The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease.

Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter.

Early silent microstructural degeneration and atrophy of the thalamocortical network in multiple sclerosis

Recent studies on patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) demonstrated thalamic atrophy. Here we addressed the following question: Is early thalamic atrophy in patients with CIS and relapsing-remitting MS (RRMS) mainly a direct consequence of white matter (WM) lesions-as frequently claimed-or is the atrophy stronger correlated to "silent" (nonlesional) microstructural thalamic alterations? One-hundred and ten patients with RRMS, 12 with CIS, and 30 healthy controls were admitted to 3 T magnetic resonance imaging. Fractional anisotropy (FA) was computed from diffusion tensor imaging (DTI) to assess thalamic and WM microstructure. The relative thalamic vol…

Testing the effects of pre-processing on voxel based morphometry analysis

Voxel based morphometry (VBM) is an automated analysis technique which allows voxel-wise comparison of mainly grey-matter volumes between two magnetic resonance images (MRI). Two main analysis processes in VBM are possible. One is cross-sectional data analysis, where one group is compared with another to depict see the regions in the brain, which show changes in their grey-matter volume. Second is longitudinal data analysis, where MRIs, taken at different time points, are compared to see the regions in the brain that show changes in their grey matter volume for one time point with respect to another time point. Both types of analyses require pre-processing steps before performing the statis…

Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

AbstractThreat detection is essential for protecting individuals from adverse situations, in which a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) regions are involved in fear processing. Excitability regulation in the dmPFC might be crucial for fear processing, while abnormal patterns could lead to mental illness. Notwithstanding, non-invasive paradigms to measure excitability regulation during fear processing in humans are missing. To address this challenge we adapted an approach for excitability characterization, combining electroencephalography (EEG) and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm, to dynamica…

Power estimation for non-standardized multisite studies

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this…

Cross-frequency coupling between gamma oscillations and deep brain stimulation frequency in Parkinson's disease.

Abstract The disruption of pathologically enhanced beta oscillations is considered one of the key mechanisms mediating the clinical effects of deep brain stimulation on motor symptoms in Parkinson’s disease. However, a specific modulation of other distinct physiological or pathological oscillatory activities could also play an important role in symptom control and motor function recovery during deep brain stimulation. Finely tuned gamma oscillations have been suggested to be prokinetic in nature, facilitating the preferential processing of physiological neural activity. In this study, we postulate that clinically effective high-frequency stimulation of the subthalamic nucleus imposes cross-…

Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans.

Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question w…

Multifocal Repetitive Transcranial Magnetic Stimulation—A Novel Paradigm in Migraine Treatment

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation method used for analyzing structural and functional interactions in brain, assess cortical reactivity, and map functionally relevant brain regions inducing a controlled current pulse in a defined region of the cortex. From a clinical point of view, TMS has shown promising results in the therapeutic approach in a large number of psychiatric and neurological conditions such as anxiety, depression, OCD, headache disorders—migraine being one of the most encountered, etc. In patients with migraine, the pharmacologic therapy can be divided in abortive and preventive treatment of the attack. Usually the treatment is starte…

Multimodal quantitative MRI assessment of cortical damage in relapsing-remitting multiple sclerosis

Purpose To investigate magnetization transfer ratio (MTR), T1 relaxation time, and proton density (PD) as indicators of gray matter damage in relapsing-remitting multiple sclerosis (RRMS), reflecting different aspects of microstructural damage and as imaging correlates of clinical disability. We aimed to determine which of these parameters may optimally quantify cortical damage, and serve as an imaging surrogate of clinical disability. In this study, cortical values of MTR, a surrogate for demyelination in MS, of PD, reflecting replacement of neural tissue by water, and of T1 , indicating a complex array of microstructural changes, were assessed in a group of RRMS patients in comparison to …

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Abstract Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency …

Increased migraine-free intervals with multifocal repetitive transcranial magnetic stimulation.

Introduction: Episodic migraine is a debilitating condition associated with vast impairments of health, daily living, and life quality. Several prophylactic treatments exist, having a moderate ratio of action related to side effects and therapy costs. Repetitive transcranial magnetic stimulation (rTMS) is an evidence based therapy in several neuropsychiatric conditions, showing robust efficacy in alleviating specific symptoms. However, its efficacy in migraine disorders is unequivocal and might be tightly linked to the applied rTMS protocol. We hypothesized that multifocal rTMS paradigm could improve clinical outcomes in patients with episodic migraine by reducing the number of migraine day…

Normative vs. patient-specific brain connectivity in Deep Brain Stimulation

AbstractBrain connectivity profiles seeding from deep brain stimulation (DBS) electrodes have emerged as informative tools to estimate outcome variability across DBS patients. Given the limitations of acquiring and processing patient-specific diffusion-weighted imaging data, most studies have employed normative atlases of the human connectome. To date, it remains unclear whether patient-specific connectivity information would strengthen the accuracy of such analyses. Here, we compared similarities and differences between patient-specific, disease-matched and normative structural connectivity data and retrospective estimation of clinical improvement that they may generate.Data from 33 patien…

MSJ765666_supplementary_figure_1 – Supplemental material for Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

