The clinical and immunological features of 100 patients with encephalitis associated with antibodies against NR1-NR2 heteromers of the NMDA receptor were analyzed in a study at the Children’s Hospital of Philadelphia, and University of Pennsylvania. Median age was 23 years (range 5-76 years), and 91 were female. One boy (11 years old, without tumor) and 21 girls (12 with ovarian tumor) were a median age of 15 years (range 5-18 years). Prodromal symptoms in 86% consisted of headache, low-grade fever, or a non-specific viral-like illness within 2 weeks before hospital admission. Presenting symptoms were psychiatric or memory problems in 100%, seizures in 76%, decreased consciousness in 88%, dyskinesias, chiefly orofacial (86%), autonomic instability (69%), and hypoventilation (59%). Seizures were generalized tonic-clonic in 45 and partial complex in 10. EEG was abnormal in 92, and showed slow activity in 71 and epileptic activity in 21. Brain MRI was abnormal in 55, with increased FLAIR or T2 signal, and limited to the medial temporal lobes in 16. CSF was abnormal in 95, with pleocytosis in 91, increased protein in 32, and oligoclonal bands positive in 26 of 39 tested. Brain biopsy in 14 patients was nonspecific. Ovarian teratoma or other tumors were associated in 59%. Seventy-five patients recovered or had mild deficits, and 25 had severe deficits or died. Among those who recovered with mild deficits, 64 (85%) had signs of frontal lobe dysfunction including poor attention, impulsivity, and behavioral dysinhibition. Patients with better outcomes and fewer neurological relapses had received early tumor treatment, usually with immunotherapy (P=004). Improvement was associated with a dcrease of serum antibody titers. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Patients’ antibodies decreased the numbers of cell-surface NMDA receptors and clusters in postsynaptic dendrites. [1]

COMMENT. Anti-NMDA-receptor encephalitis is a new category of immune-mediated disorders of adolescents or young adults, often paraneoplastic (60%), diagnosed serologically, and amenable to surgical and/or immunotherapy. This disorder is not uncommon, almost 100 cases identified at the Univ Pennsylvania in 2 years. CSF findings are helpful in diagnosis but MR1 abnormalities are nonspecific. Seizures, attention and behavior disorders are common sequelae in the 75% patients who recover. The role of prodromal viral infection or other event in triggering the immune response requires further study. The antibody-induced modulation of the target antigens is similar to the Lambert-Eaton myasthenic syndrome that occurs with or without tumor association. In Lambert-Eaton syndrome the presence of small-cell lung cancer confers a poor neurological outcome, whereas in anti-NMDA-receptor encephalitis, cases associated with teratoma of the ovary or testis and treated early have a good prognosis. [2]