Clinical–radiological features of methotrexate-induced subacute leukoencephalopathy in patients with acute lymphoblastic leukemia: 'Panda eye sign' on diffusion weighted-magnetic resonance imaging

Background and Purpose: Subacute leukoencephalopathy in ALL is a rare complication after high dose methotrexate (HDMTX) administration and recognizing this self-remitting entity has important therapeutic implications. We did a retrospective study to evaluate the role of magnetic resonance imaging (MRI) in diagnosing this entity and asses the incremental value of diffusion weighted MR (DW-MRI). Materials and Methods: We did a retrospective analysis of adult ALL patients being treated with the modified Berlin-Frankfurt-Münster (BFM)-90 protocol at our center between January 2014 and January 2015 and identified those who developed neurotoxicity after HDMTX. All these patients underwent a contrast enhanced CT and contrast enhanced MRI of brain with DW-MRI within 48 hours of presentation. Results: Eleven patients were identified from a cohort of 239 patients (~5%). They presented with focal neurological deficits within ~14 days after HDMTX that resolved completely with conservative measures. The CT scans were normal in all these patients. A consistent finding seen in all these cases was the occurrence of restricted diffusion in the region of the centrum semiovale on DW-MRI. On diffusion maps, symmetrical areas of hyperintensity resembled Panda eyes and mean apparent diffusion coefficient cut-off of our series was 0.000453 x 10–3 +/- 0.000120 cm2/sec. Conclusion: CT brain and conventional MR imaging have no significant role to play in diagnosing this entity however restricted diffusion in the centrum semiovale is a consistent imaging finding and the 'panda eye sign' as seen on DW imaging can be considered diagnostic for methotrexate induced subacute leukoencephalopathy and this sign can help in timely establishment of the diagnosis and appropriate management.