What are the treatment options for Stiff Man Syndrome?

Treatment of Stiff Person Syndrome

Diazepam is the first-line treatment for Stiff Person Syndrome, with doses typically ranging from standard anxiolytic dosing up to high-dose therapy (often requiring substantial doses for symptom control), and should be combined with physical therapy to address mobility, hyperlordosis, and gait abnormalities. 1, 2

First-Line Symptomatic Treatment: GABAergic Therapy

Benzodiazepines (Primary Agent)

• Diazepam is FDA-approved specifically for stiff-man syndrome and remains the cornerstone of treatment 1
• Start with standard dosing and titrate upward based on response; many patients require high-dose oral diazepam for adequate symptom control 3
• Diazepam decreases muscle spasms effectively, though some spasms typically persist despite treatment 2
• Intravenous diazepam provides marked amelioration of symptoms and can be used diagnostically when the diagnosis is uncertain 3

Additional GABAergic Options

• Add levetiracetam or pregabalin if symptoms persist on benzodiazepines alone 4
• Oral baclofen is recommended as second-line therapy over other immunosuppressive agents 4
• Baclofen addresses the reflex spasm component and spasticity associated with the syndrome 1

Immunotherapy (Based on Autoimmune Pathophysiology)

When to Consider Immunotherapy

• The association with autoimmune diseases (diabetes, organ-specific autoimmune disorders) and presence of anti-GAD65 antibodies supports early immunotherapy 5, 6
• Patients with antibodies against glutamic acid decarboxylase and pancreatic islet cells in serum/CSF are candidates for immune-directed treatment 6

Immunotherapy Options

• Intravenous immunoglobulin (IVIG) for patients resistant to GABAergic therapy 7, 4
• Monthly IVIG is commonly used but may fail in severe cases 7
• Corticosteroids show favorable response based on preliminary reports 6
• Rituximab is recommended over tacrolimus as second-line immunotherapy 4
• Plasma exchange (plasmapheresis) and corticosteroid therapy demonstrate favorable responses 6

Refractory Disease Management

For Severe, Treatment-Resistant Cases

• Intrathecal baclofen and IVIG are more effective than plasmapheresis in refractory symptoms 4
• Therapeutic plasma exchange (TPE) offers significant improvement in mobility and resolution of muscle spasms in patients who have failed diazepam, baclofen, and monthly IVIG 7
• Approximately half of SPS patients treated with TPE report benefits 7
• Propofol may serve as bridge therapy before initiating permanent treatment 4

Essential Rehabilitation Component

Physical Therapy Integration

• Rehabilitation is an important adjunct that improves function even when muscle spasms persist 2
• Focus rehabilitation on:
  • Treatment of low-back pain and hyperlordosis (a characteristic finding) 2, 3
  • Mobility problems and gait abnormalities 2
  • Muscular stiffness management 2
• Physical therapy should be instituted to prevent disability progression 7

Diagnostic Confirmation Before Treatment

Key Clinical Features to Verify

• Slowly progressive stiffness of axial and proximal limb muscles making ambulation difficult 3
• Hyperlordosis of the lumbar spine 3
• Episodic spasms precipitated by jarring, sudden movement, or startle 3
• Normal intellectual, sensory, and motor examination when not in spasm 3
• Continuous motor unit activity on EMG in affected muscles 2
• Exclude peripheral neuropathy, radiculopathy, or other movement disorders through thorough neurological examination 5

Common Pitfalls to Avoid

• Do not misdiagnose as simple acute or chronic low back pain and muscle spasm—this is easily overlooked in the emergency setting 3
• Do not rely solely on medication; rehabilitation must be incorporated early 2
• Do not abandon treatment if some spasms persist on diazepam—this is expected, and combination therapy is often needed 2
• Screen for associated conditions: insulin-dependent diabetes, epilepsy, and organ-specific autoimmune disorders 6