Acute Disseminated Encephalomyelitis in Childhood: Epidemiologic, Clinical and Laboratory Feature

John A. D. Leake, MD, MPH; Salvatore Albani, MD, PhD; Annie S. Kao, MS, MPH; Melvin O. Senac, MD; Glenn F. Billman, MD; Mark P. Nespeca, MD; Amy D. Paulino, BS; Eileen R. Quintela, BS; Mark H. Sawyer, MD; John S. Bradley, MD


Pediatr Infect Dis J. 2004;23(8) 

In This Article


We reviewed all cases of ADEM diagnosed among persons age < 20 years evaluated at the Children's Hospital and Health Center, the University of California, San Diego Medical Center and Kaiser-Permanente San Diego Hospital from 1991 to 2000. Most children and adolescents with serious acute neurologic abnormalities occurring in San Diego County are referred to these facilities. Medical records of all cases were examined, and parents of children (1998-2000) were interviewed. Cases were ascertained via database search of International Classification of Diseases, 9th revision, codes 052.0, 055.0, 136.9, 323.5, 323.6, 323.8 and 323.9; systematic review of radiology reports; and prospective identification by study participants. We collected standardized data on patient demographics, clinical course, therapy, laboratory testing, radiographic findings and outpatient follow-up. Risk factor data included recent infections and vaccinations, contact with ill persons including those with a rash, cold sores among patients or close contacts, animal and insect exposures, travel and head trauma. Incidence rates were calculated using annual numbers of newly diagnosed ADEM cases occurring among full time San Diego County residents and age- and race-specific population denominators (2000 census data). We assessed the geographic distribution of ADEM by standardizing incidence per 100,000 persons per ZIP code and by comparing cases with population density (ZIP code population per 1000 acres). IRB approval was granted for this study.

ADEM cases were defined as persons age < 20 years evaluated at a study site during the study period with acute or subacute onset of abnormal neurologic signs or symptoms (weakness, sensory changes, ataxia or decreased level of consciousness) and imaging evidence of CNS demyelination not clearly explained by another etiology (eg, neoplastic, metabolic, vascular). Cases were excluded if they had no magnetic resonance (MR) or computerized tomography (CT) evidence of demyelination or had only focal cerebellar demyelination. We defined recurrent ADEM as 2 distinct clinical and radiographic episodes of demyelination within a 12-month period with complete resolution of symptoms. Persons initially diagnosed with ADEM who subsequently developed MS were all diagnosed with the latter by pediatric neurologists and had 3 or more clinically and radiographically distinct episodes of demyelination during a period of ≥12 months. Neurologic outcome was ascertained with follow-up reports by pediatric neurologists and primary care providers; the duration of follow-up was determined by the clinical judgment of the physicians providing care.

Available CSF specimens collected from ADEM patients during 1998-2000 were compared with 2 control groups of CSF specimens obtained during the same period from subjects age < 20 years. The first CSF control group was randomly selected among EV positive specimens confirmed by polymerase chain reaction (PCR); this group was chosen to represent the cytokine activity present during active viral encephalomyelitis. The second control group was randomly selected from CSF specimens without pleocytosis, defined as < 10 white blood cells/mm3 of CSF and CSF culture negative for pathogenic bacteria. These specimens were collected from patients evaluated for fever without localizing signs in the emergency department, to serve as surrogates for healthy persons (negative controls). All lumbar punctures were performed for routine clinical indications before therapy with antibiotics or corticosteroids.

We measured CSF IL-12, IFN-γ and IL-10 concentrations using an enzyme-linked immunosorbent assay (BD PharMingen, San Diego, CA). Investigators performing the assays were blinded to the case or control status of the specimens. One specimen per patient was used for analysis. All specimens were kept at 4°C for < 7 days and then frozen at -70°C until assay. Intraexperimental variation was < 10%, and all samples were normalized to a standard positive control.

Data were analyzed using Epi Info version 6.04. Analysis of variance was used for intergroup comparison of CSF cytokine levels. Fisher exact test 2-tailed P values were calculated for cell values ≤5. Geographic distribution of case households was mapped with global positioning system software (ArcView version 3.2; ArcView, Redlands, CA).


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