Stiff person syndrome

Stiff person syndrome (SPS) is a rare disorder that manifests with progressive muscle stiffness and rigidity. It is caused by an autoimmune process in which antibodies are formed against glutamic acid decarboxylase (GAD) or another protein in the gamma-aminobutyric acid (GABA) synthesis pathway. This leads to reduced levels of GABA, which then causes loss of CNS inhibition and increasing muscle stiffness. SPS is associated with autoimmune disorders (particularly type 1 diabetes mellitus). Less commonly, it occurs as a paraneoplastic process. Treatment of SPS consists of symptomatic treatment with benzodiazepines and muscle relaxants as well as immune modulation therapy with IVIG and immunosuppressants. Prognosis is poor, with most patients experiencing progressive gait disorders and disability.

• Autoimmune disease: Anti-GAD or anti-amphiphysin antibodies (proteins involved in the GABA synthesis pathway) are present in approx. 70% of cases.
• Antibody production may be:
  • Idiopathic
  • Paraneoplastic (rare; secondary to breast cancer, lung cancer, and lymphoma)
  • Associated with autoimmune diseases (type 1 diabetes mellitus, thyroiditis, vitiligo, pernicious anemia)

References:^[1]

Anti-GAD antibodies → decreased GAD → decreased GABA → loss of CNS inhibition → increased muscle tone and rigidity

References:^[1]

• Generalized increase in skeletal muscle rigidity (hands, feet, and face remain unaffected); particularly in the muscles of the proximal extremities, neck and back.
• Progressive rigidity may lead to lumbar or cervical hyperlordosis as well as gait abnormalities that may, in turn, cause falls and fractures.
• Episodic painful muscle spasms triggered by external (e.g., noise) and internal (e.g., emotional upset) stimuli
• Partial SPS: disease variant in which symptoms are limited to one extremity

References:^[1]

• Laboratory findings
  • Detection of anti-GAD antibodies (in 60–90% of cases)
  • Paraneoplastic SPS is usually anti-GAD antibody-negative; anti-amphiphysin antibodies may be detected in some cases
• Electromyography: continuous motor unit activity that can be reduced by administering intravenous diazepam
• CSF: possible pathological findings: oligoclonal bands

References:^[1][2]

Curative

• For suspected paraneoplastic etiology: identification of the tumor and treatment!

Symptomatic

• Enhancement of GABA signaling
  • High-dose oral diazepam or clonazepam (first-line treatment)
  • Oral baclofen (muscle relaxant) (second-line treatment in combination with benzodiazepines or as an alternative to benzodiazepines)
• Immunosuppressive therapy: immunoglobulins, plasmapheresis, rituximab

References:^[1]