What is Stiff Man Syndrome (Stiff Person Syndrome)?

From the Guidelines

Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle stiffness, rigidity, and painful spasms primarily affecting the trunk and limb muscles, often associated with antibodies targeting glutamic acid decarboxylase (GAD) 1. The condition is also known as Stiff Man Syndrome, and its diagnosis is based on clinical presentation and the presence of specific antibodies.

• Key features of SPS include:
  • Progressive muscle stiffness and rigidity
  • Painful spasms
  • Primarily affecting the trunk and limb muscles
  • Association with antibodies targeting GAD, which disrupts GABA synthesis and leads to excessive motor neuron excitability and muscle contractions 1
• Treatment of SPS typically involves a combination of medications to manage symptoms and address the underlying autoimmune process, including:
  • Benzodiazepines, such as diazepam or clonazepam, to enhance GABA activity and reduce muscle spasms
  • Baclofen as a muscle relaxant
  • Immunotherapy, including intravenous immunoglobulin (IVIG), plasmapheresis, or rituximab, for patients with confirmed autoimmune etiology
  • Antiepileptic medications, such as gabapentin or pregabalin, to help with pain and spasms
• The most effective treatment approach for SPS is often a multidisciplinary one, incorporating pharmacological interventions, physical therapy, and monitoring for associated conditions like diabetes, thyroiditis, and other autoimmune disorders 1.
• Patients with SPS should be monitored regularly for disease progression and associated conditions, and treatment should be tailored to individual needs and response to therapy.
• The presence of antibodies targeting GAD is a key diagnostic feature of SPS, and testing for these antibodies can help confirm the diagnosis 1.

From the Research

Definition and Characteristics of Stiff Man Syndrome

• Stiff-person syndrome (SPS) is a rare, autoimmune, neuromuscular disorder characterized by axial and proximal muscle stiffness, rigidity, and painful muscle spasms, often causing progressive disability due to limited movement 2.
• 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.
• SPS is characterized by symmetrical muscle stiffness and spasms that may lead to skeletal deformity, and variants of the syndrome may involve one limb only or be associated with malignant disease 4.

Clinical Symptoms and Diagnosis

• Clinical symptoms of SPS include continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest, and spasms that are precipitated by tactile stimuli, passive stretch, volitional movement of affected or unaffected muscles, startling noises, and emotional stimuli 5.
• The diagnosis of SPS is often elusive, but electromyographic abnormalities and the presence of autoantibodies against glutamic acid decarboxylase (GAD) in both serum and cerebrospinal fluid can help establish the correct diagnosis 4.

Treatment Options

• First-line therapies for SPS comprise symptomatic management with γ-aminobutyric acid-modulating drugs such as benzodiazepines and baclofen 2.
• Patients resistant to these treatments may be given intravenous immunoglobulin (IVIg), and severe disease refractory to first-line therapy and IVIg may be treated with therapeutic plasma exchange (TPE) or immunomodulatory agents such as rituximab 2, 3.
• Intrathecal baclofen may be used for refractory SPS, and continuous intrathecal trialing may be advocated to determine the effective therapeutic dose and ensure post-trialing successful therapy 6.