Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with Natalizumab: Diagnostic Precision with MR Imaging

Hodel, Jérôme; Outteryck, Olivier; Dubron, Céline; Dutouquet, Bastien; Benadjaoud, Mohamed Amine; Duhin, E.; Verclytte, Sébastien; Zins, Marc; Luciani, Alain; Rahmouni, Alain; Pruvo, Jean‐Pierre; Vermersch, Patrick; Leclerc, Xavier

doi:10.1148/radiol.2015150673

Cited by 39 publications

(34 citation statements)

References 21 publications

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“…In previous studies, punctiform T2/FLAIR hyperintense lesions in the vicinity of the main PML lesions, also described as ‘milky way appearance’ when being present in high numbers,22 showed to be common in symptomatic and asymptomatic natalizumab-associated PML 21 22 30 33. Punctiform T2 lesions are also seen further away from the main PML lesion, even in the hemisphere contralateral to the main PML lesion, and can have a perivascular distribution pattern suggestive of perivascular inflammation 22 26 30.…”

Section: Discussionmentioning

confidence: 92%

“…Indeed, the recent study by Hodel et al 33 nicely showed that a subcortical lesion location, involving the U fibres, was predictive for asymptomatic natalizumab-associated PML. In contrast, a focal lesion appearance and lesions located in the periventricular white matter were strongly associated with new MS lesions instead of asymptomatic PML, which is not surprising since this type of lesion is one of the well-known stereotype MS lesions included in the MRI diagnostic criteria for MS 31.…”

Section: Discussionmentioning

confidence: 97%

“…A recent study by Hodel et al 33 comparing natalizumab-treated patients with MS without new lesions to patients with asymptomatic natalizumab-associated PML described useful MRI features predictive for asymptomatic PML lesions (DWI hyperintensity and U fibre involvement). In our study, we tried to make one important step further by simulating the real-life pharmacovigilance setting with reference MRI scans and aimed to directly compare the lesion characteristics of new asymptomatic PML lesions and new MS lesions in natalizumab-treated patients with MS. We describe rather conclusive MRI lesion characteristics which can aid in differentiating asymptomatic PML lesions from new MS lesions in a pharmacovigilance setting of natalizumab-treated patients with MS, thereby potentially increasing the chance of an early and specific diagnosis of asymptomatic PML based on brain MRI.…”

Section: Discussionmentioning

confidence: 99%

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MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance

Wijburg

Witte

Vennegoor

et al. 2016

J Neurol Neurosurg Psychiatry

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ObjectiveDifferentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain magnetic resonance imaging (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. MethodsReference and follow-up brain MRI of natalizumab-treated MS patients 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 analyzed using a receiver operating characteristic (ROC) curve. ResultsPresence of punctuate 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 >3cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localization were associated with new MS lesions. In the multivariable model, punctuate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localization predict for new MS lesions (area under the curve: 0.988, 95% CI: 0.977-1.0, sensitivity: 100%, specificity: 80.6%). InterpretationThe 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 punctuate T2 lesions, cortical grey matter involvement, focal lesion appearance, and periventricular localization, allows an early diagnosis of PML.3

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance

Wijburg

Witte

Vennegoor

et al. 2016

J Neurol Neurosurg Psychiatry

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“…In addition, perilesional contrast enhancement around confluent PML-suspicious lesions suggestive of IRIS was detectable (Figure 2). Diffusion weighted MRI did not show intralesional hyperdiffusivity nor signs of restricted diffusion at the edge of the lesions (Figure 3); both of which are considered to be typical of PML [14]. …”

Section: Case Presentationmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy in a Multiple Sclerosis Patient Diagnosed after Switching from Natalizumab to Fingolimod

Sinnecker

Othman

Kühl

et al. 2016

Case Reports in Neurological Medicine

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Background. Natalizumab- (NTZ-) associated progressive multifocal leukoencephalopathy (PML) is a severe and often disabling infectious central nervous system disease that can become evident in multiple sclerosis (MS) patients after NTZ discontinuation. Recently, novel diagnostic biomarkers for the assessment of PML risk in NTZ treated MS patients such as the anti-JC virus antibody index have been reported, and the clinical relevance of milky-way lesions detectable by MRI has been discussed. Case Presentation and Conclusion. We report a MS patient in whom PML was highly suspected solely based on MRI findings after switching from NTZ to fingolimod despite repeatedly negative (ultrasensitive) polymerase chain reaction (PCR) testing for JC virus DNA in cerebrospinal fluid. The PML diagnosis was histopathologically confirmed by brain biopsy. The occurrence of an immune reconstitution inflammatory syndrome (IRIS) during fingolimod therapy, elevated measures of JCV antibody indices, and the relevance of milky-way-like lesions detectable by (7 T) MRI are discussed.

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“…3,4 Awareness of these specific lesion patterns and the use of an adequate MR imaging protocol facilitate an earlier diagnosis of asymptomatic NTZ-PML, associated with a more favorable prognosis.…”

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confidence: 99%

REPLY:

Hodel¹,

Outteryck²,

Verclytte³

et al. 2015

AJNR Am J Neuroradiol

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Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with Natalizumab: Diagnostic Precision with MR Imaging

Abstract: Recognition of the most predictive imaging features and comparison with previous MR imaging data may facilitate the detection of asymptomatic NTZ PML.

Cited by 39 publications

References 21 publications

MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance

MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance

Progressive Multifocal Leukoencephalopathy in a Multiple Sclerosis Patient Diagnosed after Switching from Natalizumab to Fingolimod

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