Michael Deppe

• Prof. Dr.
• Professor at University of Münster

Background and Objectives To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein–IgG–associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). Methods Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI,...

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...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities th...

Background Today, no specific test for the diagnosis of multiple sclerosis (MS) is available due to the lack of characteristic symptoms at beginning. This circumstance also complicates estimation of disease progression. Recent findings provided evidence for early, non-lesional cerebellar damage in patients with (clinically definite) relapsing-remit...

Objective: The absence of neurobiological diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We investigated if changes in fractional anisotropy (FA) could help to differentiate BD from UD in the state of depression. Methods: Using diffusion tensor imaging (DTI) we employed a voxel-based a...

Objective To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration. Methods Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehe...

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 stro...

Background: There is an unmet need for screening methods to detect and quantify cerebral small vessel disease (SVD). Transcranial Doppler ultrasound (TCD) flow spectra of the larger intracranial arteries probably contain relevant information about the microcirculation. However, it has not yet been possible to exploit this information as a valuable...

Background Deterioration of fine motor control of the tongue is common in Multiple Sclerosis (MS) and has a major impact on quality of life. However, the underlying neuronal substrate is largely unknown. Here, we aimed to explore the association of tongue motor dysfunction in MS patients with overall clinical disability and structural brain damage....

Es ist an der Zeit, den Hirnvolumenverlust als weitere Domäne in das NEDA-Modell zu integrieren, meint Professor Friedemann Paul. Professor Michael Deppe ist nicht prinzipiell dagegen, findet aber, dass die Hirnatrophie aktuell als sinnvoller Parameter zur Verlaufsbeurteilung aus Verfahrens-, Validierungs- und Qualitätsgründen problematisch ist.

Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We...

FDG-PET detects hypometabolism in premanifest and symptomatic Huntington's disease (HD). A cross-sectional study suggested that whole-brain FDG-PET is capable to detect a phenotype in transgenic (tg) HD rats. Recently, a longitudinal follow-up study showed no FDG-PET changes in tgHD rats. Both studies applied small sample sizes and analysis was lim...

In light of the increased risk of progressive multifocal encephalopathy (PML) development under long-term treatment with the monoclonal antibody natalizumab which is approved for treatment of active relapsing remitting multiple sclerosis (RRMS), there is a clear need for alternative treatment options with comparable efficacy and reduced PML risk. O...

The underlying pathophysiology of neurological complications in patients with hemolytic-uremic syndrome (HUS) remains unclear. It was recently attributed to a direct cytotoxic effect of Shiga toxin 2 (Stx2) in the thalamus. Conventional MRI of patients with Stx2-caused HUS revealed - despite severe neurological symptoms - only mild alterations if a...

Background Common symptoms of multiple sclerosis (MS) such as gait ataxia, poor coordination of the hands, and intention tremor are usually the result of dysfunctionality in the cerebellum. Magnetic resonance imaging (MRI) has frequently failed to detect cerebellar damage in the form of inflammatory lesions in patients presenting with symptoms of c...

Variability in brain tissue volumes derived from magnetic resonance images is attributable to various sources. In quantitative comparisons it is therefore crucial to distinguish between biologically and methodically conditioned variance and to take spatial accordance into account. We introduce volume transition analysis as a method that not only pr...

Multi-centre MRI studies of the brain are essential for enrolling large and diverse patient cohorts, as required for the investigation of heterogeneous neurological and psychiatric diseases. However, the multi-site comparison of standard MRI data sets that are weighted with respect to tissue parameters such as the relaxation times (T1, T2) and prot...

A particularly popular automated magnetic resonance imaging (MRI) hippocampal subfield mapping technique is the one described by Van Leemput et al. (2009: Hippocampus 19:549–557) that is currently distributed with FreeSurfer software. This method assesses the probabilistic locations of subfields based on a priori knowledge of subfield topology dete...

In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and assoc...

In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphom...

We tested the hypothesis in sense of a proof of principle that white matter (WM) degeneration after cardiopulmonary arrest (CPA) can be assessed much earlier by diffusion tensor imaging (DTI) than by conventional MRI. We performed DTI and T2-weighted FLAIR imaging over four serial acquisitions of a 76-year-old man with unresponsive wakefulness synd...

Objective: White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple scl...

