What are the diagnostic criteria for Stiff Person Syndrome?

Diagnostic Criteria for Stiff Person Syndrome

Stiff Person Syndrome (SPS) is diagnosed based on clinical presentation, electrophysiological findings, and the presence of specific autoantibodies, particularly anti-glutamic acid decarboxylase (anti-GAD) antibodies.

Clinical Diagnostic Criteria

The diagnosis of SPS requires the following core clinical features:

1. Progressive, fluctuating muscular rigidity and stiffness

   • Primarily affecting axial muscles (trunk, abdominal, paraspinal)
   • Often extends to proximal limb muscles
   • Characteristic lumbar hyperlordosis

2. Superimposed painful spasms

   • Triggered by tactile stimuli
   • Exacerbated by passive stretch
   • Precipitated by emotional stress or startle
   • Worsened by volitional movement

3. Characteristic relief patterns

   • Symptoms relieved by sleep
   • Symptoms relieved by general anesthesia
   • Symptoms relieved by GABA-enhancing medications

4. Absence of other neurological disorders that could explain the symptoms

   • Normal brain MRI
   • No evidence of structural lesions explaining symptoms

Electrophysiological Criteria

• Continuous motor unit activity in agonist and antagonist muscles at rest
• Failure of muscle relaxation
• Normal nerve conduction studies

Immunological Criteria

• Presence of anti-GAD65 antibodies in serum and/or CSF (found in 60-80% of classic SPS cases)
• Alternative antibodies may be present in variant forms:
  • Anti-amphiphysin antibodies (in paraneoplastic SPS)
  • Anti-gephyrin antibodies
  • Anti-GABAA receptor-associated protein antibodies

SPS Variants and Classification

SPS can be classified into three main types:

1. Classic SPS

   • Symmetric rigidity and spasms predominantly affecting axial and proximal limb muscles
   • Strong association with anti-GAD65 antibodies
   • Often associated with other autoimmune disorders (especially type 1 diabetes)

2. Paraneoplastic SPS

   • Associated with underlying malignancy
   • Often positive for anti-amphiphysin antibodies
   • May have more rapid progression

3. SPS Variants

   • Stiff limb syndrome (symptoms confined to limbs)
   • Progressive encephalomyelitis with rigidity and myoclonus (PERM)
   • Jerking stiff person syndrome

Supportive Features

• Association with other autoimmune disorders (type 1 diabetes, thyroiditis, vitiligo, pernicious anemia)
• CSF abnormalities (mild pleocytosis in some cases)
• Response to immunotherapy or GABA-enhancing medications
• Autonomic disturbances (profuse sweating, tachycardia, blood pressure fluctuations)

Exclusion Criteria

The diagnosis requires exclusion of other conditions that can mimic SPS:

• Neuromyotonia (Isaac's syndrome)
• Tetanus
• Dystonia
• Parkinson's disease
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Psychogenic movement disorders

Diagnostic Algorithm

1. Establish clinical suspicion based on characteristic stiffness and spasms
2. Perform EMG to document continuous motor unit activity
3. Test for anti-GAD65 antibodies in serum (and CSF if available)
4. Rule out structural, toxic, and metabolic causes with brain/spine MRI
5. Consider paraneoplastic workup, especially if anti-amphiphysin antibodies are present
6. Assess for associated autoimmune conditions

SPS remains a clinical diagnosis supported by laboratory findings. The heterogeneity in presentation can lead to misdiagnosis, particularly as psychiatric illness 1, 2, which delays appropriate treatment and worsens patient outcomes. Early recognition and treatment are essential to prevent disability and improve quality of life 3.