Stiff-person syndrome is a CNS disorder that causes progressive muscle stiffness and spasms.
Stiff-person syndrome affects the central nervous system (CNS) but has neuromuscular manifestations.
Most patients with stiff-person syndrome have antibodies against glutamic acid decarboxylase (GAD), the enzyme involved in the production of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid). Stiff-person syndrome may be
Autoimmune
Paraneoplastic
Idiopathic
The autoimmune type often occurs with type 1 diabetes, as well as other autoimmune disorders including thyroiditis, vitiligo, and pernicious anemia. Autoantibodies against several proteins involved in GABA synapses are present, affecting primarily inhibitory neurons that originate in the anterior horn of the spinal cord.
The paraneoplastic type occurs rarely. Antiamphiphysin antibodies are often present; anti-GAD are usually not. Paraneoplastic stiff-person syndrome is most often associated with breast cancer but may also occur in patients with lung, renal, thyroid, or colon cancer or Hodgkin lymphoma.
Symptoms and Signs of Stiff-Person Syndrome
Clinical manifestations of stiff-person syndrome are similar in all types. Muscle stiffness, rigidity, and spasms progress insidiously in the trunk and abdomen and, to a lesser degree, in the legs and arms. Examination detects only muscle hypertrophy and stiffness. Stiff-person syndrome typically progresses, leading to stiffness throughout the body and disability.
Diagnosis of Stiff-Person Syndrome
Diagnosis of stiff-person syndrome is based on recognizing the symptoms and is supported by antibody testing, response to diazepam, and results of electromyography (EMG) studies, which show the electrical activity of apparent normal contraction.Diagnosis of stiff-person syndrome is based on recognizing the symptoms and is supported by antibody testing, response to diazepam, and results of electromyography (EMG) studies, which show the electrical activity of apparent normal contraction.
Treatment of Stiff-Person Syndrome
Benzodiazepines (diazepam or clonazepam)Benzodiazepines (diazepam or clonazepam)
Antispasmodic drugs (baclofen)Antispasmodic drugs (baclofen)
Antiepileptics (gabapentin, vigabatrin)Antiepileptics (gabapentin, vigabatrin)
IV immune globulin (IVIG)
Sometimes rituximab or plasma exchangeSometimes rituximab or plasma exchange
Symptomatic therapy is available for stiff-person syndrome. Diazepam and clonazepam most consistently relieve muscle stiffness and are considered first-line therapy, but there can be difficulties with adverse effects (somnolence, fatigue) and there is a risk of dependence. Baclofen, given orally or intrathecally (with great caution taken to avoid catheter leakage), can be considered. Gabapentin is the most frequently trialed antiepileptic medication and can treat muscle spasms. These recommendations are supported by observational studies, in the absence of randomized trials.Symptomatic therapy is available for stiff-person syndrome. Diazepam and clonazepam most consistently relieve muscle stiffness and are considered first-line therapy, but there can be difficulties with adverse effects (somnolence, fatigue) and there is a risk of dependence. Baclofen, given orally or intrathecally (with great caution taken to avoid catheter leakage), can be considered. Gabapentin is the most frequently trialed antiepileptic medication and can treat muscle spasms. These recommendations are supported by observational studies, in the absence of randomized trials.
Glucocorticoids have shown limited benefit and should be avoided because of the adverse effects associated with prolonged use of the high doses needed to control symptoms.
IVIG can be effective in patients who do not respond to the GABA-enhancing and antispasmodic medications listed above (1). If patients do not respond to IVIG, rituximab (). If patients do not respond to IVIG, rituximab (2) or plasma exchange may be suggested.
Treatment references
1. Dalakas MC. Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2023;10(3):e200109. Published 2023 Apr 14. doi:10.1212/NXI.0000000000200109
2. Ortiz JF, Ghani MR, Cox AM, et al. Stiff-person syndrome: A treatment update and new directions. Cureus. 12 (12):e11995, 2020. doi: 10.7759/cureus.11995
Key Points
Stiff-person syndrome may be autoimmune, paraneoplastic, or idiopathic.
Stiff-person syndrome affects the CNS but causes progressive muscle stiffness, rigidity, and spasms, mainly in the trunk and abdomen.
Diagnose based on symptoms, response to diazepam, and results of antibody testing and EMG studies.Diagnose based on symptoms, response to diazepam, and results of antibody testing and EMG studies.
Treat with diazepam or, if it is ineffective, baclofen; other options include IVIG, rituximab, and plasma exchange.Treat with diazepam or, if it is ineffective, baclofen; other options include IVIG, rituximab, and plasma exchange.
Drug Information for the Topic
