Stiff-person syndrome is a CNS disorder that causes progressive muscle stiffness and spasms.
(See also Overview of Peripheral Nervous System Disorders.)
Stiff-person syndrome (formerly called stiff-man 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). However, 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 in the autoimmune type, affecting primarily inhibitory neurons that originate in the anterior horn of the spinal cord.
Very few patients have the paraneoplastic type. Antiamphiphysin antibodies are often present; anti-GAD are usually not. Paraneoplastic stiff-person syndrome is commonly 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. Patients are otherwise normal, and examination detects only muscle hypertrophy and stiffness. Stiff-person syndrome typically progresses, leading to disability and stiffness throughout the body.
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.
Treatment of Stiff-Person Syndrome
Diazepam or baclofen
IV immune globulin (IVIG)
Sometimes rituximab or plasma exchange.
Symptomatic therapy is available for stiff-person syndrome. Diazepam is the medication of choice; it most consistently relieves muscle stiffness. If diazepam is ineffective, baclofen, given orally or intrathecally, can be considered. However, these recommendations are not supported by randomized trials.
Corticosteroids are now avoided because adverse effects are associated with prolonged use of the high doses needed to control symptoms. Azathioprine, methotrexate, and mycophenolate mofetil are no longer used.
IVIG can result in improvement lasting up to a year (1). If patients do not respond to IVIG, rituximab (2) or plasma exchange may be suggested.
Treatment references
1. Dalakas MC, Fujii M, Li M, et al: High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 27;345 (26):1870–1876, 2001. doi: 10.1056/NEJMoa01167
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
There are 3 types of stiff-person syndrome: autoimmune, paraneoplastic, and 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.
Treat with diazepam or, if it is ineffective, baclofen; other options include IVIG, rituximab, and plasma exchange.
