Postinfectious inflammatory disorders Subgroups based on prospective follow-up E. Marchioni, MD; S. Ravaglia, MD, PhD; G. Piccolo, MD; M. Furione, MD; E. Zardini, BS; D. Franciotta, MD; E. Alfonsi, MD; L. Minoli, MD; A. Romani, MD; A. Todeschini, MD; C. Uggetti, MD; E. Tavazzi, MD; and M. Ceroni, MD Abstract—Background: Acute disseminated encephalomyelitis (ADEM) refers to a monophasic acute multifocal inflam- matory CNS disease. However, both relapsing and site-restricted variants, possibly associated with peripheral nervous system (PNS) involvement, are also observed, and a systematic classification is lacking. Objective: To describe a cohort of postinfectious ADEM patients, to propose a classification based on clinical and instrumental features, and to identify subgroups of patients with different prognostic factors. Methods: Inpatients of a Neurologic and Infectious Disease Clinic affected by postinfectious 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%), encephalomyeloradiculoneuri- tis (26.7%), and myeloradiculoneuritis (16.7%). Thirty patients (50%) had a favorable outcome. Fifteen patients (25%) showed a relapsing course. Poor outcome was related with older age at onset, female gender, elevated CSF proteins, and spinal cord and PNS involvement. All but two 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 prevalence of “atypical variants” was found in this series, with site-restricted damage or additional peripheral nervous system (PNS) involvement. Prognosis and response to steroids were generally good, except for some patient subgroups. In patients with PNS involvement and steroid failure, a favorable effect of IV immunoglobulin was observed. NEUROLOGY 2005;65:1057–1065 Acute disseminated encephalomyelitis (ADEM) cur- rently refers to a monophasic disease characterized by postinfectious multifocal CNS involvement 1 not directly caused by a known infective agent. This widely adopted definition is now somewhat inade- quate, as both relapsing and site-restricted disease variants, which share the same antecedent events and comparable laboratory features of classic ADEM, have long been recognized. 2,3 In particular, cases the differential diagnosis between multiple sclerosis (MS), Devic neuromyelitis optica, and CNS vasculitis could be difficult and reached just through clinical, neuroimaging, and laboratory findings. 4,5 Co- occurrence of ADEM with peripheral nervous system (PNS) involvement, mainly with features of polyra- diculoneuropathy, has also been reported. 6,7 As the ADEM clinical spectrum is heterogeneous, a tenta- tive subdivision in distinct patient subgroups may predict a therapeutic outcome. We describe the clini- cal and laboratory findings in a large sample of patients presenting with ADEM features during a long-term follow-up. Methods. Patients consecutively admitted to our institute be- tween January 1996 and December 2001 due to acute or subacute onset of a CNS or CNS + PNS syndrome, occurring within 30 days from a systemic infection or vaccination, were submitted to clini- cal and extensive laboratory workup. Disseminated as well as site-restricted variants have been considered for inclusion in our study. Criteria for inclusion were adopted considering the defini- tion of classic ADEM, 3 as well as of “site-restricted” variants (my- elitis, cerebellitis, optic neuritis, and brainstem encephalitis). 2,3 Though presenting with “classic” or “site-restricted” ADEM fea- tures, patients with a previous diagnosis of an inflammatory CNS disease were excluded from the study. Patients with a clinical history or laboratory investigations suggestive of systemic autoim- mune disorders and vasculitis were also excluded. Clinical assess- ment included recording of the prodromic infectious event with its etiology, when available, and of the time interval between the infectious prodrome and the onset of the neurologic symptoms. Baseline and early repeated neurologic examination were per- formed, and clinical features at the time of maximum worsening were recorded, along with assessment of functional impairment using the Scripps Neurologic Scale (SNS). 8 Clinical and functional records were taken by members of the same neurologic team at least every 2 weeks until the achievement of a stable neurologic improvement (at least 1 month of steady neurologic status), then every 3 months over at least 2-year follow-up period or as soon as possible in case of relapse. According to Poser, 4 patients who relapsed were classified as recurrent disseminated enceph- alomyelitis (R-DEM) or multiphasic disseminated encephalomy- elitis (M-DEM). Patients who satisfied inclusion criteria and did not present systemic contraindications early received IV steroids (6- methylprednisolone [6-MP], 500 to1,000 mg daily, depending on the patient’s age, older or younger than age 65) until a maximum From the Institute of Neurology IRCCS “C. Mondino,” (Drs. Marchioni, Ravaglia, Piccolo, Franciotta Alfonsi, Romani, Todeschini, Uggetti, and Tavazzi, E. Zardini), University of Pavia, Infectious Diseases Clinic (Dr. Minoli), Policlinico San Matteo, and Laboratory of Virology (Dr. Furione), Policlinico San Matteo, Pavia, and Department of Neurology (Dr. Ceroni), Policlinico di Monza, Monza, Italy. Disclosure: The authors report no conflicts of interest. Received February 9, 2005. Accepted in final form June 21, 2005. Address correspondence and reprint requests to Dr. E. Marchioni, Institute of Neurology IRCCS “C. Mondino,” University of Pavia, Via Mondino 2, 27100 Pavia, Italy; e-mail: enrico.marchioni@mondino.it Copyright © 2005 by AAN Enterprises, Inc. 1057