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Objective To test whether 1) quantitative analysis of EEG reactivity (EEG-R) using machine learning (ML) is superior to visual analysis, and 2) combining quantitative analyses of EEG-R and EEG background pattern increases prognostic value for prediction of poor outcome after cardiac arrest (CA). Methods Several types of ML models were trained with twelve quantitative features derived from EEG-R and EEG background data of 134 adult CA patients. Poor outcome was a Cerebral Performance Category score of 3–5 within 6 months. Results The Random Forest (RF) trained on EEG-R showed the highest AUC of 83% (95-CI 80–86) of tested ML classifiers, predicting poor outcome with 46% sensitivity (95%-CI 40–51) and 89% specificity (95%-CI 86–92). Visual analysis of EEG-R had 80% sensitivity and 65% specificity. The RF was also the best classifier for EEG background (AUC 85%, 95%-CI 83–88) at 24 h after CA, with 62% sensitivity (95%-CI 57–67) and 84% specificity (95%-CI 79–88). Combining EEG-R and EEG background RF classifiers reduced the number of false positives. Conclusions Quantitative EEG-R using ML predicts poor outcome with higher specificity, but lower sensitivity compared to visual analysis of EEG-R, and is of some additional value to ML on EEG background data. Significance Quantitative EEG-R using ML is a promising alternative to visual analysis and of some added value to ML on EEG background data.

Tremor is thought to be an effect of oscillatory activity within the sensorimotor network. To date, the underlying pathological brain networks are not fully understood. Disentangling tremor activity from voluntary motor output and sensorimotor feedback systems is challenging. To better understand the intrinsic sensorimotor fingerprint underlying tremor, we aimed to disentangle the sensorimotor system into driving (motor) and feedback/compensatory (sensory) neuronal involvement, and aimed to pinpoint tremor activity in essential tremor (ET) and tremor-dominant Parkinson's disease (PD) with a novel closed-loop approach. Eighteen ET patients, 14 tremor-dominant PD patients, and 18 healthy controls were included. An MR-compatible wrist manipulator was employed during functional MRI (fMRI) while muscle activity during (in)voluntary movements was concurrently recorded using electromyography (EMG). Tremor was quantified based on EMG and correlated to brain activity. Participants performed three tasks: an active wrist motor task, a passive wrist movement task, and rest (no wrist movement). The results in healthy controls proved that our experimental paradigm activated the expected motor and sensory networks separately using the active (motor) and passive (sensory) task. ET patients showed similar patterns of activation within the motor and sensory networks. PD patients had less activity during the active motor task in the cerebellum and basal ganglia compared to ET and healthy controls. EMG showed that in ET, tremor fluctuations correlated positively with activity in the inferior olive region, and that in PD tremor fluctuations correlated positively with cerebellar activity. Our novel approach with an MR-compatible wrist manipulator, allowed to investigate the involvement of the motor and sensory networks separately, and as such to better understand tremor pathophysiology. In ET sensorimotor network function did not differ from healthy controls. PD showed less motor-related activity. Focusing on tremor, our results indicate involvement of the inferior olive in ET tremor modulation, and cerebellar involvement in PD tremor modulation.

Objective: A role of the motor cortex in tremor generation in essential tremor (ET) is assumed, yet the directionality of corticomuscular coupling is unknown. Our aim is to clarify the role of the motor cortex. To this end we also study ‘familial cortical myoclonic tremor with epilepsy’ (FCMTE) and slow repetitive voluntary movements with a known cortical drive. Methods: Directionality of corticomuscular coupling (EEG-EMG) was studied with renormalized partial directed coherence (rPDC) during tremor in 25 ET patients, 25 healthy controls (mimicked) and in seven FCMTE patients; and during a self-paced 2 Hz task in eight ET patients and seven healthy controls. Results: Efferent coupling around tremor frequency was seen in 33% of ET patients, 45.5% of healthy controls, all FCMTE patients, and, around 2 Hz, in all ET patients and all healthy controls. Ascending coupling, seen in the majority of all participants, was weaker in ET than in healthy controls around 5–6 Hz. Conclusions: Possible explanations are that tremor in ET results from faulty subcortical output bypassing the motor cortex; rate-dependent transmission similar to generation of rhythmic movements; and/or faulty feedforward mechanism resulting from decreased afferent (sensory) coupling. Significance: A linear cortical drive is lacking in the majority of ET patients.

