Ri/Nova gene‐associated paraneoplastic subacute motor neuronopathy

RI/NOVA GENE-ASSOCIATED PARANEOPLASTIC SUBACUTE MOTOR NEURONOPATHY Flanagan and colleagues describe a patient with subacute lower motor neuronopathy (SMN) that preceded the diagnosis of Hodgkin lymphoma (HL). We encountered a patient with high titers of anti-Ri or anti-neuronal nuclear autoantibody type 2 (ANNA-2). This antibody is usually associated with paraneoplastic opsoclonus myoclonus ataxia (POMA) syndrome and breast cancer instead of SMN. A 49-year-old woman noted fatigue, cramps, twitching, and gait ataxia in early 2010 followed 3 months later by asymmetrical left leg weakness. Detection of a breast lump heralded moderately differentiated ductal carcinoma. A serum anti-Ri (ANNA-2) antibody titer was 1:7680 (normal<1:240) from among a panel of paraneoplastic autoantibodies that were otherwise negative. Treatment with 4 cycles of doxorubicin, cyclophosphamide and dexamethasone, and paclitaxel preceded increased leg weakness and adjustment of chemotherapy to 3 courses of cyclophosphamide, methotrexate, fluorouracil, and dexamethasone. Nystagmus on bilateral gaze, saccadic eye movements, startle myoclonus, and cataplexy supervened. In early 2011, she received radiation to the breast and involved nodes. Soon thereafter, wasting, fasciculation, brisk reflexes, ankle clonus, and left Babinski sign were noted. There was no evidence of cancer recurrence on whole body fluoro-deoxyglucose positron emission tomography/computed tomography (FDG PET-CT) or abnormal gadolinium-enhancement of the brain or spinal cord on contrast enhanced MRI. Lumbar cerebrospinal fluid (CSF) was normal with a CSF anti-Ri titer of 1:256 and a serum anti-Ri titer of 1:960. Left soleus muscle biopsy showed mild neurogenic changes. Sural nerve biopsy showed well populated myelinated fascicles. Treatment with 1.6 g/kg intravenous immunoglobulin (IVIg) monthly for 6 months did not lead to further improvement, however plasma exchange (PE) for an additional 6 months led to sustained improvement in weakness, fasciculation, hyperreflexia of the legs and ankle clonus on last examination in September 2012, at which time the anti-Ri titer was<1:240.