Anti-Amphiphysin Paraneoplastic Syndrome

Anti-amphiphysin antibodies are intracellular onconeural antibodies most commonly associated with paraneoplastic neurologic syndromes in patients with breast cancer, although small-cell lung cancer and other tumors have also been reported. Amphiphysin is a presynaptic protein involved in synaptic vesicle endocytosis.

The most characteristic clinical presentation is paraneoplastic stiff-person syndrome (SPS), with progressive axial and limb rigidity, painful muscle spasms triggered by stimuli and lumbar hyperlordosis. Other manifestations include myelopathy, encephalitis, sensory neuronopathy and brainstem involvement.

Diagnosis requires confirmation of anti-amphiphysin antibodies (typically by immunoblot or immunoprecipitation), exclusion of other causes and search for an underlying tumor with comprehensive imaging including PET-CT and mammography. Treatment combines tumor-directed therapy with immunomodulation and symptomatic anti-spasticity medications.