Stiff-person syndrome mimicking ankylosing spondylitis
DOI:
https://doi.org/10.15305/ijrci/v14i1/358Keywords:
Stiff-Person Syndrome, Ankylosing Spondylitis, Axial Stiffness, Anti-GAD AntibodiesAbstract
Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle rigidity and episodic spasms, predominantly affecting the axial and proximal limb muscles. Its atypical presentation can lead to diagnostic delays and misdiagnosis, particularly as musculoskeletal disorders such as ankylosing spondylitis (AS) in patients presenting with persistent back stiffness and reduced spinal mobility. The present study reports the case of a 35-year-old male with no significant comorbidities who presented with a 4-month history of backache and progressive stiffness involving the axial skeleton and upper limbs. He was initially evaluated for AS; however, normal inflammatory markers, negative HLA-B27 status, and normal spinal magnetic resonance imaging findings raised diagnostic uncertainty. Electromyography demonstrated continuous motor activity in the paraspinal muscles, while markedly elevated anti-glutamic acid decarboxylase (GAD) antibody titers (1716.05 IU/mL) supported the diagnosis of SPS. Treatment with benzodiazepines, baclofen, and immunomodulatory therapy resulted in substantial clinical improvement. This case highlights the importance of considering SPS in patients with persistent axial stiffness despite normal inflammatory markers and imaging findings. Early recognition and appropriate GABAergic and immunomodulatory therapy may prevent unnecessary investigations and interventions and improve long-term outcomes. Greater awareness of SPS among rheumatologists and neurologists is essential for timely diagnosis and management.
References
1. Dalakas MC. The clinical spectrum of anti-GAD antibody–positive patients with stiff-person syndrome. Neurology. 2000;55(11):1531–1535.
2. Levy LM, Dalakas MC, Floeter MK. The stiff-person syndrome: An autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999;131(7):522–530.
3. Hadavi S, Nouri N, Brown SC, Vincent A, Clover L, Karlsson J. Stiff person syndrome and variants: Clinical course, treatments, and outcomes. Brain. 2011;134(Pt 6):1587–1598.
4. Murinson BB, Butler M, Marini SG. Stiff-person syndrome diagnosis: A case-based tutorial. Pract Neurol. 2016;16(4):274–278.
5. Meinck HM, Thompson PD. Stiff man syndrome and related conditions. Mov Disord. 2002;17(5):853–866.
6. Solimena M, De Camilli P. Autoimmunity to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome. Trends Neurosci. 1991;14(10):452–457.
7. Ameli R, Snow J, Rakocevic G, Dalakas MC. A randomized, placebo-controlled trial of rituximab in stiff person syndrome. Neurology. 2019;92(1):e20–e27.
8. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti–GAD antibody–positive patients with stiff-person syndrome. Neurology. 2000;55(10):1531–1535.
9. Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet. 2017;390(10089):73–84.
10. Poddubnyy D, van Tubergen A, Landewé R, van der Heijde D. Assessment of spondyloarthritis. Nat Rev Rheumatol. 2021;17(7):357–374.
11. Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis. Ann Rheum Dis. 2009;68(6):777–783.
12. Dalakas MC. Progress and stiff challenges in understanding the role of GAD-antibodies in stiff-person syndrome. Exp Neurol. 2021;336:113524.
13. Blum PA, Jankovic J. Generalized stiffness: the stiff-man syndrome. Arch Neurol. 1988;45(7):780–782.
14. . Rosenbaum RB, Nardone R. Update on stiff-person syndrome: new insights into pathogenesis and clinical variations. Curr Neurol Neurosci Rep. 2021;21(9):47.
15. Moersch FP, Woltman HW. Progressive fluctuating muscular rigidity and spasm (“stiff-man” syndrome): report of a case and some observations in 13 other cases. Mayo Clin Proc. 1956;31(15):421–427.
16. Solimena M, Folli F, Denis-Donini S, et al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med. 1988;318(16):1012–1020.
17. Jankovic J. Stiff-person syndrome: from GAD to GABA therapy. Lancet Neurol. 2006;5(2):158–160.
18. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti–GAD antibody–positive patients with stiff-person syndrome. Neurology. 2000;55(10):1531–1535.
19. Lo SE, Jones HN, DeLong R, et al. Stiff-person syndrome in the pediatric population: two case reports and a literature review. Pediatr Neurol. 2020;108:110–114.
20. Kumar N, Ahlskog JE, Klein CJ, et al. Stiff-person syndrome research: Immunopathogenesis, guided therapy, and future directions. J Neurol Sci. 2020;415:116926.
21. Rakocevic G, Raju R, Dalakas MC. Comparison of IVIg and PLEX in stiff-person syndrome. Neurology. 2007;68(21):1781–1782.
22. Henningsen H, Meinck HM. Specific phobias in stiff-man syndrome. J Neurol Neurosurg Psychiatry. 2003;74(10):1337–1339.
23. Zeigler L, McEntee B, Cunningham J, et al. A multidisciplinary approach for treating stiff-person syndrome. J Clin Neuromuscul Dis. 2019;20(3):139–145.
