(See also Overview of Peripheral Nervous System Disorders Overview of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more .)
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 Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , as well as other autoimmune disorders including thyroiditis Hashimoto Thyroiditis Hashimoto thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration. Findings include painless thyroid enlargement and symptoms of hypothyroidism. Diagnosis... read more , vitiligo Vitiligo Vitiligo is a loss of skin melanocytes that causes areas of skin depigmentation of varying sizes. Cause is unknown, but genetic and autoimmune factors are likely. Diagnosis is usually clear... read more 
, and pernicious anemia Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more . 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.
Fewer than 1 to 2% 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 Hodgkin Lymphoma Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more 
.
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 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 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.
IVIG can result in improvement lasting up to a year. If patients do not respond to IVIG, rituximab or plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more may be suggested.
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.
