Atypical N-methyl-D-aspartate receptor encephalitis and a hippocampal tumour

To the Editor

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is caused by a reversible decrease of synaptic N-methyl-D-aspartate receptor (NMDAR) through cross-linking and internalization by an immunoglobulin G (IgG) antibody (Dalmau et al., 2011). The disease can be autoimmune or paraneoplastic; it responds to immune therapy and removal of causative tumour. Early stages of NMDAR encephalitis are characterized by anxiety, insomnia, grandiose and paranoid delusions and mania, which are often misdiagnosed as schizophreniform psychosis (Dalmau et al., 2011). A presentation with isolated depression has been described in only one case (Kayser et al., 2013).

An 18-year-old Caucasian male, with no psychiatric or medical history, reported 3 months of depressive symptoms and brief mood-congruent derogatory auditory hallucinations, culminating in intentional overdoses. Preceding this was a relationship breakdown and difficulty completing university studies. He was admitted and commenced on mirtazapine 15 mg nocte. Physical and neurological examination was normal. Serum metabolic, inflammatory and tumour markers were normal. NMDAR-IgG was detected in serum. Cerebrospinal fluid (CSF) examination found a lymphocytic pleocytosis (white cell count [WCC]: 30 × 10⁶/L); CSF NMDAR-IgG was initially negative, but positive on repeat sampling. Electroencephalogram showed diffuse encephalopathy without epileptiform activity. Magnetic resonance imaging (MRI) of the brain showed a non-enhancing right hippocampal mass, interpreted as a low-grade tumour. He received 5 days of intravenous immunoglobulin (IVIG) and rapidly improved, returning to premorbid mental state within 4 days.

He had two further deteriorations in mood within the next 8 weeks, each time responding rapidly to IVIG. After administration of Rituximab, both clinical and imaging parameters stayed unchanged over an 11-month follow-up.

We describe an NMDAR encephalitis case, characterized by isolated psychotic depression, highlighting the heterogeneity of early presentations of this illness. The presence of a right temporal lobe tumour is unusual and its relationship to the encephalitis is unclear. No histology is available, but tumours can express NMDAR and could provide a basis for sensitization (Dalmau et al., 2011). Also, focal disruption of the blood–brain barrier could facilitate an immune response to NMDAR. Reversible MRI abnormalities resembling glioma have been seen in a single case of seronegative autoimmune limbic encephalitis (Najjar et al., 2011), but in our case successful treatment did not alter MRI appearances. A direct effect of the tumour on brain parenchyma seems insufficient to explain the clinical presentation and rapid treatment response, as does the effect of anti-depressant therapy.

To our knowledge, this is the first case report of NMDAR encephalitis presenting with depression in context of a hippocampal lesion; it could provide additional insights into the underlying mechanisms and immunopathology of NMDAR encephalitis.