Objective:Explore associations between quantitative markers of resting-state electroencephalography (EEG), severe chronic kidney disease (CKD), and neurocognition in children and young adults. Methods:We included 25 patients with CKD with an estimated glomerular filtration rate < 30 ml/min/1.73m2 aged 8-30 years, on different treatment modalities (pre-dialysis [n = 6], dialysis [n = 8], transplanted [n = 11]). EEG parameters of power spectrum analysis and functional connectivity were obtained using the Fourier transformation and amplitude envelope correlation (AEC) analysis, respectively. Neurocognition was measured using a comprehensive neurocognitive test battery. Mixed model analyses assessed relations between CKD parameters, EEG parameters and neurocognitive functions. Results:A longer time on dialysis in the past was significantly related to a higher delta and lower alpha power, which related to poorer Processing Speed and Working Memory. Patients on kidney replacement therapy had significantly higher delta AEC than pre-dialysis patients. A higher eGFR after transplantation was related to a higher delta AEC. Delta AEC was not related to neurocognitive performance. Conclusion:Abnormal high delta power may be indicative of clinically apparent encephalopathy in young patients with kidney failure. The role of increased functional connectivity as potential compensatory mechanism should be further explored. Significance:Minimizing dialysis-time by early transplantation may be advantageous in the prevention of encephalopathy in young CKD patients.

Introduction:Orthostatic tremor (OT) is a highly disabling condition. Effectiveness of treatments is largely unverified and no treatment guideline exists. The objective of this study is to evaluate the efficacy and adverse effects of treatments used for OT. Methods:Patients from our online OT-registry were compared to findings from a systematic search in PUBMED. The search included original articles describing clinical features in human primary OT (electromyography peak frequency ≥ 13 Hz), in English or Dutch, and published after 1985. Outcome measures were prescribed treatments and their efficacy (percentage of patients per treatment with a reduction of tremor symptoms) and adverse effects. Results:A total of 78 primary OT patients in the Netherlands and 613 OT patients from 74 articles, mostly case reports and cohort studies, were included. In the cohort from the Netherlands, perampanel showed both the highest efficacy and adverse effects. In the literature, clonazepam showed the highest efficacy, while data on adverse effects was lacking. Overall, pharmacological treatments were reported often to be insufficient. Bilateral deep brain stimulation (DBS) was reported to be effective in the majority of patients, without a higher prevalence of adverse effects. Conclusion:Pharmacological treatment is sufficient in some patients, although overall efficacy is limited and often accompanied by adverse effects. Perampanel and clonazepam are first choice treatments. Surgical interventions seem suitable alternatives for medication resistant patients, although this is based on small studies. Future studies should use diagnostic criteria, standardized outcome scales and good study designs, to increase reliability of findings and comparability.

OBJECTIVES:To investigate whether rhythmic/periodic EEG patterns (RPP) appearing after propofol discontinuation are more likely to be related to the elimination phase of propofol, or are an expression of severe brain damage. METHODS:In a retrospective cohort of comatose postanoxic patients, EEG was assessed one hour before (baseline) and on hour after discontinuation of propofol. Presence and duration of RPP were related to (changes in) EEG background pattern and duration of sedation. RESULTS:In eleven (of 36 eligible) patients RPP appeared after propofol discontinuation and disappeared in seven of these patients within one hour. A continuous background pattern at baseline and shorter duration of propofol infusion seemed associated with (earlier) spontaneous disappearance of RPP. In ten patients with RPP at baseline, the EEG did not change, and in one patient it changed into burst-suppression. CONCLUSION:Our findings suggest that RPP after propofol discontinuation could be propofol-related. DISCUSSION:RPP might be related to propofol discontinuation rather than an expression of severe brain damage, especially in case of, and congruent with, a continuous pattern at the time of propofol discontinuation. This opens a new insight in this phenomenon and its transient nature. In clinical practice, we suggest to consider the timing of propofol discontinuation when assessing the EEG signal in postanoxic patients.

