Matthijs C Brouwer

Academisch Medisch Centrum Universiteit van Amsterdam | AMC · Department of Neurology

Background: Staphylococcus aureus is an uncommon cause of community-acquired bacterial meningitis. We aimed to describe patients with this disease. Methods: We evaluated clinical characteristics and outcome of adults with community-acquired S. aureus meningitis from prospective nationwide cohort studies from Denmark (2015-2020) and the Netherlan...

Background Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observat...

Background Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induc...

Abstract We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 p...

Background In patients with central nervous system (CNS) infections identification of the causative pathogen is important for treatment. Metagenomic next-generation sequencing techniques are increasingly being applied to identify causes of CNS infections, as they can detect any pathogen nucleic acid sequences present. Viromic techniques that enrich...

Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe invasive infections upon ingestion with contaminated food. Clinically, listerial disease, or listeriosis, most often presents as bacteremia, meningitis or meningoencephalitis, and pregnancy-associated infections manifesting as miscarriage or neonatal...

Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma host response biomarkers in general ward patients before and after implementation of dexamethasone as standard of care. 48 patients without and 126 patients with dexamethasone treatm...

Background Seizures can be part of the clinical presentation of central nervous system (CNS) infections. We describe patients suspected of a neurological infection who present with a seizure and study diagnostic accuracy of clinical and laboratory features predictive of CNS infection in this population. Methods We analyzed all consecutive patients...

Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for...

Objectives We aimed to derive and validate a risk score to differentiate patients with bacterial meningitis from those with viral meningitis or encephalitis, among patients presenting with CSF leukocytosis and a negative Gram stain. Methods We included adults with bacterial and viral meningitis or encephalitis, presenting with CSF leukocytes >10 p...

There is a growing awareness of the importance of sex and gender in medicine and research. Women typically have stronger immune responses to self and foreign antigens than men, resulting in sex-based differences in autoimmunity and infectious diseases. In both animals and humans, males are generally more susceptible than females to bacterial infect...

Unfavorable outcome in bacterial meningitis is related to excessive inflammation and higher inflammatory markers have been reported in female than in male patients. Sex steroid hormones have immunomodulatory properties and can be found in the cerebrospinal fluid (CSF); however, their actions have not been studied in bacterial meningitis. We investi...

Background Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. Methods This randomised, double-blind, placebo-controll...

Diagnosing central nervous system (CNS) infections quickly is often difficult. Neurofilament light chain (NfL) is a component of the axonal cytoskeleton and identified as marker of neuronal damage in several CNS diseases. We evaluated the diagnostic accuracy of NfL for diagnosing CNS infections. We included patients from a prospective cohort of con...

Background and Objectives Few prospective well-designed diagnostic accuracy studies have been performed to study the parameters of infection in patients suspected for external ventricular catheter-associated infection. Our objective was to analyze the diagnostic accuracy of clinical characteristics and biochemical and microbiological parameters in...

The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefor...

Background Few studies have reported the long-term consequences of bacterial meningitis during infancy, and studies that have been done usually do not include a comparison cohort. We aimed to assess short-term and long-term risk of mortality, neurodevelopmental impairment (NDI), and health-care use and household income in cohorts of children with a...

Objective: To determine the incidence, clinical course, radiological patterns, and clinical outcome of intracerebral haemorrhage (ICH) complicating community-acquired bacterial meningitis. Methods: The clinical characteristics and outcome of patients with ICH complicating bacterial meningitis were studied in a prospectively nationwide cohort in...

Objective To study the clinical features of bacterial meningitis in myeloma patients. Methods We analyzed myeloma patients included in a nationwide cohort of patients >16 years old with community-acquired bacterial meningitis in the Netherlands between 2006 and 2018. Subsequently, we reviewed the literature for articles reporting myeloma patients...

Hydrocephalus is reported in approximately one-tenth of neurosarcoidosis patients. However, data on clinical characteristics and outcome are lacking. In this retrospective study, we present 11 patients with neurosarcoidosis and hydrocephalus on neuroimaging. Median age was 52 years and seven were female (64%). Presenting symptoms consisted of heada...

We evaluated the clinical features and treatment response of patients with muscular sarcoidosis. A retrospective cohort of 12 patients showed muscle weakness in 11 and myalgia in seven. One had focal myositis. Four had a negative medical history for sarcoidosis. Muscle imaging showed muscle edema in all and replacement of muscle tissue by fat in ha...

