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What is Stiff Person Syndrome (SPS)
- Rare neurologic disorder characterized by severe muscle rigidity
- Stiff Person Syndrome is a fluctuating motor disturbance characterized by persistent muscular stiffness due to coactivation of agonist and antagonist muscles with superimposed spasms.
- As with tetanus, generalized spasms can be precipitated by movements, noise, touch, or emotional stimulation
- Unlike tetanus, stiff person syndrome does not include trismus or facial spasms and responds quickly to diazepam
- The symptoms of this syndrome are fluctuating trunk and limb stiffness, painful muscle spasms, task-specific phobia, an exaggerated startle response, and ankylosing deformities such as fixed lumbar hyperlordosis.
- a disorder characterized by muscle rigidity and episodic muscle spasms, primarily involving the trunk.
- Episodes can be prolonged, painful, and precipitated by loud noises.
Synonyms
- Moersch Woltman syndrome
- SMS
- SPS
- Stiff man syndrome
Pathophysiology of Stiff Person Syndrome
An insight into the pathophysiology of Stiff Person Syndrome was provided by the finding that 20 of 33 patients had autoantibodies against glutamic acid dehydroxylase.
The hypothesis of an autoimmune etiology of SPS is further supported by the presence of other autoantibodies (to islet cells and gastric parietal cells, for example), coexistent autoimmune diseases such as insulin-dependent diabetes mellitus, vitiligo, thyroid disease, family history of presumed autoimmune conditions, and improvement with plasmapheresis and corticosteroid drugs.
Symptoms and Signs of Stiff Person Syndrome
Patients with this rare disorder may present with progressive, usually symmetric, rigidity of the axial muscles that may fluctuate in intensity.
The classical form predominantly affects the axial and proximal limb muscles and is aggravated by emotional, somatosensory, or acoustic stimuli.
Very Common Symptoms and Signs (80%-98%)
- Anxiety
- EMG abnormality
- Falls
- Hyperhidrosis
- Intermittent painful muscle spasms
Common Symptoms and Signs (30%-79%)
- Agoraphobia
- Autoimmune antibody positivity
- Difficulty walking
- Emotional lability
- Exaggerated startle response
- Paraspinal muscle hypertrophy
- Rigidity
Occasional Symptoms and Signs (5%-29%)
- Diabetes mellitus
- Hypothyroidism
- Lumbar hyperlordosis
What are the triggering factors of the spasms
Motion, tactile stimulation, emotion, and startle are common triggering factors of the spasms.
Types of Stiff Person Syndrome
There are three types:
• The most common (60%–80%) type is associated with antibodies against glutamic acid decarboxylase (GAD65) and frequently with autoimmune diseases (e.g., type I DM, Graves’ disease, hypothyroidism, pernicious anemia, vitiligo) because of its high association with HLA DQ-0201. Electromyography demonstrates involuntary motor unit firing. It is postulated that the anti-GAD antibodies inhibit the enzymes in the CNS responsible for production of gamma-aminobutyric acid (GABA), which is an inhibitory neurotransmitter. In addition, many of these patients also have antibodies that inhibit GABA-associated receptor protein, which prevents GABA from binding to its receptor. Consequently, neural transmission is unopposed and can lead to muscle rigidity. This type of SPS is treated with diazepam, baclofen, plasmapheresis, immunosuppressives including rituximab, and/or IV gammaglobulin.
• The other two types of SPS are not associated with anti-GAD antibodies or a certain HLA phenotype. One type (5% of cases) is a paraneoplastic manifestation of cancers (lymphoma, breast, lung, colon), whereas the other type (15%–35% of cases) is idiopathic. Paraneoplastic SPS tends to involve the neck and arms, has a rapid onset, and is very painful. Patients with SPS associated with breast cancer have been found to have antiamphiphysin (128-kd protein on the surface of synaptic vesicles) antibodies. These two SPS types do not respond to immune-modulating therapies and are treated with high doses of muscle relaxants such as diazepam or baclofen that are GABA agonists.
• Variants of SPS: (1) stiff-limb syndrome has stiffness limited to one limb, usually the leg. Up to 25% will develop other manifestations of classical SPS over time; (2) progressive encephalomyelitis with rigidity has brainstem, cerebellar, and spinal cord involvement with autonomic dysfunction; and (3) jerking man syndrome begins as classical SPS, but patient develops limb myoclonic jerks over time.
How is this condition diagnosed?
Antiglutamic acid decarboxylase (GAD) antibodies are present in the serum and cerebrospinal fluid at high levels.
Stiff Person Syndrome can be a paraneoplastic condition more commonly associated with antiampiphysin autoantibodies.
EMG demonstrates a continuous low-frequency firing of normal motor unit potentials that persists at rest.
The diagnosis is supported by
- relief of the rigidity with general and spinal anesthesia,
- peripheral nerve blocks
- Electromyography shows continuous normal motor unit potentials in the affected muscles despite the patient’s attempts to relax.
- diazepam, (which is still the first-line treatment of Stiff Person Syndrome)
How is Stiff Person Syndrome treated?
A significant symptomatic improvement is achieved by oral administration of benzodiazepines, primarily diazepam (10 to 100 mg/day).
Baclofen and valproic acid also may help the symptoms.
Immunomodulation by corticosteroids, plasmapheresis may be necessary in some patients.
In refractory cases propofol, rituximab, and intravenous immunoglobulin have been reported to be of benefit.
It should be noted that use of general anesthesia in patients with Stiff Person Syndrome carries a risk of postoperative hypotonia especially with concomitant use with muscle relaxants.
Sources
- Chang VC, Frucht SJ: Myoclonus. Curr Treat Options Neurol 10(3):222-229, 2008.
- Jankovic J: Treatment of hyperkinetic movement disorders. Lancet Neurol 8(9):844-856, 2009.
