Predicting Motor Outcome and Quality of Life After Subthalamic Deep Brain Stimulation for Parkinson's Disease: The Role of Standard Screening Measures and Wearable-Data.

BACKGROUND: Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson's disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim. OBJECTIVE: To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery. METHODS: Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function. RESULTS: Eighty-three patients were included (median (interquartile range) age 63 (56-68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models. CONCLUSION: Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.

Medical and Surgical Treatment for Medication-Induced Tremor: Case Report and Systematic Review.

Objective: To present a case of refractory medication-induced tremor successfully treated with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) and to propose a medical and surgical treatment algorithm based on a systematical review of the literature. Methods: Patient data were retrospectively collected. A systematic search was performed in PubMed, Embase, and Cochrane Library. Subjective and objective data were pooled for analysis by classifying them into 5 predefined categories(no, minimal, moderate, good, and excellent effects). Results: The patient presented with lithium-induced bilateral progressive hand tremor lasting 25 years. After DBS, he reported excellent tremor suppression until the last follow-up (36 months after Vim-DBS). For the review, 34 of 140 studies were included and evaluated (178 unique subjects, 31 different treatments). A good-to-excellent tremor suppression (50%-100%) in at least 50% of subjects was achieved using propranolol (12 studies, 50% of 56 subjects), tetrabenazine (5 studies, 51% of 13 subjects), and metoprolol (4 studies, 75% of 8 subjects). The effect of benztropine and diphenhydramine was none or only minimal to moderate (up to 50% improvement; both: 3 studies, 50% of 4 patients). One article reported minimal-to-moderate effectiveness after DBS of the ventral oral posterior nucleus of the thalamus. Methods were highly heterogeneous. All studies scored grade III or IV quality of evidence, which was insufficient for recommendations (level U). Conclusion: Treatment decision making should be performed on a case-by-case basis considering the low level of evidence, and we propose a practically oriented treatment algorithm. Propranolol, tetrabenazine, and metoprolol might be effective. For selected and refractory cases, DBS might be considered.

Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease.

A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 × 10-11), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 × 10-8) and WWOX (HR = 2.12, P = 2.37 × 10-8) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.

Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner. METHODS: In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases. RESULTS: In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%). INTERPRETATION: We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41-48.

Parkinson's Disease Subtypes: Critical Appraisal and Recommendations.

BACKGROUND: In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice. OBJECTIVE: To critically evaluate PD subtyping systems. METHODS: We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists. RESULTS: We included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown. CONCLUSION: Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed.

Assessing walking adaptability in stroke patients.

PURPOSE: The ability to adapt walking is important for safe ambulation. Assessments of impairments in walking adaptability with the Interactive Walkway may aid in the development of individualized therapy strategies of stroke patients. The Interactive Walkway is an overground walkway with Kinect v2 sensors for a markerless registration of full-body kinematics, which can be augmented with (gait-dependent) visual context to assess walking adaptability. This study aims to evaluate the potential of the Interactive Walkway as a new technology for assessing walking adaptability in stroke patients. Materials and methods: 30 stroke patients and 30 controls performed clinical tests, quantitative gait assessments and various walking-adaptability tasks on the Interactive Walkway. Outcome measures were compared between stroke patients and controls to examine known-groups validity. Pearson's correlation coefficients were calculated to assess the relationship between walking-adaptability outcomes and commonly used clinical test scores of walking ability and spatiotemporal gait parameters of unconstrained walking. Results: Good known-groups validity for walking-adaptability outcomes was demonstrated. In addition, the vast majority of walking-adaptability outcomes did not or only moderately correlate with clinical test scores of walking ability and unconstrained walking parameters. Conclusion: Interactive Walkway walking-adaptability outcomes have good known-groups validity and complement standard clinical tests and spatiotemporal gait parameters.IMPLICATIONS FOR REHABILITATIONThe Interactive Walkway allows for a comprehensive walking-adaptability assessment.Good known-groups validity for walking-adaptability tasks was demonstrated and walking-adaptability tasks complemented clinical tests and gait parameters.The Interactive Walkway has potential for monitoring recovery of walking after stroke.Assessments of walking adaptability may contribute to individualized interventions.

The Cervical Radiculopathy Impact Scale: development and evaluation of a new functional outcome measure for cervical radicular syndrome.

