High Acute Lymphoblastic Leukemia is one of the most common childhood malignancy, which is treated with high dose of intra thecal methotrexate. The drug has a poor oral bioavailability but has the ability to cross the blood brain barrier. This property is utilized in cases where disease has spread to involve CNS and specifically targets the leukemic cells. In addition, high doses of MTX not only thwart CNS recurrence but also hematologic relapses. MTX is usually associated with neurotoxicity manifesting as acute, sub-acute or chronic presentation and involves periventricular deep white matter region. Diffusion weighted magnetic resonance imaging (DW-MRI) is habitually used in clinical practice to recognize acute stroke and also to differentiate acute stroke from non-stroke like conditions.