Supplemental material, MSJ765666_supplementary_figure_1 for Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis by Nelly Siller, Jens Kuhle, Muthuraman Muthuraman, Christian Barro, Timo Uphaus, Sergiu Groppa, Ludwig Kappos, Frauke Zipp and Stefan Bittner in Multiple Sclerosis Journal

Community driven dynamics of oscillatory network responses to threat

AbstractPhysiological responses to threat stimuli involve neural synchronized oscillations in cerebral networks with distinct organization properties. Community architecture within these networks and its dynamic adaptation could play a critical role in achieving optimal physiological responses.Here we applied dynamic network analyses to address the early phases of threat processing at the millisecond level, describing multi-frequency (theta and alpha) integration and basic reorganization properties (flexibility and clustering) that drive physiological responses. We quantified cortical and subcortical network interactions and captured illustrative reconfigurations using community allegiance …

revised_supplementary_TAN-18-OR-0100 – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, revised_supplementary_TAN-18-OR-0100 for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Advanced technologies for detecting tremor in Parkinson's disease.

Objective Accurate and reliable detection of tremor onset in Parkinson’s disease (PD) is critical to the success of adaptive deep brain stimulation (aDBS) therapy. Here, we investigated the potential use of feature engineering and machine learning methods for more accurate detection of rest tremor in PD. Methods We analyzed the local field potential (LFP) recordings from the subthalamic nucleus region in 12 patients with PD (16 recordings). To explore the optimal biomarkers and the best performing classifier, the performance of state-of-the-art machine learning (ML) algorithms and various features of the subthalamic LFPs were compared. We further used a Kalman filtering technique in feature…

Sex-specific signatures of intrinsic hippocampal networks and regional integrity underlying cognitive status in multiple sclerosis

Abstract The hippocampus is an anatomically compartmentalized structure embedded in highly wired networks that are essential for cognitive functions. The hippocampal vulnerability has been postulated in acute and chronic neuroinflammation in multiple sclerosis, while the patterns of occurring inflammation, neurodegeneration or compensation have not yet been described. Besides focal damage to hippocampal tissue, network disruption is an important contributor to cognitive decline in multiple sclerosis patients. We postulate sex-specific trajectories in hippocampal network reorganization and regional integrity and address their relationship to markers of neuroinflammation, cognitive/memory per…

White Matter Pathology

Lack of Accredited Clinical Training in Movement Disorders in Europe, Egypt, and Tunisia.

BACKGROUND: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa.OBJECTIVE: To survey the accessible MD clinical training in these regions.METHODS: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practic…

Identification of Potential Distinguishing Markers for the Use of Cannabis-Based Medicines or Street Cannabis in Serum Samples

Increasing prescription numbers of cannabis-based medicines raise the question of whether uptake of these medicines can be distinguished from recreational cannabis use. In this pilot study, serum cannabinoid profiles after use of cannabis-based medicines were investigated, in order to identify potential distinguishing markers. Serum samples after use of Sativex®, Dronabinol or medical cannabis were collected and analyzed for 18 different cannabinoids, using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Analytes included delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, …

Longitudinal quantitative MRI assessment of cortical damage in multiple sclerosis: A pilot study

PURPOSE Quantitative MRI (qMRI) allows assessing cortical pathology in multiple sclerosis (MS) on a microstructural level, where cortical damage has been shown to prolong T1 -relaxation time and increase proton density (PD) compared to controls. However, the evolution of these changes in MS over time has not been investigated so far. In this pilot study we used an advanced method for the longitudinal assessment of cortical tissue change in MS patients with qMRI in comparison to cortical atrophy, as derived from conventional MRI. MATERIALS AND METHODS Twelve patients with relapsing-remitting MS underwent 3T T1 /PD-mapping at two timepoints with a mean interval of 12 months. The respective co…

Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex

AbstractWhile deep brain stimulation of the subthalamic nucleus (STN-DBS) has evolved to an evidence-based standard treatment for Parkinson’s disease (PD), the targeted cerebral networks are poorly described and no objective predictors for the postoperative clinical response exist. To elucidate the systemic mechanisms of DBS, we analysed cerebral grey matter properties using cortical thickness measurements and addressed the dependence of structural integrity on clinical outcome. Thirty one patients with idiopathic PD without dementia (23 males, age: 63.4 ± 9.3, Hoehn and Yahr: 3.5 ± 0.8) were selected for DBS treatment. The patients underwent whole-brain preoperative T1 MR-Imaging at 3 T. G…

Intensity of Respiratory Cortical Arousals Is a Distinct Pathophysiologic Feature and Is Associated with Disease Severity in Obstructive Sleep Apnea Patients

Background: We investigated whether the number, duration and intensity of respiratory arousals (RA) on C3-electroencephalographic (EEG) recordings correlate with polysomnography (PSG)-related disease severity in obstructive sleep apnea (OSA) patients. We also investigated if every patient might have an individual RA microstructure pattern, independent from OSA-severity. Methods: PSG recordings of 20 OSA patients (9 female

Supplement_TAND_050219 – Supplemental material for Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis

