Phenotypical Stiff-Person Syndrome Associated with the Unclassified Synaptic Antibody SNAP-91-IgG: A Case Report
Omar Hage-Hassan1, Marta Paratsii3, Philip Ross2, Andrew McKeon4, Morgan Aguirre2, Wazim Mohamed2
1Neurology, Detroit Medical Center/Wayne State University, 2Detroit Medical Center/Wayne State University, 3Henry Ford Hospital, 4Mayo Clinic
Objective:
To describe a case of progressive spasms and rigidity with negative standard markers for stiff-person syndrome and positive SNAP-91-IgG unclassified synaptic antibody, highlighting a potential new autoimmune marker for immune-mediated rigidity disorder.
Background:
Stiff-person syndrome is a rare neurologic disorder characterized by progressive painful spasms and rigidity. Workup typically includes serum GAD65, glycine receptor, or amphiphysin antibodies (often paraneoplastic) and characteristic EMG findings.
Results:
A previously independent 34-year-old female presented with progressive back and bilateral lower extremity spasms and rigidity starting November 2024, with near-complete quadriparesis by December 2025, raising concern for stiff-person syndrome. Initial MRI brain and spine were unrevealing. Diagnostic workup included mildly elevated serum GAD65 antibody, a weakly positive amphiphysin antibody, and negative CSF studies. Symptomatic treatment and IVIG were initiated, but she was lost to follow-up. At the end of 2025, she presented quadriparetic with concerns for respiratory failure. Repeated imaging and electrographic studies were negative for continuous motor activity. She failed IVIG and rituximab and became ventilator-dependent due to diaphragmatic involvement. Repeat serum and CSF workup was performed; CSF immunohistochemistry identified an unclassified neural antibody (UNA), SNAP-91-IgG (SNAP91). SNAP91 demonstrated a nearly identical immunofluorescent staining pattern on murine brain tissue to amphiphysin antibody, most commonly seen in stiff-person syndrome. The presence of SNAP91 suggests an alternative active autoimmune process. Due to her previous intolerance of IVIG and failure of rituximab, the patient subsequently underwent empirical treatment with plasmapheresis in addition to targeted symptomatic management with antispasmodics and botulinum injections, with mild subjective improvement in frequency of spasms.
Conclusions:
Only three known cases have tested positive for this unclassified antibody. This case of progressive spasticity and rigidity with positive SNAP-91-IgG could help identify a new autoimmune marker for rigidity disorders or better differentiate overlapping immune-mediated neuromuscular disorders.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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