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Juerd Wijntjes, Malik Bechakra, Marco W J Schreurs, Joost L M Jongen, Aart Koppenaal, Maarten J Titulaer
No abstract text is available yet for this article.
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Marleen H van Coevorden-Hameete, Sam F B van Beuningen, Matthieu Perrenoud, Lena M Will, Esther Hulsenboom, Jean-Francois Demonet, Lidia Sabater, Johan M Kros, Jan J G M Verschuuren, Maarten J Titulaer, Esther de Graaff, Peter A E Sillevis Smitt, Casper C Hoogenraad
Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay...
September 2017: Annals of Clinical and Translational Neurology
Anna E M Bastiaansen, Agnes van Sonderen, Maarten J Titulaer
PURPOSE OF REVIEW: Twenty years since the discovery of voltage-gated potassium channel (VGKC)-related autoimmunity; it is currently known that the antibodies are not directed at the VGKC itself but to two closely associated proteins, anti-leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2). Antibodies to LGI1 and Caspr2 give well-described clinical phenotypes. Anti-LGI1 encephalitis patients mostly have limbic symptoms, and anti-Caspr2 patients have variable syndromes with both central and peripheral symptoms...
June 2017: Current Opinion in Neurology
Agnes van Sonderen, Dave L Roelen, Johannes A Stoop, Robert M Verdijk, Geert W Haasnoot, Roland D Thijs, Paul W Wirtz, Marco W J Schreurs, Frans H J Claas, Peter A E Sillevis Smitt, Maarten J Titulaer
Leucine-rich glioma-inactivated1 (LGI1) encephalitis is an antibody-associated inflammation of the limbic area. An autoimmune etiology is suspected but not yet proven. We performed human leukocyte antigen (HLA) analysis in 25 nontumor anti-LGI1 patients and discovered a remarkably strong HLA association. HLA-DR7 was present in 88% compared to 19.6% in healthy controls (p = 4.1 × 10-11 ). HLA-DRB4 was present in all patients and in 46.5% controls (p = 1.19 × 10-7 ). These findings support the autoimmune hypothesis...
February 2017: Annals of Neurology
James B Lilleker, Matthew S Jones, Rajiv Mohanraj, Tianrong Yeo, Josiah Y.H. Chai, Kevin Tan, Agnes van Sonderen, Marco W J Schreurs, Marienke A A M de Bruijn, Peter A E Sillevis Smitt, Maarten J Titulaer
No abstract text is available yet for this article.
October 25, 2016: Neurology
Agnes van Sonderen, Roland D Thijs, Elias C Coenders, Lize C Jiskoot, Esther Sanchez, Marienke A A M de Bruijn, Marleen H van Coevorden-Hameete, Paul W Wirtz, Marco W J Schreurs, Peter A E Sillevis Smitt, Maarten J Titulaer
OBJECTIVE: This nationwide study gives a detailed description of the clinical features and long-term outcome of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. METHODS: We collected patients prospectively from October 2013, and retrospectively from samples sent to our laboratory from January 2007. LGI1 antibodies were confirmed with both cell-based assay and immunohistochemistry. Clinical information was obtained in interviews with patients and their relatives and from medical records...
October 4, 2016: Neurology
A van Sonderen, M W J Schreurs, P W Wirtz, P A E Sillevis Smitt, M J Titulaer
A wide variety of clinical syndromes has been associated with antibodies to voltage-gated potassium channels (VGKCs). Six years ago, it was discovered that patients do not truly have antibodies to potassium channels, but to associated proteins. This enabled the distinction of three VGKC-positive subgroups: anti-LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both antibodies. Patients with LGI1-antibodies have a limbic encephalitis, often with hyponatremia, and about half of the patients have typical faciobrachial dystonic seizures...
October 2016: Autoimmunity Reviews
Johanna G Mitterreiter, Maarten J Titulaer, Gijsbert P van Nierop, Jeroen J A van Kampen, Georgina I Aron, Albert D M E Osterhaus, Georges M G M Verjans, Werner J D Ouwendijk
Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR-associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions...
2016: PloS One
Marienke A A M De Bruijn, Maarten J Titulaer
Over the last few year, antibodies to various central nervous system receptors, particularly the glutamate and γ-aminobutyric acid (GABA) receptors, have been found to be associated with autoimmune neurologic disorders. The receptors include the N-methyl-d-aspartate receptor (NMDAR), the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), the metabotropic glutamate receptors (mGluRs), and GABA type A and B receptors (respectively GABAAR and GABABR). Compared to the previously described paraneoplastic antibodies directed at intracellular targets, the patients with receptor antibodies are often younger, they less frequently have malignancies, and they respond better to immunotherapy...
2016: Handbook of Clinical Neurology
Eugenia Martinez-Hernandez, Helena Ariño, Andrew McKeon, Takahiro Iizuka, Maarten J Titulaer, Mateus M Simabukuro, Eric Lancaster, Mar Petit-Pedrol, Jesús Planagumà, Yolanda Blanco, Robert J Harvey, Albert Saiz, Francesc Graus, Josep Dalmau
IMPORTANCE: Symptoms of stiff-person syndrome (SPS), stiff-limb syndrome (SLS), or progressive encephalomyelitis with rigidity, myoclonus, or other symptoms (SPS-plus) can occur with several autoantibodies, but the relative frequency of each antibody, syndrome specificity, and prognostic implications are unclear. OBJECTIVE: To report the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD), including SPS, SLS, and SPS-plus...
