Stem Cell Transplantation for Stiff Person Syndrome (SPS) (SPS)

This is an interventional treatment trial for Stiff-Person Syndrome focused on measuring Autoimmune Diseases, Autologous Hematopoietic Stem Cell Transplantation Read More

Inclusion Criteria:

1. Diagnosis of Stiff-person Syndrome and

   • Age between 18 and 60 years old
   • Failure of medically tolerable doses (20-40 mg/day) of diazepam
   • Failure of either intravenous immunoglobulin (IVIg) and or plasmapheresis
   • Stiffness in the axial muscles, prominently in the abdominal and thoracolumbar paraspinal muscle leading to a fixed deformity (hyperlordosis)
   • Superimposed painful spasms precipitated by unexpected noises, emotional stress, tactile stimuli
   • Confirmation of the continuous motor unit activity in agonist and antagonist muscles by electromyography when off diazepam and anti-spasmatic medications
   • Absence of neurological or cognitive impairments that could explain the stiffness
   • Inability to run or walk, or abnormal gait

2. Diagnosis of a SPS variant- Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) defined as:

   Acute onset of painful rigidity and muscle spasms in the limbs and trunk

   • Brainstem dysfunction (nystagmus, opsoclonus, ophthalmoparesis, deafness, dysarthria, dysphagia)
   • Profound autonomic disturbance.
   • Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
   • MRI may show increased signal intensity throughout the spinal cord and the brainstem

3. Diagnosis of a SPS variant - anti-GAD positive cerebellar ataxia

   • Subacute or chronic onset of cerebellar symptoms-gait or limb ataxia, dysarthria, nystagmus
   • Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
   • Anti-GAD antibody in cerebrospinal fluid
   • Abnormal MRI imaging of brainstem or cerebellum other than cerebellar atrophy
   • Negative history of toxin or alcohol
   • Absence of Vitamin B12 or Vitamin E deficiency
   • Absence of positive HIV, syphilis or whipple disease
   • Absence of consanguinity, positive family history for ataxia or positive genetic screen for spinocerebellar ataxia (SCA) 1, SCA 2, SCA 3, SCA 6, SCA 7 or SCA 8 mutation

Exclusion Criteria:

• Current or prior history of a malignancy or paraneoplastic syndrome
• Inability to sign and understand consent and be compliant with treatment
• Positive pregnancy test
• Inability to or comprehend irreversible sterility as a possible side effect
• Amphiphysin antibody positive
• Left ventricular ejection fraction (LVEF) < 45% or ischemic coronary artery disease on dobutamine stress echocardiogram
• Diffusing capacity of the lungs for carbon monoxide (DLCO) < 60% predicted
• Serum creatinine > 2.0 mg/dl
• Bilirubin >2.0 mg/dl
• Platelet count < 100,000 / ul, white blood cell count (WBC) < 1,500 cells/mm3
• History of toxin or alcohol abuse
• History of Vitamin B12 or Vitamin E deficiency
• Positive HIV, syphilis, or whipple disease
• Consanguinity, positive family history for ataxia or positive genetic screen for SCA1, SCA2, SCA3, SCA6, SCA 7 or SCA8 mutation (if ataxia present)
• Absence of at least one SPS associated antibody such as anti-GAD, or gamma-aminobutyric acid (GABA)-A receptor associated protein, or synaptophysin, or gephyrin, or GABA-transaminase