Treatment of Stiff Person Syndrome
Begin treatment with benzodiazepines as first-line therapy, add IVIG for refractory cases, and consider immunosuppression with corticosteroids or rituximab for patients with inadequate response. 1, 2
First-Line Symptomatic Treatment: GABAergic Therapy
Benzodiazepines are the drugs of first choice for symptomatic management of muscle rigidity and spasms in Stiff Person Syndrome. 1, 2 Diazepam is the most commonly used agent, though other benzodiazepines are effective. 1, 3
- If symptoms persist despite benzodiazepine therapy, add levetiracetam or pregabalin as adjunctive GABAergic agents. 1
- Gabapentin is also used in clinical practice for additional symptom control. 4
Second-Line Therapy: Oral Baclofen
Oral baclofen is recommended as second-line therapy when first-line GABAergic agents provide insufficient relief. 1 Baclofen should be prioritized over rituximab and tacrolimus at this stage. 1
Immunomodulatory Treatment
Corticosteroids
Immunomodulation with front-loaded methylprednisolone reduces stiffness and spasms and improves neurological symptoms in the majority of patients. 2 This approach recognizes SPS as an autoimmune-mediated chronic encephalomyelitis. 2
- Typical regimens include intravenous methylprednisolone followed by oral corticosteroid taper. 4
- Corticosteroids address the underlying autoimmune pathophysiology, particularly in patients with anti-GAD65 antibodies. 4
Rituximab
Rituximab should be considered for patients requiring immunosuppression, particularly when corticosteroids alone are insufficient. 1, 4 While clinical trial data remain limited, case reports demonstrate moderate improvement when rituximab is added to the treatment regimen. 4, 3
Refractory Disease Management
For patients with treatment-refractory symptoms despite oral medications and corticosteroids, three options exist:
Intrathecal Baclofen
Intrathecal baclofen via an implanted pump device is more effective than plasmapheresis for refractory symptoms. 1, 2 This represents an alternative of last resort for severe, uncontrolled rigidity and spasms. 2
Intravenous Immunoglobulin (IVIG)
IVIG is more effective than plasmapheresis in patients with refractory symptoms. 1 However, IVIG is effective less frequently than corticosteroids. 2
- IVIG is typically administered as part of combination therapy with other immunomodulatory agents. 4
- Response rates vary, with some patients showing minimal improvement despite prolonged treatment. 5
Plasmapheresis
Plasmapheresis is the least effective of the three refractory treatment options but may be considered when intrathecal baclofen and IVIG are not feasible or have failed. 1, 2
Bridging Therapy
Propofol may be used as temporary bridge therapy before initiating permanent treatment in patients with severe, acute exacerbations. 1
Treatment Algorithm Summary
- Start with benzodiazepines (diazepam preferred) for all patients 1, 2
- Add levetiracetam or pregabalin if inadequate response 1
- Add oral baclofen as second-line agent 1
- Initiate immunomodulation with methylprednisolone (front-loaded regimen) followed by oral corticosteroid taper 2
- Consider rituximab for additional immunosuppression if needed 1, 4
- For refractory disease, choose in order of effectiveness:
Important Caveats
SPS is frequently misdiagnosed as psychogenic movement disorder, delaying appropriate treatment. 2 Confirm diagnosis with electromyographic abnormalities showing continuous motor unit activity and the presence of anti-GAD65 antibodies in serum and cerebrospinal fluid. 2
The paraneoplastic variant of SPS requires different management, as it is associated with malignancies (most commonly breast cancer with amphiphysin antibodies, followed by colon cancer, lung cancer, Hodgkin's disease, and malignant thymoma). 3 Screen for underlying malignancy in appropriate clinical contexts.
Cognitive behavioral therapy (CBT) combined with standard pharmacotherapy shows promise for improving quality of life beyond symptom control alone. 3