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Competing Interests: Competing interests: None declared.

Objective: We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy., Methods: We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS., Results: We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (β[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (β[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS., Conclusions: Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS., Significance: qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Distinguishing normal, neuropathic and myopathic electromyography (EMG) traces can be challenging. We aimed to create an automated time series classification algorithm., Methods: EMGs of healthy controls (HC, n = 25), patients with amyotrophic lateral sclerosis (ALS, n = 20) and inclusion body myositis (IBM, n = 20), were retrospectively selected based on longitudinal clinical follow-up data (ALS and HC) or muscle biopsy (IBM). A machine learning pipeline was applied based on 5-second EMG fragments of each muscle. Diagnostic yield expressed as area under the curve (AUC) of a receiver-operator characteristics curve, accuracy, sensitivity, and specificity were determined per muscle (muscle-level) and per patient (patient-level)., Results: Diagnostic yield of the classification ALS vs. HC was: AUC 0.834 ± 0.014 at muscle-level and 0.856 ± 0.009 at patient-level. For the classification HC vs. IBM, AUC was 0.744 ± 0.043 at muscle-level and 0.735 ± 0.029 at patient-level. For the classification ALS vs. IBM, AUC was 0.569 ± 0.024 at muscle-level and 0.689 ± 0.035 at patient-level., Conclusions: An automated time series classification algorithm can distinguish EMGs from healthy individuals from those of patients with ALS with a high diagnostic yield. Using longer EMG fragments with different levels of muscle activation may improve performance., Significance: In the future, machine learning algorithms may help improve the diagnostic accuracy of EMG examinations., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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.

Aim: To evaluate quantitative electroencephalogram (EEG) measures as predictors of long-term neurodevelopmental outcome in infants with a postconceptional age below 46 weeks, including typically developing infants born at term, infants with heterogeneous underlying pathologies, and infants born preterm., Method: A comprehensive search was performed using PubMed, Embase, and Web of Science from study inception up to 8th January 2021. Studies that examined associations between neonatal quantitative EEG measures, based on conventional and amplitude-integrated EEG, and standardized neurodevelopmental outcomes at 2 years of age or older were reviewed. Significant associations between neonatal quantitative EEG and long-term outcome measures were grouped into one or more of the following categories: cognitive outcome; motor outcome; composite scores; and other standardized outcome assessments., Results: Twenty-four out of 1740 studies were included. Multiple studies showed that conventional EEG-based absolute power in the delta, theta, alpha, and beta frequency bands and conventional and amplitude-integrated EEG-related amplitudes were positively associated with favourable long-term outcome across several domains, including cognition and motor performance. Furthermore, a lower presence of discontinuous background pattern was also associated with favourable outcomes. However, interpretation of the results is limited by heterogeneity in study design and populations., Interpretation: Neonatal quantitative EEG measures may be used as prognostic biomarkers to identify those infants who will develop long-term difficulties and who might benefit from early interventions., (© 2021 Mac Keith Press.)

Parkinson's disease (PD) diagnosis is based on clinical criteria, i.e., bradykinesia, rest tremor, rigidity, etc. Assessment of the severity of PD symptoms with clinical rating scales, however, is subject to inter-rater variability. In this paper, we propose a deep learning based automatic PD diagnosis method using videos to assist the diagnosis in clinical practices. We deploy a 3D Convolutional Neural Network (CNN) as the baseline approach for the PD severity classification and show the effectiveness. Due to the lack of data in clinical field, we explore the possibility of transfer learning from non-medical dataset and show that PD severity classification can benefit from it. To bridge the domain discrepancy between medical and non-medical datasets, we let the network focus more on the subtle temporal visual cues, i.e., the frequency of tremors, by designing a Temporal Self-Attention (TSA) mechanism. Seven tasks from the Movement Disorders Society - Unified PD rating scale (MDS-UPDRS) part III are investigated, which reveal the symptoms of bradykinesia and postural tremors. Furthermore, we propose a multi-domain learning method to predict the patient-level PD severity through task-assembling. We show the effectiveness of TSA and task-assembling method on our PD video dataset empirically. We achieve the best MCC of 0.55 on binary task-level and 0.39 on three-class patient-level classification.

