Article Figures & Data
Figures
- Fig 1.
Infratentorial natalizumab-associated PML. Axial FLAIR (A and B) images of a patient demonstrating extensive hyperintense signal involving the cerebellum, middle cerebellar peduncle, and pons. This had progressed from prior imaging. Note minimal mass effect. Postadministration of gadolinium, there is no enhancement demonstrated (C).
- Fig 2.
A typical example of natalizumab-associated PML. There is a FLAIR hyperintense lesion involving the right precentral gyrus (A, arrows) abutting the cortex. The susceptibility-weighted sequence reveals a hypointense rim involving the subcortical U-fibers adjacent to the PML lesion (B, arrows). Reprinted from Hodel et al.34
- Fig 3.
Axial T2-weighted and contrast-enhanced T1-weighted images showing imaging signs suggestive of natalizumab-associated PML (A and B) with follow-up imaging post-withdrawal of medication suggestive of PML–immune reconstitution inflammatory syndrome. This patient demonstrates the most frequent pattern of PML IRIS, with patchy contrast enhancement in the border of the lesion (arrows). Reproduced from Wattjes et al39 with permission from BMJ Publishing Group Ltd.
- Fig 4.
DIR (A), PSIR (B), and FLAIR (C) images from a single patient with MS at the same section location. An intracortical lesion is evident in the left parietal area. Also, note the excellent overall delineation of the gray-white matter border on PSIR. Reprinted from Nelson et al.100
Tables
Clinical Indication Frequency of Imaging Imaging Protocol RRMS, routine surveillance Annually for at least the first 2 or 3 years after starting therapy or switching DMT T2-weighted and contrast-enhanced T1-weighted Higher risk patients (positive for JC virus serum antibodies) with >24 mo of NTZ exposure Every 3–6 months T2WI, T2 FLAIR, DWI, SWI (if indicated) Low risk of PML (negative for JC virus serum antibodies) Annually T2WI, T2 FLAIR, DWI, SWI (if indicated) Patients at high risk of developing opportunistic infections who are switching DMT MRI when the current treatment is discontinued and 3–6 months after the new treatment is started T2WI, T2 FLAIR, DWI, SWI (if indicated) Patients who switch from NTZ to other therapeutics (including fingolimod, alemtuzumab, and dimethyl fumarate) Enhanced pharmacovigilance, including brain MRI every 3–4 mo for up to 12 mo T2WI, T2 FLAIR, DWI, SWI (if indicated) Patients who require enhanced pharmacovigilance for other reasons Every 3–6 mo As indicated Note:—RRMS indicates relapsing-remitting MS.
Risk Factors for PML Development in Patients Treated with NTZ Duration of Therapy ≥24 Months Risk stratification of patients High risk Prior immunosuppressive therapy Evidence of JCV antibody seropositivity Presence of anti-JCV antibodies Increased treatment duration, especially beyond 2 yr Immunosuppressant use prior to receiving NTZ High JCV titers Low risk Patients negative for anti-JCV antibody (risk is <0.09/1000) Methods of reducing risk All patients receiving NTZ should be screened for previous JCV infection Serologic testing for patients negative for JCV every 6 mo Patients positive for JCV who have been treated with NTZ for >2 yr should be switched to another second-line therapy Increased frequency of imaging surveillance for high-risk patients (eg, every 3–4 mo) Comparison of surveillance images with previous MR imaging Note:—JCV indicates John Cunningham virus.
Features Location Subcortical white matter U-fibers Predilection for frontal lobe > occipital lobe > parietal lobe Size Small, <3 cm when asymptomatic In symptomatic patients, lesions are often large (>3 cm) Morphology Punctate lesions often identified in asymptomatic PML Symptomatic PML typically demonstrates more confluent and diffuse lesions Microcysts No associated edema or mass effect T1WI and T2WI FLAIR hyperintensity with corresponding T1 hypointense lesions T1 hypointesity is less pronounced in asymptomatic PML DWI Hyperintensity on DWI T1 postcontrast 30% will demonstrate linear or punctate enhancing lesions; if nodular or rim enhancement is present, active MS plaque or IRIS should be considered SWI Low signal intensity in U-fibers Differential diagnosis MS plaque Acute disseminated encephalomyelitis Tumefactive lesion Ischemic changes Posterior reversible encephalopathy syndrome
