Case studySuccessful treatment of two paediatric cases of anti-NMDA receptor encephalitis with Cyclophosphamide: The need for early aggressive immunotherapy in tumour negative paediatric patients
Highlights
► We report the response to immunotherapy in three girls aged 27 months to 4 years with anti-NMDA receptor encephalitis. ► All cases presented with the classical multi-stage clinical syndrome. ► All had poor response to first line immunotherapy. ► Monthly cycles of Cyclophosphamide were associated with complete remission in all cases.
Introduction
Though anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis was originally reported in young adult women as a paraneoplastic disorder in association with ovarian teratoma, it is being increasingly recognised in the paediatric population, with 40% of patients in a case series of 81 being under 18 years of age.1 The disease is caused by antibodies that target the NR1 subunit of the NMDAR. The mainstay of treatment includes tumour removal, immune suppressing medications and supportive care. It is recognised that tumour negative patients may not respond to first line immunotherapy and a recent review of anti-NMDAR encephalitis suggests Cyclophosphamide and rituximab, either alone or in combination as the second line immunotherapy in these patients.2 We describe two paediatric cases of anti-NMDAR encephalitis, both aged 27 months at presentation, who had limited or ill-sustained clinical benefit from a combination of high dose steroids, IVIg and plasma exchange, but responded dramatically to monthly cycles of Cyclophosphamide. This case report adds to the increasing pool of clinical experience of anti-NMDAR encephalitis and suggests the benefit of early consideration of second line immunotherapy even for the youngest paediatric patients.
Section snippets
Case reports
Both cases were 27 months old unrelated Caucasian females who presented in 2009 and 2010 respectively.
Both presented with a stereotypical course, consisting of an initial neuropsychiatric phase lasting for nearly two weeks manifesting as speech regression, change in personality and sleep pattern, with progressive deterioration leading to an encephalopathic stage with a florid movement disorder involving the oral-buccal region and limbs.
During the encephalopathic stage, case 2 demonstrated
Discussion
The immune mediated pathogenesis of anti-NMDAR encephalitis was initially described by Dalmau et al who demonstrated presence of antibodies in serum and cerebrospinal fluid (CSF) that react with cell surface of neurons.4 These antibodies were demonstrated to be specific to the NR1 subunit of the NMDAR and further characterized to be of the complement-fixing IgG1 subclass.5 The clinical phenotype of anti-NMDAR encephalitis has been well described in the form of distinct stages which include an
Conclusion
Immunotherapy is the mainstay of treatment for anti-NMDAR encephalitis.
Based on the treatment algorithm outlined by the recent review of the condition by Dalmau et al.2 and our own clinical experience, we propose that in cases with an incomplete response to first line agents, second line immunotherapy should be considered early even in the youngest paediatric patients.
Case 3
Case 3 was a previously healthy 14 year old girl referred to us subsequent to submission of the manuscript reporting the two cases described above. She had presented to her local hospital with a four day history of neuropsychiatric symptoms consisting of confusion, forgetfulness (forgetting her dance steps), expressive dysphasia, decreased co-ordination and a twenty four hour history of right hand paraesthesia and weakness. She was initially locally treated for presumed encephalitis but
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