Background: Caregivers of Parkinson's disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have been reported after DBS. However, a comparison between preoperative and postoperative burden and associated factors has been insufficiently studied., Objective: To investigate the influence of DBS on caregiver burden, and to identify the differential impact of patient-related factors on caregiver burden before and after DBS., Methods: Consecutive patients referred for DBS eligibility screening or during one-year follow-up assessments were included. Caregiver burden was measured with the short Zarit Burden Interview (ZBI-12). Inverse Probability Weighting (IPW) was used to compare caregiver burden between preoperative and postoperative assessments., Results: We included 47 patients (24 screening, 23 follow-up) (median age 65 years, 29.4% female sex). DBS did not impact caregiver burden (screening: median ZBI-12 9.5 (IQR 3.25, 16.75); follow-up median ZBI-12 6 (IQR 4, 14); IPW-coefficient 0.57 (95% CI -2.75, 3.89)). Worse caregiver burden during DBS screening was associated with worse patient-related scores on depressive symptoms, anxiety, QoL, and impulsiveness. Worse scores on depressive symptoms, anxiety, apathy, postural-instability-gait-disorder, and QoL were associated with worse caregiver burden at one-year follow-up., Conclusion: DBS appears not associated with changes in caregiver burden. Various symptoms are valued differently between screening and follow-up assessments in terms of caregiver burden. Early recognition of caregivers "at risk" may improve guidance of patient-caregiver dyads throughout the DBS process.

Background: It is currently unknown whether results from intraoperative test stimulation of two types of Deep Brain Stimulation (DBS), either during awake pallidal (GPi) or thalamic (Vim), are comparable to the results generated by chronic stimulation through the definitive lead. Objective: To determine whether side-effects-thresholds from intraoperative test stimulation are indicative of postoperative stimulation findings. Methods: Records of consecutive patients who received GPi or Vim were analyzed. Thresholds for the induction of either capsular or non-capsular side-effects were compared at matched depths and at group-level. Results: Records of fifty-two patients were analyzed (20 GPis, 75 Vims). The induction of side-effects was not significantly different between intraoperative and postoperative assessments at matched depths, although a large variability was observed (capsular: GPi DBS: p = 0.79; Vim DBS: p = 0.68); non-capsular: GPi DBS: p = 0.20; and Vim DBS: p = 0.35). Linear mixed-effect models revealed no differences between intraoperative and postoperative assessments, although the Vim had significantly lower thresholds (capsular side-effects p = 0.01, non-capsular side-effects p < 0.01). Unpaired survival analyses demonstrated lower intraoperative than postoperative thresholds for capsular side-effects in patients under GPi DBS ( p = 0.01), while higher intraoperative thresholds for non-capsular side-effects in patients under Vim DBS ( p = 0.01). Conclusion: There were no significant differences between intraoperative and postoperative assessments of GPi and Vim DBS, although thresholds cannot be directly extrapolated at an individual level due to high variability., Competing Interests: Unrelated to this study, JH reports grants from The Netherlands Organisation for Health Research and Development, The Netherlands Organisation for Scientific Research, Hoffmann-La Roche, AbbVie, Lundbeck, Hersenstichting, Stichting Parkinson Fonds, Alkemade-Keuls Foundation, and Centre of Human Drug Research. AM reports travel support from Boston Scientific. CH reports travel support from Boston Scientific. NG reports travel support from Boston Scientific. MC reports support for advisory board from Medtronic (fees to institution), consultancy fees: Medtronic (fees to institution), CHDR (fees to institution), research support: Medtronic (to institution), AbbVie (to institution), research support in kind from Global Kinetics Corporation, travel support: Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Geraedts, van Ham, van Hilten, Mosch, Hoffmann, van der Gaag and Contarino.)

Background: Subthalamic deep brain stimulation (STN DBS) may relieve refractory motor complications in Parkinson's disease (PD) patients. Despite careful screening, it remains difficult to determine severity of alpha-synucleinopathy involvement which influences the risk of postoperative complications including cognitive deterioration. Quantitative electroencephalography (qEEG) reflects cognitive dysfunction in PD and may provide biomarkers of postoperative cognitive decline., Objective: To develop an automated machine learning model based on preoperative EEG data to predict cognitive deterioration 1 year after STN DBS., Methods: Sixty DBS candidates were included; 42 patients had available preoperative EEGs to compute a fully automated machine learning model. Movement Disorder Society criteria classified patients as cognitively stable or deteriorated at 1-year follow-up. A total of 16,674 EEG-features were extracted per patient; a Boruta algorithm selected EEG-features to reflect representative neurophysiological signatures for each class. A random forest classifier with 10-fold cross-validation with Bayesian optimization provided class-differentiation., Results: Tweny-five patients were classified as cognitively stable and 17 patients demonstrated cognitive decline. The model differentiated classes with a mean (SD) accuracy of 0.88 (0.05), with a positive predictive value of 91.4% (95% CI 82.9, 95.9) and negative predictive value of 85.0% (95% CI 81.9, 91.4). Predicted probabilities between classes were highly differential (hazard ratio 11.14 [95% CI 7.25, 17.12]); the risk of cognitive decline in patients with high probabilities of being prognosticated as cognitively stable (>0.5) was very limited., Conclusions: Preoperative EEGs can predict cognitive deterioration after STN DBS with high accuracy. Cortical neurophysiological alterations may indicate future cognitive decline and can be used as biomarkers during the DBS screening. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline., Methods: A fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance., Results: Both groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (β = -0.23 (95% confidence interval (-0.29, -0.18)))., Conclusions: Particularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature., Significance: Automated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Caregivers of patients with Parkinson's Disease (PD) often provide important support in the pre- and postoperative phase of Deep Brain Stimulation (DBS). DBS-associated changes of patient-functioning may affect caregiver wellbeing and impact the support system. Factors influencing caregiver-wellbeing under these circumstances are incompletely known., Objective: to systematically review studies of sufficient methodological quality on the impact of DBS on caregivers of PD patients., Methods: using PRISMA guidelines, major databases were searched up to May 2020. Five subcategories were identified: Caregiver burden, Caregiver cognitive and psychiatric functioning, Caregiver Quality of Life (QoL), Marital Satisfaction/Conflicts, and Caregiver Satisfaction. Quality was assessed using an in-house checklist., Results: 293 studies were identified; 12 were ultimately included. Caregiver burden, psychiatric and cognitive functioning and QoL remained relatively unchanged. Results on marital satisfaction/conflicts were contrasting: an increase in marital conflicts despite improved relationship quality scores DBS. Caregiver satisfaction with surgery was low with 50-58% of caregivers being disappointed with DBS outcomes. Concerning caregiver related factors: a higher preoperative caregiver QoL, younger age, lower scores on psychiatric rating scales, and more favourable preoperative relationship quality scores, were associated with better caregiver wellbeing. A favourable patient-profile includes younger age and age-at-onset, shorter disease duration, lower medication requirements, and lower scores on psychiatric rating scales., Conclusion: Although most patient- and caregiver-related subdomains remained unchanged after DBS, dissatisfaction among caregivers and marital problems may constitute a large risk for a well-functioning patient-caregiver dyad. Early recognition of potential problem situations may improve post-DBS care for both patients and caregivers., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9-10 years of age. Fifty-five children born <32 weeks' of gestation underwent EEG at 9-10 years of age and were assessed for motor development and cognitive outcome. Relative frequency power and functional connectivity, as measured by the Phase Lag Index (PLI), were calculated for all frequency bands. Per subject, power spectrum and functional connectivity results were averaged over all channels and pairwise PLI values to explore differences in global frequency power and functional connectivity between EP and VP children. Brain networks were constructed for the upper alpha frequency band using the Minimum Spanning Tree method and were compared between EP and VP children. In addition, the relationships between upper alpha quantitative EEG results and cognitive and motor outcomes were investigated. Relative power and functional connectivity were significantly higher in VP than EP children in the upper alpha frequency band, and VP children had more integrated networks. A strong positive correlation was found between relative upper alpha power and motor outcome whilst controlling for gestational age, age during EEG recording, and gender (ρ = 0.493, p = 0.004). These results suggest that 9-10 years after birth, the effects of the degree of prematurity can be observed in terms of alterations in functional brain activity and that motor deficits are associated with decreases in relative upper alpha power., Competing Interests: Declaration of competing interest CPS is founder and consultant at Neurophyxia BV. She holds several patents and stocks of Neurophyxia BV. None of this work has a relationship with the current manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality., Methods: Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson's disease., Results: In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction., Conclusion: Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease-related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided., (© 2019 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Although subthalamic Deep Brain Stimulation (STN DBS) is proven effective in improving symptoms of Parkinson's Disease (PD), previous literature demonstrates a discrepancy between objective improvement and patients' perception thereof. We aimed to examine whether postoperative stimulation challenge tests (SCT) alters patients' satisfaction after STN DBS for PD., Methods: Fifty-four PD patients underwent preoperative levodopa challenge tests and were routinely invited for SCT 1-2 years postoperatively. SEverity of predominantly Nondopaminergic Symptoms in PD (SENS-PD) scores quantified non-dopaminergic disease severity. Motor functioning was quantified using Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores; a ratio between conditions ON and OFF (preoperative Med-ON vs. Med-OFF, and postoperative Med-ON/Stim-ON vs. Med-OFF/Stim-OFF) reflected treatment benefit. 'Global Impression of Change' (GIC) and 'Global Satisfaction with Surgery' (GSS) Likert scales were filled out before and immediately after SCT., Results: Postoperative Med-ON/Stim-ON severity was lower than preoperative ON severity. Disease severity scores were not different between assessments. GIC and GSS scores were higher after SCT versus before (GIC: Z = -3.80, r = 0.37, subjects indicating maximum scores before SCT: 32.1%, after SCT: 57.1%; GSS: Z = -3.69, r = 0.35, maximum scores before SCT: 25.0%, after SCT: 46.4%). Higher non-dopaminergic disease severity was associated with lower GIC and GSS scores (GIC: OR 1.2 (95%CI 1.0-1.3); GSS: OR 1.2 (95%CI 1.1-1.3), while motor-scores and magnitude of DBS-effects were not., Conclusion: SCT improves patients' satisfaction and is recommended especially in case of suboptimal subjective valuations. This information should be considered in clinical practice and in the context of clinical trials., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The response to levodopa (LR) is important for managing Parkinson's Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson's Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

