Anti-NMDA-receptor encephalitis and autism: research ascendancy

The paper by Reza Kiani and colleagues [1] (open-access available here) detailing the presence of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis in two people "with autism and intellectual disability presenting with neuropsychiatric symptoms of catatonia and neuroleptic malignant syndrome" caught my eye recently.

Having previously talked about anti-NMDA-receptor encephalitis and autism in a previous blog post (see here) back in 2013 with the emphasis on a possible link to 'autistic regression', I've been intrigued by the rise and rise of peer-reviewed material on this subject in the intervening years. Subsequent descriptions such as the one from González-Toro and colleagues [2] again talking about children diagnosed with anti-NMDA receptor encephalitis after suffering a "regression of previously acquired abilities that developed into autism" further adds to my interest in this potentially important connection. That also there may be several roads leading to a diagnosis of autism is also an important take-away point from such work.

Kiani et al continue with the idea that there may be an "aetiological role of the immune system in the pathogenesis of various psychiatric disorders" on the back of various studies looking at anti-NMDA receptor encephalitis. On this occasion, they detail two case reports where autism and learning (intellectual) disability were already diagnosed but deteriorations in behaviour were noted. The first case report of a woman in her early-30s who "presented with social withdrawal and a persistently low mood" that subsequently led into "objective evidence of hallucinations" illustrates how various tests followed various symptoms ultimately leading the authors to suspect anti-NMDA receptor encephalitis. Importantly, they detail how psychotropic medication was the first choice of intervention and how, only after this 'failed', did they look for anti-NMDA-receptor antibodies. Of importance to the female presentation of anti-NMDA receptor encephalitis were the further investigations looking for any signs of "an underlying tumour, particularly an ovarian teratoma" given previous suggestions of a possible link [3].

The second case report focused on a middle-aged man "with moderate intellectual disability, autism and a history of affective psychosis in remission." Again, antipsychotic medication was the first thing to be reached for when "his condition deteriorated and he displayed aggressive outbursts and insomnia." Alas, this did not improve his state and neuroleptic malignant syndrome (NMS) was eventually diagnosed as a result of such intervention. Anti-NMDA-receptor encephalitis was finally considered when "further investigations revealed positive anti-NMDA-receptor antibodies."

Of note for both these individuals was the effect of treating anti-NMDA receptor encephalitis. This involved the use of methylprednisolone, an anti-inflammatory compound, normally administered for various autoimmune conditions. Interestingly, as a corticosteroid, prednisolone (the un-methylated version of methylprednisolone) has been talked about with 'regressive autism' in mind before in the peer-reviewed literature (see here). Kiani et al note that delivery of methylprednisolone was associated with a gradual recovery in behavioural symptoms "with no evidence of psychosis or cognitive deficit."

"In both patients the diagnosis was made with delay owing to the complexity of their presentation." This is an important sentence from Kiani and colleagues. Not only in respect to the various behavioural and somatic issues that were present (including comorbid diagnoses) but also insofar as issues with communication for example. I've talked about similar things before on this blog (see here). Further, the authors reiterate "the complex presentation of anti-NMDA-receptor encephalitis in... patients with intellectual disability and autism" and how further research is required to see whether diagnostic conditions such autism and/or learning disability "are more prone to develop this type of encephalitis or have a worse prognosis in comparison with the rest of the population." I struggle to disagree with such sentiments.

Music: Hozier - Take Me To Church.

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[1] Kiani R. et al. Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism. BJPsych Bull. 2015 Feb;39(1):32-5.

[2] González-Toro MC. et al. Anti-NMDA receptor encephalitis: two paediatric cases. Rev Neurol. 2013 Dec 1;57(11):504-8.

[3] Dabner M. et al. Ovarian teratoma associated with anti-N-methyl D-aspartate receptor encephalitis: a report of 5 cases documenting prominent intratumoral lymphoid infiltrates. Int J Gynecol Pathol. 2012 Sep;31(5):429-37.

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Kiani R, Lawden M, Eames P, Critchley P, Bhaumik S, Odedra S, & Gumber R (2015). Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism. BJPsych bulletin, 39 (1), 32-5 PMID: 26191422