Autoimmune encephalitis (AIE) based on review by Garg et al 2020
Autoimmune encephalitis (AIE) is being increasingly recognized as a significant as well as frequent cause of encephalopathy in the pediatric age group. Despite a plethora of antibodies being described against the central nervous system, a significant proportion of childhood autoimmune encephalitis do not exhibit detectable known antibodies, spawning a diagnostic challenge . These children may have as yet unidentified antibodies or other immune mechanisms. AIE incorporates proven syndromes based on clinical phenomenology and based on autoantibody associations. Of these, syndromes with antibodies to cell surface antigens have evidence to suggest pathogenicity. Rarely, antibodies to intracellular antigens can be a biomarker but their role is unproven. The most common antibody associated with AIE in children is anti-NMDA receptor (NMDAR) antibody. Unlike adult AIE, association with cancer is less frequent in children . Early diagnosis and treatment leads to better neurocognitive outcomes. Pediatricians and intensivists need to be aware of this entity so that they can ensure timely and appropriate diagnosis and treatment. This review will provide readers with an updated account of clinical presentation, diagnosis and treatment options in autoimmune encephalitis in children, with discussion of future priorities and challenges.
EPIDEMIOLOGY
Data on the epidemiology of pediatric AIE is limited. A retrospective study of anti-NMDAR encephalitis conducted over seven years in Hong Kong estimated an incidence of 2.2/ million children per year . This disorder likely accounts for a large number of cases of encephalitis in children. Anti-NMDAR encephalitis may also contribute to recurrence of encephalitis following herpes simplex virus encephalitis in both children and adults . Other non-herpes viruses may also act as triggers for anti-NMDAR encephalitis . Anti-NMDAR encephalitis accounts for 4% of all encephalitis and is the most common cause of seropositive AIE in children. Almost 40% of all reported cases are below 18 years of age. Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) or Hashimoto’s encephalopathy has a prevalence of 2/100,000 in adults but its frequency in children is much less . Anti-thyroid antibodies may be detected in up to 10% of normal children, entailing caution while interpreting these in the presence of neurological impairment in children .
Overlapping Encephalitis
A recent study showed that some patients with antiNMDAR encephalitis had an overlap in terms of clinical features or magnetic resonance imaging (MRI) findings with neuromyelitis optica (NMO). Syndromes with dual-positive antibodies have also started to be recognized, for e.g. anti-NMDAR and anti-MOG or antiAQP4 or anti-D2 receptor positivity, anti-GAD and antiGABA-A etc . The proportion of anti-GABA-B antibodies with overlap seem to be more. Among 20 patients with anti-GABA-B receptor encephalitis, seven showed overlap with other antibodies . AntiNDMAR encephalitis may also overlap with opsoclonus syndrome.
Seronegative Autoimmune Encephalitis
Only up to 44% of patients with AIE have an antibody positive status. ‘Seronegative but suspected autoimmune encephalitis’ has received a consensus definition. The definition includes rapid progression of symptoms, along with exclusion of well-defined AIE syndromes such as typical limbic encephalitis, absence of serum and CSF antibodies along with two of: MRI abnormalities suggestive of autoimmune encephalitis, CSF pleocytosis, CSF-specific oligoclonal bands or elevated CSF IgG index or brain biopsy showing inflammatory infiltrates, along with exclusion of other causes .