Martijn T Wijburg1, Birgit I Witte2, Anke Vennegoor3, Stefan D Roosendaal4, Esther Sanchez5, Yaou Liu6, Carine O Martins Jarnalo7, Bernard Mj Uitdehaag3, Frederik Barkhof5, Joep Killestein3, Mike P Wattjes5. 1. Department of Neurology, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 2. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. 3. Department of Neurology, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 4. Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. 5. Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 6. Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China. 7. Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
Abstract
OBJECTIVE: Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation. METHODS: Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters. We tested the association with PML for each characteristic and constructed a multivariable prediction model which we analysed using a receiver operating characteristic (ROC) curve. RESULTS: Presence of punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localisation were associated with new MS lesions. In the multivariable model, punctate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localisation predict for new MS lesions (area under the curve: 0.988, 95% CI 0.977 to 1.0, sensitivity: 100%, specificity: 80.6%). INTERPRETATION: The MRI characteristics of asymptomatic natalizumab-associated PML lesions proved to differ from new MS lesions. This led to a prediction model with a high discriminating power. Careful assessment of the presence of punctate T2 lesions, cortical grey matter involvement, focal lesion appearance and periventricular localisation allows for an early diagnosis of PML. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation. METHODS: Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters. We tested the association with PML for each characteristic and constructed a multivariable prediction model which we analysed using a receiver operating characteristic (ROC) curve. RESULTS: Presence of punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localisation were associated with new MS lesions. In the multivariable model, punctate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localisation predict for new MS lesions (area under the curve: 0.988, 95% CI 0.977 to 1.0, sensitivity: 100%, specificity: 80.6%). INTERPRETATION: The MRI characteristics of asymptomatic natalizumab-associated PML lesions proved to differ from new MS lesions. This led to a prediction model with a high discriminating power. Careful assessment of the presence of punctate T2 lesions, cortical grey matter involvement, focal lesion appearance and periventricular localisation allows for an early diagnosis of PML. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Matteo Paoletti; Shaun Ivan Muzic; Francesca Marchetti; Lisa Maria Farina; Stefano Bastianello; Anna Pichiecchio Journal: Radiol Med Date: 2021-01-24 Impact factor: 3.469
Authors: Robbert-Jan Gieselbach; Annemarie H Muller-Hansma; Martijn T Wijburg; Marjolein S de Bruin-Weller; Bob W van Oosten; Dennis J Nieuwkamp; Frank E Coenjaerts; Mike P Wattjes; Jean-Luc Murk Journal: J Neurol Date: 2017-05-23 Impact factor: 4.849
Authors: Martijn T Wijburg; Iris Kleerekooper; Birgit I Lissenberg-Witte; Marlieke de Vos; Clemens Warnke; Bernard M J Uitdehaag; Frederik Barkhof; Joep Killestein; Mike P Wattjes Journal: JAMA Neurol Date: 2018-07-01 Impact factor: 18.302
Authors: Kedar R Mahajan; Moein Amin; Matthew Poturalski; Jonathan Lee; Danielle Herman; Yufan Zheng; Caroline Androjna; Mark Howell; Robert J Fox; Bruce D Trapp; Stephen E Jones; Kunio Nakamura; Daniel Ontaneda Journal: Mult Scler Date: 2021-03-22 Impact factor: 5.855