To describe a rare development of anti-CRMP5 parkinsonism and worsening ataxia while on atezolizumab (PD-L1 inhibitor therapy) for small cell lung cancer (SCLC) treatment. 

Overall, we describe progression of anti-CRMP5 disease on checkpoint inhibitor treatment (atezolizumab), with cerebellar ataxia, and now, parkinsonism. CRMP5 has been associated with peripheral neuropathy (47%) and cerebellar ataxia (26%) but limited literature to date describes anti-CRMP5 disease on checkpoint inhibitors to cause parkinsonism. This case is compelling due to the worsening and widespread parkinsonism on exam with corresponding basal ganglia MRI FLAIR hyperintensities suggestive of CRMP5 paraneoplastic disease.

Case

A 46-year-old woman with PMH of 7.5 pack-year smoking history, SCLC with known metastasis to right supraclavicular lymph node and left parietal lobe (treated with carboplatin/etoposide, then atezolizumab), associated paraneoplastic LEMS (anti-P/Q calcium Abs+), CRMP5 optic neuropathy and myelopathy (CRMP5 csf titers 1:2048 and serum titers 1:7680), presented with worsening leg weakness, increased oral secretions, and reduced speech volume. She first developed ataxia ~2 months after starting atezolizumab, and was continued on IVIG for this and LEMS. Neurologic exam was significant for hypophonic speech, facial hypomimia, diffuse bradykinesia, with preserved full motor strength throughout, decremental finger tapping, and intermittent bilateral hand resting tremor, and a short-stepped, mildly stooped gait, requiring a walker.  Brain MRI revealed interval increase in previously asymptomatic T2 FLAIR hyperintensities in bilateral basal ganglia. 

She was treated inpatient with PLEX and high dose steroids, then rituximab, pulse cyclophosphamide, monthly IVIg and escalating doses of levodopa with no improvement in her parkinsonism. Follow up MRI after 6 months revealed resolution of basal ganglia hyperintensities with residual bilateral striatal atrophy, explaining her continued symptomatic CRMP5 parkinsonism/ataxia.

Atezolizumab (PD-L1 inhibitor therapy) treatment of SCLC can worsen and expand the spectrum of paraneoplastic anti-CRMP5 disease. Caution should be used when prescribing atezolizumab in this clinical context.