Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.

Background Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF‐L] and total tau protein [t‐tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. Aims To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. Methods Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. Results Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty‐eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9‐65.1) years. Age‐adjusted CSF‐NF‐L, CSF‐t‐tau, and CSF‐GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. Conclusion In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF‐L, t‐tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations.