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.

COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.

BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease.

BACKGROUND: The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson's disease (PD) are understudied. OBJECTIVE: To investigate clinical predictors of STN-DBS effects on ICB. METHODS: In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into 'QUIP-RS improvement or worsening' and analysed between-group differences. RESULTS: We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the 'QUIP-RS worsening' group had more severe baseline impairment in the NMSS attention/memory domain. CONCLUSIONS: Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS. TRIAL REGISTRATION NUMBER: DRKS00006735.

Emotional well-being and pain could be a greater determinant of quality of life compared to motor severity in cervical dystonia.

Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case-control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p < 0.001). Pain, insomnia and stigma were the most prevalent NMS and HRQoL was significantly impaired in CD patients compared to HC. There was strong correlation of NMS burden with HRQoL (CDQ-24: r = 0.72, EQ-5D: r = - 0.59; p < 0.001) in CD patients. Regression analysis between HRQoL and NMS suggested that emotional well-being (standardized beta = - 0.352) and pain (standardized beta = - 0.291) had a major impact on HRQoL while, in contrast motor severity had no significant impact in this model. Most NMS with the exception of pain, stigma and ADL did not correlate with motor severity. NMS are highly prevalent in CD patients and occur independent of age, sex, disease duration, duration of botulinum neurotoxin therapy and socio-economic status. Specific NMS such as emotional well-being and pain have a major impact on HRQoL and are more relevant than motor severity.

Neurology training and research in the COVID-19 pandemic: a survey of the Resident and Research Fellow Section of the European Academy of Neurology.

BACKGROUND AND PURPOSE: The COVID-19 (SARS-CoV-2) outbreak has disrupted residency programmes due to university and hospitals' priorities to face this emergency at all cost. Most research projects and clinical trials were temporarily stopped or postponed. The Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN) has decided to assess the impact of the COVID-19 pandemic on neurology training. METHODS: All EAN RRFS members were invited to fill out an online questionnaire of 40 items concerning their clinical involvement during the COVID-19 emergency, and the impact of the pandemic on their training (Appendix S1). RESULTS: Of the 227 RRFS members who completed the questionnaire, 222 were from Europe, and of those 111 were from Portugal, Italy or France. Responders highlighted that severe restrictions have been imposed to face this pandemic, including reduction of inpatient beds, prohibition of in-person visits and limitation to hospital access for patients' relatives. This was accompanied by an increase in email correspondence and phone calls with 50% of countries allowing telemedicine to reach outpatients. Seventy-nine per cent of the respondents felt that the pandemic will probably have a serious impact on their training and career. CONCLUSION: The pandemic led to a disruption of neurology activities, including medical training and research. The long-run impact of these changes remains unknown, but it will probably change the way neurology practice and training will be organized for future generations.

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.

Evaluation of the effect of bilateral subthalamic nucleus deep brain stimulation on fatigue in Parkinson's Disease as measured by the non-motor symptoms scale.

BACKGROUND: Fatigue is a common and disabling non-motor symptom (NMS) in Parkinson's disease (PD) patients. However, the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on fatigue has not been widely studied. OBJECTIVE: To determine the effect of STN DBS on fatigue in PD patients, measured by the Non-motor symptoms scale (NMSS). METHODS: Cross-sectional analysis of 50 patients with PD who underwent STN DBS at King's College Hospital and Salford Royal Hospital with fatigue scores (measured by question number 4 from domain 2 (sleep/fatigue) of the NMSS as the primary outcome measure. Secondary outcome measures included the PD Sleep Scale (PDSS), Scales for Outcome in PD (SCOPA)-motor examination, activities of daily living, motor complications, Hoehn and Yahr (HY) stage and changes in Levodopa Equivalent Daily Dose (LEDD). RESULTS: 50 patients with a mean follow-up period of 1.98 ± 1.36 years were studied. Significant improvement in median fatigue scores (4.00 (0.75-9.00) to 1.00 (0.00-4.50); p = .001) was observed. In addition, improvements in question 5 (sleep maintenance and fragmentation; 8.00 (4.00-12.00) to 0.00 (0.00-4.00); p < .001) and in domain 2 total score (sleep/fatigue; 20.00 (8.75-27.25) to 6.00 (0.75-16.00); p < .001) were also significant, together with improvements in NMSS total score, SCOPA scores and HY stage (p ≤ .02). Moreover, LEDD but especially dopamine agonists LEDD was significantly reduced after DBS (310.00 (0.00-480.00) to 150.00 (0.00-300.00); p < .020). CONCLUSIONS: Even though open label and not using a validated fatigue scale, this observational analysis suggest that fatigue improves significantly after STN DBS with persisting benefits at two years follow-up.

A prospective, controlled study of non-motor effects of subthalamic stimulation in Parkinson's disease: results at the 36-month follow-up.

