Paraneoplastic Neurologic Syndromes with ANNA-2/anti-Ri: a Contrasting Story of Two Cases
Nanthaya Tisavipat1, Bryce Chang1, Farwa Ali1, Sean Pittock1, Eoin Flanagan1
1Neurology, Mayo Clinic College of Medicine and Science
Objective:
To highlight the clinical spectrum of paraneoplastic neurologic disease associated with antineuronal-nuclear-autoantibody-type-2 (ANNA-2/anti-Ri).
Background:
ANNA-2/anti-Ri is a marker of a T-cell-mediated paraneoplastic neurologic disease with a strong cancer association that can present with opsoclonus-myoclonus syndrome, ataxia, jaw dystonia, and laryngospasm.
Design/Methods:
Case report of two patients at a tertiary referral center. ANNA-2 was detected by tissue immunofluorescence and western blot.
Results:

Case 1: A 61-year-old woman presented with horizontal binocular diplopia, progressive trismus, jaw spasms causing tongue biting, and trouble eating over 5 weeks. Brain MRI revealed dorsal pons and medulla T2-hyperintensity without enhancement. CSF showed no cells, protein 70 mg/dL, and 4 oligoclonal bands. ANNA-2 was present in CSF (1:128) and serum (1:7680), and invasive ductal breast carcinoma (stage 2) was found and treated with right mastectomy and chemotherapy. She developed episodic cyanosis from laryngospasm. Botox moderately helped her jaw opening dystonia, and tracheostomy was recommended for laryngospasm. She did not have improvement with steroids, intravenous immunoglobulin, rituximab, plasma exchange, or cyclophosphamide.  

Case 2:  A 51-year-old woman with a history of recurrent right breast cancer previously treated with bilateral mastectomy, chemotherapy, radiation, and hormonal treatment developed opsoclonus-myoclonus and progressive imbalance over 3 months leading to wheelchair dependence. ANNA-2 was detected in CSF (1:4096) and serum (1:15360). She received seven plasma exchange treatments and a 1-month course of high-dose oral steroids, followed by 1-month tapering. FDG-PET revealed cervical lymph node avidity presumed to be breast cancer recurrence that was treated with chemotherapy. Overall, she reported 70-80% symptom improvement and could walk independently. She was maintained on monthly plasma exchange.

Conclusions:
These two cases highlight the clinical spectrum of ANNA-2/anti-Ri paraneoplastic neurologic disorders. While outcome is often poor with ANNA-2/anti-Ri and other antibodies targeting intracellular antigens, our second case shows that some patients can have robust response to immunotherapy and cancer treatment.
10.1212/WNL.0000000000202444