Objectives: We describe clinical characteristics and outcome of adults with bacterial meningitis presenting with a normal CSF leukocyte count. Methods: We studied community-acquired bacterial meningitis with a normal CSF leukocyte count (≤ 5 per mm3) in adults from a prospective nationwide cohort study. Results: From 2006 through 2020, 39 of 2...

Background: Advanced age is a risk factor for unfavorable outcome in community-acquired bacterial meningitis, but clinical characteristics and outcome in meningitis patients of 80 years or older have not been defined. Methods: We compared clinical characteristics and outcome of community-acquired bacterial meningitis patients aged 80 years or ol...

Objective: To describe the patients with myelitis due to neurosarcoidosis. Methods: We performed a retrospective cohort study and a systematic review and meta-analysis on neurosarcoidosis associated myelitis. Results: Myelitis was identified in 41 of 153 (27%) neurosarcoidosis patients seen at our clinic from 2015 to 2020. Classification of ne...

Background: The early-onset sepsis calculator (EOSC) reduces unnecessary antibiotic treatment in newborns. However, its performance in identifying cases with early-onset disease (EOD) is unclear. We compared the sensitivity of the EOSC to the current Dutch and National Institute for Health and Care Excellence (NICE) guidelines when applied to a co...

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Abstract Recently, we reported the phase II portion of the adaptive phase II/III PANAMO tr...

Confusion developed in a 49-year-old woman with relapsed diffuse large B-cell lymphoma within days after she received CAR-T therapy. She had difficulty putting words together and was disoriented but had no focal abnormalities noted during the neurologic examination.

Background and objectives: Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquire...

COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy anthranilic acid and quinolinic acid in lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)...

Background The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective. Methods This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1...

Objectives: To study the differential diagnosis of HIV-infected patients with suspected central nervous system (CNS) infections and the association of CD4 counts with the final diagnosis. Methods: We analyzed HIV-infected patients from a prospective cohort study on the diagnostic accuracy of clinical and laboratory characteristics in adults with su...

Objectives : To analyze clinical and laboratory characteristics of vertebral osteomyelitis in community-acquired bacterial meningitis patients Methods We analyzed all the episodes of vertebral osteomyelitis included in a cohort study of adult patients with community-acquired bacterial meningitis in the Netherlands. Subsequently, we performed a sys...

In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterd...

Introduction: Subarachnoid hemorrhage (SAH) has been described as an uncommon complication of community-acquired bacterial meningitis. However, the incidence, clinical course, and outcome are unclear. Methods: We assessed the clinical characteristics, incidence, and clinical outcome of patients with SAH complicating bacterial meningitis in a pro...

In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the c...

Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods Genome-wide association study performed to identify genetic variants influencing susceptibility to C...

Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the inci...

Background Detecting SARS-CoV-2 antibodies may help to diagnose COVID-19. Head-to-head validation of different types of immunoassays in well-characterized cohorts of hospitalized patients remains needed. Methods We validated three chemiluminescence immunoassays (CLIAs) (Liaison, Elecsys, and Abbott) and one single molecule array assay (SIMOA) (Qua...

Background The epidemiology and treatment of pneumococcal meningitis has changed with the implementation of conjugate vaccines and the introduction of adjunctive dexamethasone therapy. Methods We analysed episodes of community-acquired pneumococcal meningitis in adults (≥16 years) in the Netherlands, identified by the National Reference Laboratory...

Background Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood...

Background Colonization and transmission precede invasive group B streptococcal (GBS) disease. Data on GBS colonization prevalence, detection methods and risk factors for carriage are relevant for vaccine development and to understand GBS pathogenesis. Objectives To evaluate GBS colonization prevalence after the first week of life in the healthy n...

Objective: We studied genetic risk factors associated with sarcoidosis within a family with a high prevalence of this disease. Methods: We studied 41 members of a family with a high rate of sarcoidosis, including an index patient with treatment-resistant neurosarcoidosis. Whole genome sequencing was performed for six affected family members and...

The pneumococcal conjugate vaccine (PCV) primarily reduces disease burden in adults through a reduction in carriage prevalence of invasive serotypes in children. Current vaccine formulations are the same for both adults and children, but tailoring these formulations to age category could optimize vaccine efficacy. Identification of specific pneumoc...

Background : Haemophilus influenzae is an uncommon cause of meningitis in adults. Methods : We analyzed episodes of community-acquired H. influenzae meningitis in adults included in a prospective nationwide cohort study in the Netherlands. Results : From 2006 to July 2018, 82 of 2272 (4%) bacterial meningitis episodes were caused by H. influenzae...

