N‐methyl‐D‐aspartate receptor antibodies in pediatric dyskinetic encephalitis lethargica

Abstract

Encephalitis lethargica (EL) describes an encephalitis with psychiatric, sleep, and extrapyramidal movement disorders. Dyskinetic and parkinsonian forms have been described. EL shares clinical features with the anti-N-methyl-D-aspartate receptor (NMDAR-Ab) encephalitis. We studied 20 sera from pediatric patients with contemporary EL. Ten sera (from 2 males and 8 females, aged 1.3-13 years) and 6/6 cerebrospinal fluid samples were positive for NMDAR-Ab. NMDAR-Ab-positive patients had dyskinesias, agitation, seizures, and insomnia, whereas parkinsonism and somnolence dominated in the NMDAR-Ab-negative children. We were unable to identify any tumors. The dyskinetic form of EL is an NMDAR-Ab encephalitis and can affect very young children.

The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

“…However, akinetic-rigid-mute presentations can predominate. Many of these patients are reminiscent of von Economo' s encephalitis lethargica (EL) cases and, indeed, around half of the children originally given a diagnosis of EL have NMDAR-antibodies 26 . In children, the movement disorder may be the presenting feature 27 , there is a very low frequency of tumours and often a preceding infection, which is associated with a variety of organisms 21 .…”

Relevance of Autoantibodies for the Classification and Pathogenesis of Neurological Diseases

“…In their study, O`Connor and colleges used a tetramer radioimmunoassay and detected serum antibodies directed to folded MOG tetramer in patients with ADEM in higher concentrations compared to adult MS cases (O'Connor et al, 2007). This observation was confirmed by several other publications (Brilot et al, 2009;Di Pauli et al, 2011;Lalive et al, 2011). Serum antibodies to native MOG were most commonly reported in pediatric ADEM patients.…”

“…However, the origin of the autoantibodies remains unresolved, as recent publications reported numerous of non-teratoma associated cases. Among some adults, most of these non-paraneoplastic NMDA-R encephalitis cases occurred in children (Dale et al, 2009;Florance et al, 2009;Irani et al, 2010). Anti-NMDA-R encephalitis is associated with a strong female predominance (female:male ratio is 8:1) occurring primarily at a median age of 23 years (Dalmau et al, 2008).…”

“…Concerning CSF parameters, 60% of patients show OCB and mild lymphocyte pleocytosis (Dalmau et al, 2011). Interestingly, intrathecal NMDA-R antibody synthesis was observed in a majority of patients and CSF titer levels were more likely to correlate with clinical severity, compared to serum titers (Dalmau et al, 2008;Dale et al, 2009;Florance et al, 2009;Irani et al, 2010). Although the disease can be lethal in some rare cases and despite the severity of the symptoms, more than 70% of patients recover after treatment and less than 30% of patients show incomplete recovery with memory, cognitive and motor deficits.…”

“…Latest findings showed increased anti-MOG antibody titers in a subgroup of patients with acute disseminated encephalomyelitis (ADEM) and childhood MS, but not in adult MS (O'Connor et al, 2007;Brilot et al, 2009;Di Pauli et al, 2011;Lalive et al, 2011). The target antigen MOG is expressed on the outer surface of the myelin sheath ( Figure 1) and can only be detected using cell based assays expressing MOG on their surface.…”