research recruitment. Despite wide literature outlining the barriers, enablers and recommendations for driving inclusion and diversity in research, there is still little evidence for successful diversity in research participation, which has a direct impact on the quality of care provided to ethnically diverse individuals. A new, comprehensive approach to recruitment strategies is therefore necessary. Study design: service improvement initiative. Methods: In the light of the Covid-19 pandemic and the key public health need to address the disparity in care provided to non-white populations, we used a novel, comprehensive approach (The King's Model) comprising of local and community actions to promote inclusive research recruitment. We then compared rates of diverse recruitment in studies where the novel approach, was applied to studies which had been closed to recruitment at the time of analysis and where ethnicity data was available. Results: Our results demonstrate that following the introduction of the King's Model for diverse recruitment, commercial interventional study diverse recruitment increased from 6.4% to 16.1%, and for non-commercial studies, from 30.2% to 41.0% and 59.2% in the selected studies. Conclusions: King's Model is potentially a useful tool in enhancing non-Caucasian recruitment to clinical research. Enriched by additional recommendations based on our experiences during the Covid-19 research recruitment drive, we propose the King's Model is used to support ethnically diverse research recruitment. Further evidence is needed to replicate our findings, although this preliminary evidence provides granular details necessary to address the key unmet need of validating clinical research outcomes in non-white populations.

Grey-matter correlates of empathy in 4-Repeat Tauopathies.

Loss of empathy is an early and central symptom of frontotemporal lobar degeneration spectrum diseases. We aimed to investigate the topographical distribution of morphometric brain changes associated with empathy in Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS) patients. Twenty-seven participants with CBS and 31 with PSP were evaluated using Interpersonal Reactivity Index scales in correlation with gray matter atrophy using a voxel-based morphometry approach. Lower levels of empathy were associated with an increased atrophy in fronto-temporal cortical structures. At subcortical level, empathy scores were positively correlated with gray matter volume in the amygdala, hippocampus and the cerebellum. These findings allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions in patients with neurodegenerative disorders and suggest that the cerebellum may play a more prominent role in social cognition than previously appreciated.

SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson's disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions.

Neurofilament light predicts worse nonmotor symptoms and depression in Parkinson's disease.

BACKGROUND: The identification of biomarkers that reflect worse progression of nonmotor symptoms (NMS) in Parkinson's disease (PD) is currently an unmet need. The main aim of this study was to investigate whether cerebrospinal fluid (CSF) and serum neurofilament light (NfL), measured at baseline or longitudinally, can be used to predict the progression of NMS in patients with PD. METHODS: Baseline and longitudinal NfL levels were measured in the CSF and serum in 392 PD patients and 184 healthy controls from the Parkinson's Progression Marker Initiative. NMS were assessed using several scales, including, but not restricted to, the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). The relationship between baseline and longitudinal NfL levels with changes in NMS was assessed using linear mixed effects models (LME) in PD patients. In addition, we compared CSF and serum NfL levels between groups and assessed the relationship between NfL biomarkers with baseline NMS. Finally, to assess the specificity of our findings we ran the previous LME models using other biomarkers such as CSF amyloid-ß1-42, total tau, phosphorylated tau181 and total α-synuclein and we also ran the models in healthy controls. RESULTS: Baseline levels and longitudinal changes in serum and CSF NfL predicted worse longitudinal MDS-UPDRS-I and depression scores over time in PD (p < 0.01). This relationship remained significant only for CSF NfL when controlling for motor and cognitive status. Furthermore, longitudinal changes in serum and CSF NfL were associated with worse anxiety over time in PD patients (p < 0.05). In contrast to CSF NfL, serum NfL levels were slightly higher at baseline (p = 0.043) and showed significant longitudinal increases (p < 0.001) in PD patients compared to controls. There were no significant correlations between NfL levels (CSF or serum) with other NMS scales, baseline NMS variables, other biomarkers or in healthy controls. CONCLUSIONS: Our findings indicate that both serum and CSF NfL are associated with worse longitudinal NMS burden, particularly in relation to the progression of depression and anxiety. Serum NfL showed stronger associations with NMS suggesting it could potentially be used as a non-invasive marker of NMS progression for PD.

Non-motor symptoms in amyotrophic lateral sclerosis: lessons from Parkinson's disease.

Amyotrophic lateral sclerosis and Parkinson's disease are neurodegenerative diseases of the motor system which are now recognized also to affect non-motor pathways. Non-motor symptoms have been acknowledged as important determinants of quality of life in Parkinson's disease, and there is increasing interest in understanding the extent and role of non-motor symptoms in amyotrophic lateral sclerosis. We therefore reviewed what is known about non-motor symptoms in amyotrophic lateral sclerosis, using lessons from Parkinson's disease.

