Anti-N-methyl-d-aspartate receptor encephalitis: A primer for acute care healthcare professionals

Abstract

This primer summarizes the diagnosis, treatment, complications, and prognosis of anti-N-methyl-d-aspartate receptor encephalitis for healthcare professionals, especially those in acute care specialities. Anti-N-methyl-d-aspartate receptor encephalitis is an immune-mediated encephalitis that is classically paraneoplastic and associated with ovarian teratomas in young women. Other less common neoplastic triggers include testicular cancers, Hodgkin lymphoma, lung and breast cancers. It may also be triggered by infection, occurring as a para-infectious phenomenon, seen most commonly after herpes simplex-1 encephalitis. Presentation varies but typically consists of behavioural and cognitive manifestations, seizures, dysautonomia, movement disorders, central hypoventilation, and coma, necessitating intensive care unit admission. Diagnosis of anti-N-methyl-d-aspartate receptor encephalitis requires high clinical suspicion plus ancillary testing, the most sensitive being cerebrospinal fluid analysis for anti-N-methyl-d-aspartate receptor antibodies. Imaging in search of an ovarian teratoma should be exhaustive and tumours need to be surgically treated. Treatment should be expeditious with pulsed steroids and either plasma exchange or intravenous immunoglobulin. Second-line treatments include intravenous rituximab, cyclophosphamide, azathioprine, and intrathecal methotrexate. Most patients recover to be functionally independent, but the in-hospital course can be months long followed by extensive rehabilitation. Given the lengthy course of illness, we explain why education and debriefing are important for staff, and where families can obtain additional help.

Keywords: Anti-N-methyl-d-aspartate receptor encephalitis; encephalitis; intensive care unit; ovarian teratoma.

Figure 1.

Ten summary points for ICU staff related to NMDA-r encephalitis. CSF: cerebrospinal fluid; EEG: electroencephalogram; HSV: herpes simplex virus; ICU: intensive care unit; IVIg: intravenous immunoglobulin; NMDA-r: anti-N-methyl-d-aspartate receptor.

Figure 2.

Algorithmic approach to NMDA-R encephalitis. ALP: alkaline phosphatase; ALT: alanine transaminase; ANA: antinuclear antibody; ANCA: anti-neutrophil cytoplasmic antibodies; AST: aspartate aminotransferase; CNS: central nervous system; CRP: c-reative protein; CSF: cerebrospinal fluid; CT: computed tomography; EEG: electroencephalogram; EKG: electrocardiogram; GGT: gamma-glutamyl transferase; HSV-1: herpes simplex virus-1; INR: international normalized ratio; IVIg: intravenous immunoglobulin; MRI: magnetic resonance imaging; NMDA-r: anti-N-methyl-d-aspartate receptor; PET: positron emission tomography; PTT: partial thromboplastin time; RF: rheumatoid factor; SSA: anti-Sjogren's syndrome type a; SSB: anti-Sjogren's syndrome type b; TPO: thyroid peroxidase; TSH: thyroid stimulating hormone; VZV: varicella zoster virus.

Figure 3.

The mRS. A 0–6 scale for quantifying disability or dependence following a neurological illness (especially stroke). mRS: modified Rankin scale. Note: In contrast, the Glasgow Outcome Score (GOS) is a 1–5 scale used to assess neurologic recovery, usually cerebral trauma. A low GOS equates with worse outcome (i.e. score of 1 equates death and 5 equates low disability).

Figure 4.

Resources for families following the diagnosis of NMDA-r encephalitis. NMDA-r: anti-N-methyl-d-aspartate receptor.