Stiff person syndrome

# Overview
Stiff person syndrome (SPS) (or occasionally, stiff-man syndrome) is a rare neurologic disorder of unknown etiology.

# Historical Perspective
SPS was first described by Moersch and Woltman at the Mayo Clinic in 1956.

# Classification
There are 3 categories of SPS, and they are as follows:
- SPS
- Progressive encephalomyelitis with rigidity (rapidly progressive disorder, fatal within 16 weeks)
- Stiff-limb syndrome (asymmetric rigidity and spasms in the distal extremities or face)

# Causes
Because many patients with SPS have circulating antibodies to the enzyme glutamic acid decarboxylase (GAD), an autoimmune cause of the disease has been postulated.  However, GAD antibodies cannot be the sole cause, as most Type I diabetics possess anti-GAD antibodies, yet the frequency of SPS among Type I diabetics is 1 in 10,000.  The GAD protein regions (epitopes) recognized by these antibodies may differ in each disease.

# Differeniating Stiff Person Syndrome from other Diseases
One the basis of stiffness and fever it can be differentiated from:
- Tetanus
- Neuroleptic malignant syndrome
- Meningitis
- Tardive dyskinesia
- Parkinsonism

# Natural History, Complications and Prognosis
Prognosis is variable and there is no reliable predictor of speed and severity of disease onset.  Muscle tetany may lead to muscle rupture and broken bones, or problems swallowing and breathing in severe cases.

# Diagnosis

## History
- 10% of patients have generalized seizures or myoclonus.
- Fixed thoracolumbar lordosis of the spine develops in nearly all cases from co-contraction of abd/paraspinal muscles.

## Symptoms
Those with the illness experience progressive, fluctuating tonic muscle contractions, particularly the axial musculature.  Depression and anxiety are often noted although this may be a result of discomfort due to stiffness, rather than underlying neurochemical abnormalities.  
MRI detection of GABA in the brain have demonstrated reduced levels in stiff-person syndrome. Some of the symptoms are listed below.
- Marked rigidity and painful spasms, particularly in the thoracic and lumbosacral paraspinal, abdominal, and proximal lower extremity muscles
- Onset usually insidious
- Persistent contraction leads to a board-like quality.
- Intermittent painful spasms which may lead to falls due to instability.
- Spasms are NOT present during sleep.

## Laboratory Findings
- Paraneoplastic cases often are GAD negative, and they have anti-Amphyphysin.
- The CSF is abnormal with increased IgG and oligoclonal bands.
- 65% have anti-GAD antibodies.
- Serum CK levels are often elevated due to a constant state of contraction of muscles.

# Treatment
Treatment is mostly palliative with muscle relaxants which enhance GABA production such as benzodiazepines, which lose their effectiveness as the illness progresses.
In the absence of double-blind, placebo-controlled class A trials to determine treatment efficacy, some authorities recommend humane trials of immunosuppressive therapy, plasmapheresis or intravenous immunoglobulin infusion.

## Pharmacotherapy

### Acute Pharmacotherapies
- Benzodiazepines (enhance the affinity of GABA receptors)
- Oral or intrathecal baclofen
- Vigabatrin (irreversible inhibitor of GABA transaminase)
- Valproic Acid, Neurontin
- Injected botulinum toxin benefits some
- Prednisone, plasmapheresis, IVIG all used with some success, but no randomized trials