A recent prospective study demonstrated that neuronal autoantibodies were not uncommon in patients with lung cancer, and the analysis estimated they occur in more than one-third of patients. Study results were published in JAMA Oncology.

For patients who have paraneoplastic neurological syndromes (PNSs), lung cancer is a common underlying condition. Neuronal autoantibodies are often found in association with paraneoplastic syndrome. However, as the study investigators explained in their report, research regarding their presence and cognitive associations in patients with small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) has been limited.

Patients in this study had lung cancer and were seen at a center in Berlin, Germany. The patients underwent serum sampling for neuronal autoantibodies, in addition to neuropsychological testing. Results were evaluated to determine if associations existed between neuronal autoantibodies and evidence of cognitive impairment.

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A total of 167 patients with lung cancer were assessed, of whom 127 had NSCLC and the remaining 40 patients had SCLC. The median patient age was 66.0 years. PNS was seen in 4.8% of patients, all of whom had SCLC.

Autoantibodies associated with the brain were found in 36.5% of the total population (95% CI, 29.2%-44.3%). Neuronal autoantibodies were seen in 45.0% of patients with SCLC (95% CI, 29.3%-61.5%) and in 33.9% of those with NSCLC (95% CI, 25.7%-42.8%). Previously known autoantibodies were detected in 19.8% of total patients, and autoantibodies directed against unknown antigens were found in 16.8%.

Cognitive impairment was detected in 67.0% of evaluated patients. In the subgroup of patients with SCLC, the presence of neuronal autoantibodies was associated with an odds ratio (OR) of 11.0 for cognitive impairment (95% credible interval [CrI], 1.2-103.6), compared with not having detected autoantibodies.

In patients with NSCLC, verbal memory deficit was associated with immunoglobin A autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). This relationship had an OR of 182.8 (95% CrI, 3.1-10,852.4). Immunoglobulin M autoantibodies to the NMDAR were not associated with cognitive impairment or verbal memory deficit.

In the overall patient population, regardless of tumor subtype, cognitive impairment showed an association with currently unidentified neuronal autoantibodies with an OR of 2.8 (95% CrI, 0.6-12.1). Overall, 75.7% of patients who had neuronal autoantibodies showed neurologic deficits upon neurological examination, whereas 55.9% of patients who tested negative for autoantibodies had neurologic deficits.

“In this cross-sectional study, a high prevalence of neuronal autoantibodies was observed among patients with lung cancer, and these neuronal autoantibodies were associated with clinically relevant cognitive impairment,” the study investigators concluded in their report.


Bartels F, Wandrey MM, Aigner A, et al. Association between neuronal autoantibodies and cognitive impairment in patients with lung cancer. JAMA Oncol. Published online July 1, 2021. doi:10.1001/jamaoncol.2021.2049