Patients with advanced Parkinson's Disease (PD) may be eligible for Deep Brain Stimulation (DBS) in case of medication-related motor fluctuations or tremor refractory to oral medication. However, several PD symptoms are unresponsive to DBS and constitute relative contra-indications for DBS. Patients referred for DBS undergo an eligibility screening during which motor functioning and contra-indications for surgery are assessed. During this pre-screening the potential benefits and drawbacks of surgery are discussed, together with patients' expectations of the results of DBS. Unrealistic expectations on the benefits of DBS may contribute to reduced patient satisfaction and poor clinical outcomes after surgery. The aim of this multicenter study (289 patients) was to assess the reasons for rejection after an outpatient-based pre-screening visit for DBS referrals, with particular emphasis on the role of patient expectations of DBS. The most frequent reason contributing to rejection was suboptimal oral treatment or satisfying symptom-control with oral medication (50% of rejections). Unrealistic expectations were identified in 38% of rejected patients and were the singular reason for rejection in 4%. Incorporating the assessment of unrealistic expectations increased the accuracy (Area Under the Curve) of determining DBS eligibility from 0.92 ((95% confidence interval (95%CI) 0.88-0.97) to 0.97 (95%CI 0.96-0.99). Patients' expectations of DBS are easily checked, and better education of patients and treating neurologists with regard to unrealistic expectations of this procedure may improve efficiency of referrals and avoid unnecessary stress and disappointments during screening., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: It is unknown whether intraoperative testing during awake Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) can be used to postoperatively identify the best settings for chronic stimulation., Objective: To determine whether intraoperative test stimulation is indicative of postoperative stimulation results., Methods: Records of consecutive Parkinson's Disease patients who received STN DBS between September 2012 and December 2017 were retrospectively analyzed. The best depth identified after intraoperative stimulation via the microelectrode's stimulation tip was compared with the depth of the contact selected for chronic stimulation after a standard monopolar contact review. Moreover, thresholds for induction of clinical effects (optimal improvement of rigidity and induction of side-effects) were compared between stimulation at the postoperatively selected contact and at the corresponding intraoperative depth., Results: Records of 119 patients were analyzed (mean (SD) age 60.5 (6.5) years, 31.9% female, 238 STNs). In 75% of cases, the postoperatively selected contact corresponded with the intraoperative depth with the largest therapeutic window or was immediately dorsal to it. Higher stimulation intensities were required postoperatively than intraoperatively to relieve rigidity (p = 0.002) and induce capsular side-effects (p = 0.016)., Conclusion: In the majority of cases, the postoperative contact for chronic stimulation was at a similar level or immediately dorsal with respect to the identified best intraoperative depth. Postoperatively, relief of rigidity and induction of capsular side-effects occur at higher stimulation intensities than during intraoperative test stimulation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD-affected brain. The available articles could be separated into motor network-focused and whole-brain focused studies. Motor network studies revealed PD-related changes in beta band (13-30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole-brain studies PD-related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD-specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