Objective To show that eye movement abnormalities differ between essential tremor (ET) and tremor dominant Parkinson’s disease (PD-T), and that these abnormalities reflect cerebellar dysfunction in ET and basal ganglia pathology in PD-T. Methods In this exploratory study, in 23 patients with ET, 21 age-matched patients with PD-T, and 19 age-matched healthy controls (HCs), we investigated visually guided saccades, antisaccades, and smooth pursuit eye movements (SPEM). Results While the ET group had a normal gain (saccade amplitude/target amplitude) and latency of saccades, the PD-T group had hypometric visually guided saccades, and a prolonged latency of visually guided saccades and antisaccades. The SPEM gain was similarly low in both ET and PD-T and was significantly lower in both patient groups than in the HC group. Conclusions In ET, SPEM gain was reduced in the presence of normal saccades, whereas in PD-T, the reduced SPEM gain was accompanied by delayed saccade initiation and hypometric saccades, in line with cerebellar dysfunction in ET and basal ganglia dysfunction in PD-T. Significance These findings support the presumed cerebellar pathology in ET. In addition, the difference in saccade features may contribute to the groundwork for a quantitative diagnostic test to differentiate between these disorders.

Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI.Methods: Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity.Results: In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls.Conclusion: The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. (c) 2015 Elsevier Ltd. All rights reserved.

Introduction: We investigated the relation between changes in clinician-based and patient-based measures of tremor severity, within the Fahn-Tolosa-Marin Tremor Rating Scale (IRS) and Visual Analogue Scale (VAS) in essential tremor patients.Methods: Thirty-seven patients were assessed twice: on- and off-medication. Clinician-based, objective TRS assessments, consisting of part A (postures/movements) and part B (tremor-inducing tasks) were conducted by a blinded assessor using video-tapes. Patients completed TRS part C (limitations in activities of daily life) and indicated subjective tremor severity using VAS.Results: Patients' total TRS and VAS scores improved on-medication (both p Discussion: We found no correlation between changes in clinician-based TRS-A, and patient-based measures TRS-C or VAS scores, and a weak correlation between clinician-based TRS-B and VAS scores. The limited correlations between changes in clinician-based and patient-based measures of tremor severity suggest that the different scales measure different aspects of tremor severity and support the additional use of subjective patient-based assessments in clinical practice and clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.

Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements. Electronic supplementary material The online version of this article (doi:10.1007/s12311-015-0734-0) contains supplementary material, which is available to authorized users.

Objectives: Essential tremor (ET), the most prevalent hyperkinetic movement disorder, is characterized by an action tremor (4-7 Hz). The role of the sensorimotor cortex in tremor generation is uncertain. Previous corticomuscular coupling studies in ET showed either a cortical drive, an afferent input, or both. In contrast, familial cortical myoclonic tremor with epilepsy (FCMTE) with tremulous movements, clinically resembling ET, is characterized by a cortical drive around 15-20Hz. Methods: Corticomuscular directionality was investigated with renormalized partial directed coherence (rPDC) in ET (n=16), FCMTE (n=7), and healthy controls (HC; n=16). EEG-EMG was recorded during 2 minutes of postural tremor (ET and FCMTE right arm outstretched; HC mimicking tremor ±5Hz), and 1 minute of self-paced slow movements

Background and purpose Median nerve somatosensory evoked potential (SEP) recordings play an important role in outcome algorithms in comatose patients after cardiopulmonary resuscitation. Knowledge of technical difficulties, clinical implications and uniform interpretation of SEP recordings is crucial. The aim of this study was to evaluate the skills of neurologists to interpret SEP recordings in post-anoxic patients. Methods Nationwide Dutch clinical neurophysiology examinations from 2007, 2008 and 2011, containing SEP related questions, were analysed. Participants were classified as neurology residents, neurologists with less than 10 years of experience, neurologists with more than 10 years of experience and clinical neurophysiologists. End-points were the knowledge of all participants about SEP recordings per year as well as improvement in knowledge over the years, as reflected by the test scores. Results A total of 194 participants completed the examination in 2007, 200 in 2008 and 263 in 2011. Between 2007 and 2008, all groups of respondents showed a significant increase in percentage of correct answers to SEP questions. Sixty-six participants completed all three examinations. The SEP score of this group improved in 2008 [75%, interquartile range (IQR) 50–75, P