OBJECTIVE:Deep learning methods have shown potential in automating the detection of interictal epileptiform discharges (IEDs) in electroencephalography (EEG). We compared IED detection using our previously trained deep neural network with a group of experts to assess its potential applicability. METHODS:First, we performed clinical validation on an internal data set. Seven experts reviewed all EEG studies. Performance agreement between experts and the network was compared at both the EEG and IED levels. All EEG recordings were also processed with Persyst. Subsequently, we performed external validation, with data from four centers, using a hybrid approach, where detections by the deep neural network were reviewed by an expert. In case of disagreement with the original report, the EEG recording was annotated independently by five experts. RESULTS:For internal validation we included 22 EEG studies with IEDs and 28 EEG studies from controls. At the EEG level, our network showed performance similar to that of the experts. For individual IED detection, the sensitivities between experts ranged from 20.7%-86.4%, whereas the sensitivity of our network was 82.5% (confidence interval [CI]: 77.7%-87.4%) at 99% specificity and a false detection rate (FDR) of <.2/min, outperforming Persyst, with 64.6% sensitivity (CI: 61.4%-67.9%) at 98% specificity. External validation in 174 EEG studies demonstrated that all 85 EEG recordings classified as normal in the original report were classified correctly, with an FDR of .10/min. Of the 89 EEG studies with IEDs according to the report, 56 were correctly classified (Cohen's κ = .62). Visual analysis of the remaining 33 EEG recordings showed high interobserver variability among the five experts (Fleiss' κ = .13). SIGNIFICANCE:Our deep neural network detects IEDs on par with clinical experts. The external validation in a hybrid approach showed substantial agreement with the original report. Disagreement was due mainly to high interobserver variability. Our deep neural network may support visual EEG analysis and assist in diagnostics, particularly when human resources are limited.

BackgroundPrimary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects.ObjectiveTo evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects.MethodsNine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures.ResultsAverage maximum standing time increased from 41.0 s +/- 51.0 s to 109.3 s +/- 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS.ConclusionVim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

OBJECTIVES:Rhythmic and periodic patterns (RPPs) on EEG in patients in a coma after cardiac arrest are associated with a poor neurologic outcome. We characterize RPPs using qEEG in relation to outcomes. METHODS:Post hoc analysis was conducted on 172 patients in a coma after cardiac arrest from the TELSTAR trial, all with RPPs. Quantitative EEG included corrected background continuity index (BCI*), relative discharge power (RDP), discharge frequency, and shape similarity. Neurologic outcomes at 3 months after arrest were categorized as poor (CPC = 3-5) or good (CPC = 1-2). RESULTS:A total of 16 patients (9.3%) had a good outcome. Patients with good outcomes showed later RPP onset (28.5 vs 20.1 hours after arrest, p < 0.05) and higher background continuity at RPP onset (BCI* = 0.83 vs BCI* = 0.59, p < 0.05). BCI* <0.45 at RPP onset, maximum BCI* <0.76, RDP >0.47, or shape similarity >0.75 were consistently associated with poor outcomes, identifying 36%, 22%, 40%, or 24% of patients with poor outcomes, respectively. In patients meeting both BCI* >0.44 at RPP onset and BCI* >0.75 within 72 hours, the probability of good outcomes doubled to 18%. DISCUSSION:Sufficient EEG background continuity before and during RPPs is crucial for meaningful recovery. Background continuity, discharge power, and shape similarity can help select patients with relevant chances of recovery and may guide treatment. TRIAL REGISTRATION INFORMATION:February 4, 2014, ClinicalTrial.gov, NCT02056236.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for disabling fluctuations in motor symptoms in Parkinson’s disease (PD) patients. However, iterative exploration of all individual contact points (four in each STN) by the clinician for optimal clinical effects may take months. Objective: In this proof of concept study we explored whether magnetoencephalography (MEG) has the potential to noninvasively measure the effects of changing the active contact point of STN-DBS on spectral power and functional connectivity in PD patients, with the ultimate aim to aid in the process of selecting the optimal contact point, and perhaps reduce the time to achieve optimal stimulation settings. Methods: The study included 30 PD patients who had undergone bilateral DBS of the STN. MEG was recorded during stimulation of each of the eight contact points separately (four on each side). Each stimulation position was projected on a vector running through the longitudinal axis of the STN, leading to one scalar value indicating a more dorsolateral or ventromedial contact point position. Using linear mixed models, the stimulation positions were correlated with band-specific absolute spectral power and functional connectivity of i) the motor cortex ipsilateral tot the stimulated side, ii) the whole brain. Results: At group level, more dorsolateral stimulation was associated with lower low-beta absolute band power in the ipsilateral motor cortex (p = .019). More ventromedial stimulation was associated with higher whole-brain absolute delta (p = .001) and theta (p = .005) power, as well as higher whole-brain theta band functional connectivity (p = .040). At the level of the individual patient, switching the active contact point caused significant changes in spectral power, but the results were highly variable. Conclusions: We demonstrate for the first time that stimulation of the dorsolateral (motor) STN in PD patients is associated with lower low-beta power values in the motor cortex. Furthermore, our group-level data show that the location of the active contact point correlates with whole-brain brain activity and connectivity. As results in individual patients were quite variable, it remains unclear if MEG is useful in the selection of the optimal DBS contact point.

