The Evolving Diagnosis and Treatment Strategies for Stiff Person Syndrome: Marinos C. Dalakas, MD

WATCH TIME: 6 minutes

"Patients have difficulty walking because of the stiffness, and they have unprotected falls. They have anxiety, which triggers a lot of muscle spasms. Muscle spasms and pain along with stiffness are the key clinical criteria. But this leads to disability, because, as we have found out in our longitudinal studies, this is a progressive disease. The patients have more difficulty walking, and they remain with disability."

Stiff person syndrome (SPS) is a rare, disabling neuroimmunological condition with no consensus diagnostic criteria, often leading to misdiagnosis because of limited clinician awareness of its atypical symptoms and presentations. According to a study published in the Journal of Neurology, recognizing key diagnostic features and common misdiagnosis patterns may help providers make more accurate and timely diagnoses. This could reduce both misdiagnosis and overdiagnosis, facilitate earlier treatment, and ensure appropriate patient selection for future interventional clinical trials in SPS.¹

Treatment options for SPS generally include GABAergic therapies and immunotherapies, with benzodiazepines commonly used as a first-line option. Oral baclofen, rituximab, or tacrolimus may be used as second-line therapies, with some studies favoring baclofen or rituximab over tacrolimus. For patients with refractory symptoms, treatment options may include intrathecal baclofen, intravenous immunoglobulin (IVIG), or plasmapheresis. Some evidence suggests that intrathecal baclofen and IVIG may offer greater benefit than plasmapheresis in refractory cases.²

Marinos C. Dalakas, MD, professor of neurology at Thomas Jefferson University, spoke with NeurologyLive^® to discuss his experience studying SPS, emphasizing how the condition has shifted from being underdiagnosed to now often overdiagnosed. He reviewed the key clinical features and the importance of confirming diagnosis with high-titer antibodies against GAD or glycine receptors. He outlined symptomatic therapies and immunotherapies, noting that IVIG remains the first-line immune treatment, though response may decline over time. He also shared updates on ongoing research, including a CAR T-cell trial and planned studies of FcRN and IL-6 inhibitors for patients with refractory disease.

REFERENCES
1. Roy S, Huang Y, Hu C, Fitzgerald KC, Wang Y, Newsome SD. Core diagnostic features of stiff person syndrome: insights from a case-control study. J Neurol. 2025 May 5;272(5):377. doi: 10.1007/s00415-025-13103-2. PMID: 40323494; PMCID: PMC12053319.
2. Ortiz JF, Ghani MR, Morillo Cox Á, et al. Stiff-Person Syndrome: A Treatment Update and New Directions. Cureus. 2020;12(12):e11995. Published 2020 Dec 9. doi:10.7759/cureus.11995