Anti-CASPR2 encephilitis patients present with depression as the first diagnostic feature

Abstract

Abstract Background and Purpose Although depression has been reported in patients with anti-contact protein-associated protein-2 (CASPR2) encephalitis, it rarely occurs as the first diagnostic feature in these patients, and it can be easily missed or misdiagnosed as a psychiatric disorder. This study evaluated the clinical features and pathogenesis of depression in patients with anti-CASPR2 encephalitis.Methods This was a prospective study in which patients with anti-CASPR2 encephalitis and co-current depression were recruited. Between 2020 and 2022, demographic data, clinical manifestations, Self-rating Depression scale (SDS), Self-rating Anxiety Scale(SAS), and antibody levels in cerebrospinal fluid (CSF) and serum of 6 patients with depression as the first manifestation were collected and analyzed.Results A total of 23 anti-CASPR2 encephalitis patients with depression and six patients (five females) with anti-CASPR2 encephalitis and depression as the first presentation were recruited in the present study. All patients showed subacute onset and were misdiagnosed with psychiatric disorders, with depression as the first symptom, accompanied by anxiety and cognitive impairment, and autonomic dysfunction. Good response to immunotherapy. After a follow-up for 6 months, all symptoms were significantly alleviated, and the anti-CASPR2 antibodies were negative.Conclusion Depression, as the first manifestation of anti-CASPR2 encephalitis, is more common in middle-aged and older women. The most common subtypes of depression are anxiety-distress, often accompanied by cognitive and autonomic disorders. A single serum antibody may improve the diagnosis of patients. Therefore, immunotherapy is an effective treatment modality. Immune activation is potentially the pathogenesis of depressive disorders in patients with anti-CASPR2 encephalitis.