Anti-Homer-3 antibodies in cerebrospinal fluid and serum samples from a 58-year-old woman with subacute cerebellar degeneration and diffuse breast adenocarcinoma.

introductionSubacute cerebellar ataxia combined with cerebrospinal fluid (CSF) pleocytosis is the result of an immune response that can occur due to viral infections, paraneoplastic diseases or autoimmune-mediated mechanisms. In the following we present the first description of a patient with anti-Homer-3 antibodies in serum and CSF who has been diagnosed with paraneoplastic subacute cerebellar degeneration due to a papillary adenocarcinoma of the breast. CASE PRESENTATION: A 58-year-old female was admitted to our clinical department because of increasing gait and visual disturbances starting nine months ago. The neurological examination revealed a downbeat nystagmus, oscillopsia, a severe standing and gait ataxia and a slight dysarthria. Cranial MRI showed no pathological findings. Examination of CSF showed a lymphocytic pleocytosis of 11 cells/µl and an intrathecal IgG synthesis of 26%. Initially, standard serological testing in serum and CSF did not indicate any autoimmune or paraneoplastic aetiology. However, an antigen-specific indirect immunofluorescence test (IIFT) revealed the presence of anti-Homer-3 antibodies (IgG) with a serum titer of 1: 32,000 and a titer of 1: 100 in CSF. Subsequent histological examination of a right axillary lymph node mass showed papillary adenocarcinoma cells. Breast MRI detected multiple bilateral lesions as a diffuse tumour manifestation indicative of adenocarcinoma of the breast. Treatment with high-dose methylprednisolone followed by five plasmaphereses and treatment with 4-aminopyridine resulted in a moderate decrease of the downbeat nystagmus and she was able to move independently with a wheeled walker after 3 weeks. The patient was subsequently treated with chemotherapy (epirubicin, cyclophosphamide) and two series of immunoglobulins (5 × 30 g each). This resulted in a moderate improvement of the cerebellar symptoms with a decrease of ataxia and disappearance of the downbeat nystagmus.

conclusionThe presented case of anti-Homer-3 antibody-associated cerebellar degeneration is the first that is clearly associated with the detection of a tumour. Interestingly, the Homer-3 protein interaction partner metabotropic glutamate receptor subtype 1A (mGluR1A) is predominantly expressed in Purkinje cells where its function is essential for motor coordination and motor learning. Based on our findings, in subacute cerebellar degeneration, we recommend considering serological testing for anti-Homer-3 antibodies in serum and cerebrospinal fluid together with tumor screening.