OBJECTIVE: To examine 36-month effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS) compared with standard-of-care medical treatment (MED) in Parkinson's disease (PD). METHODS: Here we report the 36-month follow-up of a prospective, observational, controlled, international multicentre study of the NILS cohort. Assessments included NMSScale (NMSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). Propensity score matching resulted in a pseudo-randomised sub-cohort balancing baseline demographic and clinical characteristics between the STN-DBS and MED groups. Within-group longitudinal outcome changes were analysed using Wilcoxon signed-rank and between-group differences of change scores with Mann-Whitney U test. Strength of clinical responses was quantified with Cohen's effect size. In addition, bivariate correlations of change scores were explored. RESULTS: Propensity score matching applied on the cohort of 151 patients (STN-DBS n=67, MED n=84) resulted in a well-balanced sub-cohort including 38 patients per group. After 36 months, STN-DBS significantly improved NMSS, PDQ-8, SCOPA-motor examination and -complications and reduced LEDD. Significant between-group differences, all favouring STN-DBS, were found for NMSS, SCOPA-motor complications, LEDD (large effects), motor examination and PDQ-8 (moderate effects). Furthermore, significant differences were found for the sleep/fatigue, urinary (large effects) and miscellaneous NMSS domains (moderate effects). NMSS total and PDQ-8 change scores correlated significantly. CONCLUSIONS: This study provides Class IIb evidence for beneficial effects of STN-DBS on NMS at 36-month follow-up which also correlated with quality of life improvements. This highlights the importance of NMS for DBS outcomes assessments.

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease.

OBJECTIVE: Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD). METHODS: In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics. RESULTS: In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome. CONCLUSIONS: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. © 2019 International Parkinson and Movement Disorder Society.

Impact of ethnicity on the natural history of Parkinson disease.

Parkinson disease (PD) affects people of all races and ethnicity worldwide. PD is a multineurotransmitter and multisystem disorder and our current concept of the natural history of PD has changed considerably over the past decades. Many aspects of this heterogeneous condition still remain unexplained; one aspect that is poorly studied is the role of ethnicity and manifest motor and non-motor PD. Some preliminary data suggest that the prodromal risk of developing PD, clinical symptom expression and the experience of living with the condition may vary between different ethnic groups. Several factors might play a role in the influence of ethnicity on PD, such as pharmacogenetics, sociocultural aspects and environmental exposures. Increased knowledge on the role of ethnicity in PD may help shed light on the symptom expression and treatment response of PD, address inequalities in health care delivery worldwide and improve the delivery of personalised medicine.

Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients.

BACKGROUND: The objective of this study was to investigate in vivo the ability of levodopa/carbidopa intestinal gel infusions to produce sustained striatal dopamine levels and to improve clinical outcomes in Parkinson's disease patients. METHODS: Six advanced Parkinson's disease patients had serial [11 C]raclopride PET to assess levodopa/carbidopa intestinal gel infusion-induced rises in striatal dopamine as reflected by a fall in dopamine-D2/3 receptor availability. Parkinson's disease patients had baseline scan OFF-dopaminergic stimulation and 2 scans following initiation of levodopa/carbidopa intestinal gel infusions. Striatal D2/3 binding was measured in striatal subregions corresponding to sensorimotor, limbic, and cognitive/associative function. RESULTS: Mean striatal [11 C]raclopride nondisplaceable binding potential decreased by 14.0% to 16.7% in sensorimotor, 12.0%-14.4% in limbic, and 8.7%-11.6% in cognitive/associative function subregions at 1- to 10-hour points (P < 0.01). Sensorimotor subregion [11 C]raclopride nondisplaceable binding potential reductions correlated with reductions in Unified Parkinson's Disease Rating Scale Part III scores over the course of the infusion (r = 0.81; P < 0.05). CONCLUSIONS: Levodopa/carbidopa intestinal gel infusions generate a stable rise in striatal dopamine levels and are associated with improvements in motor manifestations. © 2016 International Parkinson and Movement Disorder Society.

Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations.

BACKGROUND: Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson's disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. SUMMARY: We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apathy were most prevalent when applying the health-professional completed NMSS. Key Messages: NMS are generally prevalent and highly burdensome within selected Asian PD populations living in countries included in this review. Our review suggests that NMS-driven phenotypic heterogeneity is present in Asian patients, and compared to Western PD populations there might be variations in assessed NMS.

Cognitive impairment in idiopathic Parkinson's disease.

BACKGROUND: Cognitive symptoms are common in advanced Parkinson's disease (PD). However, assessment of cognitive impairment is difficult in PD because of accompanying motor symptoms and the coexistence of nonmotor symptoms. Specific subdomains affected in the disease are not reflected in the conventional scales used for assessing cognition. OBJECTIVES: This study was aimed at looking at the spectrum of cognitive impairment in the various phenotypes and stages of PD and the correlation of cognitive impairment with motor and nonmotor symptoms of PD. PATIENTS AND METHODS: Fifty PD patients fulfilling the UK PD Society Brain Bank's criteria were selected after obtaining explicit consent. Patients were assessed clinically and by using various scales like Scales for Outcomes in PD-Cognition (SCOPA-COG), mini-mental state examination, and Beck's Depression Inventory and Scoring. RESULTS: The mean age was 58 years, 82% of the patients were male, and the mean modified Hoehn and Yahr staging was 2. The most commonly affected domains were memory and executive functioning. Cognitive impairment was more in those with late-onset disease, more advanced stage of disease, and in the postural instability and gait disorder (PIGD) subgroup. The cognitive function deteriorated with increasing age and duration of the illness. Significant correlation with cognitive impairment was obtained for the manifestations of increased motor disability, presence of coexistent psychotic symptoms and depression. CONCLUSIONS: Cognitive impairment was common among PD patients, and it was more prevalent with increasing duration of the disease, in older patients, in late-onset disease, and in the PIGD subgroup. Increasing motor disability and associated psychotic symptoms as well as depression significantly increased the cognitive impairment.

