Wolfgang Brück

Wolfgang Brück
Universitätsmedizin Göttingen · Department of Neuropathology

MD

About

377
Publications
64,105
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28,851
Citations
Citations since 2017
125 Research Items
14184 Citations
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201720182019202020212022202305001,0001,5002,0002,500
201720182019202020212022202305001,0001,5002,0002,500

Publications

Publications (377)
Article
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PURPOSE: To assess outcomes and biological parameters of children younger than 4 years with metastatic medulloblastoma treated within the MET-HIT2000-BIS4 trial or outside the protocol. PATIENTS AND METHODS: 48 trial participants received either carboplatin/etoposide (years 2001 to 2005, n=18) or an intensified Head-Start-based induction (years 200...
Article
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Objectives: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS. Methods: We performed 3 studies: (1) a...
Article
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Background: In patients with Alzheimer's disease (AD), bacterial infections are often associated with a cognitive decline. Animal models of genuine acute infections with viable bacteria which induce deterioration of neurodegenerative diseases are missing. Objective: We assessed the effect of an intracerebral infection with E. coli in a mouse mod...
Article
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As extremely sensitive immune cells, microglia act as versatile watchdogs of the central nervous system (CNS) that tightly control tissue homeostasis. Therefore, microglial activation is an early and easily detectable hallmark of virtually all neuropsychiatric, neuro-oncological, neurodevelopmental, neurodegenerative and neuroinflammatory diseases....
Article
Objective To compare clinical characteristics across immunopathological subtypes of patients with multiple sclerosis. Methods Immunopathological subtyping was performed on specimens from 547 patients with biopsy and/or autopsy confirmed CNS demyelination. Results The frequency of immunopathological subtypes were pattern I (23%), II (56%), and III...
Article
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Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging—and almost exclusively performed at 7 T field strength—depicting the tissue architecture of the entire brain in fine detail is invaluable since...
Article
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Objective Histology reveals that early active multiple sclerosis lesions can be classified into three main inter-individually heterogeneous but intra-individually stable immunopathological patterns of active demyelination (patterns I-III). In pattern I and II, a T-cell- and macrophage-associated demyelination is suggested, with pattern II only show...
Article
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Cerebral disease manifestation occurs in about two thirds of males with X-linked adrenoleukodystrophy (CALD) and is fatally progressive if left untreated. Early histopathologic studies categorized CALD as an inflammatory demyelinating disease, which led to repeated comparisons to multiple sclerosis (MS). The aim of this study was to revisit the rel...
Article
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Natalizumab, a recombinant humanized monoclonal antibody directed against the α4 subunit of the integrins α4ß1 and α4ß7, has been approved for the treatment of active relapsing-remitting MS. Although natalizumab is a highly beneficial drug that effectively reduces the risk of sustained disability progression and the rate of clinical relapses, some...
Article
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Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitorin...
Preprint
Full-text available
Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging - and almost exclusively performed at 7T field strength - depicting the tissue architecture of the entire brain in fine detail is invaluable sin...
Article
Full-text available
OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for n...
Article
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Objective Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients’ brains suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is current...
Article
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Significance Anti-CD20–mediated B cell depletion is a highly effective therapy in MS. However, long-term effects of this approach on the immune system are not yet characterized in detail. After cessation of anti-CD20 treatment, B cells reappear immature yet highly activated. In addition, anti-CD20 treatment exerts long-lasting effects on T cells, w...
Article
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Anti-CD20-mediated B-cell depletion effectively reduces acute multiple sclerosis (MS) flares. Recent data shows that antibody-mediated extinction of B cells as a lasting immune suppression, harbors the risk of developing humoral deficiencies over time. Accordingly, more selective, durable and reversible B-cell-directed MS therapies are needed. We h...
Article
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Tumefactive multiple sclerosis (MS) is a rare variant of MS that may lead to a rapidly progressive clinical deterioration requiring a multidisciplinary diagnostic workup. Our report describes the diagnostic and therapeutic approach of a rare and extremely severe course of MS. A 51-year-old man with an 8-year history of relapsing-remitting MS (RRMS)...
Article
Introduction Sepsis-associated encephalopathy (SAE) and septic encephalitis (SE) are associated with increased mortality, long-term cognitive impairment and focal neurological deficits. Areas covered The PUBMED database was searched 2016-2020. The clinical manifestation of SAE is delirium, SE additionally is characterized by focal neurological sym...
Article
Background Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment. Objective To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years. Methods We assessed ALC at baseline, monthly till...
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Objective To investigate serum neurofilament light chain (sNfL) as a potential biomarker for disease activity and treatment response in pediatric patients with multiple sclerosis (MS). Methods In this retrospective cohort study, sNfL levels were measured in a pediatric MS cohort (n = 55, follow-up 12–105 months) and in a non-neurologic pediatric c...
Article
Multiple sclerosis is an immune-mediated chronic inflammatory disease of the CNS that leads to demyelinated lesions in the grey and white matter. Inflammatory, active demyelinating white matter lesions predominate in the relapsing-remitting disease stages, whereas in the progressive stage the so-called slowly expanding lesion is characteristic. The...
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Objective We examined the effect of glatiramer acetate (GA) on B-cell maturation, differentiation, and antigen presentation in MS and experimental autoimmune encephalomyelitis (EAE). Methods A cross-sectional study of blood samples from 20 GA-treated and 18 untreated patients with MS was performed by flow cytometry; 6 GA-treated patients with MS w...
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Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non‐inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late‐onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar...