Objective: To develop and validate an outcome scale for the cervical radicular syndrome and to build a mapping, predicting EQ-5D utility from the new scale.Study design and setting: An item pool was developed based on literature and patient and clinician interviews. Item selection was based on symptomatology, factor analysis, and internal consistency. We assessed: (a) test-retest reliability by standard error of measurement and intraclass correlation coefficients; (b) construct validity by testing 22 hypotheses on relationships with existing measures and known-group differences. For the mapping, performance was assessed by mean absolute error and root mean squared error.Results: A total of 254 patients with cervical radicular syndrome completed the first questionnaire, 61 stable patients a retest. Item selection led to a 21-item questionnaire consisting of three subscales: Symptoms, Energy and postures, and Actions and activities. Standard error of measurement values ranged from 6.7 to 11.2 on a 0 to 100 scale. All subscales showed good reliability (intraclass correlation coefficients: 0.84, 0.87, and 0.94). All hypotheses for construct validity were confirmed. A linear utility mapping was preferred, with reasonable statistical performance.Conclusion: We developed a reliable and valid cervical radicular syndrome specific outcome scale, called the Cervical Radiculopathy Impact Scale (CRIS). This new questionnaire may facilitate (cost-)effectiveness studies in this field.Implications for RehabilitationThe cervical radicular syndrome is a frequently occurring and invalidating health problem, which causes severe radiating pain in the arm and/or hand, which can be accompanied by motor and/or sensory deficits.The Cervical Radiculopathy Impact Scale (CRIS) is a newly developed self-report questionnaire which covers measurement of symptoms and limitations in patients with cervical radiculopathy due to irradiating pain, tingling sensations and sensory loss in the arm in combination with neck disability.The CRIS consists of 21 items divided over three subscales: (i) symptoms, (ii) energy and postures, and (iii) actions and activities.The CRIS shows good content validity, test-retest reliability, construct validity and is able to discriminate between groups.The CRIS predicts EQ-5D utility and is therefore useful for (cost)effectiveness studies in this field.

Genetic modifiers of risk and age at onset in GBA associated Parkinson's disease and Lewy body dementia.

Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute to the risk of Parkinson's disease, and currently 90 independent risk variants have been identified by genome-wide association studies. Thus far, a number of genes (including SNCA, LRRK2, and GBA) have been shown to contain variability across a spectrum of frequency and effect, from rare, highly penetrant variants to common risk alleles with small effect sizes. Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson's disease and Lewy body dementia. These variants, which reduce or abolish enzymatic activity, confer a spectrum of disease risk, from 1.4- to >10-fold. An outstanding question in the field is what other genetic factors that influence GBA-associated risk for disease, and whether these overlap with known Parkinson's disease risk variants. Using multiple, large case-control datasets, totalling 217 165 individuals (22 757 Parkinson's disease cases, 13 431 Parkinson's disease proxy cases, 622 Lewy body dementia cases and 180 355 controls), we identified 1691 Parkinson's disease cases, 81 Lewy body dementia cases, 711 proxy cases and 7624 controls with a GBA variant (p.E326K, p.T369M or p.N370S). We performed a genome-wide association study and analysed the most recent Parkinson's disease-associated genetic risk score to detect genetic influences on GBA risk and age at onset. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall Parkinson's disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Notably, this effect was consistent across all tested GBA risk variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Risk variants in the CTSB locus were identified to decrease mRNA expression of CTSB. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls. These data provide a genetic basis for modification of GBA-associated Parkinson's disease risk and age at onset, although the total contribution of common genetics variants is not large. We further demonstrate that common variability at genes implicated in lysosomal function exerts the largest effect on GBA associated risk for disease. Further, these results have implications for selection of GBA carriers for therapeutic interventions.

Regional Structural Hippocampal Differences Between Dementia with Lewy Bodies and Parkinson's Disease.

BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are considered subtypes of the α-synucleinopathy continuum that show similar and dissimilar clinical and morphological features. OBJECTIVE: To further our understanding of brain abnormalities that might differentiate both disorders more clearly, we performed quantitative magnetic resonance (MR) imaging of the subcortical and cortical grey matter. METHODS: Three-dimensional T1 weighted 3 tesla MR images of 14 DLB and 62 age- and gender-matched PD patients were examined to study cortical and subcortical grey matter structure. We used volumetric measurements to study total grey matter, and volumes of the pallidum, amygdala, putamen, caudate nucleus, thalamus and hippocampus. Whole-brain and structural network-based methods were used to identify local differences in grey matter and vertex-based shape analysis was used to assess focal hippocampal changes. RESULTS: Volumetric, whole-brain and network-based analyses showed reduced hippocampal (p = 0.008) and right parahippocampal region volumes (p = 0.030) in DLB compared to PD patients. Shape analysis showed atrophy in the head and body of the right (p = 0.040) and in the head of the left (p = 0.030) hippocampus of DLB patients. CONCLUSION: DLB patients showed atrophy of the hippocampus and parahippocampal gyrus compared to PD patients with a differential involvement of the head and body of the hippocampus. Further studies should examine if these group-based findings can be used to differentiate both disorders on an individual level.

Age- and disease-related cerebral white matter changes in patients with Parkinson's disease.

As age and Parkinson's disease (PD) both play a role in the degeneration of brain white matter, we aimed to investigate a possible interaction effect of age and disease presence on white matter integrity in patients with PD. We studied white matter hyperintensity volume, global fractional anisotropy, mean diffusivity and mean magnetization transfer ratio of normal appearing white matter in 163 patients with PD and 218 age- and gender-matched healthy control subjects. We investigated the relationship between age and these parameters in both groups, and interaction between age and disease presence. Patients with PD had a higher load of white matter hyperintensities with a preferential periventricular and anterior distribution as compared with healthy control subjects. Visuospatial functioning was related to total and postural instability and gait difficulty was related to periventricular white matter hyperintensity volume in patients with PD. The age-related decline of white matter integrity was similar for both groups. Global microstructural integrity of the normal appearing white matter did not differ between patients and healthy control subjects, suggesting that PD-specific changes do not exceed normal age-associated change in white matter without lesions.

Peripheral mitochondrial function correlates with clinical severity in idiopathic Parkinson's disease.

BACKGROUND: Parkinson's disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patient stratification. Mitochondrial function, which is impaired in and central to PD pathogenesis, may represent one such surrogate indicator. METHODS: Mitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n = 47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine-learning-based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. The effects of mitochondrial respiration on α-synuclein stress were assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions. RESULTS: Bioenergetic properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients, and the correlation is stronger with predominantly nondopaminergic signs. Bioenergetic analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients' fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors α-synuclein stress in different cellular experimental systems. Machine-learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration. CONCLUSION: The suppression of mitochondrial activity in PD may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures in fibroblasts are potential peripheral biomarkers to follow disease progression. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and α-synuclein mechanisms.

BACKGROUND: Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. OBJECTIVES: To identify the genetic determinants of PD age at onset. METHODS: Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. RESULTS: We estimated that the heritability of PD age at onset attributed to common genetic variation was ∼0.11, lower than the overall heritability of risk for PD (∼0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in α-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. CONCLUSIONS: Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. © 2019 International Parkinson and Movement Disorder Society.

Walking adaptability for targeted fall-risk assessments.

BACKGROUND: Most falls occur during walking and are due to trips, slips or misplaced steps, which suggests a reduced walking adaptability. The objective of this study was to evaluate the potential merit of a walking-adaptability assessment for identifying prospective fallers and risk factors for future falls in a cohort of stroke patients, Parkinson's disease patients, and controls (n = 30 for each group). RESEARCH QUESTION: Does an assessment of walking-adaptability improve the identification of fallers compared to generic fall-risk factors alone? METHODS: This study comprised an evaluation of subject characteristics, clinical gait and balance tests, a quantitative gait assessment and a walking-adaptability assessment with the Interactive Walkway. Subjects' falls were registered prospectively with falls calendars during a 6-month follow-up period. Generic and walking-related fall-risk factors were compared between prospective fallers and non-fallers. Binary logistic regression and Chi-square Automatic Interaction Detector analyses were performed to identify fallers and predictor variables for future falls. RESULTS: In addition to fall history, obstacle-avoidance success rate and normalized walking speed during goal-directed stepping correctly classified prospective fallers and were predictors of future falls. Compared to the use of generic fall-risk factors only, the inclusion of walking-related fall-risk factors improved the identification of prospective fallers. SIGNIFICANCE: If cross-validated in future studies with larger samples, these fall-risk factors may serve as quick entry tests for falls prevention programs. In addition, the identification of these walking-related fall-risk factors may help in developing falls prevention strategies.

