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Updated: Mar 16, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance
Martijn T Wijburg1, Birgit I Witte2, Anke Vennegoor3
1Department 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.
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.
Insights
Differentiating progressive multifocal leukoencephalopathy (PML) from new multiple sclerosis (MS) lesions on MRI is crucial. Specific MRI features like punctate T2 lesions and cortical involvement help distinguish PML, enabling early diagnosis in natalizumab-treated patients.
Area of Science:
- Neurology
- Radiology
- Immunology
Background:
- Differentiating progressive multifocal leukoencephalopathy (PML) from new multiple sclerosis (MS) lesions on brain MRI is clinically significant, especially during natalizumab pharmacovigilance.
- Asymptomatic lesions pose a diagnostic challenge, necessitating reliable MRI markers for accurate identification.
Purpose of the Study:
- To define specific MRI characteristics that can aid in differentiating asymptomatic PML from new MS lesions.
- To develop a predictive model for early PML diagnosis in patients treated with natalizumab.
Main Methods:
- Retrospective analysis of brain MRIs from natalizumab-treated patients with asymptomatic PML (n=21) or new MS lesions (n=20).
- Evaluation of newly detected lesions by four blinded raters for specific characteristics.
- Construction of a multivariable prediction model and analysis using receiver operating characteristic (ROC) curves.
Main Results:
- PML lesions were associated with punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined borders, larger size (>3 cm), and contrast enhancement.
- New MS lesions were associated with focal appearance and periventricular localization.
- The multivariable model identified punctate T2 lesions and cortical grey matter involvement as predictors for PML, and focal appearance and periventricular localization for MS lesions (AUC: 0.988).
Conclusions:
- Asymptomatic natalizumab-associated PML lesions exhibit distinct MRI characteristics compared to new MS lesions.
- A prediction model incorporating these MRI features demonstrates high discriminating power for early PML diagnosis.
- Careful assessment of specific MRI findings enables early differentiation and diagnosis of PML.