Article
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PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventr...
Article
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Despite many years of research efforts and clinical trials the prognosis of patients diagnosed with glioblastoma remains very poor. The oligodendrocyte transcription factor 2 (Olig2) was identified as a marker for glioma stem cells, which are believed to be responsible for glioma recurrence and therapy resistance. In this retrospective analysis we...
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Objective PARADIG MS demonstrated superior efficacy and comparable safety of fingolimod versus interferon β-1a (IFN β-1a) in paediatric-onset multiple sclerosis (PoMS). This study aimed to report all predefined MRI outcomes from this study. Methods Patients with multiple sclerosis (MS) (aged 10–<18 years) were randomised to once-daily oral fingoli...
Article
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Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I–III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complemen...
Article
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Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The...
Article
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Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, the application of clinical and imaging biomarkers is currently not able to allow individual characterization and prediction. Complementary, molecular biomarkers which are...
Article
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Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS...
Article
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Background: In the past, multiple sclerosis (MS) medications have been primarily designed to modulate T cell properties. Based on the emerging concept that B cells are equally important for the propagation of MS, we compared the effect of four commonly used, primarily T cell-targeting MS medications on B cells. Methods: Using flow cytometry, we...
Article
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Rosette-forming glioneuronal tumor (RGNT) is a rare brain neoplasm that primarily affects young adults. Although alterations affecting the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathway have been associated with this low-grade entity, comprehensive molecular investigations of RGNT in larger series hav...
Article
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Rituximab exerts its clinical efficacy by its specific pattern of depletion of CD20 ⁺ B lymphocytes and it has been demonstrated that rituximab is an effective treatment for relapsing remitting multiple sclerosis. X-linked adrenoleukodystrophy (X-ALD), the most common monogenetic neuroinflammatory disorder, shares substantial overlap with multiple...
Article
Poor vitamin D status is associated with a higher relapse rate and earlier disability in multiple sclerosis. Based on these associations, patients with multiple sclerosis are frequently supplemented with the vitamin D precursor cholecalciferol, although it is unclear whether this regimen is of therapeutic benefit. To model consequences of this comm...
Article
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Nach Jahren niedriger Inzidenz ist in Deutschland seit 2015 eine starke Zunahme gemeldeter Tuberkulose(TB)-Neuerkrankungen zu beobachten. Neue Immuntherapien zur Behandlung der Multiplen Sklerose (MS) gehen mit einer reduzierten Immunkompetenz und einem potenziell erhöhten Infektionsrisiko einher, wobei den meisten behandelnden Neurologen spezifisc...
Article
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 acu...
Article
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Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the...
Article
We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which leads to amino acid substitution T94M, were present among the unaffected relatives tested or in the 60,000 exomes of the ExAC...
Preprint
Full-text available
We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which leads to amino acid substitution T94M, were present among the unaffected relatives tested or in the 60,000 exomes of the ExAC...
Article
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Michael W. Sereda was incorrectly associated with the Department of Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Str. 1, 30625 Hanover, Germany. The correct affiliations for Michael W. Sereda are Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany and Department...
Article
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In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I...
Article
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Background Quinoline-3-carboxamides, such as laquinimod, ameliorate CNS autoimmunity in patients and reduce tumor cell metastasis experimentally. Previous studies have focused on the immunomodulatory effect of laquinimod on myeloid cells. The data contained herein suggest that quinoline-3-carboxamides improve the immunomodulatory and anti-tumor eff...
Article
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X‐linked adrenoleukodystrophy (X‐ALD) and metachromatic leukodystrophy (MLD) are two relatively common examples of hereditary demyelinating diseases caused by a dysfunction of peroxisomal or lysosomal lipid degradation. In both conditions, accumulation of nondegraded lipids leads to the destruction of cerebral white matter. Because of their high li...
Article
Enhanced glial fibrillary acidic protein (GFAP) expression occurs in most diseases of the central nervous system. Thus far, little is known about the effect that GFAP exerts on astrocyte cell signaling. In the present study, we observed that silencing GFAP expression in isolated astrocytes leads to enhanced CCL2 and CXCL10 release, whereas overexpr...
Article
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In multiple sclerosis (MS), the effect of dimethyl fumarate (DMF) treatment is primarily attributed to its capacity to dampen pathogenic T cells. Here, we tested whether DMF also modulates B cells, which are newly recognized key players in MS, and to which extent DMF restricts ongoing loss of oligodendrocytes and axons in the central nervous system...
Article
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Background: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. Objective and methods: This retrospective cohort study summarizes clinical, laboratory, radio...
Article
Background Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population. Methods In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receiv...
Article
Full-text available
Significance B cell depletion via anti-CD20 monoclonal antibodies is a novel, highly efficient therapy for multiple sclerosis (MS). In a murine MS model, we investigated three mechanistic questions that cannot be addressed in humans. First, we established that a fraction of mature B cells in the spleen is resistant to anti-CD20. Second, we determin...
Conference Paper
Objective: Dermoid cysts are benign intracranial tumours, butmalignant transformation into a squamous cell carcinomamay rarely occur. We present the special features of a case in which the second relapse of a dermoid was diagnosed as a squamous cell carcinoma. Methods: A young, with the exception of a congenital trochlear palsy otherwise healthy w...