Transient Punctuate Gadolinium-Enhancing Lesions Preceding Natalizumab-Associated Progressive Multifocal Leukoencephalopathy (PML) (P2.246)

BACKGROUND PML is a rare complication of natalizumab therapy. The diagnosis relies mainly on the detection of the JCV in CSF and on MRI. Large T2 hyperintense and T1 hypointense lesions are typically observed. Punctuate gadolinium-enhancement in vicinity of the T2 hyperintense lesions, is observed in 40% of cases, in the early phase of PML (i.e. when T2 hyperintensity is already present) or later on. We report a patient with multiple sclerosis (MS) developing PML under natalizumab treatment where transient punctuate gadolinium-enhancement preceded PML-related T2 hyperintensities. CASE REPORT A 52-year-old woman developed PML after 43 months of natalizumab therapy. Routine brain MRI at 41 months of natalizumab therapy showed frontal, parietal and thalamic punctuate gadolinium-enhancement in the absence of T2 hyperintensity suggestive of PML (i.e. with stable MS-related T2 lesions). The PCR for JCV in CSF was negative. MRI performed 6 weeks later showed disappearence of the gadolinium-enhancing lesions, still in absence of new T2 hyperintense lesions. Clinical examination was unchanged. Natalizumab was administrated 14 days after this last MRI. Three weeks later, cognitive dysfunction and ataxia occurred progressively. MRI showed new T2 hyperintense lesions without gadolinium-enhancement. PCR for JCV in the CSF was positive DISCUSSION Conditions showing gadolinium-enhancing MRI lesions in MS patients under natalizumab include new demyelinating MS lesions, PML, IRIS, or primary CNS lymphoma. In our patient, the clinical course and the radiological findings are in favor of inflammatory PML. Interpretation of the transient gadolinium enhanced lesions is not evident. We suppose than disappearance of initial enhancing lesions reflecting variation blood-brain permeability CONCLUSION This case illustrates that gadolinium-enhancing lesions, even when transient and in the absence of T2 signal changes, might be the first manifestation of PML infection. We recommend gadolinium-enhanced T1-weighted imaging in addition to other MRI sequences to detect PML in MS patients under natalizumab. Disclosure: Dr. Castelnovo has nothing to disclose. Dr. Thouvenot has received personal compensation for activities with Teva Neuroscience as a scientific advisory board member, and with Biogen Idec and Novartis as a speaker. Dr. Renard has nothing to disclose. Dr. Taieb has nothing to disclose.