Makindo Medical Notes

🧍‍♂️ About

• Stiff Person Syndrome (SPS): A rare autoimmune neurological disorder causing progressive muscle stiffness and spasms. Anti-GAD (glutamic acid decarboxylase) antibodies are commonly positive, supporting an autoimmune mechanism.
• Paraneoplastic Variant: Seen with cancers (esp. breast, lung), as part of broader paraneoplastic syndromes 🎗️.

🧬 Aetiology

• Role of GAD: Converts glutamate → GABA (main inhibitory neurotransmitter). In SPS, antibodies attack GAD → ↓ GABA → loss of inhibition → hyperexcitable neurons.
• In paraneoplastic forms, antibodies may target amphiphysin or other antigens.

⚠️ Clinical Features

• Typical Presentation: Middle-aged adults, slowly progressive.
• Muscle Stiffness: Axial muscles (back, trunk), leading to a stiff, “board-like” gait 🚶‍♂️.
• Painful Spasms: Triggered by stimuli (sudden touch, noise, stress) ⚡.
• Falls: Common due to stiffness and loss of postural reflexes → ↑ injury risk.
• Posture: Hyperlordosis or hyperextended posture may develop.
• Labile BP & Autonomic Symptoms: Due to autonomic involvement.
• Associated Autoimmunity: Up to 30% have type 1 diabetes; others include autoimmune thyroiditis, pernicious anaemia, vitiligo 🦠.

💡 Exam Pearl: Think SPS in a patient with progressive stiffness, falls, exaggerated startle response, and positive anti-GAD antibodies.

🧪 Investigations

• Antibody Testing: Anti-GAD65 (positive in ~60%); anti-amphiphysin in paraneoplastic cases.
• EMG: Continuous motor unit firing even at rest → hallmark finding.
• MRI Brain/Spine: Typically normal; helps exclude mimics (MS, structural lesions).

🩺 Management

• Immunomodulation:
  • IVIG (first-line, strong evidence ✅)
  • Plasmapheresis (if refractory)
  • High-dose steroids
  • Rituximab has been tried in resistant cases
• Symptomatic Treatment:
  • Baclofen (GABA_B agonist) → reduces rigidity
  • Diazepam (benzodiazepine, GABA_A agonist) → relieves spasms + anxiety
  • Other options: Gabapentin, Tiagabine (GABAergic drugs)
• Paraneoplastic Forms: Treat underlying malignancy (surgery, chemo, immunotherapy) 🎗️.
• Supportive Care: Physiotherapy, occupational therapy, and fall prevention are essential.

📈 Prognosis

• Chronic course with gradual progression if untreated.
• Early immunotherapy + symptomatic treatment can stabilise symptoms and improve mobility.
• Falls and injury are major morbidity risks ⚠️.

📚 References

• Stiff Person Syndrome: A Comprehensive Review
• NIH: SPS Overview