Supplemental material, Supplement_TAND_050219 for Longitudinal cortical network reorganization in early relapsing–remitting multiple sclerosis by Vinzenz Fleischer, Nabin Koirala, Amgad Droby, René-Maxime Gracien, Ralf Deichmann, Ulf Ziemann, Sven G. Meuth, Muthuraman Muthuraman, Frauke Zipp and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

NfL predicts relapse-free progression in a longitudinal multiple sclerosis cohort study

Background: Easily accessible biomarkers enabling the identification of those patients with multiple sclerosis (MS) who will accumulate irreversible disability in the long term are essential to guide early therapeutic decisions. We here examine the utility of serum neurofilament light chain (sNfL) for forecasting relapse-free disability progression and conversion to secondary progressive MS (SPMS) in the prospective Neurofilament and longterm outcome in MS (NaloMS) cohort. Methods: The predictive ability of sNfL at Baseline and sNfL follow-up (FU)/ Baseline (BL) ratio with regard to disability progression was assessed within a development cohort (NaloMS, n=196 patients with relapsing-remitt…

Translational Model of Cortical Premotor-Motor Networks.

Abstract Deciphering the physiological patterns of motor network connectivity is a prerequisite to elucidate aberrant oscillatory transformations and elaborate robust translational models of movement disorders. In the proposed translational approach, we studied the connectivity between premotor (PMC) and primary motor cortex (M1) by recording high-density electroencephalography in humans and between caudal (CFA) and rostral forelimb (RFA) areas by recording multi-site extracellular activity in mice to obtain spectral power, functional and effective connectivity. We identified a significantly higher spectral power in β- and γ-bands in M1compared to PMC and similarly in mice CFA layers (L) 2/…

Gray matter integrity predicts white matter network reorganization in multiple sclerosis

Abstract Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing–remitting MS were acquired at two time points with a follow‐up after 1 year. White matter network integrity was assessed based on probabilistic tractography performed on diffusion‐weighted data using graph theoretical analyses. We ev…

Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

AbstractBackgroundThreat detection is essential for protecting individuals from precarious situations. Early studies suggested a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) involved in fear processing. Excitability regulation in the dmPFC might be crucial for physiological fear processing, while an abnormal excitability pattern could lead to mental illness. Non-invasive paradigms to measure excitability regulation during fear processing in humans are missing.MethodsWe adapted an experimental approach of excitability characterization using electroencephalography (EEG) recordings and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed …

Structural brain network fingerprints of focal dystonia

Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minim…

Normative vs. patient-specific brain connectivity in deep brain stimulation

Abstract Brain connectivity profiles seeding from deep brain stimulation (DBS) electrodes have emerged as informative tools to estimate outcome variability across DBS patients. Given the limitations of acquiring and processing patient-specific diffusion-weighted imaging data, a number of studies have employed normative atlases of the human connectome. To date, it remains unclear whether patient-specific connectivity information would strengthen the accuracy of such analyses. Here, we compared similarities and differences between patient-specific, disease-matched and normative structural connectivity data and their ability to predict clinical improvement. Data from 33 patients suffering from…

Discrimination of physiological tremor from pathological tremor using accelerometer and surface EMG signals.

BACKGROUND AND OBJECTIVE: Although careful clinical examination and medical history are the most important steps towards a diagnostic separation between different tremors, the electro-physiological analysis of the tremor using accelerometry and electromyography (EMG) of the affected limbs are promising tools. METHODS: A soft-decision wavelet-based decomposition technique is applied with 8 decomposition stages to estimate the power spectral density of accelerometer and surface EMG signals (sEMG) sampled at 800 Hz. A discrimination factor between physiological tremor (PH) and pathological tremor, namely, essential tremor (ET) and the tremor caused by Parkinson’s disease (PD), is obtained by s…

Testing different ICA algorithms and connectivity analyses on MS patients.

Multiple sclerosis (MS) is a progressive neurological disorder that affects the central nervous system. Functional magnetic resonance imaging (fMRI) has been employed to track the course and disease progression in patients with MS. The two main aims of this study were to apply in a data-driven approach the independent component analysis (ICA) in the spatial domain to depict the active sources and to look at the effective connectivity between the identified spatial sources. Several ICA algorithms have been proposed for fMRI data analysis. In this study, we aimed to test two well characterized algorithms, namely, the fast ICA and the complex infomax algorithms, followed by two effective conne…

Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.

Background: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Objective: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. Methods: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Results: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSFIgA and CSFIgM showed higher functional disabilit…

Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Makin…

Characterizing microstructural tissue properties in multiple sclerosis with diffusion MRI at 7 T and 3 T: The impact of the experimental design

The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy contr…

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

ObjectiveTo determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS).MethodsSerum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing–remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we re…

Imaging in mice and men: Pathophysiological insights into multiple sclerosis from conventional and advanced MRI techniques

Abstract Magnetic resonance imaging (MRI) is the most important tool for diagnosing multiple sclerosis (MS). However, MRI is still unable to precisely quantify the specific pathophysiological processes that underlie imaging findings in MS. Because autopsy and biopsy samples of MS patients are rare and biased towards a chronic burnt-out end or fulminant acute early stage, the only available methods to identify human disease pathology are to apply MRI techniques in combination with subsequent histopathological examination to small animal models of MS and to transfer these insights to MS patients. This review summarizes the existing combined imaging and histopathological studies performed in M…