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., (© 2018 American Academy of Neurology.)

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 ± 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 + β) 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., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Reperfusion status after intra-arterial thrombectomy (IAT) is a critical predictor of functional outcome after acute ischemic stroke. However, most prognostic models have not included a detailed assessment of reperfusion status after IAT., Objective: The aim of this work was to assess the association between successful reperfusion and clinical outcome., Methods: Clinical, radiological, and procedural variables of patients treated with IAT were extracted from our prospective stroke registry. The association with functional outcome using the modified Rankin Scale (mRS) after 3 months was assessed using multivariable logistic regression. An extension of the modified TICI score, eTICI, was used to classify reperfusion status. The prognostic value of reperfusion status after IAT in addition to age, stroke severity, imaging characteristics, treatment with intravenous thrombolysis, and time from symptom onset to the end of IAT was assessed with logistic regression and summarized with receiver operating characteristic curves., Results: In total, 119 patients were included (mean age 66 years). In multivariable analysis, age >80 years (OR 6.8, 95% CI 1.2-39.8), NIHSS at presentation >15 (OR 7.3, 95% CI 2.3-23.5), and incomplete reperfusion status (eTICI score <2C; OR 10.3, 95% CI 3.5-30.6) were the strongest predictors of a poor outcome (mRS 3-6). Adding reperfusion status to the model improved the prognostic accuracy (AUC 0.88, 95% CI 0.91-0.94). Our results indicate a large difference between using an eTICI cutoff of ≥2C versus ≥2B: a cutoff ≥2C improved the predictive value for a good clinical outcome (2C: positive predictive value, PPV, 0.78; 2B: PPV 0.32)., Conclusion: Our results promote using reperfusion status for assessing prognosis in ischemic stroke patients treated with IAT. A model using eTICI ≥2C had greater PPV than eTICI ≥2B and could improve prognostic accuracy.