Objective: To clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome.Design: Post hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resus-citation (TELSTAR) trial.Setting: Eleven ICUs in the Netherlands and Belgium.Patients: One hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. Interventions: Anti-seizure medication vs no anti-seizure medication in addition to standard care.Measurements and Main Results: Of 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16-0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64-9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03-3.32).Conclusions: Myoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.

Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions in the FPN has been related to better executive functioning. Brain networks can be constructed using different modalities: diffusion MRI (dMRI) can be used to reconstruct structural networks, while resting-state fMRI (rsfMRI) and magnetoencephalography (MEG) yield functional networks. These networks are often studied in a unimodal way, which cannot capture potential complementary or synergistic modal information. The multilayer framework is a relatively new approach that allows for the integration of different modalities into one ‘network of networks’. It has already yielded promising results in the field of neuroscience, having been related to e.g. cognitive dysfunction in Alzheimer’s disease. Multilayer analyses thus have the potential to help us better understand the relation between brain network organization and executive functioning. Here, we hypothesized a positive association between centrality of the FPN and executive functioning, and we expected that multimodal multilayer centrality would supersede unilayer centrality in explaining executive functioning. We used dMRI, rsfMRI, MEG, and neuropsychological data obtained from 33 healthy adults (age range 22-70 years) to construct eight modality-specific unilayer networks (dMRI, fMRI, and six MEG frequency bands), as well as a multilayer network comprising all unilayer networks. Interlayer links in the multilayer network were present only between a node’s counterpart across layers. We then computed and averaged eigenvector centrality of the nodes within the FPN for every uni- and multilayer network and used multiple regression models to examine the relation between uni- or multilayer centrality and executive functioning. We found that higher multilayer FPN centrality, but not unilayer FPN centrality, was related to better executive functioning. To further validate multilayer FPN centrality as a relevant measure, we assessed its relation with age. Network organization has been shown to change across the life span, becoming increasingly efficient up to middle age and regressing to a more segregated topology at higher age. Indeed, the relation between age and multilayer centrality followed an inverted-U shape. These results show the importance of FPN integration for executive functioning as well as the value of a multilayer framework in network analyses of the brain. Multilayer network analysis may particularly advance our understanding of the interplay between different brain network aspects in clinical populations, where network alterations differ across modalities. Highlights: Multimodal neuroimaging and neurophysiology data were collected in healthy adults Multilayer frontoparietal centrality was positively associated with executive functioning Unilayer (unimodal) centralities were not associated with executive functioning There was an inverted-U relationship between multilayer centrality and age

