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 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
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.
In the paraneoplastic type, antiamphiphysin antibodies are often present; anti-GAD and anti-Ri antibodies may be present. This type is commonly associated with breast cancer but may also occur in patients with lung, renal, thyroid, or colon cancer or lymphoma.
Clinical manifestations 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. Electromyography (EMG) shows only the electrical activity of 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 EMG studies, which show continuous motor unit activity in agonist and antagonist muscles.
Only symptomatic therapy is available. Diazepam is the drug of choice; it most consistently relieves muscle stiffness. If diazepam is ineffective, baclofen, given orally or intrathecally, can be considered.
Corticosteroids are reportedly effective but have many long-term adverse effects.
Results of plasma exchange are inconsistent, but IVIG appears to result in improvement lasting up to a year.
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