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
Treatment of Stiff-Person Syndrome
IV immune globulin (IVIG)
IVIG can result in improvement lasting up to a year (12) 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.
