Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis.

We describe the clinical courses of 3 children with a psychochoreiform encephalitis associated with anti-N-methyl D-aspartate receptor autoantibodies. These cases, including the most severely medically complicated survivor to date, illustrate the challenges of diagnosis, supportive care, and immune-modulating therapy. Clinical and laboratory features are similar to those of viral encephalitis, and the condition is often reversible with appropriate diagnosis and treatment.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents.

OBJECTIVE: To report the clinical features of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients < or = 18 years old. METHODS: Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1. RESULTS: Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were < or =18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls < or =18 years old (p = 0.05), and 9% in girls < or =14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients < or =18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03). INTERPRETATION: Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11-18.

Balamuthia mandrillaris, agent of amebic encephalitis: detection of serum antibodies and antigenic similarity of isolates by enzyme immunoassay.

We report the development of an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to Balamuthia mandrillaris, a free-living ameba that is an etiologic agent of granulomatous amebic encephalitis (GAE). As part of the California Encephalitis Project (CEP), we have tested serum and cerebrospinal fluid (CSF) samples from a subgroup of 130 hospitalized encephalitis patients (out of approximately 430 samples) over a 16-month period. Case criteria were based on clinical, laboratory, and occupational/recreational histories. All serum samples initially underwent screening by immunofluorescent antibody (IFA) staining with results ranging from no detectable ameba antibodies to titers of 1:256. In addition to the 130 samples tested prospectively, sera and/or CSF from 11 previously confirmed cases of balamuthiasis, six healthy individuals, and earlier CEP submissions with high IFA antibody titers were also tested retrospectively. Among the 130 samples, two cases of balamuthiasis were identified by ELISA and confirmed by the polymerase chain reaction (PCR). The availability of sera from human and animal cases and from varied geographic areas allowed comparisons of serologic similarities of the different Balamuthia strains and human sera. All sera, whether from human or other mammals, reacted with all strains of Balamuthia, as they did with Balamuthia amebae from different geographic areas. Enzyme-linked immunosorbent assay results were consistent with the IFA results. Differences between readings were likely due to cross-reactivity between Balamuthia antigens and unidentified antibodies in serum.

Detection of antibodies against free-living amoebae Balamuthia mandrillaris and Acanthamoeba species in a population of patients with encephalitis.

BACKGROUND: Balamuthia mandrillaris and Acanthamoeba species are 2 free-living amoebae responsible for granulomatous amoebic encephalitis in humans and animals. We have screened serum samples from hospitalized patients with encephalitis for antibodies against these 2 amoebae as a means of detecting a disease with few defining symptoms and a poor prognosis. METHODS: Indirect immunofluorescence antibody (IFA) staining of serum samples from patients with encephalitis was conducted over a period of 6 years to detect amoeba antibodies. More than 250 serum samples from patients hospitalized with encephalitis were screened. Most of the samples were from patients in California and were screened as part of the California Encephalitis Project, with a small number of specimens from other states. RESULTS: During the course of the study, 7 cases of Balamuthia encephalitis were detected; all cases were detected in Hispanic individuals, and all cases were fatal. Examination of hematoxylin-eosin-stained and immunostained sections of brain tissue obtained at biopsy or autopsy for amoebae confirmed balamuthiasis in all serum samples with positive IFA results. One case of Acanthamoeba encephalitis was detected in an immunocompromised individual with a normal antibody titer by identification of amoebae in immunostained brain tissue obtained at autopsy. CONCLUSIONS: IFA can be successfully used in screening for balamuthiasis and acanthamoebiasis in patients whose clinical presentation, laboratory results, and neuroimaging findings are suggestive of amoebic encephalitis. Ideally, this can lead to an earlier definitive diagnosis and earlier start of antimicrobial therapy. Without IFA staining, the balamuthiasis cases in our study would have been diagnosed as neurocysticercosis, tumor, tuberculosis, or viral encephalitis or would have been undiagnosed.

SARS and common viral infections.

In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.

Human neurobrucellosis with intracerebral granuloma caused by a marine mammal Brucella spp.

We present the first report of community-acquired human infections with marine mammal-associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26.

Exposure to rodents and rodent-borne viruses among persons with elevated occupational risk.

Persons who have frequent contact with rodents as part of their occupation may be at increased risk of exposure to rodent-borne viruses such as Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome, and Whitewater Arroyo virus (WWA), a New World arenavirus. Eighty-one persons with possible occupational exposure to rodents completed questionnaires and provided specimens for serologic testing. Seventy-two participants reported handling rodents as part of their job. The mean total number of rodents handled during participants' careers was approximately 2200. IgG antibody to lymphocytic choriomeningitis virus was detected in serum from one (1.2%) participant. IgG antibody to SNV, WWA, and Amapari viruses was not detected in any of the serum specimens. Despite considerable exposure to rodents, participants did not have significant serological evidence of exposure to rodent-borne viruses.

Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result.

A statewide encephalitis diagnostic project of the California State Department of Health Services found that herpes simplex virus 1 DNA may not be detectable by molecular methods early in the clinical course of herpes simplex encephalitis.