Universität zu Köln

Wijburg, Martijn T., Kleerekooper, Iris ORCID: 0000-0001-6456-9034, Lissenberg-Witte, Birgit I., de Vos, Marlieke, Warnke, Clemens, Uitdehaag, Bernard M. J., Barkhof, Frederik ORCID: 0000-0003-3543-3706, Killestein, Joep and Wattjes, Mike P. (2018). Association of Progressive Multifocal Leukoencephalopathy Lesion Volume With JC Virus Polymerase Chain Reaction Results in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis. JAMA Neurol., 75 (7). S. 827 - 834. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6157

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Abstract

IMPORTANCE The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF. OBJECTIVE To investigate the association of PML lesion characteristics on MRI with both qualitative and quantitative JCV PCR results in CSF of patients with NTZ-PML. DESIGN, SETTING AND PARTICIPANTS This was a retrospective, cross-sectional study conducted from January 2007 to December 2014 in patients considered to have NTZ-PML based on a set of predefined criteria. Follow-up was at least 6 months. Data of patients from the Dutch-Belgian NTZ-PML cohort and patients treated at multiple medical centers in Belgium and the Netherlands and selected for research purposes were included as a convenience sample. MAIN OUTCOMES AND MEASURES Brain MRI scans were analyzed for PML lesion volume, location, dissemination, and signs of inflammation. Associations of the qualitative and quantitative CSF JCV PCR results with PML MRI characteristics were calculated. RESULTS Of the 73 patients screened, 56 were included (37 were women). At inclusion, 9 patients (16.1%) had undetectable JCV DNA in CSF. Patients with a positive PCR had larger total PML lesion volumes than those with undetectable JCV DNA (median volume, 22.9 mL; interquartile range, 9.2-60.4 mL vs median volume, 6.7 mL; interquartile range, 4.9-14.7 mL; P = .008), and logistic regression showed that a lower PML lesion volume significantly increased the probability for undetectable JCV DNA. There was a positive correlation between PML lesion volume and JCV copy numbers (Spearman rho, 0.32; P = .03). Progressive multifocal leukoencephalopathy lesion volume was higher in patients with PML symptoms and in patients with more widespread lesion dissemination. No association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms. CONCLUSIONS AND RELEVANCE Smaller NTZ-PML lesions are associated with a higher likelihood of undetectable JCV DNA in CSF. This may preclude a formal diagnosis of PML and can complicate patient treatment in patients with small MRI lesions highly suggestive of PML detected early through pharmacovigilance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wijburg, Martijn T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleerekooper, Iris UNSPECIFIED orcid.org/0000-0001-6456-9034 UNSPECIFIED Lissenberg-Witte, Birgit I. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Vos, Marlieke UNSPECIFIED UNSPECIFIED UNSPECIFIED Warnke, Clemens UNSPECIFIED UNSPECIFIED UNSPECIFIED Uitdehaag, Bernard M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barkhof, Frederik UNSPECIFIED orcid.org/0000-0003-3543-3706 UNSPECIFIED Killestein, Joep UNSPECIFIED UNSPECIFIED UNSPECIFIED Wattjes, Mike P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-180454
DOI:	10.1001/jamaneurol.2018.0094
Journal or Publication Title:	JAMA Neurol.
Volume:	75
Number:	7
Page Range:	S. 827 - 834
Date:	2018
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2168-6157
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MS PATIENTS; ASYMPTOMATIC PML; MRI; PREDICTORS; SURVIVAL; PHARMACOVIGILANCE; RECOMMENDATIONS; GUIDELINES; DIAGNOSIS; OUTCOMES Multiple languages Clinical Neurology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18045