PERM associated with thymic carcinoma with triple-autoantibody positivity: case report and literature review

Abstract

Introduction

Progressive encephalomyelitis with rigidity and myoclonus (PERM) represents a severe Stiff-person syndrome (SPS) variant with brainstem and autonomic involvement. Although PERM is occasionally paraneoplastic—typically associated with antibodies such as anti-GAD, anti-GlyR, and anti-amphiphysin—its association with thymic carcinoma has not been previously described.

Objective

To report a case of PERM associated with thymic carcinoma and triple autoantibody positivity in cerebrospinal fluid (CSF), and to review the literature on paraneoplastic and multiple-antibody PERM.

Methods

A literature review of paraneoplastic and multiple-antibody PERM cases was conducted in English. The case report follows CARE guidelines.

Case report

A 47-year-old Mexican-mestizo female patient was diagnosed with PERM secondary to stage IIIB thymic carcinoma. Brain MRI revealed hyperintensities in the mesial temporal and orbitofrontal regions. CSF analysis showed anti-GAD65, anti-amphiphysin, and anti-titin antibodies. Intravenous immunoglobulin therapy resulted in marked clinical improvement.

Discussion

The literature review demonstrated wide clinical and immunological heterogeneity. Most patients were female, typically presenting in later adulthood. Anti-GAD was the most frequent antibody, often coexisting with others in thymoma-associated cases. Presentations were consistently severe, often involving neuropsychiatric, autonomic, and brainstem symptoms, despite frequently unremarkable MRI findings. Coexisting antibodies in paraneoplastic cases were linked to more aggressive disease, while anti-GlyR positivity was associated with milder presentations and better treatment response. Early immunotherapy was generally beneficial.

Conclusion

This case highlights the need for timely oncologic and immunologic evaluation in atypical SPS presentations and underscores the therapeutic importance of early diagnosis and treatment.