Neuropsychiatric Autoimmune Encephalitis without VGKC-Complex, NMDAR, and GAD Autoantibodies

Abstract

We report a patient with a seronegative autoimmune panencephalitis, adding a subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we review the sparse literature on isolated psychiatric presentations of autoimmune encephalitis. (A PubMed search for "seronegative autoimmune encephalitis," "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms revealed <25 cases.) A 15-year-old girl developed an acute-onset isolated psychosis with prominent negative symptoms and intermittent encephalopathy. Despite clinical worsening, her brain magnetic resonance imaging (MRI) scans remained normal for 7 years. Serology was negative for voltage-gated potassium channel (VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic, paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms remitted fully with immune therapy, but recurred in association with widespread bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic inflammation and prominent vascular hyalinization. Immune therapy with plasma exchanges cleared the MRI abnormalities but, 10 years after onset, the patient still suffers neuropsychiatric sequelae. We conclude that autoimmune panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a subtype of autoimmune encephalitis that can present with pure neuropsychiatric features and a normal brain MRI. Immunologic mechanisms may account for psychiatric symptoms in a subset of patients now diagnosed with classical psychotic disorders. Delay in starting immune therapy can lead to permanent neuropsychiatric sequelae. We propose a standardized classification system for the autoimmune encephalitides, integrating earlier pathology-oriented terms with more recently defined serologic and clinical phenotypes.

Ethical Implications of the Mild Encephalitis Hypothesis of Schizophrenia

“…Inflammatory events could also play an important part in the development of bipolar disorder, major depression, and obsessive–compulsive disorder (21, 33, 52–55). Furthermore, neuroinflammation potentially contributes to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia (56).…”

“…Indeed, several cases of patients with anti-NMDAR encephalitis and misdiagnosed with schizophrenia have been reported (42). Somatic examination and adequate antibody screening should become standard procedure in first-episode psychosis patients in order to find possible organic causes (9, 52, 54, 55, 66). …”

Successful treatment of DRESS syndrome with plasmapheresis during the course of sero-negative autoimmune encephalitis: a case report

“…Sero-negative autoimmune encephalitis is inflammation of the brain secondary to autoimmune processes and by definition there is no identifiable autoantibody [2]. Both the vague neuropsychiatric presentation and the lack of definitive tests, make the diagnosis of autoimmune encephalitis elusive.…”

A Neuropsychiatric Presentation of Seronegative Autoimmune Encephalitis: A Case Report

“…Autoimmune encephalitis is an acute inflammation of the brain secondary to autoimmune process that manifests as seizures, cognitive impairment, and neuropsychiatric symptoms [1]. Seronegative autoimmune encephalitis is a subgroup of encephalitis with suspected immunologic origin but with no identifiable pathogenic autoantibody [1].…”

“…Seronegative autoimmune encephalitis is a subgroup of encephalitis with suspected immunologic origin but with no identifiable pathogenic autoantibody [1].…”