Diagnostic value of CSF findings in antibody-associated limbic and anti-NMDAR-encephalitis

PURPOSE: In people with suspected inflammatory CNS disease, cerebrospinal fluid (CSF) is commonly analyzed. Antibody-associated limbic encephalitis (ab-LE) and anti-NMDAR-encephalitis are recognized as two major syndromes of autoimmune epilepsies. Here, we investigated the diagnostic value of CSF findings in these two entities. METHODS: We reviewed patients from our tertiary epilepsy centre with ab-LE and anti-NMDAR-encephalitis in whom CSF examination including oligoclonal bands (OCB) was performed. Ab-LE patients were subdivided according to antibodies (voltage-gated potassium channels, VGKC; glutamic acid decarboxylase, GAD) or presence of onconeural antibodies/presence of tumour into three groups: VGKC-LE, GAD-LE or paraneoplastic LE (PLE). As controls, patients with CSF investigations in whom autoimmune origin was initially assumed but not confirmed later on were included. In addition, a review of published ab-LE and anti-NMDAR-encephalitis cases with reported CSF data was performed. RESULTS: 55 ab-LE (23 VGKC-LE, 25 GAD-LE, 7 PLE) and 14 anti-NMDAR-encephalitis patients were identified at our centre. OCB were significantly more frequent in ab-LE and anti-NMDAR-encephalitis than in controls. Literature review identified 150 ab-LE and 95 NMDAR cases. Analysis of pooled data confirmed that presence of OCB was significantly more frequent in ab-LE and anti-NMDAR-encephalitis (especially in people with GAD-LE and anti-NMDAR encephalitis) as compared to controls. Sensitivity and specificity of OCB in the pooled ab-LE and anti-NMDAR-encephalitis patients was 34% and 96%, respectively. In patients with ab-LE and anti-NMDAR-encephalitis, the likelihood of OCB in CSF was 8.5-fold higher as compared to controls. Furthermore, in the pooled ab-LE and anti-NMDAR-encephalitis patients, cell counts in CSF were more frequently elevated (especially in those with anti-NMDAR encephalitis) than in controls, whereas protein content of CSF was not different between the groups. CONCLUSION: OCB, and to a lesser extent cell counts in CSF, appear to be helpful additional CSF markers in the diagnostic evaluation of people presenting with a constellation suggestive for GAD-LE, PLE and anti-NMDAR-encephalitis, prompting subsequent analysis of specific antibodies.