June 1, 2016: JAMA Neurology
Agnes van Sonderen, Marco W J Schreurs, Marienke A A M de Bruijn, Sanae Boukhrissi, Mariska M P Nagtzaam, Esther S P Hulsenboom, Roelien H Enting, Roland D Thijs, Paul W Wirtz, Peter A E Sillevis Smitt, Maarten J Titulaer
OBJECTIVE: To assess the clinical relevance of a positive voltage-gated potassium channel (VGKC) test in patients lacking antibodies to LGI1 and Caspr2. METHODS: VGKC-positive patients were tested for LGI1 and Caspr2 antibodies. Patients lacking both antibodies were matched (1:2) to VGKC-negative patients. Clinical and paraclinical criteria were used to blindly determine evidence for autoimmune inflammation in both groups. Patients with an inconclusive VGKC titer were analyzed in the same way...
May 3, 2016: Neurology
Renske Konings, Matthijs H van Gool, Martin P L Bard, Anthonie Zwijnenburg, Bart M Titulaer, Tjeerd S Aukema, Renato A Valdés Olmos, Karolina Sikorska, Houke M Klomp, Herman Rijna
INTRODUCTION: In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection. METHODS: This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department...
June 2016: Annals of Nuclear Medicine
Francesc Graus, Maarten J Titulaer, Ramani Balu, Susanne Benseler, Christian G Bien, Tania Cellucci, Irene Cortese, Russell C Dale, Jeffrey M Gelfand, Michael Geschwind, Carol A Glaser, Jerome Honnorat, Romana Höftberger, Takahiro Iizuka, Sarosh R Irani, Eric Lancaster, Frank Leypoldt, Harald Prüss, Alexander Rae-Grant, Markus Reindl, Myrna R Rosenfeld, Kevin Rostásy, Albert Saiz, Arun Venkatesan, Angela Vincent, Klaus-Peter Wandinger, Patrick Waters, Josep Dalmau
Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis...
April 2016: Lancet Neurology
Peter Maat, Janet W de Beukelaar, Casper Jansen, Maaike Schuur, Cornelia M van Duijn, Marleen H van Coevorden, Esther de Graaff, Maarten Titulaer, Annemieke J Rozemuller, Peter Sillevis Smitt
OBJECTIVE: To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD). METHODS: The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998-2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in CSF obtained postmortem by immunohistochemistry on fresh frozen rat brain sections, by Luminex assay for the presence of well-characterized onconeural antibodies, and by cell-based assays for antibodies against NMDAR, GABABR1/2, GABAAR GLUR1/2, LGI1, Caspr2, and DPPX...
December 2015: Neurology® Neuroimmunology & Neuroinflammation
Frederick J A Meijer, Anouke van Rumund, Anil M Tuladhar, Marjolein B Aerts, Imke Titulaer, Rianne A J Esselink, Bastiaan R Bloem, Marcel M Verbeek, Bozena Goraj
INTRODUCTION: The aim of this study is to evaluate whether the diagnostic accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of diffusion tensor imaging (DTI), to differentiate between neurodegenerative atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage parkinsonism. METHODS: We performed a prospective observational cohort study of 60 patients presenting with early stage parkinsonism and initial uncertain diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI...
July 2015: Neuroradiology
Tom Cornelis, Natascha J H Broers, Denise C L M Titulaer, Yvonne M Henskens, Rene van Oerle, Frank M van der Sande, Henri M Spronk, Hans Vink, Karel M Leunissen, Hugo ten Cate, Jeroen P Kooman
BACKGROUND: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. METHODS: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B...
2014: Blood Purification
F J A Meijer, A van Rumund, B A C M Fasen, I Titulaer, M Aerts, R Esselink, B R Bloem, M M Verbeek, B Goraj
BACKGROUND AND PURPOSE: The differentiation between Parkinson disease and atypical parkinsonian syndromes can be challenging in clinical practice, especially in early disease stages. Brain MR imaging can help to increase certainty about the diagnosis. Our goal was to evaluate the added value of SWI in relation to conventional 3T brain MR imaging for the diagnostic work-up of early-stage parkinsonism. MATERIALS AND METHODS: This was a prospective observational cohort study of 65 patients presenting with parkinsonism but with an uncertain initial clinical diagnosis...
March 2015: AJNR. American Journal of Neuroradiology
M J Titulaer, J Dalmau
No abstract text is available yet for this article.
October 2014: Molecular Psychiatry
Ethan M Goldberg, Maarten Titulaer, Peter M de Blank, Angela Sievert, Nicole Ryan
BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is an increasingly well-recognized inflammatory encephalitis in children and adults. PATIENT: We report a previously healthy 21-month-old girl who presented with behavioral change, self-mutilatory behavior, and echolalia. Over the ensuing weeks, symptoms progressed to include unilateral upper extremity dystonia, gait impairment, dysphagia, and mutism. Magnetic resonance imaging of the brain showed a tiny area of signal abnormality in the subcortical white matter, but was otherwise normal...
February 2014: Pediatric Neurology
M H van Coevorden-Hameete, E de Graaff, M J Titulaer, C C Hoogenraad, P A E Sillevis Smitt
Over the last decade multiple autoantigens located on the plasma membrane of neurons have been identified. Neuronal surface antigens include molecules directly involved in neurotransmission and excitability. Binding of the antibody to the antigen may directly alter the target protein's function, resulting in neurological disorders. The often striking reversibility of symptoms following early aggressive immunotherapy supports a pathogenic role for autoantibodies to neuronal surface antigens. In order to better understand and treat these neurologic disorders it is important to gain insight in the underlying mechanisms of antibody pathogenicity...
March 2014: Autoimmunity Reviews
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