A 31-year-old previously healthy woman presented with hallucinations and altered mental status, which was eventually found to be due to anti-N-methyl-D-aspartate receptor encephalitis. In this case report, we discuss the broad differential diagnosis of encephalitis with infectious and autoimmune causes. Furthermore, we consider empirical treatment...

Background and purposeThere are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands.Methods We used data fr...

Aims: Cerebral venous thrombosis (CVT) is a rare but severe complication of bacterial meningitis. The histopathological features of CVT in meningitis patients have not been described. Materials and methods: We studied histopathology findings of brain autopsy material from 2 patients with bacterial meningitis complicated by CVT and compared findi...

Background Patients with pneumococcal meningitis are at risk for death and neurological sequelae including cognitive impairment. Functional genetic polymorphisms of macrophage migration inhibitory factor (MIF) alleles have shown to predict mortality of pneumococcal meningitis. Methods We investigated whether MIF concentrations during the acute pha...

Background Streptococcus agalactiae (group B streptococcus) causes invasive disease in all age groups. In the Netherlands, the incidence of group B streptococcal sepsis in early infancy is increasing because of a specific genetic subtype, clonal complex (CC) 17-A1. We assessed the molecular epidemiology, incidence, and mortality of group B streptoc...

Background The epidemiology of acute bacterial meningitis has changed substantially since the introduction of conjugate vaccines. Methods We analysed nationwide surveillance data of all cerebrospinal fluid isolates received from 1988 to 2019 in the Netherlands. We assessed the impact of conjugate vaccines on incidence (defined as episodes per 100,...

Neisseria meningitidis causes sepsis and meningitis in humans. It has been suggested that pathogen genetic variation determines variance in disease severity. Here we report results of a genome-wide association study of 486 N. meningitidis genomes from meningococcal meningitis patients and their association with disease severity. Of 369 meningococca...

Introduction Community-acquired bacterial meningitis may be complicated by cerebral venous thrombosis (CVT), but this has not systematically been studied. Methods We evaluated clinical characteristics and outcome of CVT in adults with community-acquired bacterial meningitis in a prospective nationwide cohort study of bacterial meningitis (2006–201...

Background Recurrent bacterial meningitis has been found to occur in about 5% of meningitis cases. Methods We analyzed adults with recurrent episodes in a prospective nationwide cohort study of community-acquired bacterial meningitis. Results Of 2264 episodes of community-acquired bacterial meningitis between 2006 and 2018, 143 (6%) were identifi...

Background Severe COVID-19 is characterised by inflammation and coagulation in the presence of complement system activation. We aimed to explore the potential benefit and safety of selectively blocking the anaphylatoxin and complement protein C5a with the monoclonal antibody IFX-1 (vilobelimab), in patients with severe COVID-19. Methods We did an...

Objective To assess the efficacy and risks of treatment with infliximab (anti–tumor necrosis factor alpha) in pathology-confirmed neurosarcoidosis. Methods In a retrospective study in 2 tertiary referral centers in the Netherlands, we analyzed clinical characteristics, complications, and outcome of patients with neurosarcoidosis treated with infli...

We studied population genomics of 486 Neisseria meningitidis isolates causing meningitis in the Netherlands during the period 1979–2003 and 2006–2013 using whole-genome sequencing to evaluate the impact of a hyperendemic period of serogroup B invasive disease. The majority of serogroup B isolates belonged to ST-41/44 (41 %) and ST-32 complex (16 %)...

Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of ane...

In addition to the conventional respiratory symptoms, patients with COVID-19 can exhibit neurological complications. In this concise review, we aim to report the most frequent neurologic manifestations related to Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) infection. SARS-CoV2 can reach the central nervous system from the bloodstrea...

Objectives Confirming the diagnosis in viral central nervous system (CNS) infections can be difficult with current available diagnostic tools. Virus discovery cDNA-AFLP next generation sequencing (VIDISCA-NGS) is a promising viral metagenomic technique, which enables detection of all viruses in a single assay. We performed a retrospective study on...

Headache is a common presenting symptom in patients with intracranial infections, such as bacterial meningitis, viral encephalitis, brain abscess, and tuberculous meningitis, and may be the only symptom. The headache during intracranial infections is caused by several factors, such as increased intracranial pressure, stimulation of meningeal nocice...