Individual differences in executive functioning and brain morphology are considerable. In this study, we investigated their interrelation in a large sample of healthy older individuals. Digit span, trail-making, and Stroop tasks were used to assess different executive subfunctions in 367 nondemented community-dwelling individuals (50-81 years). Tas...

Ischemic small vessel disease (SVD) is a common finding on routine scans in older people, but cognitive sequelae vary considerably. To improve understanding of mechanisms underlying decline or preservation of cognitive function in this condition, we assessed cognition and cortical plasticity in 20 elderly subjects with severe SVD and 20 age-matched...

Background: The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analys...

Various types of multiple sclerosis (MS) related pain have been discussed. One concept is that deafferentation secondary to lesions in the spino-thalamo-cortical network can cause central pain. However, this hypothesis is somehow limited by a lack of a robust association between pain episodes and sites of lesion location. We tested the hypothesis t...

In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atr...

(A) DTI and volumetric differences between patients and controls using matched sample sizes. (B) Correlations between FA and age in patients and controls. (DOC)

Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials. It was previously shown that gri...

The sensitivity of diffusion tensor imaging (DTI) for detecting microstructural white matter alterations has motivated the application of voxel-based statistics (VBS) to fractional anisotropy (FA) images (FA-VBS). However, detected group differences may depend on the spatial registration method used. The objective of this study was to investigate t...

Susac syndrome was named after J.O. Susac who first described the syndrome in 1979. It is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. It mainly occurs in young women. This underdiagnosed disease needs to be considered in the differential diagnosis of a broad variety of diso...

Background Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). Methods We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance im...

Microstructural alterations of the putamen were recently reported in patients with partial and generalized epilepsy disorders. However, it is unknown whether these alterations pre-exist or are secondary to recurrent seizures. Here we investigated the progression of putamen fractional anisotropy (FA) alterations in a case of recurrent psychomotor se...

There has been recent motivation to search for neuroanatomical asymmetries in nonhuman primates in order to provide comparative information on how the human brain is structurally organized to support specific cognitive capabilities, such as language functions. We took the opportunity to study Broca's area homologue in a novel sample of 80 preserved...

The neurovascular coupling describes a vasoregulative principle of the brain that adapts local cerebral blood flow in accordance with the underlying neuronal activity. It is the basis of modern indirect brain imaging techniques. Because of its wide availability and high tolerability the functional transcranial Doppler has been often used to assess...

Freely available automated MR image analysis techniques are being increasingly used to investigate neuroanatomical abnormalities in patients with neurological disorders. It is important to assess the specificity and validity of automated measurements of structure volumes with respect to reliable manual methods that rely on human anatomical expertis...

To determine regional alterations of fractional anisotropy (FA) and mean diffusivity (MD) in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy with unknown cause (TLEu) using diffusion tensor imaging (DTI) and voxel-based statistics (VBS). Ten patients with left TLEu and no abnormality on conventional MRI and 81 age-mat...

Das Susac-Syndrom, benannt nach dem Erstbeschreiber John Susac, ist gekennzeichnet durch die Trias Enzephalopathie, retinale Astarterienverschlüsse und sensorineurale Hörstörungen. Obwohl es zweifellos zu den seltenen Erkrankungen zählt, muss das Susac-Syndrom aufgrund der bunten klinischen Präsentation bei einer Vielzahl anderer, häufigerer Erkran...

It has long been suspected that cortical interhemispheric asymmetries may underlie hemispheric language dominance (HLD). To test this hypothesis, we determined interhemispheric asymmetries using stereology and MRI of three cortical regions hypothesized to be related to HLD (Broca's area, planum temporale, and insula) in healthy adults in whom HLD w...

Purpose: Patients with juvenile myoclonic epilepsy (JME) show evidence of microstructural white matter (WM) damage of thalamocortical fiber tracts and changes of blood oxygen level dependent (BOLD) signal in a striatothalamocortical network. The objective of the present study was to investigate microstructural and volumetric alterations of the puta...

Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy. In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulat...

Ischemic small vessel disease (SVD) may lead to cognitive impairment, but cognitive deficits with a given burden of SVD vary significantly. The underlying mechanisms of impaired or preserved cognition are unknown. Here, we investigated the impact of ischemic SVD on rapid-onset cortical plasticity, as induced with a paired-associative stimulation pr...

Susac syndrome, named after John Susac, the first to describe this condition, is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Although certainly a rare disease, Susac syndrome needs to be considered in the differential diagnosis of a broad variety of diseases. The pathogenes...

