To retrospectively characterise patients with encephalitis of unknown cause and ‘mimics’ of autoimmune encephalitis in patients aged 15 or older in northern New Zealand between 2009 and 2018.

The proportion of patients with encephalitis of unknown cause ranges from 30-70%. Despite constituting a large subset of patients presenting with encephalitis, clinical characterisation remains poor.

Residents in Auckland and Northland presenting with encephalitis between 2009 and 2018 were identified from three laboratory databases. Patients fulfilling diagnostic criteria for suspected autoimmune encephalitis (Graus et al, 2016) without an identified neuronal auto-antibody were included, and demographic, clinical and laboratory information obtained. Patients with a non-encephalitis final diagnosis were also characterised as ‘mimics’ of autoimmune encephalitis. 

Of 166 patients with a final diagnosis of encephalitis, 56 (33.7%) was infectious, 32 (19.3%) autoimmune, and 48 (28.9%) had encephalitis of unknown cause. Seven patients fulfilled diagnostic criteria for ‘definite’, 10 ‘probable’ and 27 ‘possible’ autoimmune encephalitis. Four had probable viral encephalitis. Thirty (62.5%) were female. There were no significant demographic differences amongst the groups. Confusion and other cognitive abnormalities were the most common symptoms. Seizures were present in 58.3%. Eighteen (37.5%), including 5 of 8 with ‘definite’ seronegative autoimmune encephalitis required intensive care unit support. Twenty-five (52.1%) received immunomodulatory treatment. Methylprednisolone was the most common acute immunosuppressant, azathioprine the most common long-term. Mortality was 10.4% (5 patients). Eight (16.7%) had a clinical relapse. Seventeen were initially diagnosed as having encephalitis of unknown cause, but had an alternative final diagnosis. Four were due to CNS vasculitis, 2 due to primary CNS neoplasms, 2 neuro-syphilis and 9 other causes.

Encephalitis of unknown cause represents a significant proportion of patients presenting with suspected encephalitis. A high degree of suspicion for non-encephalitis causes should be held when evaluating patients with suspected encephalitis.