Concrete-filled FRP tubes (CFFTs), which consist of a confining tube made of FRP, the internal concrete core and optional longitudinal reinforcements made of FRP or steel, are a novel type of structural member particularly attractive for new civil and industrial structures. Existing studies on CFFTs are mainly about specimens fabricated with a circular, a square or a rectangular FRP tube, while there are rather limited studies on CFFTs with an elliptical FRP tube. Similar to circular CFFTs, elliptical CFFTs have a cross-section with a continuous curved circumference, leading to effective confinement to the internal concrete. Elliptical CFFTs are attractive for engineering applications due to their appealing aesthetic appearance as well as different bending capacities around two symmetrical axes. This paper systematically investigated elliptical CFFTs reinforced with longitudinal steel rebars (ER-CFFTs) under combined lateral cyclic load and vertical constant load with special research attentions on the influences of elliptical aspect ratio (i.e., the ratio of the sectional major axis over the sectional minor axis, which was ranging from 1.0 to 2.5 with an interval of 0.5). The effects of the FRP thickness and the bending direction of lateral cyclic load were also investigated. Test results indicated that, the elliptical FRP tube had been effectively utilized to provide confinement during the cyclic loading process; ER-CFFTs exhibited generally rounded hysteretic curves with limited pinching, even for the specimen with a large elliptical aspect ratio of 2.5; the ductility of ER-CFFTs showed a general tendency to increase with the elliptical aspect ratio except the specimen with an elliptical aspect ratio of 2.5. A numerical model was established to simulate the seismic performance of ER-CFFTs, which was able to yield predictions with reasonable accuracy. In practical engineering, the elliptical aspect ratio for ER-CFFTs should be optimized according to the bending demand around two symmetrical axes.

Familial adult myoclonus epilepsy (FAME) is characterized by cortical myoclonus and often epileptic seizures, but the pathophysiology of this condition remains uncertain. Here, we review the neuroimaging and neuropathological findings in FAME. Imaging findings, including functional magnetic resonance imaging, are in line with a cortical origin of involuntary tremulous movements (cortical myoclonic tremor) and indicate a complex pattern of cerebellar functional connectivity. Scarce neuropathological reports, mainly from a single family, provide evidence of morphological changes in the Purkinje cells. Cerebellar changes seem to be part of the syndrome, in at least some FAME pedigrees. Cortical hyperexcitability in FAME, resulting in the cardinal clinical symptoms, might be the result of decreased cortical inhibition via the cerebellothalamocortical loop. The pathological findings might share some similarities with other pentanucleotide repeat disorders. The relation with genetic findings in FAME needs to be elucidated.

Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is common, often unresponsive to treatment, and may contribute to disability. We aim to investigate whether tremor is associated with disability as measured in daily practice and clinical trials, independent of other impairments. We included 76 CIDP patients in this cross-sectional study. We assessed tremor with the Tremor Research Group essential tremor rating assessment scale (TETRAS) and the Fahn-Tolosa-Marin clinical rating scale (FTM). Disability was measured with the inflammatory Rasch-built overall disability scale (I-RODS) and the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT-DS, categorized separately in arm score, or total score). Impairments including strength, sensory impairment, and fatigue were measured using specific impairment scales. We tested whether "the presence of a clinically relevant tremor" (based on TETRAS and FTM) or "tremor severity" (FTM part B sum score) was associated with disability scores (I-RODS, INCAT-DS total score, and INCAT-DS arm score), independent of the impairment scores, using multivariate regression. Both "the presence of a clinically relevant tremor" and "tremor severity" were significantly associated with disability measured by the INCAT-DS (arm score and total score), but not the I-RODS, independent of strength, sensory impairment, and fatigue. The explained variances were low. Clinically relevant tremor can (partly) explain disability in CIDP, as measured with the INCAT-DS, independent of muscle strength, sensory deficits, and fatigue. To assess disease activity in CIDP patients with tremor, both impairment and disability outcomes should be assessed, as disability is caused partly by tremor while the effect of immunotherapy on tremor seems limited.

