Table 2.

Summary of Selected Immune-Mediated Causes of Encephalitis in Children

Acute Disseminated Encephalomyelitis (ADEM): ADEM is an inflammatory demyelinating CNS condition; it is the most commonly identified immune mediated encephalitis with highest incidence in early childhood (mean 5–8 years)69,70. A temporal association with a prodromal illness (commonly upper respiratory tract infection), or rarely vaccination, in the preceding 3 weeks can often be identified71,72. Clinical symptoms include acute onset encephalopathy with multifocal sensory and motor deficits which depend on the location of the lesions in the brain and spinal cord71. MRI of the brain and spine demonstrate asymmetric, bilateral, poorly marginated, hyperintense lesions in the subcortical white and deep gray matter70. Over half have abnormal CSF, most commonly mild lymphocytic pleocytosis with elevated protein72. Oligoclonal bands are rarely found, unlike in multiple sclerosis70,73. Around 25% of children will have myelin oligodendrocyte gylcoprotein antibodies, which are associated with relapse and optic neuritis70. First line therapy is high dose intravenous corticosteroids with second line IVIG or PLEX70. Mortality is rare with around 80% of children fully recovering with treatment71.

Anti-N-methyl-D-aspartate Receptor (anti-NMDAR) Encephalitis: Anti-NMDAR encephalitis is the second leading cause of identified immune-mediated encephalitis in children74. In teenagers, a prodromal illness is followed days to weeks later by psychiatric and behavioral symptoms progressing to encephalopathy, seizures, and abnormal movements. Young children eventually develop a similar syndrome but may have more prominent initial behavioral changes (particularly agitation and aggression), speech changes, personality changes, sleep changes, seizures, and movement disorders (particularly gait disturbance)60,69. Dysautonomia and hypoventilation are less common in children than in adults60. MRI is abnormal in less than half of cases, but CSF is abnormal in most (lymphocytic pleocytosis and possibly elevated protein or oligoclonal bands) and EEG is abnormal in nearly all (diffuse background slowing, focal slowing, or seizures)69. Diagnosis is confirmed by antibodies to the NR1 subunit of NMDAR found in serum or CSF, the latter being more specific, with level of titer correlating with prognosis. Though tumor is rare in children60 (particularly males), if identified, removal improves outcome69. Immunotherapy includes first line treatment with corticosteroids, IVIG, PLEX, or a combination, and secondary options include rituximab and cyclophosphamide46,69. Around 80% of patients have substantial recovery46, though relapse is seen in around 25% of children60.