What is Stiff Person Syndrome?

Stiff Person Syndrome: A Rare Autoimmune Neurological Disorder

Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle rigidity and painful spasms primarily affecting the axial and proximal limb muscles, with most cases showing antibodies against glutamic acid decarboxylase (GAD). 1

Clinical Features

Core Symptoms

• Progressive muscle rigidity and stiffness, predominantly affecting:
  • Spine/axial muscles
  • Lower extremities
• Painful muscle spasms with simultaneous contraction of agonist and antagonist muscles
• Heightened sensitivity to external stimuli (tactile, auditory) that can trigger spasms
• Continuous motor unit activity detectable on electromyography (EMG)

Clinical Variants

1. Classic SPS: Most common form with axial and limb rigidity, associated with anti-GAD antibodies in up to 80% of cases 2, 3
2. Paraneoplastic SPS: Comprises approximately 5% of cases, associated with malignancies (breast, lung, thymus, colon) and often linked to anti-amphiphysin antibodies 2, 4
3. Stiff Limb Syndrome: A variant where symptoms are confined to the limbs 2

Associated Conditions

• Autoimmune disorders, particularly type 1 diabetes mellitus 1, 3
• Other autoimmune diseases may coexist

Pathophysiology

SPS is considered an autoimmune disorder with the following characteristics:

• Most patients have antibodies against glutamic acid decarboxylase (GAD), the enzyme that synthesizes gamma-aminobutyric acid (GABA) 3
• Reduced GABA-mediated inhibition in the central nervous system leads to excessive motor neuron activity
• In paraneoplastic cases, anti-amphiphysin or anti-SOX1 antibodies may be present 4

Diagnosis

Diagnostic Criteria

1. Progressive muscle rigidity and stiffness, primarily in axial and proximal limb muscles
2. Superimposed painful spasms
3. Electromyographic evidence of continuous motor unit activity
4. Positive response to benzodiazepines
5. Serological testing for:
   • Anti-GAD antibodies (positive in approximately 80% of classic SPS)
   • Anti-amphiphysin antibodies (in paraneoplastic cases)
   • Other autoantibodies (anti-SOX1) in some cases 4

Differential Diagnosis

• Tetanus
• Dystonia
• Parkinson's disease and parkinsonian syndromes
• Functional neurological disorder
• Multiple sclerosis
• Neuromyotonia

Treatment

First-line Treatments

• GABA-enhancing medications:
  • Benzodiazepines (particularly diazepam) for symptomatic relief 3
  • Baclofen (oral or intrathecal)

Immunomodulatory Therapy

• Intravenous immunoglobulin (IVIg): Demonstrated effectiveness in treating SPS 3, 4
• Plasmapheresis
• Rituximab
• Corticosteroids
• Other immunosuppressants (azathioprine, mycophenolate mofetil)

Management Challenges

• Treatment is often unsatisfactory and not well tolerated 2
• Requires personalized, multifaceted approach based on symptom severity
• Medication side effects may limit patient compliance

Prognosis and Complications

• Progressive disorder that can cause significant disability if untreated 5
• Poor quality of life with excess rates of comorbidity and mortality 5
• Potential complications:
  • Fractures due to falls or severe muscle spasms 4
  • Respiratory complications in severe cases, potentially requiring ventilatory support 6
  • Psychological impact due to chronic pain and disability

Clinical Pearls

• SPS is often misdiagnosed initially as a psychiatric disorder due to exacerbation of symptoms by emotional stressors 3
• The female-to-male ratio is approximately 2:1 3
• Clinical presentation can be highly variable, with some patients showing unusual features such as recurrent vomiting and progressive dysarthria 2
• Early diagnosis and treatment are essential to prevent progression and disability
• Despite being rare, awareness of this condition is crucial as it remains underdiagnosed 5