Treatable clinical condition NMDAr encephalitis can mimic autistic regression

N-methyl-aspartate receptor antibodies (NMDAR-Ab) encephalitis is an acute form of encephalitis. It is a well-recognized, clinical-immunological syndrome caused by an autoimmune reaction to neuronal NMDA receptors. While in adults the initial symptoms are mostly psychiatric in nature, there is often a rapid deterioration to medically urgent symptoms including hypoventilation, catatonia, cerebellar ataxia and loss of consciousness. The symptoms in children can be less severe and more difficult to recognise.

“Patterns of presentation and etiology of anti-NMDA-receptor antibody encephalitis are dependent on age and can be challenging to recognize in very young children.”

One of the main presenting features of NMDAR-Ab in children is loss of language and social skills and reduced interest in surroundings, all hallmarks of idiopathic autism. Other presenting features in children can include: seizures, status epilepticus, sleep disturbances, temper tantrums, lack of appetite, dystonia, abnormal gait, tics, hyperactivity, psychotic episodes, irritability and agitation, including physical aggression. All of these features, in varying degrees of severity, are commonly present in many cases of idiopathic autism.

In their recently published paper Hacohen and colleagues describe two cases of toddlers who presented with developmental regression that mimicked an autistic regression, namely behavioural change, irritability, disrupted sleep, and loss of motor, language, and social communication skills.

“Although both patients had some other neurological features, they were subtle, which resulted in delayed diagnosis of NMDAR-Ab encephalitis. Importantly, immunotherapy was beneficial in both patients, with significant improvement of their language skills and behaviour.”

NMDAR-Ab were found in the serum and cerebrospinal fluid, and both patients responded well to standard immunotherapy consisting of a combination of intravenous methylprednisolone and immunoglobulin, plasma exchange and rituximab. In one of the two patients a total and lasting remission of all symptoms was noted, including recovery of lost language. These improvements match those seen in other cases of autism-mimicking NMDAR-Ab previously reported in the literature, where immunotherapy treatments also resulted in resolution of movement disorders and reacquisition of language and social skills.

“The EEG usually shows nonspecific slowing without epileptiform discharges or subclinical seizures. Much more difficult to recognize are psychiatric symptoms…, where multiple visits to the emergency room were dismissed as very young child separation anxiety and temper tantrums.”

Also see: Autistic Regression Linked to Autoimmunity (Issue 2)

This article is part of Treating Autism Clinical & Research Newsletter: Issue 1

References:

Hacohen Y, Wright S, Gadian J, et al. (2016) N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression. Dev Med Child Neurol. Oct;58(10):1092-4. doi:
10.1111/dmcn.13169.

Further reading:

Creten C, van der Zwaan S, Blankespoor RJ, et al. (2011) Late onset autism and anti-NMDA-receptor encephalitis. Lancet; 378: 98. doi: 10.1016/S0140-6736(11)60548-5.

Matoq AA, Rappoport AS, Yang Y, et al. (2015) Anti-NMDA-receptor antibody encephalitis in infants. Epilepsy Behav Case Rep. Nov 4;4:99-101. doi: 10.1016/j.ebcr.2015.07.005.

Schieveld JNM. Section IV Case reports with a child psychiatric exploration of catatonia, autism, and delirium. In: Dhossche DM, Wing L, Ohta M, Neum.rker KJ, eds. Catatonia in autism spectrum disorders. International Review of Neurobiology, vol 72. London: Academic Press, 2006: 195–206.

Scott O, Richer L, Forbes K, et al. (2014) Anti-N-Methyl-DAspartate (NMDA) receptor encephalitis: an unusual cause of autistic regression in a toddler. J Child Neurol; 29: 691–94. doi: 10.1177/0883073813501875.

Suthar R, Saini AG, Sankhyan N, et al. (2016) Anti-NMDA Receptor Encephalitis. Indian J Pediatr. Jul;83(7):628-33. doi: 10.1007/s12098-015-1988-8.