Sex matters in complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) is much more prevalent in women than men but potential differences in clinical phenotype have not been thoroughly explored to date. Differences in the clinical presentation between sexes may point at new avenues for a more tailored management approach of CRPS. We therefore explored if in CRPS, the patient's sex is associated with differences in clinical and psychological characteristics. METHODS: In this cross-sectional study of 698 CRPS patients (599 females) fulfilling the Budapest clinical or research criteria, CRPS signs and symptoms, CRPS severity, pain (average pain intensity in the previous week and McGill pain rating index), pain coping (Pain Coping Inventory), physical limitations (Radboud Skills Questionnaire (upper limb), Walking and Rising questionnaire (lower limb)), anxiety and depression (Hospital Anxiety and Depression scale) and kinesiophobia (Tampa scale for kinesiophobia) were evaluated. RESULTS: Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia. CONCLUSION: Sex-related differences are present in CRPS, but the effect is generally small and mainly concerns psychological functioning. A greater awareness of sex-specific factors in the management of CRPS may contribute to achieving better outcomes. SIGNIFICANCE: What is known? Nonsex-specific clinical data of CRPS patients. What is new? Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.

Assessment Scales for Patients with Advanced Huntington's Disease: Comparison of the UHDRS and UHDRS-FAP.

BACKGROUND: The standard clinical assessment tool in Huntington's disease is the Unified Huntington's Disease Rating Scale (UHDRS). In patients with advanced Huntington's disease ceiling and floor effects of the UHDRS hamper the detection of changes. Therefore, the UHDRS-For Advanced Patients (UHDRS-FAP) has been designed for patients with late-stage Huntington's disease. OBJECTIVES: This cross-sectional study aims to examine if the UHDRS-FAP can differentiate better between patients with advanced Huntington's disease than the UHDRS. METHODS: Forty patients, who were institutionalized or received day-care, were assessed with the UHDRS, UHDRS-FAP, and Care Dependency Scale (CDS). The severity of Huntington's disease was defined by the Total Functional Capacity (TFC). Comparisons between consecutive TFC stages were performed for all domains of the UHDRS, UHDRS-FAP, and CDS using Mann-Whitney U tests. RESULTS: The motor scores of the UHDRS-FAP and UHDRS were the only subscales with significantly worse scores in TFC stage 5 compared to stage 4. In TFC stages 4-5, the range of the UHDRS-FAP motor score was broader, the standard error of measurement was lower, and the effect size r was higher than for the UHDRS motor score. The CDS declined significantly across all TFC stages. CONCLUSIONS: Our results suggest that the UHDRS-FAP motor score might differentiate better between patients with severe Huntington's disease than the UHDRS motor score. Therefore, the UHDRS-FAP motor score is potentially a better instrument than the UHDRS motor score to improve disease monitoring and, subsequently, care in patients with advanced Huntington's disease in long-term care facilities.

Clinical correlates of quantitative EEG in Parkinson disease: A systematic review.

OBJECTIVE: To assess the relevance of quantitative EEG (qEEG) measures as outcomes of disease severity and progression in Parkinson disease (PD). METHODS: Main databases were systematically searched (January 2018) for studies of sufficient methodologic quality that examined correlations between clinical symptoms of idiopathic PD and cortical (surface) qEEG metrics. RESULTS: Thirty-six out of 605 identified studied were included. Results were classified into 4 domains: cognition (23 studies), motor function (13 studies), responsiveness to interventions (7 studies), and other (10 studies). In cross-sectional studies, EEG slowing correlated with global cognitive impairment and with diffuse deterioration in other domains. In longitudinal studies, decreased dominant frequency and increased θ power, reflecting EEG slowing, were biomarkers of cognitive deterioration at an individual level. Results on motor dysfunction and treatment yielded contrasting findings. Studies on functional connectivity at an individual level and longitudinal studies on other domains or on connectivity measures were lacking. CONCLUSION: qEEG measures reflecting EEG slowing, particularly decreased dominant frequency and increased θ power, correlate with cognitive impairment and predict future cognitive deterioration. qEEG could provide reliable and widely available biomarkers for nonmotor disease severity and progression in PD, potentially promoting early diagnosis of nonmotor symptoms and an objective monitoring of progression. More studies are needed to clarify the role of functional connectivity and network analyses.