Selective Brain Network and Cellular Responses Upon Dimethyl Fumarate Immunomodulation in Multiple Sclerosis

Background: Efficient personalized therapy paradigms are needed to modify the disease course and halt gray (GM) and white matter (WM) damage in patients with multiple sclerosis (MS). Presently, promising disease-modifying drugs show impressive efficiency, however, tailored markers of therapy responses are required. Here, we aimed to detect in a real-world setting patients with a more favorable brain network response and immune cell dynamics upon dimethyl fumarate (DMF) treatment. Methods: In a cohort of 78 MS patients we identified two thoroughly matched groups, based on age, disease duration, disability status and lesion volume, receiving DMF (n = 42) and NAT (n = 36) and followed them ove…

Increased structural white and grey matter network connectivity compensates for functional decline in early multiple sclerosis

Background: The pathology of multiple sclerosis (MS) consists of demyelination and neuronal injury, which occur early in the disease; yet, remission phases indicate repair. Whether and how the central nervous system (CNS) maintains homeostasis to counteract clinical impairment is not known. Objective: We analyse the structural connectivity of white matter (WM) and grey matter (GM) networks to understand the absence of clinical decline as the disease progresses. Methods: A total of 138 relapsing–remitting MS patients (classified into six groups by disease duration) and 32 healthy controls were investigated using 3-Tesla magnetic resonance imaging (MRI). Networks were analysed using graph the…

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on Septem…

Postoperative rehabilitation after deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy for a set of neurological and psychiatric conditions and especially movement disorders such as Parkinson's disease, essential tremor and dystonia. Recent developments have improved the DBS technology. However, no unequivocal algorithms for an optimized postoperative care exist so far. The aim of this review is to provide a synopsis of the current clinical practice and to propose guidelines for postoperative and rehabilitative care of patients who undergo DBS. A standardized work-up in the DBS centers adapted to each patient's clinical state and needs is important, including a meticulous evaluation of clinical improve…

Clinical implications of serum neurofilament in newly diagnosed MS patients: a longitudinal multicentre cohort study

Abstract Background We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. Methods In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. Findings Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (R…

Pre-dopa Deep Brain Stimulation: Is Early Deep Brain Stimulation Able to Modify the Natural Course of Parkinson’s Disease?

Deep brain stimulation (DBS) is an established therapy for the management of Parkinson's disease (PD). However, DBS is indicated as the disease progresses and motor complications derived from pharmacological therapy arise. Here, we evaluate the potential of DBS prior to levodopa (L-Dopa) in improving quality of life (QoL), challenging the state of the art for DBS therapy. We present data on clinical manifestation, decision finding during early indication to DBS, and trajectories after DBS. We further discuss current paradigms for DBS and hypothesize on possible mechanisms. Six patients, between 50 and 67 years old, presenting at least 5 years of PD symptoms, and without L-Dopa therapy initi…

Author response: Differential contributions of the two human cerebral hemispheres to action timing

Dissecting the Phenotype and Genotype of PLA2G6-Related Parkinsonism.

Background Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration. Objectives The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported. Methods We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review. Results PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cere…

Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

Background: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous…

Grey Matter Microstructural Integrity Alterations in Blepharospasm Are Partially Reversed by Botulinum Neurotoxin Therapy.

OBJECTIVE Benign Essential Blepharospasm (BEB) and hemifacial spasm (HFS) are the most common hyperkinetic movement disorders of facial muscles. Although similar in clinical presentation different pathophysiological mechanisms are assumed. Botulinum Neurotoxin (BoNT) is a standard evidence-based treatment for both conditions. In this study we aimed to assess grey matter microstructural differences between these two groups of patients and compared them with healthy controls. In patients we furthermore tracked the longitudinal morphometric changes associated with BoNT therapy. We hypothesized microstructural differences between the groups at the time point of maximum symptoms representation a…

Nonlinear irregularities in Parkinson's disease tremor and essential tremor.

Establishing standards for neuronavigated TMS in research and clinical studies

Breakdown of Thalamo-Cortical Connectivity Precedes Spike Generation in Focal Epilepsies

Electroencephalography (EEG) spikes and focal epileptic seizures are generated in circumscribed cerebral networks that have been insufficiently described. For precise time and spatial domain network characterization, we applied in patients with focal epilepsy dense array 256-channel EEG recordings with causal connectivity estimation by using time-resolved partial directed coherence and 3T-magnetic resonance imaging-derived cortical and thalamus integrity reconstruction. Before spike generation, significant theta and alpha bands driven information flows alterations were noted from both temporal and frontal lobes to the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ven…

Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging

Longitudinal analysis of white matter lesion changes on serial MRI has become an important parameter to study diseases with white-matter lesions. Here, we build on earlier work on cross-sectional lesion segmentation; we present a fully automatic pipeline for serial analysis of FLAIR-hyperintense white matter lesions. Our algorithm requires three-dimensional gradient echo T1- and FLAIR- weighted images at 3 Tesla as well as available cross-sectional lesion segmentations of both time points. Preprocessing steps include lesion filling and intrasubject registration. For segmentation of lesion changes, initial lesion maps of different time points are fused; herein changes in intensity are analyz…

