Introduction Cocaine abuse may be complicated by degenerative central nervous system (CNS) disorders such as leukoencephalopathy. The possibly synergistic role of adulterants, like levamisole, is also currently debated. We describe a recent case of massive CNS injury consistent with a Susac syndrome in a heavy chronic cocaine abuser. We discuss the possible combined role of cocaine-levamisole exposure in the pathogenesis of CNS lesions. Case observation A 22-year-old man, who was heavily abusing from cannabis (> 10 yrs) and cocaine (> 5 yrs), was admitted with headache, ataxia, and right-sided paresthesias. CSF analysis revealed hyperproteinorrachia (2,49 g/l) and brain MRI showed multiple small foci of T2/FLAIR hypersignal intensity within the white matter and the grey nuclei, mainly corpus callosum consistent with an inflammatory process. The diagnosis of multiple sclerosis was evoked. Despite steroids pulse therapy, the neurological condition rapidly worsened (encephalopathy, quadriparesia). Occlusion of branch retinal arteries was noted at fundoscopy. Follow-up brain MR examinations were consistent with a Susac syndrome (hyperintense lesions of the central fibres of the corpus callosum). Hearing loss could not be demonstrated at brainstem auditory evoked potentials. Despite maximal immunosuppressive therapy (steroids, cyclophosphamide), the patient remained in a minimally conscious state and he died three months later from septic complications. In order to explore toxic etiologies, the detection of cocaine (C), benzoylecgonine (B) and levamisole (L) was obtained in a hair sample. Starting from the root, the following concentrations were found (pg/mg): 0-1 cm, C 49, B Discussion Susac syndrome is a rare neurological disorder that is characterized by the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss. Lesions typically involve the central fibres of the corpus callosum, with a relative sparing of the periphery. This is an autoimmune microangiopathy triggered by an unknown antigen, with a large female prevalence. The role of some etiologic agents is still debated: viral infections, idiopathic vasospasm... Toxic causes have not been specifically investigated. Among them, the role of cocaine, mainly with levamisole adulteration is debated. Cocaine use has been less frequently associated with leukoencephalopathy than heroin, and widespread confluent vacuolar degeneration of the white matter is typically observed. On the other hand, levamisole exposure alone has been reported to induce in some individuals multifocal and symmetrical demyelinating changes, disseminated mostly in subcortical white matter and periventricular areas. In the present observation, adulteration of cocaine by levamisole was demonstrated by hair testing. However, the MRI pattern appeared different from that of multifocal inflammatory leukoencephalopathy. Triggering Susac-like syndrome by toxic agents such as the combination of cocaine + levamisole has yet not been reported in the literature, but is suggested by the herein reported observation.