The noradrenergic subtype of Parkinson disease: from animal models to clinical practice.

Many advances in understanding the pathophysiology of Parkinson disease (PD) have been based on research addressing its motor symptoms and phenotypes. Various data-driven clinical phenotyping studies supported by neuropathological and in vivo neuroimaging data suggest the existence of distinct non-motor endophenotypes of PD even at diagnosis, a concept further strengthened by the predominantly non-motor spectrum of symptoms in prodromal PD. Preclinical and clinical studies support early dysfunction of noradrenergic transmission in both the CNS and peripheral nervous system circuits in patients with PD that results in a specific cluster of non-motor symptoms, including rapid eye movement sleep behaviour disorder, pain, anxiety and dysautonomia (particularly orthostatic hypotension and urinary dysfunction). Cluster analyses of large independent cohorts of patients with PD and phenotype-focused studies have confirmed the existence of a noradrenergic subtype of PD, which had been previously postulated but not fully characterized. This Review discusses the translational work that unravelled the clinical and neuropathological processes underpinning the noradrenergic PD subtype. Although some overlap with other PD subtypes is inevitable as the disease progresses, recognition of noradrenergic PD as a distinct early disease subtype represents an important advance towards the delivery of personalized medicine for patients with PD.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Non-oral continuous drug delivery based therapies and sleep dysfunction in Parkinson's disease.

Continuous drug delivery (CDD) has emerged as a feasible and pragmatic therapeutic option for dopamine replacement therapy in advanced Parkinson's disease (PD). CDD aims to mimic the physiological tonic dopamine release from striatal dopaminergic neurons and thus reduces the severity and duration of motor and non-motor fluctuations partly related to pulsatile levodopa stimulation. Non-motor symptoms and fluctuations are ubiquitous in PD and include sleep dysfunction, a problem that occurs in over 90% of PD patients across all stages, from prodromal to palliative. In this review, we discuss the currently available and in development non-oral dopaminergic CDD strategies with a focus on their efficacy in the treatment of the burdensome sleep dysfunction in PD.

The real-life effect of catechol-O-methyltransferase inhibition on non-motor symptoms in levodopa-treated Parkinson's disease: opicapone versus entacapone.

OBJECTIVE: To evaluate the long-term, real-life effects on non-motor symptoms (NMS) of opicapone compared to entacapone in levodopa-treated people with Parkinson's disease (PwP). METHODS: A retrospective data analysis, with pre- and post-opicapone initiation data of 17 PwP with motor fluctuations compared to a comparable group of 18 PwP introduced on entacapone. The primary outcome was changes in the NMS Scale (NMSS) total score after 1-year follow-up. Secondary outcomes included changes in the NMSS domains, and Parkinson's Disease Sleep Scale (PDSS) total and item scores after the same time span. RESULTS: Groups were comparable for baseline demographics and Parkinson's-related features (p ≥ 0.314) as well as duration of follow-up (1.33 ± 0.66 years for PwP on opicapone and 1.23 ± 0.49 years for those on entacapone; p = 0.858). PwP who were introduced on opicapone showed no changes in NMSS and PDSS total scores after 1 year (p = 0.605 and p = 0.507, respectively), whereas PwP who were introduced on entacapone showed significant worsening of NMSS and PDSS total scores at follow-up (p = 0.005 and p = 0.001, respectively). In neither group changes in individual NMSS domains from baseline to follow-up were observed (p ≥ 0.288 for entacapone and p ≥ 0.816 for opicapone, respectively). In PwP on entacapone significant worsening was seen in the distressing dreams, hallucinations, and limb numbness items of the PDSS (p ≤ 0.05). CONCLUSIONS: Introduction of opicapone in real-life PwP with motor fluctuations seems to stabilise NMS burden and aspects of sleep dysfunction, in contrast to entacapone where there was a worsening of NMS burden and PDSS scores over 1 year follow-up.

The Gut Dysmotility Questionnaire for Parkinson's disease: Insights into development and pretest studies.

