Treatment of Stiff Person Syndrome
Benzodiazepines, specifically diazepam, are the first-line treatment for stiff person syndrome, followed by additional GABAergic agents if symptoms persist, with immunotherapy reserved for refractory cases. 1, 2
First-Line Pharmacological Treatment
Start with diazepam as the primary medication, as it is FDA-approved for stiff-man syndrome and acts as a GABAergic agonist to reduce muscle rigidity and spasms. 1 The FDA label specifically indicates diazepam for relief of skeletal muscle spasm in stiff-man syndrome, making it the evidence-based initial choice. 1
If symptoms persist on benzodiazepines alone, add levetiracetam or pregabalin as adjunctive GABAergic therapy. 2 Pregabalin at 150 mg three times daily has shown satisfying response in clinical cases. 3
Second-Line Treatment
For patients with inadequate response to first-line GABAergic therapy, oral baclofen is recommended over rituximab and tacrolimus. 2 Baclofen provides additional GABAergic modulation and can be titrated for effect. 2
If oral baclofen proves insufficient, rituximab should be considered over tacrolimus as the preferred immunotherapy option. 2
Refractory Disease Management
For treatment-resistant cases, three options exist with varying efficacy:
- Intrathecal baclofen is more effective than plasmapheresis for refractory symptoms, delivering GABAergic therapy directly to the central nervous system. 2
- Intravenous immunoglobulin (IVIG) is more effective than plasmapheresis and addresses the autoimmune pathophysiology associated with anti-GAD65 antibodies. 2, 4
- Plasmapheresis can be used but is less effective than the above options. 2, 5
Propofol may serve as temporary bridge therapy before establishing permanent treatment in severe cases. 2
Immunotherapy Considerations
Early immunotherapy should be strongly considered given the association with autoimmune diseases, particularly in patients with elevated anti-GAD65 antibodies. 6 The autoimmune pathogenesis supports this approach, especially when anti-GAD antibodies are detected. 3
Steroids, plasmapheresis, and IVIG all have roles in the immunotherapy armamentarium. 4 In paraneoplastic variants (associated with breast, colon, or lung cancer), tumor excision combined with plasmapheresis shows significant improvement. 5
Rehabilitation and Physical Therapy
Institute physical therapy early to prevent joint contractures and muscle atrophy from disuse, incorporating both stretching and strengthening activities. 7 Exercise has downstream effects in improving muscle function and reducing inflammation. 7
Therapeutic exercises should specifically target trunk and proximal limb stiffness to improve balance and functionality. 8 Outcome measures demonstrate improvement in muscle flexibility, balance, and functional abilities with structured rehabilitation programs. 8
Avoid splinting, as it increases attention to affected areas, promotes accessory muscle use, causes immobilization leading to muscle deconditioning, and increases risk of learned non-use and pain. 7
Diagnostic Confirmation
Before initiating treatment, confirm diagnosis with:
- Anti-GAD65 antibody testing (high titers strongly support diagnosis). 3, 5
- Electromyography showing continuous motor unit activity in agonist and antagonist muscles. 3
- Exclusion of peripheral neuropathy, radiculopathy, or other movement disorders through thorough neurological examination. 6
Common Pitfalls
The most critical pitfall is misdiagnosis as a psychiatric illness, which can delay appropriate treatment by years. 3 Patients may develop secondary phobic symptoms and adrenergic manifestations (profuse sweating, tachycardia, hypertension) that can mislead clinicians toward psychiatric diagnoses. 3 Maintain high clinical suspicion when patients present with progressive muscle stiffness and painful spasms, particularly when psychiatric treatments fail to improve symptoms. 3
Complete immobilization must be avoided, as strength loss is most dramatic during the first week of immobilization. 7 Instead, implement relative rest combined with eccentric strengthening exercises. 7