Background: Quality of life (QoL) in patients with acromegaly is reduced irrespective of disease state. The contributions of multifactorial determinants of QoL in several disease stages are presently not well known., Objective: To systematically review predictors of QoL in acromegalic patients., Methods: Main databases were systematically searched using predefined search terms for potentially relevant articles up to January 2017. Inclusion criteria included separate acromegaly cohort, non-hereditary acromegaly, QoL as study parameter with clearly described method of measurement and quantitative results, N  ≥ 10 patients, article in English and adult patients only. Data extraction was performed by two independent reviewers; studies were included using the PRISMA flow diagram., Results: We identified 1,162 studies; 51 studies met the inclusion criteria: 31 cross-sectional observational studies [mean AcroQoL score 62.7 (range 46.6-87.0, n  = 1,597)], 9 had a longitudinal component [mean baseline AcroQoL score 61.4 (range 54.3-69.0, n  = 386)], and 15 were intervention studies [mean baseline AcroQoL score 58.6 (range 52.2-75.3, n  = 521)]. Disease-activity reflected by biochemical control measures yielded mixed, and therefore inconclusive results with respect to their effect on QoL. Addition of pegvisomant to somatostatin analogs and start of lanreotide autogel resulted in improvement in QoL. Data from intervention studies on other treatment modalities were too limited to draw conclusions on the effects of these modalities on QoL. Interestingly, higher BMI and greater degree of depression showed consistently negative associations with QoL. Hypopituitarism was not significantly correlated with QoL in acromegaly., Conclusion: At present, there is insufficient published data to support that biochemical control, or treatment of acromegaly in general, is associated with improved QoL. Studies with somatostatin receptor ligand treatment, i.e., particularly lanreotide autogel and pegvisomant have shown improved QoL, but consensus on the correlation with biochemical control is missing. Longitudinal studies investigating predictors in treatment-naive patients and their follow-up after therapeutic interventions are lacking but are urgently needed. Other factors, i.e., depression and obesity were identified from cross-sectional cohort studies as consistent factors associated with poor QoL. Perhaps treatment strategies of acromegaly patients should not only focus on normalizing biochemical markers but emphasize improvement of QoL by alternative interventions such as psychosocial or weight lowering interventions.

Objective: Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications., Methods: Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365)., Results: The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results., Conclusions: In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself., (© 2016 American Academy of Neurology.)

Introduction: Remission criteria of acromegaly are based on biochemical variables, i.e., normalization of increased hormone levels. However, the established reduction in Quality of Life (QoL) is suggested to be independent of biochemical control. The aim of this study was to test which aspects predict QoL best in acromegaly., Methods/design: This is a prospective cohort study in 80 acromegalic patients, with a cross-sectional and longitudinal part. The main outcome measure was health-related QoL, measured by a generic and a disease-specific questionnaire (the SF-36 and AcroQoL). Main predictors were age, gender, biochemical control, disease characteristics, treatment modalities, and psychopathology., Results: Our cohort of 80 acromegalics had a mean age 54.7 ± 12.3 years with an average disease duration of 10.8 ± 10.0 years. Ratio macro-/microadenoma was 54/26. In adjusted mixed method models, we found that psychopathology significantly predicts QoL in acromegaly (in models including the variables age, gender, disease duration, tumor size, basal hormone levels, relevant treatment modalities, and relevant comorbidities), with a higher degree of psychopathology indicating a lower QoL (depression vs. AcroQoL: B = -1.175, p < 0.001, depression vs. SF-36: B = -1.648, p < 0.001, anxiety vs. AcroQoL: B = -0.399, p < 0.001, anxiety vs. SF-36: B = -0.661, p < 0.001). The explained variances demonstrate superiority of psychopathology over biochemical control and other variables in predicting QoL in our models., Discussion: Superiority of psychopathology over biochemical control calls for a more extensive approach regarding diagnosing depression and anxiety in pituitary adenomas to improve QoL. Depressive symptoms and anxiety are modifiable factors that might provide valuable targets for possible future treatment interventions.