EEG and MEG primers for tracking DBS network effects

Deep brain stimulation (DBS) is an effective treatment method for a range of neurological and psychiatric disorders. It involves implantation of stimulating electrodes in a precisely guided fashion into subcortical structures and, at a later stage, chronic stimulation of these structures with an implantable pulse generator. While the DBS surgery makes it possible to both record brain activity and stimulate parts of the brain that are difficult to reach with non-invasive techniques, electroencephalography (EEG) and magnetoencephalography (MEG) provide complementary information from other brain areas, which can be used to characterize brain networks targeted through DBS. This requires, howeve…

Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease.

L-DOPA is still the most effective pharmacological therapy for the treatment of motor symptoms in Parkinson's disease (PD) almost four decades after it was first used. Deep brain stimulation (DBS) is a safe and highly effective treatment option in patients with PD. Even though a clear understanding of the mechanisms of both treatment methods is yet to be obtained, the combination of both treatments is the most effective standard evidenced-based therapy to date. Recent studies have demonstrated that DBS is a therapy option even in the early course of the disease, when first complications arise despite a rigorous adjustment of the pharmacological treatment. The unique feature of this therapeu…

Gray matter network reorganization in multiple sclerosis from 7‐Tesla and 3‐Tesla MRI data

[Objective]: The objective of this study was to determine the ability of 7T‐MRI for characterizing brain tissue integrity in early relapsing‐remitting MS patients compared to conventional 3T‐MRI and to investigate whether 7T‐MRI improves the performance for detecting cortical gray matter neurodegeneration and its associated network reorganization dynamics.

Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis

Background: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Methods: Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. …

Multifocal TMS for temporo-spatial description of cortico-cortical connectivity patterns

Deficient Interhemispheric Connectivity Underlies Movement Irregularities in Parkinson’s Disease

Background: Movement execution is impaired in patients with Parkinson’s disease. Evolving neurodegeneration leads to altered connectivity between distinct regions of the brain and altered activity at interconnected areas. How connectivity alterations influence complex movements like drawing spirals in Parkinson’s disease patients remains largely unexplored. Objective: We investigated whether deteriorations in interregional connectivity relate to impaired execution of drawing. Methods: Twenty-nine patients and 31 age-matched healthy control participants drew spirals with both hands on a digital graphics tablet, and the regularity of drawing execution was evaluated by sample entropy. We recor…

Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS

ObjectiveWe applied longitudinal 3T MRI and advanced computational models in 2 independent cohorts of patients with early MS to investigate how white matter (WM) lesion distribution and cortical atrophy topographically interrelate and affect functional disability.MethodsClinical disability was measured using the Expanded Disability Status Scale Score at baseline and at 1-year follow-up in a cohort of 119 patients with early relapsing-remitting MS and in a replication cohort of 81 patients. Covarying patterns of cortical atrophy and baseline lesion distribution were extracted by parallel independent component analysis. Predictive power of covarying patterns for disability progression was tes…

7 Tesla MRI will soon be helpful to guide clinical practice in multiple sclerosis centres – No

Primary Sensorimotor Cortex Drives the Common Cortical Network for Gamma Synchronization in Voluntary Hand Movements

Background: Gamma synchronization (GS) may promote the processing between functionally related cortico-subcortical neural populations. Our aim was to identify the sources of GS and to analyze the direction of information flow in cerebral networks at the beginning of phasic movements, and during medium-strength isometric contraction of the hand. Methods: We measured 64-channel electroencephalography in 11 healthy volunteers (age: 25 ± 8 years; four females); surface electromyography detected the movements of the dominant hand. In Task 1, subjects kept a constant medium-strength contraction of the first dorsal interosseus muscle, and performed a superimposed repetitive voluntary self-paced br…

Treatment choices and neuropsychological symptoms of a large cohort of early MS

ObjectiveTo assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS.MethodsThe German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline characteristics and the prevalence of neuropsychological symptoms.ResultsOf 1,124 patients, with a 2.2:1 female-to-male ratio and median age at onset of 31.71 years (interquartile range [IQR]: 26.06–40.33), 44.6% and 55.3% had CIS and RRMS, respectively. The median Expanded …

Large-scale network architecture and associated structural cortico-subcortical abnormalities in patients with sleep/awake-related seizures.

Study objectives In this study, we aimed to estimate the alterations of brain networks and structural integrity linked to seizure occurrence during sleep and awake states. Methods Using a graph theory approach to magnetic resonance imaging-derived volumes of cortical and subcortical regions, we investigated the topological organization of structural networks in patients with sleep seizures (n = 13), patients with awake seizures (n = 12), and age- and sex-matched healthy controls (n = 10). Abnormalities in regional structural substrates (cortical volume/surface area, subcortical volumes) associated with sleep seizures and awake seizures were further analyzed. Results Brain networks in patien…

Combining transcranial magnetic stimulation and subdural electrodes for pain modulation

Establishing and validating a new source analysis method using phase.

Electroencephalogram (EEG) measures the brain oscillatory activity non-invasively. The localization of deep brain generators of the electric fields is essential for understanding neuronal function in healthy humans and for damasking specific regions that cause abnormal activity in patients with neurological disorders. The aim of this study was to test whether the phase estimation from scalp data can be reliably used to identify the number of dipoles in source analyses. The steps performed included: i) modeling different phasic oscillatory signals using auto-regressive processes at a particular frequency, ii) simulation of two different noises, namely white and colored noise, having differen…

Alterations in White Matter Network and Microstructural Integrity Differentiate Parkinson’s Disease Patients and Healthy Subjects

Parkinson’s disease (PD) is a neurodegenerative disease, neuropathologically characterized by progressive loss of neurons in distinct brain areas. We hypothesize that quantifiable network alterations are caused by neurodegeneration. The primary motivation of this study was to assess the specific network alterations in PD patients that are distinct but appear in conjunction with physiological aging. 178 subjects (130 females) stratified into PD patients, young, middle-aged and elderly healthy controls (age- and sex-matched with PD patients), were analyzed using 3D-T1 magnetization-prepared rapid gradient-echo (MPRAGE) and diffusion weighted images acquired in 3T MRI scanner. Diffusion modeli…

Cortical network fingerprints predict deep brain stimulation outcome in dystonia.

AbstractBackgroundDeep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigate whether patients optimally responding to DBS present distinct brain network organization and structural patterns.MethodsBased on a German multicentre cohort of eighty-two dystonia patients with segmental and generalized dystonia, who received DBS implantation in the globus pallidus internus patients were classified based on the clinical response 36 months after DBS, as superior-outcome group or moderate-outcome group, as above or below 70% motor improvement, respectively. Fifty-one patients met MRI-quality and treat…

Graph Theoretical Framework of Brain Networks in Multiple Sclerosis: A Review of Concepts.

Abstract Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation an…

Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states.

Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record…

Differential contributions of the two human cerebral hemispheres to action timing

Rhythmic actions benefit from synchronization with external events. Auditory-paced finger tapping studies indicate the two cerebral hemispheres preferentially control different rhythms. It is unclear whether left-lateralized processing of faster rhythms and right-lateralized processing of slower rhythms bases upon hemispheric timing differences that arise in the motor or sensory system or whether asymmetry results from lateralized sensorimotor interactions. We measured fMRI and MEG during symmetric finger tapping, in which fast tapping was defined as auditory-motor synchronization at 2.5 Hz. Slow tapping corresponded to tapping to every fourth auditory beat (0.625 Hz). We demonstrate that t…

Cardiac phenotype in ATP1A3-related syndromes: A multicentre cohort study

ObjectiveTo define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes.MethodsPatients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/−) to determine the sequence of events in seizure-related cardiac death.ResultsNinety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities…

MSJ763541_supplementary_material – Supplemental material for Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis

Supplemental material, MSJ763541_supplementary_material for Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis by Christiane Graetz, Adriane Gröge, Felix Luessi, Anke Salmen, Daniela Zöller, Janine Schultz, Nelly Siller, Vinzenz Fleischer, Barbara Bellenberg, Achim Berthele, Viola Biberacher, Joachim Havla, Michael Hecker, Reinhard Hohlfeld, Carmen Infante-Duarte, Jan S Kirschke, Tania Kümpfel, Ralf Linker, Friedemann Paul, Steffen Pfeuffer, Philipp Sämann, Gerrit Toenges, Frank Weber, Uwe K Zettl, Antje Jahn-Eimermacher, Gisela Antony, Sergiu Groppa, Heinz Wiendl, Bernhard Hemmer, Mark Mühlau, Carsten Lukas, Ralf Gold, Chri…

A "kissing lesion": In-vivo 7T evidence of meningeal inflammation in early multiple sclerosis

Background: The role of cortical lesions (CLs) in disease progression and clinical deficits is increasingly recognized in multiple sclerosis (MS); however the origin of CLs in MS still remains unclear. Objective: Here, we report a para-sulcal CL detected two years after diagnosis in a relapsing-remitting MS (RRMS) patient without manifestation of clinical deficit. Methods: Ultra-high field (7T) MR imaging using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) sequence was performed. Results: A para-sulcal CL was detected which showed hypointense rim and iso- to hyperintense core. This was detected in the proximity of the leptomeninges in the left precentral gyrus extendi…

Measuring network disruption in neurodegenerative diseases: New approaches using signal analysis

Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer’s disease (AD), Lewy body dementia (LBD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. The gap between what imaging can discern and underlying pathophysiology can now be addressed by advanced techniques that explore the cortical neural synchro…

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-E…

Longitudinal prevalence and determinants of pain in multiple sclerosis: results from the German National Multiple Sclerosis Cohort study

Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determinants of pain in MS. To this end, we analyzed data from 410 patients with newly diagnosed clinically isolated syndrome or relapsing-remitting MS participating in the prospective multicenter German National MS Cohort Study (NationMS) at baseline and after 4 years. Pain was assessed by self-report using the PainDETECT Questionnaire. Neuropsychiatri…

Linking immune-mediated damage to neurodegeneration in multiple sclerosis: could network-based MRI help?

