What is Stiff Man Syndrome (Stiff Person Syndrome)?

From the Guidelines

Stiff man syndrome, also known as Stiff person syndrome, should be treated with a combination of benzodiazepines, such as diazepam or clonazepam, and baclofen as first-line therapy to manage symptoms. This approach is based on the understanding of the disorder as an autoimmune neurological condition characterized by progressive muscle stiffness and painful spasms, often associated with antibodies targeting glutamic acid decarboxylase (GAD) 1. The treatment aims to enhance GABA activity and reduce muscle rigidity.

Key Treatment Components

• Benzodiazepines: diazepam (5-10mg three times daily) or clonazepam (0.5-2mg twice daily) to enhance GABA activity
• Baclofen: (10-25mg three times daily) as a muscle relaxant
• Immunotherapy for confirmed autoimmune etiology: intravenous immunoglobulin (IVIG) at 2g/kg over 2-5 days every 4-6 weeks, plasmapheresis, or rituximab (375mg/m² weekly for 4 weeks) may be considered
• Pain management: gabapentin (300-1200mg three times daily) or pregabalin (75-300mg twice daily) as needed

Management Considerations

• Physical therapy is crucial to maintain mobility and function
• Regular monitoring for symptom progression and medication side effects is necessary
• Associated autoimmune conditions, such as diabetes or thyroiditis, require concurrent management
• The presence of other antibody-mediated disorders or organ-specific autoimmunity, or a history of previous infectious/febrile illness, should be considered in the patient's history, as noted in guidelines for recognition of neuronal surface antibody-associated syndromes 1.

From the FDA Drug Label

Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma), spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia), athetosis, and stiff-man syndrome Diazepam may be useful for the management of stiff man syndrome as an adjunct for the relief of skeletal muscle spasm.

• The drug is indicated for the relief of symptoms associated with stiff man syndrome.
• Diazepam may be used to help manage the condition, but its effectiveness in long-term use has not been assessed by systematic clinical studies 2.

From the Research

Definition and Characteristics of Stiff Man Syndrome

• Stiff man syndrome (SPS) is a rare and disabling central nervous system disorder characterized by muscle rigidity, sporadic muscle spasms, and chronic muscle pain 3.
• The syndrome is strongly correlated with autoimmune diseases, and high titers of antibodies against acid decarboxylase (GAD65) are often found in patients with SPS 3, 4, 5.
• Variants of the syndrome may involve one limb only (stiff leg syndrome), a variety of additional neurological symptoms and signs, or be associated with malignant disease (paraneoplastic SPS) 4.

Diagnosis and Treatment of Stiff Man Syndrome

• Diagnosis of SPS is often misinterpreted as psychogenic movement disturbance, but electromyographic abnormalities and the presence of autoantibodies against GAD in both serum and cerebrospinal fluid help to establish the correct diagnosis 4.
• Treatment of SPS typically involves GABAergic (gamma-aminobutyric acid) therapy and immunotherapy, with benzodiazepines as first-line treatment 3, 5.
• Additional treatments may include levetiracetam, pregabalin, oral baclofen, rituximab, and intravenous immunoglobulin (IVIG) 3, 6, 5.
• In patients with refractory symptoms, intrathecal baclofen, IVIG, or plasmapheresis may be effective 3, 6, 7.

Clinical Forms and Outcomes of Stiff Man Syndrome

• There are several clinical forms of SPS, including classic SPS, partial SPS, and progressive encephalomyelitis with rigidity and myoclonus (PERM) 6, 5.
• The severity of the evolution differs in each case, and identifying patients with SPS makes it possible to propose appropriate medical management 6.
• Recognition of classic SPS vs variants is important because appropriate therapy improves symptoms in most patients, and classification by anatomical extent and by GAD65 antibody serostatus gives important diagnostic and prognostic information 5.