CONSORT Checklist. (DOC)

Trial Protocol. (DOC)

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral...

The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and -regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis...

A case of a rapidly progressive degeneration of the visual, auditory and corticospinal tract in a patient with a HIV infection is presented. The HIV-infected patient suffered from severe and rapidly progressive sensorineural hearing loss, blindness, dysarthria, dysphagia and tetraparesis. MRI showed degeneration of the visual, auditory and corticos...

Background: The tgHD rat (von Horsten et al. 2003) carries 51 CAG repeats, which is within ranges observed in human genotypes. It was previously reported that small animal FDG-PET is able to detect hypometabolism in the whole brain of tgHD rats at 18–24 months of age. However, this initial imaging study was limited by its cross-sectional nature, th...

Regional decreases in grey matter volume as detected by magnetic resonance imaging-based volumetry have been reported in several clinical chronic pain cohorts. Here, we used voxel-based morphometry in a nonclinical cohort to investigate whether grey matter alterations also occur in older individuals (aged 40-85 years) from the general population. B...

Susac's syndrome is an underdiagnosed disease that is thought to occur mainly in young women. It is characterized by the triad of hearing loss, branch retinal artery occlusions, and encephalopathy with predominantly cognitive and psychiatric symptoms. Treatment consists of immunosuppressive therapy. Focal ischemic lesions in the central portion of...

Aphasia after middle cerebral artery (MCA) stroke shows highly variable degrees of recovery. One possible explanation may be offered by the variability of the occlusion location. Branches from the proximal portion of the MCA often supply the mesial temporal lobe including parts of the hippocampus, a structure known to be involved in language learni...

Eddy-current (EC) and motion effects in diffusion-tensor imaging (DTI) bias the estimation of quantitative diffusion indices, such as the fractional anisotropy. Both effects can be retrospectively corrected by registering the strongly distorted diffusion-weighted images to less-distorted T2-weighted images acquired without diffusion weighting. Two...

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. Most MR studies on HSP include very heterogeneous samples of patients, and findings were inconsistent. Here, we examined six patients with pure HSP and SPG4 mutations by clinical evaluation, detailed neuropsychological testing, and neuroim...

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies,...

C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). We cross-section...

Conventional structural MRI fails to identify a cerebral lesion in 25% of patients with cryptogenic partial epilepsy (CPE). Diffusion tensor imaging is an MRI technique sensitive to microstructural abnormalities of cerebral white matter (WM) by quantification of fractional anisotropy (FA). The objectives of the present study were to identify focal...

Introduction: Diffusion tensor imaging (DTI) offers the possibility of estimating quantities that are related to the brain's white matter (WM) microstructure, e.g. the fractional anisotropy (FA) [1].These quantities are frequently used for group comparisons (e.g. [2]). For DTI, at least seven images must be acquired [3]: one image with no diffusion...

Patient Information. Demographic and clinical information and language test results for the eight aphasia patients

Supporting information. Provides additional supportive information regarding patient characteristics, neuropsychological testing and functional imaging analyses and results

Brain activity changes immediately after training and at the follow-up assessment. Brain activity changes in the patients and healthy controls: Brain areas showing a) positive and b) negative correlations between short-term training success and 'post1-pre' training activity changes for trained object names (masked with the respective results for un...

To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language...

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficient activity of the enzyme α-galactosidase A, resulting in a vasculopathic involvement of various organ systems, e.g. cerebral structures. Marked cerebral vasculopathy with subsequent white matter lesions (WML) are a frequent finding in FD patients. Recent studies...

We describe a 40-year-old patient with gelastic seizures triggered by hand movement. Despite nonlesional magnetic resonance imaging (MRI), electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) are concordant with seizure onset in the right frontocentral area. Seizure semiology and EEG recordi...

The goal of this study was to explore the structural correlates of functional language dominance by directly comparing the brain morphology of healthy subjects with left- and right-hemisphere language dominance. Twenty participants were selected based on their language dominance from a cohort of subjects with known language lateralization. Structur...

The progression of white-matter changes in a case of posterior cortical atrophy (PCA) was examined over a period of 15 months using diffusion tensor imaging (DTI) and the association with neuropsychological variables was studied. Patient and A PCA patient was observed over a period of 15 months. DTI and volumetric magnetic resonance imaging were ob...