The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data

Abstract

Background A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies. Methods The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann–Whitney Test (U). The protocol was prospectively registered (CRD42018082210). Results Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04). Conclusions Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.

NMDAR autoantibodies in psychiatric disease - An immunopsychiatric continuum and potential predisposition for disease pathogenesis

“…The onset of NMDARE is often characterized by psychiatric symptoms [ 5 , 6 ]. Nevertheless, NMDAR autoantibodies are also detected in psychiatric patients who fail to fulfill NMDAR-encephalitis criteria [ [7] , [8] , [9] ]. The role NMDAR autoantibodies play in these patients is less well understood, and deserves investigation in large-scale studies.…”

“…It is essential to examine autoantibodies against NMDAR NR1 in CSF as well as serum, because their presence in CSF with typical clinical features supports the diagnosis of definite autoimmune encephalitis according to the Graus criteria [ 4 ]. In addition, a recent study by Blackman [ 9 ] demonstrated that psychiatric syndromes associated with NMDAR antibodies can differ from psychiatric syndromes associated with serum NMDAR antibodies on the basis of clinical demographic factors and diagnostic features. For example, patients presenting CSF NMDAR antibodies unlike those with serum NMDAR antibodies) were more likely to suffer a subacute onset, more likely to be female, more likely to present EEG and CSF abnormalities, and more likely to be psychotic and suffer from insomnia [ 9 ].…”

“…In addition, a recent study by Blackman [ 9 ] demonstrated that psychiatric syndromes associated with NMDAR antibodies can differ from psychiatric syndromes associated with serum NMDAR antibodies on the basis of clinical demographic factors and diagnostic features. For example, patients presenting CSF NMDAR antibodies unlike those with serum NMDAR antibodies) were more likely to suffer a subacute onset, more likely to be female, more likely to present EEG and CSF abnormalities, and more likely to be psychotic and suffer from insomnia [ 9 ]. A very recent study also demonstrated that patients in the post-acute stage of NMDAR encephalitis resemble in their cognitive abilities those with stabilized schizophrenia [ 29 ].…”

Cytokine/chemokine levels in the CSF and serum of anti-NMDAR encephalitis: A systematic review and meta-analysis

“…antibody detection (54). Interestingly, in a prior validation study of a commercial diagnostic kit based on indirect immunofluorescence on transfected cells, a false-positive rate of 1.4% has been reported for the application of serum and cell-based assay (55).…”

Philosophical Approach to Neural Autoantibodies in Psychiatric Disease—Multi-Systemic Dynamic Continuum from Protective to Harmful Autoimmunity in Neuronal Systems

“…This suggestion is based on the observation that in encephalitides associated with antibodies and intracellular antigens, CD8+ T cells were frequently found in encephalitic brain tissue [ 1 ]. The other major mechanism is characterized by the action of neural autoantibodies, such as antibodies against the N-methyl-D-aspartate receptor [ 2 ] detected in an autoimmune encephalitis of psychiatric phenotype [ 3 ]. Neural autoantibodies are part of the immune defense, which can play a protective role in destroying cancer (as paraneoplastic antibodies on the one hand), but they can also be destructive when accompanying CNS inflammation and neuronal nerve cell damage [ 4 ].…”