Abstract Inflammatory demyelination characterizes the initial stages of multiple sclerosis, while progressive axonal and neuronal loss are coexisting and significantly contribute to the long-term physical and cognitive impairment. There is an unmet need for a conceptual shift from a dualistic view of multiple sclerosis pathology, involving either inflammatory demyelination or neurodegeneration, to integrative dynamic models of brain reorganization, where, glia-neuron interactions, synaptic alterations and grey matter pathology are longitudinally envisaged at the whole-brain level. Functional and structural MRI can delineate network hallmarks for relapses, remissions or disease progression, …

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis.

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 con…

Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS

Background: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). Objective: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. Methods: Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Untreated MS patients ( n = 40) were compared to those 6 months after onset of DMF treatment ( n = 51). Clinical and magnetic resonance imaging (MRI) disease activity of DMF-treated patients were assessed in the first year un…

Network effects and pathways in Deep brain stimulation in Parkinson's disease.

Deep brain stimulation of subthalamic nucleus (STN-DBS) became a standard therapeutic option in Parkinson's disease (PD), even though the underlying modulated network of STN-DBS is still poorly described. Probabilistic tractography and connectivity analysis as derived from diffusion tensor imaging (DTI) were performed together with modelling of implanted electrode positions and linked postoperative clinical outcome. Fifteen patients with idiopathic PD without dementia were selected for DBS treatment. After pre-processing, probabilistic tractography was run from cortical and subcortical seeds of the hypothesized network to targets represented by the positions of the active DBS contacts. The …

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

Objective Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. Materials and methods Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a…

Functional connectivity analysis using whole brain and regional network metrics in MS patients

In the present study we investigated brain network connectivity differences between patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC) as derived from functional resonance magnetic imaging (fMRI) using graph theory. Resting state fMRI data of 18 RRMS patients (12 female, mean age ± SD: 42 ± 12.06 years) and 25 HC (8 female, 29.2 ± 5.38 years) were analyzed. In order to obtain information of differences in entire brain network, we focused on both, local and global network connectivity parameters. And the regional connectivity differences were assessed using regional network parameters. RRMS patients presented a significant increase of modularity in comparis…

Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

AbstractBackgroundMultiple sclerosis (MS) disease risk is associated with reduced sun exposure. This study assessed the relationship between measures of sun-exposure (vitamin D (vitD), latitude) and MS disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants.MethodsTwo multi-center cohort studies (nNationMS=946, nBIONAT=991). Outcomes were the multiple sclerosis severity score (MSSS) and the number of Gd-enhancing lesion (GELs). RNAseq of four immune cell populations before and after UV-phototherapy of five MS patients.ResultsHigh serum vitD was associated with reduced MSSS (PNationMS=0.021; PBIONAT=0.007) and reduced ris…

Is APOE ε4 associated with cognitive performance in early MS?

ObjectiveTo assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS).MethodsThis multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (ε4) and rs7412 (ε2) of the APOE haplotype were assessed by allelic discrimination assays. Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memo…

Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS.

ObjectiveWe explored the incremental value of adding multiple disease activity biomarkers in CSF and serum for distinguishing MRI-based benign from aggressive MS in early disease course.MethodsNinety-three patients diagnosed with clinically isolated syndrome (CIS) or early MS were divided into 3 nonoverlapping severity groups defined by objective MRI criteria. Ninety-seven patients with noninflammatory neurologic disorders and 48 patients with other inflammatory neurologic diseases served as controls. Leukocyte subsets in the CSF were analyzed by flow cytometry. CSF neurofilament light chain (NfL) and chitinase-3-like protein 1 (CHI3L1) levels were measured by ELISA. Serum NfL levels were e…

Patientenperspektive auf die Versorgungssituation im Krankheitsbild Morbus Parkinson in Deutschland – eine Querschnittserhebung

Zusammenfassung Hintergrund Wenig ist über die patientenseitig wahrgenommene Versorgungssituation des Morbus Parkinson in Deutschland bekannt. Im Einzelnen besteht ein gesteigertes Interesse der Versorgungsforschung, besser zu verstehen, welche Rolle verschiedene Akteure im Versorgungsprozess über den Krankheitsverlauf hinweg einnehmen, welche möglichen Unterschiede zwischen Versorgungsstrukturen bzw. -regionen bestehen und wie sich die Zufriedenheit der Patienten in Bezug auf die individuelle Versorgungssituation darstellt. Methodik Im Jahr 2016 wurde aus diesem Grund eine Querschnittsbefragung unter Mitgliedern der Deutschen Parkinson Vereinigung (dPV) durchgeführt und Daten von 1273 Mitg…

Dissecting task-specific plasticity capacity in patients with multiple sclerosis with transcranial magnetic stimulation.

