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Introduction
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December 2009 - present
Publications
Publications (150)
Background
Neurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.
Methods
We assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNf...
The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, an...
Background:
Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory diseases caused by demyelination and axonal damage in the central nervous system. Structural retinal imaging via optical coherence tomography (OCT) shows promise as a noninvasive biomarker for monitoring of MS. There are successful reports regarding the applicati...
Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), with a largely unknown etiology, where mitochondrial dysfunction significantly contributes to neuroaxonal loss and brain atrophy. Mirroring the CNS, peripheral immune cells from patients with MS, particularly CD4+ T cells, show inappropriate m...
Background and objectives:
With the increasing use of visually evoked potentials (VEPs) as quantitative outcome parameters for myelin in clinical trials, an in-depth understanding of longitudinal VEP latency changes and their prognostic potential for subsequent neuronal loss will be required. In this longitudinal multicenter study, we evaluated th...
Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from...
Background
The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagno...
Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatm...
Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS) with increasing incidence and prevalence. MS is associated with inflammatory and metabolic disturbances that, as preliminary human and animal data suggest, might be mediated by disruption of circadian rhythmicity. Nutrition habits...
Background:
Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event....
Background
Multiple Sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging, and multimodal biomarkers to define the risk of disease activity.
Methods
We have analyzed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centers, collecting disability scales at basel...
Background
Large-scale disease overarching longitudinal data are rare in the field of neuroimmunology. However, such data could aid early disease stratification, understanding disease etiology and ultimately improve treatment decisions. The Berlin Registry of Neuroimmunological Entities (BERLimmun) is a longitudinal prospective observational study,...
Background:
The diagnosis of multiple sclerosis (MS) requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinat...
Optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD) regularly leads to more profound vision loss compared to multiple sclerosis (MS) and myelin-oligodendrocyte-glycoprotein-antibody associated disease (MOGAD). Here we investigate ON-related vision loss in NMOSD compared to MS and MOGAD in order to identify neuroaxonal and retinal...
Background:
Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies...
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromye...
Background
: Aquaporin-4 immunoglobulin-G positive (AQP4-IgG⁺) neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy associated with optic neuritis (ON). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an oligodendrocytopathy with similar phenotype. Serum glial fibrillary acidic protein (sGFAP), a...
Background and objectives:
Recent studies have suggested that inter-eye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell+inner plexiform (GCIPL) thickness by spectral-domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires furthe...
Objective:
Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD.
Methods:
Eighty MOGAD p...
Reliable biomarkers quantifying neurodegeneration and neuroinflammation in central nervous system disorders such as Multiple Sclerosis, Alzheimer’s dementia or Parkinson’s disease are an unmet clinical need. Intraretinal layer thicknesses on macular optical coherence tomography (OCT) images are promising noninvasive biomarkers querying neuroretinal...
Background
The diagnosis of multiple sclerosis (MS) d requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinat...
Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory diseases caused by demyelination and axonal damage in the central nervous system. Structural retinal imaging via optical coherence tomography (OCT) shows promise as a biomarker for monitoring of MS. There are successful reports regarding application of Artificial Intelligence...
Clustered data arise frequently in many practical applications whenever units are repeatedly observed under a certain condition. One typical example for clustered data are animal experiments, where several animals share the same cage and should not be assumed to be completely independent. Standard methods for the analysis of such data are Linear Mi...
A bstract
Intraretinal layer segmentation on macular optical coherence tomography (OCT) images generates non invasive biomarkers querying neuronal structures with near cellular resolution. While first deep learning methods have delivered promising results with high computing power demands, a reliable, power efficient and reproducible intraretinal l...
Background
Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been sugg...
Introduction
Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein IgG antibody associated disorders (MOGAD) comprise two groups of rare neuroinflammatory diseases that cause attack-related damage to the central nervous system (CNS). Clinical attacks are often characterized by optic neuritis, transverse myelitis, a...
Background and Objectives: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-sero-positive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts.
Methods: The cross-sectional Collaborative Retrospective Study on retina...
Objective:
To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).
Methods:
We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort...
Retinal optical coherence tomography (OCT) with intraretinal layer segmentation is increasingly used not only in ophthalmology but also for neurological diseases such as multiple sclerosis (MS). Signal quality influences segmentation results, and high-quality OCT images are needed for accurate segmentation and quantification of subtle intraretinal...
Background:
Decreased motion perception has been suggested as a marker for visual pathway demyelination in optic neuritis (ON) and/or multiple sclerosis (MS).
Objectives:
To examine the influence of neuro-axonal damage on motion perception in MS and neuromyelitis optica spectrum disorders (NMOSD).
Methods:
We analysed motion perception with nu...
Importance
N-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration. N-acetylglucosamine (GlcNAc) is a rate-limiting substrate for N-glycan branching, but, to our knowledge, endogenous serum levels in patients with multiple sclerosis (...
Objective
To examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS).
Methods
We enrolled 61 patients with primary or secondary PMS in a randomized double-blind, paralle...
Background:Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity an...
Objective
To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.
Methods
To identify studies reporting quantitative OCT results, we performed a PubMed search for...
Background
Cross-sectional studies suggest normal appearing white matter (NAWM) integrity loss may lead to cortical atrophy in late-stage relapsing-remitting multiple sclerosis (MS).
Objective
To investigate the relationship between NAWM integrity and cortical thickness from first clinical presentation longitudinally.
Methods
NAWM integrity and c...
Background: Epigallocatechin gallate (EGCG) is an anti-inflammatory agent and has proven neuroprotective properties in animal models of multiple sclerosis (MS). Optical coherence tomography (OCT) assessed retinal thickness analysis can reflect treatment responses in MS.
Objective: To analyze the influence of EGCG treatment on retinal thickness anal...
