To describe a male patient with amphiphysin-associated Stiff-Person Syndrome(SPS) secondary to underlying breast cancer.

SPS is a rare neuroimmunological disorder that has varying clinical presentations and can be associated with different autoantibodies. Amphiphysin antibodies are most often associated with paraneoplastic-related SPS.

A 53-year-old man developed progressive upper-torso and arm stiffness/rigidity and gait instability. Subsequently, he developed foot spasms along with anxiety/agoraphobia and was diagnosed with psychogenic dystonia. Despite cognitive-behavioral-therapy, he experienced more symptoms over the ensuing year(leg stiffness requiring a cane and arm spasms) and predictable triggers for his symptoms(stress, loud noises, cold, and open spaces).

Two-years after symptom onset, he was diagnosed with SPS based on a work-up that identified positive-serum (1:7680) and CSF (1:64) amphiphysin-antibodies. Initial malignancy work-up was unremarkable including mammogram and whole-body PET CT-scan. Over the following year, he was treated with a variety of immune-therapies including IVIG, PLEX, and cyclophosphamide. His gait improved but stiffness and spasms worsened. Repeat malignancy work-up (approximately three-years out from initial symptom-onset) identified left-sided gynecomastia secondary to a retro-areolar nodule.  Core-diagnostic biopsy revealed grade-2 invasive ductal carcinoma. These results prompted a left-sided modified radical-mastectomy followed by adjuvant chemotherapy and radiation-therapy. Three-months after completing his cancer treatment, repeat amphiphysin-antibody testing was negative, although, neurophysiological-studies still demonstrated signs of SPS. Three-months out from his cancer treatment, he has experienced significant improvement in most of his symptoms and is able to walk unsupported; modified-Rankin Scale improved from grade-4 to grade-2 and his 25-foot timed walk went from 8.6 to 4.9 seconds without-assistance.

We present a rare case of paraneoplastic-related SPS in a man with breast cancer. Upper greater than lower torso/body presentations can occur in SPS particularly with amphiphysin-related-SPS. This case also highlights the importance of vigilant cancer-screening even if initial investigations are negative, especially in the setting of positive-amphiphysin antibody.