Abstract & Commentary
The Most Common Cause of Encephalitis?
By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a consultant for Siemens Diagnostic.
Synopsis: Beginning in 2007 the California Encephalitis Project (CEP) found that many cases of encephalitis of unknown etiology were found to be associated with antibodies to N-methyl-D-aspartate receptor (anti-NMDAR). This was identified >4 times as frequently as HSV-1, WNV, or VZV and was the largest single cause of encephalitis in the cohort. 65% of cases of anti-NMDAR encephalitis occurred in patients < 18 years of age and 75% of patients were female.
Source: Gable MS, et al. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012;54:899-904.
CEP first reported 10 cases of a newly recognized cause of encephalitis in 2009.1 This updated report describes a total of 32 cases of anti-NMDAR encephalitis and compares the clinical characteristics of these cases vs. those caused by enterovirus (30), HSV-1 (7), VZV (5), and West Nile Virus (5). Age range of the anti-NMDAR cases was 2-28 years (median 12.5), 75% were female, 47% were Latino and 31% were Asian/Pacific Islander. Movement disorder, aphasia, ataxia, and autonomic instability, seizures, and hallucinations were commonly reported. MRI was abnormal in only 46% of anti-NMDAR cases whereas temporal lobe abnormalities were found in 100% of cases of HSV-1 encephalitis. CSF WBC ranged from 0 to 252 (median 23) and CSF protein and glucose were generally normal. 13% of patients with anti-NMDAR encephalitis were ill enough to require ICU admission and 1 patient (3%) died.
Commentary
Anti-NMDAR encephalitis may be one of the more common causes of encephalitis, especially in children and women who present with characteristic signs and symptoms as noted above. Anti-NMDAR encephalitis is one of the immune-mediated encephalitides and is felt to be similar in etiology to the classic paraneoplastic syndromes associated with antibodies to intraneuronal targets with cytotoxic T-cell responses and to other autoimmune encephalitides in which the target epitopes are extracellular antigens. These latter entities include encephalitis associated with antibodies to other neuronal receptors such as 3-OH-5-methyl-4-isoxazolepropionic acid receptor (associated with lung, breast, and thymic tumors) and gamma-amino butyric acid B receptor (associated with small cell lung cancer) where a clinical picture of limbic encephalitis is seen.
Consideration of anti-NMDAR encephalitis and specific testing to confirm the diagnosis should be done early in the clinical evaluation of a patient with encephalitis presenting with a compatible clinical picture. While data from randomized controlled trials of various treatment modalities are not available, clinical experience suggests that the prognosis is better when immunosuppressive treatment is instituted earlier in the course of the illness. In addition, early diagnosis of anti-NMDAR encephalitis will reduce the inappropriate (and futile) empiric use of antibiotics and antiviral agents.
Interestingly, in this same issue of CID, investigators from Japan and Finland report on 4 cases of encephalitis in children (ranging in age from 8 to 60 months) where human bocavirus 1 or 2 was found in serum and CSF2, further expanding the differential diagnosis of the etiology of encephalitis.
References
- Gable MS, et al. Anti-NMDA receptor encephalitis: report of 10 cases and comparison with viral encephalitis. Eur J Clin Microbiol Infect Dis 2009; 28: 1421-9.
- Mitui MT, et al. Detection of human bocavirus in the cerebrospinal fluid of children with encephalitis. Clin Infect Dis 2012;54:964-7.
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