Paraneoplastic multifocal neuropathy with anti-CRMP5- and anti-amphiphysin antibodies and myositis preceeding recurrence of a small-cell bladder carcinoma

Background: Paraneoplastic neurological syndromes occur as cross-reactivity of the tumor-directed immune response against nervous system structures. Antibodies against several nervous system proteins have been defined that are diagnostic for a paraneoplastic cause of neurological sequelae. The second most frequent antibody specificity seems to be anti-CRMP-5-immunoglobulin G, which is frequently associated with ANNA-1/anti-Hu-antibodies, the most frequent paraneoplastic antibody, or anti-calcium channel-antibodies. Small-cell lung carcinoma is found in the majority of patients with CRMP-5-antibodies. Only rarely, anti-CRMP-5-antibodies are associated with immunoglobulin against amphiphysin, which were initially described in patients with breast cancer and stiff man-syndrome.

Case Report: Here, we report a case of a 73-year old man with a history of a small cell-bladder carcinoma who developed a subacute multifocal neuropathy. The clinical syndrome supported by nerve conduction studies, muscle MRT and increased circulating immune complexes was suggestive for vasculitis, which was ultimately proven by sural nerve biopsy. In addition, muscle biopsy revealed a myositis. A screening for a broad panel of paraneoplastic antibodies revealed high titer immunoglobulin against CRMP-5 and amphiphysin. Other common paraneoplastic antibodies were negative. A local relapse of the carcinoma was identified as the cause of the neuropathy.

Conclusion: In conclusion, this case illustrates that antibodies against CRMP-5 can occur in small-cell cancers of other origin than the lung. Furthermore, anti-CRMP-5- and anti-amphiphysin-antibodies can prove the paraneoplastic origin of a multifocal neuropathy suggestive for vasculitis. This is – to our knowlegde – the first report of myositis in patient with anti-CRMP-5- and –amphiphysin-antibodies.