Stem Cell Transplantation for Stiff Person Syndrome (SPS)

Inclusion Criteria:

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

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

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