Background
Clinical outcomes in neuromyelitis optica spectrum disorders (NMOSD) vary across different regions.
Objective
To describe clinical profiles in Japanese and German NMOSD patients.
Methods
Medical records of aquaporin-4-immunoglobulin G (AQP4-IgG) positive NMOSD patients from Japan (n = 54) and Germany (n = 38) were retrospectively analy...
Background
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disorder that damages optic nerves, brainstem, and spinal cord. In vivo corneal confocal microscopy (IVCM) is a noninvasive technique that provides corneal images with dendritic cells (DCs) and corneal subbasal nerve plexus (SBP), which arises from the trigemina...
Objectives:
Genetic variant classification is a challenge in rare adult-onset disorders as in SCA-PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA-PRKCG a comp...
OBJECTIVES
Lateral geniculate nucleus (LGN) volume is reduced after optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD). We aimed at a longitudinal assessment of LGN volume in NMOSD.
METHODS
Twenty-nine patients with aquaporin 4-IgG seropositive NMOSD (age: 47.8±14.6 years (y), female: n=27, history of ON (NMO-ON): n=17, median...
Background
Quantification of motor performance has a promising role in personalized medicine by diagnosing and monitoring, e.g. neurodegenerative diseases or health problems related to aging. New motion assessment technologies can evolve into patient-centered eHealth applications on a global scale to support personalized healthcare as well as treat...
Background:
Foveal changes were reported in Aquaporin-4 antibody(AQP4-Ab) seropositive neuromyelitis optica spectrum disorder(NMOSD) patients; however, it is unclear whether they are independent of ON, stem from subclinical ON or crossover from ON in fellow eyes.
Aim:
We used fovea morphometry and a statistical classification approach to investi...
Background
Impairment of visual function is one of the major symptoms of people with multiple sclerosis (pwMS). A multitude of disease effects including inflammation and neurodegeneration lead to structural impairment in the visual system. However, the gold standard of disability quantification, the expanded disability status scale (EDSS), relies o...
Background
Neurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder.
Objective
The study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG–associated disorders between East Asian (Japanese) and Cauca...
Purpose:
Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in N...
Objective
To investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry.
Methods
This cross-sectional study included macular spectral domain optical coherence tomography scans of 52 eyes from 28 patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD...
Background: Serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements have individually been shown to be promising biomarkers for future disease activity in multiple sclerosis (MS).
Objectives: To investigate the complementary value of sNfL and retinal OCT measurements for predicting disease activity in pati...
Spinocerebellar ataxia type 14 (SCA-PRKCG, formerly SCA14) is a rare, slowly progressive disorder caused by conventional mutations in protein kinase Cγ (PKCγ). The disease usually manifests with ataxia, but previous reports suggested PRKCG variants in retinal pathology. To systematically investigate for the first time visual function and retinal mo...
Background. Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune disease leading to disability from optic neuritis, myelitis and more rarely brain stem attacks and encephalitis. Patients with NMOSD also exhibit cognitive deficits, the cause of which remains unclear. Recent evidence highlights sensory-cognitive parallel processing conver...
Objectives
We aimed to evaluate optic chiasm (OC) measures as potential imaging marker for anterior optic pathway damage assessment in the context of neuromyelitis optica spectrum disorders (NMOSD).Materials and methodThis cross-sectional study included 39 patients exclusively with aquaporin 4-IgG seropositive NMOSD of which 25 patients had a histo...
Background
Spinocerebellar ataxia type 1 (SCA‐ATXN1) is an inherited progressive ataxia disorder characterized by an adult‐onset cerebellar syndrome combined with nonataxia signs. Retinal or optic nerve affection are not systematically described.
Objectives
To describe a retinal phenotype and its functional relevance in SCA‐ATXN1.
Methods
We appl...
Abstract Background Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be e...
PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NM...
Objective:
To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks.
Methods:
A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P1...
Neurodegenerative and neuroinflammatory diseases regularly cause optic nerve and retinal damage. Evaluating retinal changes using optical coherence tomography (OCT) in diseases like multiple sclerosis has thus become increasingly relevant. However, intraretinal segmentation, a necessary step for interpreting retinal changes in the context of these...
Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothes...
Introduction: Due to limited sample sizes, existing optical coherence tomography (OCT) studies in Neuromyelitis Optica Spectrum Disorders (NMOSD) are inconsistent regarding the volume loss after optic neuritis (ON) in aquaporin-4-antibody (AQP4-IgG) and myelin-oligodendrocyte-glycoprotein-antibody (MOG-IgG) seropositive patients, and the thinning i...
Background:
Serum antibodies against myelin-oligodendrocyte-glycoprotein (MOG-IgG) are detectable in a proportion of patients with acute or relapsing neuroinflammation. It is unclear, if neuro-axonal damage occurs only in an attack-dependent manner or also progressively. Therefore, this study aimed to investigate longitudinally intra-retinal layer...
Background:
The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood.
Objective:
The obje...
Objectives
In neuromyelitis optica spectrum disorders (NMOSD) thalamic damage is controversial, but thalamic nuclei were never studied separately. We aimed at assessing volume loss of thalamic nuclei in NMOSD. We hypothesised that only specific nuclei are damaged, by attacks affecting structures from which they receive afferences: the lateral genic...
• No volume differences were found in this preliminary analysis of the NMOSD thalamus.
• However, there were several decreased subregions in RRMS, compared to HC.
• Despite no significant decrease in the LGN or subthalamic nucleus in NMOSD vs. HC, their volumes associated with VA, suggesting that changes occur in the nuclei and affect VF in NMOSD....
Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage independent of ON (optic radiation...
Objective
To determine the optimal thresholds for inter‐eye differences in retinal nerve fiber and ganglion cell+inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis.
Background
Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite...