Stiff person syndrome

• Published in: Handbook of Clinical Neurology Vol. 203; pp. 211 - 233
• Main Authors: Cullinane, Patrick W., Carr, Aisling S., Irani, Sarosh R., Warner, Thomas T.
• Format: Book Chapter Journal Article
• Language: English
• Published: Netherlands Elsevier Health Sciences 2024
• Subjects: Autoantibodies - immunology; GABA; GAD autoimmunity; Glutamate Decarboxylase - immunology; Glycine; Humans; Progressive encephalomyelitis with rigidity and myoclonus; Stiff person syndrome; Stiff-Person Syndrome - diagnosis; Stiff-Person Syndrome - immunology; Stiff-Person Syndrome - therapy; GABA; Progressive encephalomyelitis with rigidity and myoclonus; Glycine; GAD autoimmunity; Stiff person syndrome
• ISBN: 0323908209; 9780323908207
• ISSN: 0072-9752
• DOI: 10.1016/B978-0-323-90820-7.00003-3

Stiff Person syndrome (SPS) is a rare autoimmune disorder of the central nervous system characterized by stiffness and spasms in the lumbar and proximal lower limb muscles. Nonmotor symptoms include phobias, anxiety, and depression. SPS exists on a spectrum ranging from a focal disease known as the stiff limb syndrome to progressive encephalomyelitis with rigidity and myoclonus. Collectively, these conditions may be referred to as stiff person spectrum disorders, as they share similar core clinical features and autoantibodies against several neuronal proteins, which are involved in modulating central hyperexcitability. Antibodies against the glutamic acid decarboxylase enzyme are most frequently associated with SPS but their role in disease pathogenesis remains uncertain. Other antibodies associated with SPS now include those against the glycine receptor, amphiphysin, dipeptidyl-peptidase-like protein 6, gephyrin, γ-aminobutyric acid receptor A (GABAAR), and the GABAAR-associated protein. First-line treatments for SPS include diazepam and baclofen. Patients who do not respond adequately may benefit from immunotherapy. Intravenous immunoglobulin has the most supporting evidence, and while several other immunotherapies are used, further trials are required to determine their efficacy. Further studies to establish the precise role of autoantibodies in the pathogenesis of SPS are also needed to better understand and manage this disabling condition.