Background: Acute disseminated encephalomyelitis (AD- EM)refers to a monophasic acute multifocal inflammatory CNS disease. However, both relapsing and site-restricted variants, possibly associated with peripheral nervous system (PNS) involvement, are also observed, and a systematic classifi cation is lacking. Objective: To describe a cohort of postinfectious ADEM patien ts, to propose a classification based on clinical and instrumental features, and to identify subgroups of patients with different prognostic factors. Methods: I npatients of a Neurologic and Infectious Disease Clinic affected by postinfectio us CNS syndrome consecutively admitted over 5 years were studied. Results: Of 75 patients enrolled, 60 fulfilled criteria for ADEM after follow-up lasting from 24 months to 7 years. Based on lesion distribution, patients were classified as encephalitis (20%),myelitis (23.3%), encephalomyelitis (13.3%), encephalomye loradiculoneuritis (26.7%), and myeloradiculoneuritis (16.7%). Thirty patients (50%) had a favorable outcome. Fifteen patients (25%) showed a relapsing cour se. Poor outcome was related with older age at onset, female gender, elevated CS F proteins, and spinal cord and PNS involvement. All but two patients received h igh-dose steroids as first-line treatment, with a positive response in 39 (67 %). Ten of 19 nonresponders (53%)benefited from high-dose IV immunoglobulin; 9 of 10 had PNS involvement. The data were not controlled. Conclusions: A high p revalence of “atypical variants”was found in this series, with site-restricte d damage or additional peripheral nervous system (PNS) involvement. Prognosis an d response to steroids were generally good, except for some patient subgroups. I n patients with PNS involvement and steroid failure, a favorable effect of IV im munoglobulin was observed. Background: Acute disseminated encephalomyelitis (AD-EM) refers to a monophasic acute multifocal inflammatory CNS disease. However, both relapsing and site-restricted variants, possibly associated with peripheral nervous system (PNS) involvement, are also observed, and a systematic classifi cation is lacking. Objective: To describe a cohort of postinfectious ADEM patien ts, to propose a classification based on clinical and instrumental features, and to identify subgroups of patients with different prognostic factors. Methods: I npatients of a Neurologic and Infectious Disease Clinic affected by Results: Of 75 patients enrolled, 60 fulfilled criteria for ADEM after follow-up lasting from 24 months to 7 years. Based on lesion distribution, patients were classified as encephalitis (20%) , myelitis (23.3%), encephalomyelitis (13.3%), encephalomye loradiculoneuritis (26.7%), and myeloradiculoneuritis (16.7%). Thirt Fifteen patients (25%) had a relapsing cour se. Poor outcome was related with older age at onset, female gender, elevated CS Foproteins, and spinal cord and PNS involvement. All but Two of the patients received high-dose steroids as first-line treatment, with a positive response in 39 (67%). Ten of 19 nonresponders (53%) benefited from high-dose IV immunoglobulin; 9 of 10 had PNS involvement. The data were not controlled. Conclusions: A high p revalence of “atypical variants” was found in this series, with site-restricting d damage or additional peripheral nervous system (PNS) involvement. Prognosis an d response to steroids were generally good, except for some patient subgroups. I n patients with PNS involvement and steroid failure, a favorable effect of IV im munoglobulin was observed.