Background Essential tremor (ET) is the most common tremor disorder. It has been repeatedly shown that the olivocerebellar system is involved in ET, consisting of the inferior olive nucleus (ION), dentate nucleus (DN) and cerebellar cortex. Impairment of the central timing mechanism in ET has been suggested. The olivocerebellar system plays an important role in motor timing. In order to study the functional involvement of this system in ET, we employed a task involving motor timing during functional MRI (fMRI). Methods Thirty propranolol sensitive ET patients with familial upper limb tremor and 30 healthy controls were included. T2 ∗ -weighted EPI sequences were acquired (180 volumes, TR: 2s, voxel size: 3.5 × 3.5 × 3.5 mm, 3TMRI). The task consisted of alternating rest and finger tapping (rate of 2 Hz) blocks. Task performance was measured by electromyography. Analysis was performed in SPM8 (standard preprocessing, normalization according to the spatially unbiased infra-tentorial template, 4 mm smoothing kernel). The left ION was localized with a conjunction analysis of patients and controls. For this abstract, quantified tapping performance is not yet incorporated. Results Within-group random-effects analysis restricted to the brainstem and cerebellum showed activations throughout the cerebellum (bilateral lobules V, VI, VIIIA) and in both left and right ION. Preliminary between-group analysis of the ION and CB right lobule VI showed significantly higher activations in controls compared to ET patients. Conclusions Exploratory analysis suggests altered activity in the olivocerebellar system in ET patients compared to controls during a motor timing task. Inclusion of task performance and effective connectivity analysis will be carried out to aid us in discriminating between altered activity due to task performance and pathological motor timing related to ET. Understanding the role of the olivocerebellar system in ET is of great importance for unraveling the mechanism of tremor genesis.

Background: Tremor is the most prevalent movement disorder in clinical practice. It is defined as involuntary, rhythmic, oscillatory movements. The diagnostic process of patients with tremor can be laborious and challenging, and a clear, systematic overview of available diagnostic techniques is lacking. Tremor can be a symptom of many diseases, but can also represent a distinct disease entity. Objective: The objective of this review is to give a clear, systematic and step-wise overview of the diagnostic work-up of a patient with tremor. The clinical relevance and value of available laboratory tests in patients with tremor will be explored. Methods: We systematically searched through EMBASE. The retrieved articles were supplemented by articles containing relevant data or provided important background information. Studies that were included investigated the value and/or usability of diagnostic tests for tremor. Results: In most patients, history and clinical examination by an experienced movement disorders neurologist are sufficient to establish a correct diagnosis, and further ancillary examinations will not be needed. Ancillary investigation should always be guided by tremor type(s) present and other associated signs and symptoms. The main ancillary examination techniques currently are electromyography and SPECT imaging. Unfortunately, many techniques have not been studied in large prospective, diagnostic studies to be able to determine important variables like sensitivity and specificity. Conclusion: When encountering a patient with tremor, history, and careful clinical examination should guide the diagnostic process. Adherence to the diagnostic work-up provided in this review will help the diagnostic process of these patients.

Objective: Current template-based artifact reduction methods are inadequate to reduce irregular volume- and slice-artifacts induced by limb motion in combined (surface) EMG-fMRI (electromyography-functional magnetic resonance imaging) studies. In addition, artifacts are not removed adequately for EMG frequencies above 50 Hz. We present a new fMRI artifact reduction algorithm for motion (FARM) and compare it with standard artifact correction as implemented in fMRI artifact slice-template removal (FASTR).Methods: One control subject generated motion artifacts during EMG-fMRI. Low-frequency motion artifacts and volume-artifacts were removed prior to slice-artifact correction. Slice-artifacts were phase-shifted and removed with motion adaptive templates (FARM). EMG data were also corrected applying FASTR.Results: Time traces demonstrate that artifacts related to sudden changes in wire position are contained to shorter time periods. EMG power spectra from neck and arm muscles show that FARM has improved performance at higher frequencies.Conclusions: High-pass filtering, volume-artifact removal, phase-shifting and adaptation of slice-templates to motion improve the quality of artifact-corrected EMG recorded during limb motion.Significance: The improved accuracy at which EMG-fMRI data can be obtained opens up new ways to directly relate self-paced movements to brain activations and to study patients suffering from movement disorders. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective: The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS).Methods: Silent period, motor evoked potential (MEP) recruitment curve short interval intracortical, inhibition (SICI), intracortical facilitation (ICF) and short interval intracortical facilitation (SICF), with short interstimulus intervals (ISIs) ranging from 1.2 to 3.2 ms, were studied in 15 DYT 11-positive M-D patients and their matched controls. In four patients and matched controls peripheral double pulse electrical nerve stimulation was performed.Results: All TMS parameters of cortical excitability were normal compared to healthy controls. In the SICF protocol we observed more variable and polyphasic MEPs in M-D patients. Cross-covariance analysis of MEP area revealed a significant correlation difference at ISI 2.2 and 2.8 ms. This increased variability was not seen in other TMS protocols or with peripheral nerve stimulation.Conclusions: In contrast with other types of dystonia, no changes in cortical excitability were found in DYT 11 patients. Our findings suggest that M-D is both clinically and pathophysiologically a separate entity from other dystonic disorders. Polyphasic MEPs during the SICF protocol in M-D patients could reflect central neuron membrane instability. Application of the SICF protocol in other patient groups has to prove its value in movement disorders. (c) 2008 Elsevier Inc. All rights reserved.