AIM:To increase efficiency of continuous EEG monitoring for prognostication of neurological outcome in patients after cardiac arrest, we investigated the reliability of EEG in a four-electrode frontotemporal (4-FT) montage, compared to our standard nine-electrode (9-EL) montage. METHODS:EEG recorded with Ag/AgCl cup-electrodes at 12 and/or 24 h after cardiac arrest of 153 patients was available from a previous study. 220 EEG epochs of 5 minutes were reexamined in a 4-FT montage according to the ACNS criteria. Background classification was compared to the available 9-EL classification using Cohens kappa. Reliability for prognostication was assessed in 151 EEG epochs at 24 h after CA using sensitivity and specificity for prediction of poor (cerebral performance categories (CPC) 3-5) and good (CPC 1-2) neurological outcome. RESULTS:Agreement for EEG background classification between the two montages was substantial with a kappa of 0.85 (95%-CI 0.81-0.90). Specificity for prediction of poor outcome was 100% (95%-CI 95-100) for both montages, sensitivity was 31% (95%-CI 21-43) for the 4-FT montage and 35% (95%-CI 24-47) for the 9-EL montage. Good outcome was predicted with 65% specificity (95%-CI 53-76) and 81% sensitivity (95%-CI 71-89) for the 4-FT montage, similar to the 9-EL montage. CONCLUSION:In this cohort, EEG background patterns determined in a four-electrode frontotemporal montage predict both poor and good outcome after CA with similar reliability. Our results may contribute to decreasing the workload of EEG monitoring in patients after CA without compromising reliability of outcome prediction. However, validation in a larger cohort is necessary, as is a multimodal approach.

Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is common, often unresponsive to treatment, and may contribute to disability. We aim to investigate whether tremor is associated with disability as measured in daily practice and clinical trials, independent of other impairments. We included 76 CIDP patients in this cross-sectional study. We assessed tremor with the Tremor Research Group essential tremor rating assessment scale (TETRAS) and the Fahn–Tolosa–Marin clinical rating scale (FTM). Disability was measured with the inflammatory Rasch-built overall disability scale (I-RODS) and the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT-DS, categorized separately in arm score, or total score). Impairments including strength, sensory impairment, and fatigue were measured using specific impairment scales. We tested whether “the presence of a clinically relevant tremor” (based on TETRAS and FTM) or “tremor severity” (FTM part B sum score) was associated with disability scores (I-RODS, INCAT-DS total score, and INCAT-DS arm score), independent of the impairment scores, using multivariate regression. Both “the presence of a clinically relevant tremor” and “tremor severity” were significantly associated with disability measured by the INCAT-DS (arm score and total score), but not the I-RODS, independent of strength, sensory impairment, and fatigue. The explained variances were low. Clinically relevant tremor can (partly) explain disability in CIDP, as measured with the INCAT-DS, independent of muscle strength, sensory deficits, and fatigue. To assess disease activity in CIDP patients with tremor, both impairment and disability outcomes should be assessed, as disability is caused partly by tremor while the effect of immunotherapy on tremor seems limited.

Introduction: There are currently no effective treatments for primary orthostatic tremor (POT). An adequate disease-specific POT severity scale is a prerequisite to conduct clinical trials and monitor disease severity in clinical practice. Recently, the English OT-10 scale has been developed for this purpose. Here we aimed to obtain a scale to measure the severity of POT in Dutch speaking individuals.Methods: An established translation, adaptation and validation approach was employed to obtain a Dutch version of the OT-10 scale. Validation was performed in a Dutch POT cohort (n = 46).Results: A Dutch OT-10 scale was obtained which showed good internal consistency (Cronbach's alpha > 0.80), total score test-retest reliability (intraclass correlation coefficient > 0.80), and concurrent validity (Pearson correlation > 0.80). Item-to-total correlation was good (weighted kappa > 0.40) for all items, and item test-retest reliability was good (weighted kappa > 0.40) for eight out of ten items. Overall, the Dutch OT-10 scale demonstrated acceptable validity.Conclusions: We obtained and validated a Dutch version of the OT-10 scale, capturing POT severity. Next to its use in clinical practice, translation and validation of the OT-10 scale in more languages will help to find evidence-based treatments for POT.