Cause, Development, and Progression of Stiff-Person Syndrome
Condition: Stiff-Person Syndrome
MeSH terms: Stiff-Person Syndrome; Syndrome
Study type: Observational

Summary: 
      This study will explore the role of various immune factors involved in producing the disease
      symptoms in stiff-person syndrome (SPS) and follow disease progression in patients. SPS is a
      progressive disease in which unexpected noises, touches or stressful events set off muscle
      spasms and stiffness. It is thought to be an autoimmune disease in which the body produces
      antibodies that attack certain healthy tissues. A better understanding of the disease may
      help researchers design new therapies.

      Patients of any age with SPS may be eligible for this study, except those who:

        -  Lack of serum anti-GAD antibodies

        -  Have very advanced disease that precludes traveling

        -  Have severe cardiovascular, renal, or other end-organ-disease states

      Candidates will be screened with a medical history and physical and neurological examinations
      to confirm the diagnosis of SPS.

      After screening, those enrolled in the study will be followed at the NIH Clinical Center
      every 6 months for 2 years (months 6, 12, 18, and 24) to have the following tests and
      procedures:

        -  Physical and neurological examinations and review of symptoms (every visit)

        -  Blood draw for routine tests and for research studies (every visit)

        -  Stiffness assessment (every visit) - Patients are asked a series of questions about
           their stiffness, which physicians rate according to the number of stiff areas (e.g.,
           0-no stiff areas; 1-stiffness of the lower trunk; 2-stiffness of the upper trunk, etc.).

        -  Lymphapheresis (at the beginning of the study and at 12 months) - This is a procedure
           for collecting large quantities of white blood cells. A needle is placed in a vein in
           the arm. Blood flows from the vein through a plastic tube (catheter) into a machine that
           spins the blood, separating it into its components. The white blood cells (lymphocytes)
           are removed, and the rest of the blood-plasma, red cells and platelets-is returned to
           the body through a second needle placed in the other arm.

        -  Electrophysiologic studies - These studies include electromyography and nerve conduction
           testing. For electromyography, a small needle is inserted into a few muscles and the
           patient is asked to relax or to contract the muscles. The electrical activity of the
           muscle cells is recorded and analyzed by a computer. For nerve conduction testing,
           nerves are stimulated through small wire electrodes attached to the skin, and the
           response is recorded and analyzed.

        -  Lumbar puncture (at the beginning of the study and at 12 months) - This procedure is
           done to examine the cerebrospinal fluid (CSF), which bathes the brain and spinal cord.
           After a local anesthetic is administered, a needle is inserted in the space between the
           bones in the lower back where the CSF circulates below the spinal cord. About 2
           tablespoons of fluid is collected through the needle.
    

Detailed description: 
      Stiff-person syndrome (SPS) is a progressive neurological disorder characterized by stiffness
      of the trunk or limb muscles and frequent muscle spasms induced by unexpected visual,
      auditory, or somatosensory stimuli. It is an incapacitating disorder that leads to recurrent
      falls and impaired ambulation. The cause of the disease is unknown but an autoimmune
      pathogenesis is implicated based on its association with other autoimmune diseases and
      auto-antibodies, specific HLA haplotypes and high titer antibodies against GAD, the
      rate-limiting enzyme for the synthesis of GABA. Understanding the autoimmune mechanisms of
      SPS is fundamental to refine the diagnostic criteria and develop specific therapies. The
      goals of this study are: a) define the natural history of SPS in a homogeneous cohort of
      patients, b) explore a pathogenetic link between SPS and viral infections based on the known
      peptide homology between GAD and certain viruses and c) establish GAD-specific T-cell clones
      and search for candidate antigenic epitopes using synthetic peptide libraries. Collected
      clinical data will be used to delineate the rate of disease progression and the frequency of
      association with other autoimmune illnesses, auto-antibodies, or malignancies. It is
      anticipated that the knowledge acquired from the study will help us understand the mechanism
      of the disease and design antigen-specific therapeutic strategies. This is an investigative
      study intended to define the natural history and pathogenesis of SPS. No new therapy will be
      provided except of standard care.
    

Keywords: Antigenic Epitopes; Glutamic Acid Decarboxylase (GAD); Auto-antibodies; Stiffness Index; SPS; Anti-GAD; MR Spectroscopy; GAD; Stiff Person Syndrome