Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

Abstract

BACKGROUND AND OBJECTIVES:

Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.

METHODS:

By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis).

RESULTS:

An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission.

CONCLUSIONS:

We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority.

• Authors: Sekhar C Pillai, Yael Hacohen, Esther Tantsis, Kristina Prelog, Vera Merheb, Alison Kesson, Elizabeth Barnes, Deepak Gill, Richard Webster, Manoj Menezes, Simone Ardern-Holmes, Sachin Gupta, Peter Procopis, Christopher Troedson, Jayne Antony, Robert A Ouvrier, Yann Polfrit, Nicholas W S Davies, Patrick Waters, Bethan Lang, Ming J Lim, Fabienne Brilot, Angela Vincent, Russell C Dale
• Journal: Pediatrics (Pediatrics) Vol. 135 Issue 4 Pg. e974-84 (Apr 2015) ISSN: 1098-4275 [Electronic] United States
• PMID: 25802349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by the American Academy of Pediatrics.

Chemical References

• Autoantibodies
• Autoantigens
• Nerve Tissue Proteins
• Potassium Channels, Voltage-Gated
• Receptors, N-Methyl-D-Aspartate

Topics

• Adolescent
• Autoantibodies (blood)
• Autoantigens (immunology)
• Autoimmune Diseases (diagnosis, epidemiology, immunology)
• Brain (immunology, pathology)
• Child
• Child, Preschool
• Cross-Sectional Studies
• Disability Evaluation
• Encephalitis (diagnosis, epidemiology, immunology)
• Female
• Follow-Up Studies
• Humans
• Infant
• Magnetic Resonance Imaging
• Male
• Nerve Tissue Proteins (immunology)
• Outcome Assessment, Health Care
• Potassium Channels, Voltage-Gated (immunology)
• Receptors, N-Methyl-D-Aspartate (immunology)
• Retrospective Studies