Autoimmune Encephalitis With Psychotic Manifestations and Cognitive Impairment Presenting as Schizophrenia: Case Report and Literature Review

Abstract

Autoimmune encephalitis is characterized by mental and behavioral symptoms, seizures, and cognitive impairment. The presence of schizophrenia needs to be distinguished from that of autoimmune encephalitis. Herein, we describe the case of a woman who exhibited abnormal mental behavior and cognitive impairment. The patient had experienced similar symptoms more than 20 years previously and had been diagnosed with schizophrenia. The patient's psychotic symptoms improved after treatment with antipsychotic drugs; however, cognitive impairment persisted. She was diagnosed with anti-N-methyl-D-aspartate (NMDA)-receptor concurrent with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor encephalitis. She showed improvement after treatment with steroids and intravenous immunoglobulins (IVIgs). Furthermore, we reviewed the literature and found that, including the present case, 10 patients have been diagnosed with anti-NMDA concurrent with anti-AMPA-receptor encephalitis. Three of these patients were men and seven were women, and their ages ranged from 21 to 71 years. Moreover, seven (70%) patients had a history of tumors. Symptoms of these patients included psychotic symptoms, varying degrees of consciousness disturbance, seizures, dyskinesia, dystonia, autonomic dysfunction, agitation, and verbal reduction. Brain magnetic resonance imaging findings showed scattered fluid-attenuated inversion recovery hyperintensity in subcortical white matter and/or medial temporal lobe in seven (70%) patients. After combination treatment, including tumor removal and administration of steroids, IVIg, plasma exchange, or immunity inhibitors, the symptoms improved in part of the patients. It is necessary to exclude autoimmune encephalitis for patients with psychiatric manifestations and cognitive impairment. Timely combination therapy is important in anti-NMDA-receptor concurrent with anti-AMPA-receptor encephalitis.

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults

“…Some studies report the identification of NMDAR antibody in patients with schizophrenia and psychotic disorders, as well as in healthy control subjects; however, antibody detection in these series typically relied on serum testing alone or evaluated antibody subtypes/sub-classes which are not known to be pathogenic. [29][30][31] More recent studies have confirmed that NMDAR antibodies are highly specific for AIE when detected in CSF in addition to serum. 32 In recognition of this, while balancing the desire to not miss any patient with an autoimmune cause of psychiatric symptoms, it has been suggested that certain factors should prompt further workup in patients with a first psychotic episode.…”

Overview of Paraneoplastic Autoantibody-Mediated Cognitive Impairment and Behavioral Changes: A Narrative Review

“…Progressive behavioral changes include eating soap, irritability and agitation, slowed thinking (bradyphrenia), failure to recognize family members, repetitive stereotyped words and behaviors, and decreased social interaction. All patients have memory impairment as a cardinal feature of paraneoplastic AMPAR encephalitis [38][39][40].…”

Pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: Exploring psychosis, related risk factors, and hospital outcomes in a nationwide inpatient sample: A cross-sectional study

“…Autoimmune encephalitis is associated with a range of disorders and has been observed in patients diagnosed with schizophrenia, bipolar disorder and depression [ 8 ]. There have been reports that previous research has indicated that patients initially diagnosed with bipolar disorder, autistic traits, or psychotic disorder may develop autoimmune encephalitis several years later highlighting the possibility of misdiagnosis and mistreatment of autoimmune encephalitis with predominant psychiatric manifestations [ 9 – 12 ]…”

“…Autoimmune encephalitis is associated with a range of disorders and has been observed in patients diagnosed with schizophrenia, bipolar disorder and depression [8]. There have been reports that previous research has indicated that patients initially diagnosed with bipolar disorder, autistic traits, or psychotic disorder may develop autoimmune encephalitis several years later highlighting the possibility of misdiagnosis and mistreatment of autoimmune encephalitis with predominant psychiatric manifestations [9][10][11][12] Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is commonly characterized by a relapsing pattern, with patients often experiencing persistent behavioral, memory, cognitive, and executive function alterations even during the recovery phase [13].…”