Interrater Reliability of the Unified Huntington's Disease Rating Scale-Total Motor Score Certification.

BACKGROUND: The clinical assessment of motor symptoms in Huntington's disease is usually performed with the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS). A high interrater reliability is desirable to monitor symptom progression. Therefore, a teaching video and a system for annual online certification has been developed and implemented. OBJECTIVES: The aim of this study is to investigate the interrater reliability of the UHDRS-TMS and of its subitems, and to examine the performance of raters in consecutive years. METHODS: Data from the online UHDRS-TMS certification were used. The interrater reliability was assessed for all first-time participants (n = 944) between 2009 and 2016. Intraclass correlation coefficients (ICC) were calculated for each year separately and the mean was taken as the total ICC. RESULTS: The UHDRS-TMS (ICC = 0.847), tandem walking (0.824), pronate/supinate hands left (0.713), and retropulsion pull test (0.706) showed good interrater reliability. Poor interrater reliability was found for maximal dystonia of the left and right upper extremity (0.187 and 0.322, respectively), maximal dystonia of the left and right lower extremity (0.200 and 0.256, respectively), and maximal dystonia of the trunk (0.389), tongue protrusion (0.266), and rigidity arms left (0.390). Raters performed significantly worse on follow-up certification compared to their first certification. CONCLUSIONS: Our results suggest that the rating of dystonia (absent, slight, mild, moderate, or marked) is subjective and difficult to interpret, especially on video. Therefore, changing the dystonia items of the UHDRS-TMS should be explored. We also recommend that raters should watch the UHDRS-TMS teaching video before each certification.

Cognitive-motor interference during goal-directed upper-limb movements.

Research and clinical practice have focused on effects of a cognitive dual-task on highly automated motor tasks such as walking or maintaining balance. Despite potential importance for daily life performance, there are only a few small studies on dual-task effects on upper-limb motor control. We therefore developed a protocol for assessing cognitive-motor interference (CMI) during upper-limb motor control and used it to evaluate dual-task effects in 57 healthy individuals and two highly prevalent neurological disorders associated with deficits of cognitive and motor processing (57 patients with Parkinson's disease [PD], 57 stroke patients). Performance was evaluated in cognitive and motor domains under single- and dual-task conditions. Patterns of CMI were explored to evaluate overall attentional capacity and attention allocation. As expected, patients with neurological deficits showed different patterns of CMI compared to healthy individuals, depending on diagnosis (PD or stroke) and severity of cognitive and/or motor symptoms. Healthy individuals experienced CMI especially under challenging conditions of the motor task. CMI was greater in PD patients, presumably due to insufficient attentional capacity in relation to increased cognitive involvement in motor control. Although no general increase of CMI was observed in stroke patients, correlation analyses suggested that especially patients with severe motor dysfunction experienced CMI. Clinical ratings of cognitive and motor function were weakly associated with CMI, suggesting that CMI reflects a different construct than these unidimensional clinical tests. It remains to be investigated whether CMI is an indicator of difficulties with day-to-day activities.

Quantitative EEG reflects non-dopaminergic disease severity in Parkinson's disease.

OBJECTIVE: In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD. METHODS: Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ±â€¯7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III. RESULTS: The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + ß) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters. CONCLUSIONS: EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD. SIGNIFICANCE: The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD.

Oral Health of Parkinson's Disease Patients: A Case-Control Study.

The aim of the study was to examine the oral health status of Parkinson's disease (PD) patients, to compare their oral health status to that of a control group, and to relate it to the duration and severity of PD. Materials and Methods. 74 PD patients and 74 controls were interviewed and orally examined. Among PD patients, the duration and the Hoehn and Yahr stage (HY) of the disease were registered. Results. More PD patients than controls reported oral hygiene care support as well as chewing/biting problems, taste disturbance, tooth mobility, and xerostomia, whereas dentate patients had more teeth with carious lesions, tooth root remnants, and biofilm. Both longer duration and higher HY were associated with more chewing problems and, in dentates, more teeth with restorations. In dentates, longer duration of the disease was associated with higher number of mobile teeth. Higher HY was associated with more oral hygiene care support as well as biting problems and, in dentates, more teeth with carious lesions and tooth root remnants. Conclusions. Comparatively, PD patients had weakened oral health status and reduced oral hygiene care. Both duration and severity of the disease were associated with more oral health and hygiene care problems.