Evidence for a white matter lesion size threshold to support the diagnosis of relapsing remitting multiple sclerosis

Abstract Background The number of white matter lesions (WML) in brain MRI is the most established paraclinical tool to support the diagnosis of multiple sclerosis (MS) and to monitor its course. Diagnostic criteria have stipulated a minimum detectable diameter of 3 mm per WML, although this threshold is not evidence-based. We aimed to provide a rationale for a WML size threshold for three-dimensional MRI sequences at 3 T by comparing patients with relapsing-remitting MS (RRMS) to control subjects (CS). Methods We analyzed MR images from two cohorts, obtained at scanners from two different vendors, each comprising patients with RRMS and CS. Both cohorts were examined with FLAIR and T1w seque…

Health-related quality of life in patients with poststroke epilepsy.

Abstract Background Lesional epilepsy is an important long-term sequela of stroke. Data on health-related quality of life (HrQoL) in patients with poststroke epilepsy are limited. We investigated HrQoL in patients with epilepsy after ischemic stroke and identified independent HrQoL-determinants. Methods and patients All patients with acute ischemic stroke, who were permanent residents in the district Marburg-Biedenkopf (Hessia, Germany, reference population 240,000 inhabitants) were recruited within 12 months in the population-based Marburg Stroke Register (MARSTREG). Follow-up visits were performed after 6, 12, and 24 months, and patients who developed poststroke epilepsy were identified. …

Corticoperipheral neuromuscular disconnection in obstructive sleep apnoea.

Abstract The roles of central nervous mechanisms and cortical output in obstructive sleep apnoea remain unclear. We addressed corticomuscular coupling between cortical sensorimotor areas and lower facial motor units as a mechanistic pathway and as a possible surrogate marker of corticoperipheral motor control in obstructive sleep apnoea. In this exploratory cross-sectional retrospective study, we analysed EEG (C3 and C4 leads) and chin EMG from polysomnography recordings in 86 participants (22 females; age range: 26–81 years): 27 with mild (respiratory disturbance index = 5–15 events/h), 21 with moderate (15–30 events/h) and 23 with severe obstructive sleep apnoea (>30 events/h) and 15 cont…

(Non-) invasive mapping of cortical language areas

Complex network analysis of resting-state fMRI of the brain.

Due to the fact that the brain activity hardly ever diminishes in healthy individuals, analysis of resting state functionality of the brain seems pertinent. Various resting state networks are active inside the idle brain at any time. Based on various neuro-imaging studies, it is understood that various structurally distant regions of the brain could be functionally connected. Regions of the brain, that are functionally connected, during rest constitutes to the resting state network. In the present study, we employed the complex network measures to estimate the presence of community structures within a network. Such estimate is named as modularity. Instead of using a traditional correlation …

Preservation of neuronal function as measured by clinical and MRI endpoints in relapsing-remitting multiple sclerosis: how effective are current treatment strategies?

Approved medications for relapsing-remitting multiple sclerosis have shown to be effective in terms of their anti-inflammatory potential. However, it is also crucial to evaluate what long-term effects a patient can expect from current MS drugs in terms of preventing neurodegeneration. Here we aim to provide an overview of the current treatment strategies in MS with a specific focus on potential neuroprotective effects. Areas covered: Randomized, double-blind and placebo or referral-drug controlled phase 2a/b and phase 3 trials were examined; non-blinded phase 4 studies (extension studies) were included to provide long-term data, if not otherwise available. Endpoints considered were expanded…

Supplementary_Figure_2 – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supplementary_Figure_2 for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

sup1_inks_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, sup1_inks_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Supp1_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supp1_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Supp_figure_3_inkscape_png_jpg – Supplemental material for Structural brain network fingerprints of focal dystonia

Supplemental material, Supp_figure_3_inkscape_png_jpg for Structural brain network fingerprints of focal dystonia by Venkata C. Chirumamilla, Christian Dresel, Nabin Koirala, Gabriel Gonzalez-Escamilla, Günther Deuschl, Kirsten E. Zeuner, Muthuraman Muthuraman and Sergiu Groppa in Therapeutic Advances in Neurological Disorders

Preservation of neuronal function as measured by clinical and MRI endpoints in relapsing-remitting multiple sclerosis: how effective are current treatment strategies?

Introduction: Approved medications for relapsing-remitting multiple sclerosis have shown to be effective in terms of their anti-inflammatory potential. However, it is also crucial to evaluate what long-term effects a patient can expect from current MS drugs in terms of preventing neurodegeneration. Here we aim to provide an overview of the current treatment strategies in MS with a specific focus on potential neuroprotective effects. Areas covered: Randomized, double-blind and placebo or referral-drug controlled phase 2a/b and phase 3 trials were examined; non-blinded phase 4 studies (extension studies) were included to provide long-term data, if not otherwise available. Endpoints considered…

Differential contributions of the two human cerebral hemispheres to action timing

Rhythmic actions benefit from synchronization with external events. Auditory-paced finger tapping studies indicate the two cerebral hemispheres preferentially control different rhythms. It is unclear whether left-lateralized processing of faster rhythms and right-lateralized processing of slower rhythms bases upon hemispheric timing differences that arise in the motor or sensory system or whether asymmetry results from lateralized sensorimotor interactions. We measured fMRI and MEG during symmetric finger tapping, in which fast tapping was defined as auditory-motor synchronization at 2.5 Hz. Slow tapping corresponded to tapping to every fourth auditory beat (0.625 Hz). We demonstrate that t…