New clinical trials for nonmotor manifestations of Parkinson's disease.

Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5-HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post-DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post-hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing.

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years: A Nonrandomized Controlled Trial.

Importance: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking. Objective: To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED). Design, Setting, and Participants: In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023. Exposure: Treatment for PD of STN-DBS or MED. Main Outcomes and Measures: Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed. Results: The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001). Conclusions and Relevance: This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments. Trial Registration: German ClinicalTrials Registry: DRKS00006735.

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.

Predictors of short-term anxiety outcome in subthalamic stimulation for Parkinson's disease.

The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on anxiety in Parkinson's disease (PD) are understudied. We identified clinical predictors of STN-DBS effects on anxiety in this study. In this prospective, open-label, multicentre study, we assessed patients with anxiety undergoing STN-DBS for PD preoperatively and at 6-month follow-up postoperatively. We assessed the Hospital Anxiety and Depression Scale (HADS-anxiety and depression subscales), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-motor (SCOPA-M)-activities of daily living (ADL) and -motor complications, Non-Motor Symptom Scale (NMSS), PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose. We tested changes at follow-up with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We identified patients with a clinically relevant anxiety improvement of anxiety based on a designated threshold of ½ standard deviation of baseline HADS-anxiety. Moreover, we investigated predictors of HADS-anxiety changes with correlations and linear regressions. We included 50 patients with clinically relevant baseline anxiety (i.e., HADS-anxiety ≥ 8) aged 63.1 years ± 8.3 with 10.4 years ± 4.5 PD duration. HADS-anxiety improved significantly at 6-month follow-up as 80% of our cohort experienced clinically relevant anxiety improvement. In predictor analyses, worse baseline SCOPA-ADL and NMSS-urinary domain were associated with greater HADS-anxiety improvements. HADS-anxiety and PDQ-8 changes correlated moderately. Worse preoperative ADL and urinary symptoms predicted favourable postoperative anxiety outcome, which in turn was directly proportionate to greater QoL improvement. This study highlights the importance of detailed anxiety assessments alongside other non-motor and motor symptoms when advising and monitoring patients undergoing STN-DBS for PD.

SOP: acute hyperkinetic movement disorders.

INTRODUCTION: Movement disorders emergencies describe acute-onset neurological conditions in which a delay of recognition and treatment may cause severe morbidity and mortality of patients. Hyperkinetic movement disorders include tremor, chorea/ballism, dystonia, myoclonus, and tics. Here we present a standard operating procedure (SOP) for the diagnostic work-up and different treatment options depending on the phenomenology as well as the aetiology of underlying diseases. COMMENTS: The recognition of the phenomenology is essential for the symptomatic therapy of the acute movement disorder and forms the basis for the choice of ancillary investigations to confirm the suspected underlying causes. Furthermore, we summarise diagnostic techniques, including blood and cerebrospinal fluid tests and neuroimaging, which provide rapid results and are useful for the indication of causal treatments of specific acute movement disorders. CONCLUSIONS: Despite their acute nature, most of these conditions can result in good clinical outcomes, if recognised early.

The Park Sleep subtype in Parkinson's disease: from concept to clinic.

INTRODUCTION: The heterogeneity of Parkinson's disease (PD) is evident from descriptions of non-motor (NMS) subtypes and Park Sleep, originally identified by Sauerbier et al. 2016, is one such clinical subtype associated with the predominant clinical presentation of sleep dysfunctions including excessive daytime sleepiness (EDS), along with insomnia. AREAS COVERED: A literature search was conducted using the PubMed, Medline, Embase, and Web of Science databases, accessed between 1 February 2023 and 28 March 2023. In this review, we describe the clinical subtype of Park Sleep and related 'tests' ranging from polysomnography to investigational neuromelanin MRI brain scans and some tissue-based biological markers. EXPERT OPINION: Cholinergic, noradrenergic, and serotonergic systems are dominantly affected in PD. Park Sleep subtype is hypothesized to be associated primarily with serotonergic deficit, clinically manifesting as somnolence and narcoleptic events (sleep attacks), with or without rapid eye movement behavior disorder (RBD). In clinic, Park Sleep recognition may drive lifestyle changes (e.g. driving) along with therapy adjustments as Park Sleep patients may be sensitive to dopamine D3 active agonists, such as ropinirole and pramipexole. Specific dashboard scores based personalized management options need to be implemented and include pharmacological, non-pharmacological, and lifestyle linked advice.