NMDA-R encephalitis presenting as acute psychosis in a child with human immunodeficiency virus-coincidence or correlation?

Abstract

Autoimmune encephalitides (i.e. NMDA-R) are increasingly recognized in the spectrum of autoimmune conditions. This condition has historically been described in young women in the context of paraneoplastic states. Here, we report on a fifteen year old African boy with congenital human immunodeficiency virus (HIV) infection who presented with a subacute psychotic episode characterised by three weeks of progressive delusional thoughts, manic behaviours, perceptual disturbance, severe insomnia, religious grandiosity and oropharyngeal dyskinesia. HIV infection had been diagnosed 3 years earlier, with sustained virological response achieved on anti-retroviral therapy (ART) for the previous two years. Assessment to exclude organic disease included extensive microbiological, endocrine and metabolic investigations including bronchoscopy, CSF analysis and magnetic resonance imaging (MRI). HIV RNA was not detected from blood or CSF. CMV was detected in peripheral blood and bronchoalveolar fluid (not in CSF), EBV and adenovirus were detected in bronchoalveolar fluid (not in blood or CSF). MRI brain revealed mild reduction in cerebral volume. Oligoclonal bands were raised in CSF; anti- NMDA-R antibodies were detected in serum but not in CSF. These results combined with his florid neuropsychiatric presentation suggested anti-NMDA-R encephalitis for which he was commenced on monthly high dose intravenous immunoglobulin infusions and a tapering regime of steroids. This resulted in gradual improvement in symptoms. This is the first report of anti-NMDA-R encephalitis in a patient with HIV infection. While there is no obvious direct correlation between HIV and anti-NMDA-R encephalitis, there is evidence that HIV-tat protein can penetrate CSF even in the absence of significant viral loads. HIV-tat has been reported to bind to NMDA receptors in neurons in turn inducing neuronal apoptosis. Protein complexes incorporating HIV-tat and NMDA-R in the context of inflamed and apoptotic tissues may be presented as auto-antigens by inflammatory cells, further driving the generation of anti-neuronal antibodies such as anti-NMDA-R. The implications for these findings will be discussed.L6148793352017-03-22 <br />