Case Report: Severe Adolescent Major Depressive Syndrome Turns Out to Be an Unusual Case of Anti-NMDA Receptor Encephalitis

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory condition mediated by autoantibodies against the GluN1 subunit of the receptor. Clinically, it is characterized by a complex neuropsychiatric presentation with rapidly progressive psychiatric symptoms, cognitive deficits, seizures, and abnormal movements. Isolated psychiatric manifestations of anti-NMDAR encephalitis are rare and usually dominated by psychotic symptoms. We present a case of an 18-year-old female high school student—without a previous history of psychiatric disorders—with a rapid onset severe depressive syndrome. Surprisingly, we found pleocytosis and anti-NMDAR autoantibodies in the cerebrospinal fluid (CSF), despite an otherwise unremarkable diagnostic workup, including blood test, clinical examination, and cranial magnetic resonance imaging (MRI). After intravenous immunoglobulins treatment, a complete remission of the initial symptoms was observed. In a follow-up 5 years later, the young woman did not experience any relapse or sequelae. Anti-NMDAR encephalitis can present in rare cases as an organic disorder with major depressive symptoms without distinct concomitant psychotic or neurological symptoms. A clinical presentation such as a rapid onset of symptoms, distinct disturbance in the thought process, restlessness, and cognitive deficits should prompt screening for NMDAR- and other neural autoantibodies to rule out this rare but debilitating pathology.

Anti-NMDA receptor encephalitis with initial negative markers: diagnostic and therapeutic challenges of a refractory case with 9-month-long follow-up

“…This case demonstrates that recognising the clinical manifestations of anti-NMDA receptor encephalitis early in disease onset is critical to avoiding misdiagnosis and treatment delays. Many cases reported in the literature began with similar neuropsychiatric symptoms 15–24. Within the last 2 years, four cases of anti-NMDA receptor encephalitis have been reported in association with COVID-19 infection 15 16 25 26.…”

Antineuronal Autoantibodies in the Cerebrospinal Fluid and Serum From 106 Patients With Recent-Onset Depression Compared With 106 Individually Matched Healthy Control Subjects

“…Depressed mood as part of the initial symptoms of autoimmune encephalitis (AE) has previously been reported ( 1 , 2 , 3 ), and depression has been described as the only phenotypical trait of anti-NMDA receptor (NMDAR) encephalitis at case report level ( 4 ). Despite the rarity of AE ( 5 , 6 ), commercial kits for evaluation of several antineuronal autoantibodies (Abs) that can cause AE are available, including Abs directed at NMDAR, AMPAR1 and AMPAR2 (AMPA receptors 1 and 2), CASPR2 (contactin-associated protein 2), LGI1 (leucine-rich glioma-inactivated protein 1), GABABR (gamma-aminobutyric acid B receptor) B1/B2, and GAD65 (glutamic acid decarboxylase-65) ( 7 , 8 , 9 ).…”