| Neurotoxicity occurring within 21 days of intravenous or intrathecal methotrexate with 3 characteristics that all need to be fulfilled: |
| 1. New onset of one or more of paresis or paralysis; movement disorder or bilateral weakness; aphasia or dysarthria; altered mental status including consciousness (e.g., somnolence, confusion, disorientation, and emotional lability); and/or seizures with at least one of the other symptoms. |
| 2. Either characteristic, but often transient, white matter changes indicating leukoencephalopathy on MRI or a characteristic clinical course with waxing and waning symptoms usually leading to complete (sometimes partial) resolution within a week. |
| 3. No other identifiable cause. |
| Characteristic oval-shaped lesions of the subcortical white matter (mostly frontal or parietal) on MRI are best seen on diffusion-weighted (hyperintense) or apparent diffusion coefficient (hypointense) images. Can be graded 1-5 according to CTCAEv4.03 for encephalopathy. |
| Neurotoxicity occurring within 21 days of intravenous or intrathecal methotrexate with 3 characteristics that all need to be fulfilled: |
| 1. New onset of one or more of paresis or paralysis; movement disorder or bilateral weakness; aphasia or dysarthria; altered mental status including consciousness (e.g., somnolence, confusion, disorientation, and emotional lability); and/or seizures with at least one of the other symptoms. |
| 2. Either characteristic, but often transient, white matter changes indicating leukoencephalopathy on MRI or a characteristic clinical course with waxing and waning symptoms usually leading to complete (sometimes partial) resolution within a week. |
| 3. No other identifiable cause. |
| Characteristic oval-shaped lesions of the subcortical white matter (mostly frontal or parietal) on MRI are best seen on diffusion-weighted (hyperintense) or apparent diffusion coefficient (hypointense) images. Can be graded 1-5 according to CTCAEv4.03 for encephalopathy. |
This consensus definition was developed by the Ponte de Legno international childhood ALL group to assist clinicians in differentiating methotrexate -SLS from similar neurotoxicities (eg, posterior reversible encephalopathy syndrome) and to enable reliable comparisons of incidence of methotrexate -SLS between different trials.