What is the initial treatment for Stiff Man Syndrome?

Initial Treatment for Stiff-Person Syndrome

Benzodiazepines, specifically diazepam, are the first-line treatment for Stiff-Person Syndrome (SPS), as they enhance GABAergic transmission and provide symptomatic relief of muscle stiffness and spasms. 1, 2

First-Line Pharmacologic Management

Benzodiazepines (Primary Treatment)

• Diazepam is FDA-approved for SPS and should be initiated as the primary symptomatic therapy 1
• Start at lower doses (e.g., 2-5 mg two to three times daily) and gradually titrate upward based on symptom response 2, 3
• Effective doses typically range from 10-80 mg daily in divided doses, though some patients may require higher doses 3
• Diazepam works by enhancing GABA transmission, directly addressing the reduced GABA levels that cause stiffness in SPS 2
• Treatment with diazepam has been shown to decrease muscle spasms in long-term follow-up studies 3

Alternative GABA-Enhancing Agents (If Benzodiazepines Insufficient)

• Baclofen can be added or used as an alternative, starting at 15-20 mg daily and titrating to effect (typical range 30-90 mg daily) 2, 4
• Baclofen has demonstrated efficacy in allowing previously bedridden patients to regain mobility 4
• Other GABA-enhancing options include valproate, vigabatrin, tiagabine, and gabapentin, though evidence is less robust 2

Immunotherapy Considerations

When to Add Immunotherapy

• Immunotherapy should be considered early in the treatment algorithm, particularly for patients with:
  • High titers of anti-GAD antibodies 2, 5
  • Inadequate response to GABA-enhancing medications alone 2
  • Progressive or severe symptoms 2

Immunotherapy Options

• Intravenous immunoglobulin (IVIG) has shown beneficial effects in controlled studies and provides lasting benefit 2
• Corticosteroids have demonstrated favorable responses in preliminary reports 5
• Plasmapheresis can provide additional benefit, particularly in refractory cases 2, 5
• The autoimmune nature of SPS (evidenced by anti-GAD antibodies, association with other autoimmune disorders, and intrathecal GAD-specific IgG synthesis) justifies immunotherapy use 2, 5

Refractory Cases

Intrathecal Baclofen

• For patients refractory to oral medications, intrathecal baclofen via implanted pump should be considered 6
• A continuous intrathecal trial (4 days) with gradual titration (starting at 50 μg/day up to 150 μg/day or higher) is recommended before permanent pump placement 6
• This approach is superior to single-injection trials for determining effective therapeutic doses 6
• Intrathecal baclofen can provide significant relief even in GAD-negative SPS patients who fail oral therapies 6

Adjunctive Rehabilitation

• Physical therapy and rehabilitation are essential adjuncts to pharmacologic treatment 3
• Focus rehabilitation on:
  • Treatment of low-back pain and hyperlordosis 3
  • Mobility problems and gait abnormalities 3
  • Muscular stiffness management 3
• Rehabilitation becomes particularly important because some muscle spasms typically persist despite optimal medical management 3

Common Pitfalls to Avoid

• Do not delay treatment while waiting for anti-GAD antibody results; clinical diagnosis should prompt immediate initiation of benzodiazepines 2
• Avoid undertreating with inadequate benzodiazepine doses; patients often require substantial doses for symptom control 3
• Do not rely solely on symptomatic treatment; consider immunotherapy early rather than as a last resort 2, 5
• Do not overlook rehabilitation; pharmacologic treatment alone is insufficient for optimal functional outcomes 3