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, immunemediated/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 immunemediated/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. WHAT'S KNOWN ON THIS SUBJECT:Encephalitis is a serious and disabling condition. There are infectious and immune-mediated causes of encephalitis, but many cases remain undiagnosed. WHAT THIS STUDY ADDS:This large single-center study on childhood encephalitis provides insight into the relative frequency and clinicoradiologic phenotypes of infectious, autoantibody-associated, and unknown encephalitis. Risk factors for an abnormal outcome are also defined. 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing. [6][7][8] We studied clinical and radiologic features, serum autoantibodies in acute archived samples, and longterm outcomes in a large ret...

Parechovirus Encephalitis and Neurodevelopmental Outcomes

“…Additionally, diffusion restriction on MRI has been shown to be an independent risk factor for adverse outcomes of childhood encephalitis generally. 53,54 Furthermore, neurologic deficits (especially subtle deficits) will manifest variably during this dynamic period of neurodevelopment in early childhood. There is a need for longer-term follow-up of the broad spectrum of HPeV CNS disease, stratified by genotype where it is known, to definitively determine the connection between HPeV CNS infection and long-term neurologic outcome.…”

Post-infectious encephalomyelitis in an orthopedic surgeon with motor and cognitive impairment following Campylobacter gastroenteritis with complete recovery

“…A favorable outcome, however, is unusual for antibody mediated immunologic encephalomyelitis. [17][18][19][20][21][22] To our knowledge, this is the first known reported occurrence of Campylobacter associated ADEM in the United States and documents the return of full cognitive and motor function in a surgeon.…”

Commentary: Mycoplasma pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion: Report of two pediatric cases and a comprehensive literature review

“…Recently, anti-NMDAR encephalitis, best characterized autoimmune encephalitis, has been reported [52][53][54] . It is different from MERS because of positive anti-NMDAR antibody in serum/CSF, severe clinical symptoms, older age (>12 years), female prevalence, tumor association, MRI findings (brain regions other than CC and infrequently spinal cord), relatively worse outcome (4 % mortality), recurrence of the disease, and need for immunosuppressive therapy and long hospitalization 52 .…”

“…Some of the patients with anti-NMDAR encephalitis were associated with infection, including M.pneumoniae 52 . Anti-VGKC antibody or anti-NMDAR antibody or both were found in children with M.pneumoniae-associated encephalitis 54 , suggesting that anti-VGKC-complex antibody and anti-NMDAR antibody could be induced as part of the immune response to M.pneumoniae. In anti-NMDAR encephalitis, antibody titers in CSF, and to a lesser extent in serum, were correlated with clinical outcome 53 .…”