Stiff person syndrome

Stiff person syndrome
ICD-10	G25.8
ICD-9	333.91
OMIM	184850
DiseasesDB	12428
eMedicine	neuro/353
MeSH	D016750

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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:

1. SPS
2. Progressive encephalomyelitis with rigidity (rapidly progressive disorder, fatal within 16 weeks)
3. 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.

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

See also

• Hyperekplexia

External links

• A site about the link between GAD and SPS at University of Birmingham Medical School
• Template:NINDS
• Article at Cleveland Clinic
• Article at eNotes
• GAD antibodies at antibodypatterns.com
• Amphiphysin antibodies at antibodypatterns.com