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Of 101 included patients, the 4 subgroups of >6 were the following: chemotherapy (n = 35), opiates (n = 19), acute hepatic encephalopathy (n = 14), and immunosuppressants (n = 11). Other causes (n = 22 total) notably included carbon monoxide (n = 3) metronidazole (n = 2), and uremia (n = 1). Acute hepatic/hyperammonemic encephalopathy clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91. Acute toxic leukoencephalopathy is an imaging appearance that can arise from various etiologies, with potentially reversible reduced diffusion predominately affecting the periventricular WM. Given the shared DWI appearance among this heterogeneous array of etiologies, their outcomes may differ. Thus, the neurologic symptoms completely resolved in 36%, while severe outcomes occurred in 23%. The clinical outcome was most severe with chemotherapy-related ATL.