International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis

July 30, 2021

We are excited to report the first International Consensus Recommendations for the treatment of pediatric NMDAR Antibody Encephalitis. The paper results from the hard work, dedication, and collaboration between 27 international AE experts, led by Dr. Margherita Nosadini and Dr. Russell Dale. These treatment recommendations will be of great value to children affected by AE and clinicians worldwide.

The recommendations start with general management principles, highlighting the importance of early diagnosis and careful communication with the family. The importance of raising awareness of this disorder, which may first present to psychiatrists and emergency physicians as well as neurologists, cannot be overemphasized, and the diagnostic criteria (2016) and modification for children (2020), along with the distinctive clinical characteristics, may help to get to a speedy diagnosis. Families need to be informed of the expected or potential disease evolution, the treatment possibilities, and the often long and demanding course of the illness. 

Highlights of the Consensus-based Recommendations of the treatment of Pediatric NMDAR antibody encephalitis: 

–       Corticosteroids are recommended in all children with NMDARE, with additional IV immunoglobulin or plasma exchange in severe patients. 

–       Prolonged first-line immunotherapy can be offered for up to 3–12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. 

–       Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about two weeks after the first-line initiation. 

–       Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. 

–       Maintenance immune suppression beyond six months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. 

–       For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. 

–       The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. 

–       Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), dictated by the severity and clinical course (i.e., median 3, 9, and 18 months in the best, average, and worst responders, respectively). 

–       Although tumors are rare in prepubertal children and boys, oncologic searches for ovarian teratoma (and neural crest tumors in children aged <5 years) are mandatory in all children with NMDARE, and should be performed early and completed in the first days-weeks after admission. 

AE Alliance would like to thank Dr. Nosadini and Dr. Dale, and all the physicians involved, that have worked tirelessly to make these treatment recommendations for NMDARE possible. We would also like to thank the De Vivero Family for their support and input. 

Read the full article here.