ObjectivesWe describe an atypical delayed neurologic recovery from coma and unresponsive wakefulness syndrome (i.e., persistent vegetative state) in a patient with severe drug-induced toxic leukoencephalopathy (presumably due to synthetic cannabinoid intake).MethodsThe patient underwent standardized behavioral and multimodal neuroimaging assessments to monitor clinical evolution and brain function over a 5-month period after presumed intoxication.ResultsA progressive clinical recovery was observed, from an initial state of coma to emergence from a minimally conscious state after 2 months. Despite the stability of extensive white matter lesions documented by CT and structural MRI, fluorodeoxyglucose PET showed partial recovery of cortical metabolism after 5 months.DiscussionThis case report illustrates that the temporal dynamics of recovery from toxic acute leukoencephalopathy may be atypical and delayed. Multimodal monitoring with repeated behavioral and functional neuroimaging assessments tends to improve the prognosis reliability, while early prognosis based on structural damage may result in misleading statements.