Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman

Abstract

Background: Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS).Case Description: We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot. There are coexisting long-tract disturbance and lower-extremity weakness. Treatment with diazepam provided symptomatic relief while plasma exchange (PLEX) did not lead to significant clinical improvement. The patient was bedridden within 3 months and passed away within 6 months from symptom onset.Conclusion: This case highlights the importance of recognition of uncommon presentation of SPS and its oncological significance. This entity requires a high degree of suspicion for initiation of the proper workup. The rapid identification and treatment of the underlying tumor might offer the best chance for recovery.

Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

“…Anti-amphiphysin antibodies are seen in PNS most commonly associated with breast cancer (~90% of cases) as well as ovarian and SCLC ( 24 , 25 ). This antibody was first described in a rare form of paraneoplastic stiff person syndrome (SPS), a disorder characterized by symmetric muscle stiffness and painful spasms of axial and limb muscles, without pyramidal or extrapyramidal signs ( 26 ). They do not present with “classic” SPS given other associated neurologic symptoms ( 26 ).…”

“…This antibody was first described in a rare form of paraneoplastic stiff person syndrome (SPS), a disorder characterized by symmetric muscle stiffness and painful spasms of axial and limb muscles, without pyramidal or extrapyramidal signs ( 26 ). They do not present with “classic” SPS given other associated neurologic symptoms ( 26 ). It is now recognized that anti-amphiphysin is associated with a broad range of neurologic presentations including SPS, polyradiculoneuropathy, diffuse sensory neuronopathy, encephalomyelitis, limbic encephalitis, Lambert Eaton myasthenic syndrome (LEMS), cerebellar degeneration, opsoclonus-myoclonus, as well as myelopathy ( 24 , 27 , 28 ).…”

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes

“…Breast cancer is the most common carcinoma linked to SPSSDs. Table 1 shows that from 29 studies on breast cancer, six SPSSD subtypes, including classic SPS ( 21 , 30 , 37 – 47 , 50 , 63 , 64 ), SLS ( 57 , 58 , 65 ), paraneoplastic cerebellar degeneration ( 59 ), subacute sensory neuronopathy, subacute cerebellar degeneration ( 60 ), and PERM ( 61 ), among which classic SPS is the major SPSSD subtype, were found to be involved. Patients with breast cancer and PSSD were determined to have other carcinomas, such as colon cancer, non-Hodgkin lymphoma, thymoma and lymphoma, and malignant melanoma ( 21 , 34 , 39 , 41 ).…”

“…Patients with breast cancer and PSSD were determined to have other carcinomas, such as colon cancer, non-Hodgkin lymphoma, thymoma and lymphoma, and malignant melanoma ( 21 , 34 , 39 , 41 ). Furthermore, patients with breast cancer and SPSSD were found to have other diseases, including autoimmune diseases, such as paraneoplastic encephalomyelitis, type 1 diabetes, thyroid disease, pernicious anemia, vertigo, psoriasis, thyroid disease, rheumatoid arthritis, sarcoidosis, mixed connective disease, limbic encephalitis, myelopathy, HIV, and ischemic cardiomyopathy ( 21 , 34 , 41 , 45 , 58 , 59 , 65 ). Amphiphysin ( 55 ) is the most common autoantigen in patients with breast cancer and SPSSD, followed by GAD65, Ri, acetylcholine receptor (AChR), and glycine receptor (GlyR).…”

“…The major SPSSD subtype is classic SPS ( 28 , 37 , 38 , 43 – 45 , 47 – 50 , 52 – 56 , 135 ), followed by SLS ( 58 , 65 ) and PERM ( 62 , 72 ). Moreover, the major carcinoma associated with SPSSD is breast cancer ( 28 , 37 , 38 , 43 – 45 , 47 – 50 , 52 – 56 , 58 , 135 ), followed by thymoma ( 66 , 95 , 99 ) and lung cancer ( 66 , 72 ) ( Table 6 ).…”