Objective: A total of 48% of patients with Parkinson's disease (PD) present symptoms of gastrointestinal dysfunction, particularly constipation. Furthermore, gastrointestinal tract (GIT)-related non-motor symptoms (NMSs) appear at all stages of PD, can be prodromal by many years and have a relevant impact on the quality of life. There is a lack of GIT-focused validated tools specific to PD to assess their occurrence, progress, and response to treatment. The aim of this study was to develop and evaluate a novel, disease- and symptom-specific, self-completed questionnaire, titled Gut Dysmotility Questionnaire (GDQ), for screening and monitoring gastrointestinal dysmotility of the lower GIT in patients with PD. Methods: In phase 1, a systematic literature review and multidisciplinary expert discussions were conducted. In phase 2, cognitive pretest studies comprising standard pretests, interviews, and evaluation questionnaires were performed in patients with PD (n = 21), age- and sex-matched healthy controls (HC) (n = 30), and neurologists (n = 11). Incorporating these results, a second round of cognitive pretests was performed investigating further patients with PD (n = 10), age- and sex-matched HC (n = 10), and neurologists (n = 5). The questionnaire was adapted resulting in the final GDQ, which underwent cross-cultural adaptation to the English language. Results: We report significantly higher GDQ total scores and higher scores in five out of eight domains indicating a higher prevalence of gastrointestinal dysmotility in patients with PD than in HC (p < 0.05). Cognitive pretesting improved the preliminary GDQ so that the final GDQ was rated as relevant (100/100%), comprehensive (100/90%), easy to understand concerning questions and answer options (100/90%), and of appropriate length (80/100%) by neurologists and patients with PD, respectively. The GDQ demonstrated excellent internal consistency (Cronbach's alpha value of 0.94). Evidence for good construct validity is given by moderate to high correlations of the GDQ total score and its domains by intercorrelations (r s = 0.67-0.91; p < 0.001) and with validated general NMS measures as well as with specific items that assess gastrointestinal symptoms. Interpretation: The GDQ is a novel, easy, and quick 18-item self-assessment questionnaire to screen for and monitor gastrointestinal dysmotility with a focus on constipation in patients with PD. It has shown high acceptance and efficacy as well as good construct validity in cognitive pretests.

Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease.

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

Viruses, parkinsonism and Parkinson's disease: the past, present and future.

Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A variety of viruses have been described with a potential of inducing or contributing to the occurrence of parkinsonism and Parkinson's disease (PD), although the relationship between the two remains a matter of debate originating with the description of encephalitis lethargica in the aftermath of the Spanish flu in 1918. While some viral infections have been linked to an increased risk for the development of PD, others seem to have a causal link with the occurrence of parkinsonism. Here, we review the currently available evidence on viral-induced parkinsonism with a focus on potential pathophysiological mechanisms and clinical features. We also review the evidence on viral infections as a risk factor for developing PD and the link between SARS-CoV-2 and parkinsonism, which might have important implications for future research and treatments.

Clinical trajectories and biomarkers for weight variability in early Parkinson's disease.

Unexplained weight changes that occur in Parkinson's disease (PD), are often neglected and remain a poorly understood non-motor feature in patients with PD. A specific 'Park-weight' phenotype with low body weight has been described, and our aim was to evaluate the clinical and prognostic trajectories and biomarkers of weight variability in PD. We evaluated body weight-related biomarkers in 405 de novo PD patients and 187 healthy controls (HC) over a 5-year follow-up period from the PPMI database. Body-weight variability was defined as intra-individual variability in body weight between visits. PD patients were categorized as weight losers, gainers, or patients with stable weight. The differential progression of motor and non-motor clinical variables between groups was explored using linear mixed-effects models. Finally, we estimated longitudinal changes in weight as a function of baseline and longitudinal striatal presynaptic dopaminergic transporter imaging. PD patients presented a greater weight variability compared to HC (p = 0.003). Patients who developed weight loss had lower CSF amyloid-beta 1-42 (p = 0.009) at baseline. In addition, patients with weight loss showed a faster cognitive decline (p = 0.001), whereas patients with weight gain showed a slower motor progression (p = 0.001), compared to patients with stable weight. Baseline right striatal denervation was a predictor of weight variability in both PD patients and HC (p < 0.001). Similarly, weight variability in PD patients was associated with the progression of right striatal denervation (p < 0.001). Weight variability and specifically weight loss are more frequent in PD compared to HC, and are associated with specific motor, non-motor and cognitive progression patterns. A greater CSF amyloid burden was present at baseline in patients with subsequent weight loss. Presynaptic dopaminergic imaging in the right striatum may serve as a predictor of future weight changes in PD and HC.

Relevance of sleep and associated structural changes in GBA1 mouse to human rapid eye movement behavior disorder.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry.

Gender gap in deep brain stimulation for Parkinson's disease.

Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson's disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015-09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford's Royal Hospital Manchester, and King's College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56-0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03-1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48-1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.

Restricted truncal sagittal movements of rapid eye movement behaviour disorder.

Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the 'outside-world', and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients' limited truncal/axial movements. To confirm this, a semiology analysis of video-polysomnography records of 38 RBD patients was undertaken and paradoxically restricted truncal/thoraco-lumbar movements during complex dream re-enactments demonstrated.