Background The occurrence of a second delayed paraneoplastic neurological syndrome (PNS), different from the first, in the same patient, is not well known. However, recognition of this possibility is important in the management of the patient with PNS.

Objective To describe eight patients who presented with two different PNS with a time delay of months to years.

Design, setting and patients Retrospective analysis of eight patients, included in the European PNS database, with two different PNS that occurred months to years apart.

Results The median delay between the two different PNS was 15 months. The antibody repertoire did not change between the two episodes. Anti-Hu was detected in five patients, and anti-CV2 and anti-Ri in one each. One patient did not present onconeural antibodies. Lung cancer was diagnosed in six patients. In five patients, the second PNS revealed a cancer relapse (n=4) or a second cancer (n=1) and in three it occurred without evidence of tumour recurrence. In these three patients, all with anti-Hu antibodies, the second episode consisted of a lower motor neuron disease. Median survival was not reached after a median follow-up of 5 years.

Conclusions A second PNS can reveal a cancer relapse but can also arise in its absence. The long survival of patients with a second PNS suggests that the immune response might be more effective in controlling the cancer.