Autoimmune and paraneoplastic variants of stiffperson syndrome: two case reports with anti-GAD positivity and distinct clinical courses

Background Stiff-person spectrum disorder (SPSD) is a rare disabling neurological disease characterized by progressive muscle rigidity and stiffness. Most of the cases are primarily attributed to autoimmune pathology due to the presence of anti-GAD 65 antibody; however, paraneoplastic etiology is also found in some cases. We report two distinct cases that represent the autoimmune and paraneoplastic etiologies of SPSD. Both of them shared positivity for anti-GAD65 antibody with some variation in clinical course. Case presentation The first case: A 33-year-old male patient presented with progressive generalized pain and muscle stiffness in addition to slurred speech, nasal tonation and nystagmus with a severe form of gait ataxia. The diagnostic work-up revealed positivity for anti-GAD65 antibody along with a thymoma which was surgically removed. He received muscle relaxants in addition to plasma exchange sessions followed by rituximab therapy which significantly improved his stiffness and ataxia, but his cranial nerves’ symptoms were still present. The second case: A 39-year-old male patient complained of severe low back pain associated with gradual progressive stiffness involving the entire back and proximal muscles of lower and upper limbs, as well as a significant phobia of falling and using the stairs. The diagnostic work-up showed an elevated titer of anti-GAD65 antibody, with a negative PET-CT scan. He received muscle relaxants, immunosuppressive drugs and psychological support in addition to plasma exchange and IVIG with marked improvement regarding muscle stiffness; however his persistent fear of using stairs significantly hinders his daily life activities. Conclusion These two cases highlight the clinical variability of StiffPerson Syndrome (SPS) ranging from classic autoimmune SPS with psychiatric comorbidity to a paraneoplastic SPS-plus variant with cerebellar and brainstem involvement. Elevated anti-GAD 65 antibody levels served as a diagnostic marker in both patients. These cases emphasize the importance of early recognition through autoimmune and oncologic screening with a multidisciplinary approach combining immunotherapy, physiotherapy and psychological support.