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Neurology

Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare progressive and often underdiagnosed immune-mediated disorder of the central nervous system characterized by progressive rigidity and triggered painful spasms of predominantly axial and proximal limb muscles. The condition has an insidious onset with gradual worsening over time and, if left untreated, can lead to permanent disability and mortality. This activity reviews the evaluation and treatment of patients with SPS and emphasizes the importance of the in

v1 · Reviewed Nov 7, 2026 by Automated Clinical Reviewer (Strict Verbatim v1)
  • The condition has an insidious onset with gradual worsening over time and, if left untreated, can lead to permanent disability and mortality.
  • In rare cases, respiratory muscles can be involved.
  • As the disease progresses, unexpected tactile and auditory stimuli could trigger the occurrence of autonomic failure with tachycardia, hypertension, and hyperthermia.
  • A diagnosis of SPS is usually made clinically by thorough neurological examination with the support of electrodiagnostic and laboratory findings.
  • The current diagnostic criteria for classic SPS include: Stiffness in the limb and axial muscles, prominent in the abdomen and thoracolumbar region
  • Painful spasms precipitated by unexpected tactile and auditory stimuli
  • Evidence of the continuous motor unit activity in agonist and antagonist muscles demonstrated by EMG
  • Absence of other neurological impairments that could support an alternative diagnosis
  • Positive serology for anti-GAD65 or anti-amphiphysin autoantibodies
  • Clinical response to therapy with benzodiazepines
  • Routine nerve conduction studies in SPS are usually normal.
  • Needle electromyography (EMG) in SPS shows continuous involuntary motor unit activity even at rest, despite volitional effort to relax.
  • MRI brain and spinal cord are usually non-diagnostic in classic SPS, but they are often performed to rule out other causes of rigidity and stiffness.
  • To diagnose a paraneoplastic variant, it is important to check for antibodies against amphiphysin and gephyrin and initiate a prompt neoplastic workup.
  • Since around 35 % of patients diagnosed with SPS have DM-1 and about 5 % have associated autoimmune thyroid disease, a search for coexisting autoimmune conditions is commonly performed.
  • Symptomatic management is a standard of initial therapy and focuses on decreasing stiffness, rigidity, and painful muscle spasms.
  • It is achieved using medications that promote GABA effects, such as benzodiazepines, baclofen, gabapentin, and vigabatrin.
  • Diazepam is known to be a first-line symptomatic agent for patients with SPS.
Diazepam
Not specified in source
Adult
Not specified in source
Renal
Not specified in source
Duration
Not specified in source
  • Unlike IVIG, the benefit of plasma exchange is not yet fully established, and most patients only demonstrate temporary or no improvement in symptoms.
  • Corticosteroid effectiveness is controversial in SPS.
  • Use of other immunomodulating agents including mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, tacrolimus, and sirolimus is reported with variable effects.
  • Intrathecal baclofen is also effectively used in some patients.
  • Symptom management also includes treatment of co-existing seizures and psychiatric comorbidities with anti-epileptic and antidepressant medications, respectively.
  • It is crucial to timely initiate therapy to prevent or lessen progression and avoid long-term complications.
  • Patients with SPS are at higher risk of developing orthopedic problems such as lumbar hyperlordosis, joint deformities, and muscle atrophies, leading to abnormal posturing and gait abnormalities with increased fall risk.
  • As the disease progresses, unexpected tactile and auditory stimuli could trigger the occurrence of autonomic failure with tachycardia, hypertension, and hyperthermia.
  • For patients with a paraneoplastic variant, a thorough search for underlying malignancy should be promptly initiated.
  • In addition, it is crucial to monitor patients who receive immunotherapy for possible side effects.
  • review
    Stiff Person Syndrome. StatPearls [Internet] — Alexandra Muranova, Elena Shanina — StatPearls Publishing, 2023

Decision support only. Verify against local protocols and current labeling. Source: www.ncbi.nlm.nih.gov