Cerebrospinal fluid biomarkers in psychiatric autoimmune encephalitis: a retrospective cohort study

Abstract

Background: Psychiatric autoimmune encephalitis (pAE) is a growing field of interest in diagnosis and therapy in psychiatric hospitals and institutions. This study investigates the relevant extent to which there are potential biomarkers in cerebrospinal fluid (CSF) that can differentiate against a cohort with neurodegenerative disease.

Methods: We included in this study a total of 27 patients with possible and definite psychiatric autoimmune encephalitis and compared with a cohort with CSF-based AD (n = 27) different biomarkers in CSF such as lactate, cell count, % lymphocytes, % monocytes, total protein content, albumin, immunoglobulins G (IgG), M (IgM) and A (IgA), CSF/serum albumin ratio, CSF/serum IgG ratio, CSF/serum IgA ratio, intrathecal IgG synthesis, blood-brain barrier disruption, specific antibody synthesis for measles, rubella, herpes simplex virus, varicella zoster virus, Ebstein-Barr virus and cytomegalovirus, total tau protein (t-tau), phosphorylated tau protein 181 (p-tau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40) and the amyloid beta 42/ amyloid beta 40 (Aß42/40) ratio.

Results: The p-tau 181 was elevated above cut-off values in both possible pAE and AD. However, in definitive pAE, p-tau181 levels were not elevated. When elevated p-tau181 levels in possible AE were compared with those in AD, we found relevant differences, such as a relative increase in p-tau181 in AD patients. Elevated p-tau181 levels were detected in possible psychiatric AEs with IgLON5, glycine, recoverin, titin, and nonspecific neuropil antibodies in serum and IgLON5, titin, Yo, and nonspecific neuropil autoantibodies in CSF. In addition, we detected elevated levels of p-tau181 and IgLON5 autoantibodies in serum and CSF, and Yo autoantibodies in CSF in patients with definitive pAE. Interestingly, we observed a higher CSF/serum IgM ratio in possible and definitive pAE than in AD patients.

Conclusion: Our results suggest that neuroaxonal brain damage may occur in specific psychiatric AEs associated with IgLON5, glycine, recoverin, and titin autoantibodies. Further research should focus on the CSF/serum IgM ratio as an early marker of autoantibody production in pAE compared to AD as a potential biomarker for differential diagnosis.

Keywords: Alzheimer’s disease; autoimmune encephalitis; biomarker; cerebrospinal fluid; neurodegeneration markers.

Figure 1

Frequency distribution of psychiatric syndromes in patients with possible and definitive autoimmune encephalitis. The frequency of psychiatric syndromes is shown in (A) for possible autoimmune encephalitis and in (B) for definitive autoimmune encephalitis. Abbreviations: PARAHAL, parahallucinatory syndrome; PSYORG, psychoorganic syndrome; DEPRES, depressive syndrome; MANI, maniforme syndrome; APA, apathic syndrome; VEGET, vegetative syndrome; HOST, hostility syndrome; NEUROL, neurological syndrome.

Figure 2

Markers of neuronal cell damage in patients with possible and definite autoimmune encephalitis and Alzheimer’s disease. P-tau 181 (A) and total tau protein (t-tau) (B) were significantly increased in possible (poss AE) and definite autoimmune encephalitis (def AE) compared with Alzheimer disease (AD). In addition, both amyloid beta 42 (Aß42) (D) and the amyloid beta 42/40 (Aß42/40) ratio (C) were reduced in poss AE and def AE compared with AD. (E) No relevant changes were observed in Aß40 levels between cohorts. *p < 0.05, NS = non significant.