Introduction: NMDAR-Ab encephalitis is characterized by seizures, movement disorder and psychiatric symptoms.  Cases comprising of a predominant white matter disorder have recently been reported to be associated with NMDAR-Ab.

Method: Ten children with significant white matter involvement, with or without NMDAR-Ab encephalitis, were identified from 46 consecutive NMDAR-Ab positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurological syndrome evaluated.

Results: Three distinct clinico-radiological phenotypes were recognized: brainstem encephalitis (n=3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE; n=2) and acquired demyelination syndromes (ADS; n=5). Three of the ADS had myelin oligodendrocyte glycoprotein (MOG) as well as NMDAR-Abs. Typical NMDAR-Ab encephalitis was seen in 3 patients remote from the first neurological syndrome (2 brainstem, 1 post HSVE). Six of the seven patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, intravenous immunoglobulins and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement.  The time course of clinical features, treatments and recoveries correlated broadly with available serum antibody titers.

Conclusion: Around 20% of children with NMDAR-Ab have clinico-radiological evidence of white matter involvement, often distinct from NMDAR-Ab encephalitis, and appear immunotherapy responsive, particularly when treated in the acute phase of neurological presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR-Ab levels, suggesting that these antibodies may mediate the white matter disease.