eMedicine Specialties > Neurology > Neuromuscular Diseases

Stiff Person Syndrome: Treatment & Medication

Author: Nancy Theresa Rodgers-Neame, MD, Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida; Director, Florida Comprehensive Epilepsy and Seizure Disorders Program
Contributor Information and Disclosures

Updated: Aug 27, 2009

Treatment

Medical Care

Initial medical treatment may involve either baclofen or a benzodiazepine.2 Although no studies have been performed, tizanidine (Zanaflex) may be a less sedating alternative. Other medications that have been tried include antiepileptic medications, dantrolene, and barbiturates, but no clinical trials have been performed.

  • Intrathecal baclofen therapy
    • Some patients may be candidates for intrathecal baclofen therapy for long-term treatment. Because symptoms may be variable, an externally programmable pump may be the best option.
    • Evaluation for intrathecal baclofen therapy by an experienced evaluator, the neurosurgeon involved, and the neurologist caring for the patient should coordinate the procedure so that the goals of therapy are clear. Deaths have been reported in stiff person syndrome from baclofen pump failure; share this fact with the team and the patient. Baclofen pump therapy should not be considered the sole therapy for the disease.
  • Plasmapheresis (plasma exchange)
    • In some patients, plasmapheresis has been demonstrated to be of clinical utility in the treatment of stiff person syndrome.27
    • No real prescribed dosage exists for plasmapheresis. The time of plasmapheresis, amount of supplementary albumin, and other parameters are controlled on a patient-by-patient basis by the pathologist running the blood bank involved in the procedure. A 5-treatment series administered every other day is considered a standard regimen for autoimmune diseases, but longer and shorter regimens have been used.
    • The efficacy is then evaluated and further treatment is decided on a patient-by-patient basis, usually as a collaborative effort with the insurance company physicians because it is such an expensive procedure.
    • Possible adverse effects include hypotension, bleeding, arrhythmias, and infection.
  • Intravenous immunoglobulin
    • Intravenous immunoglobulin (IVIG) has also been used in the inpatient setting for the treatment of stiff person syndrome. The usual dose is 2 g/kg, administered over 2-5 days.
    • The length of the series is variable and dependent upon patient response. Treatment may extend past the inpatient period.24 (Documentation of patient response is usually necessary for ongoing reimbursement by third party payers.)
    • Remember that IVIG is contraindicated in patients with IgA deficiency because of increased anaphylaxis in these patients.
  • Physical therapy and occupational therapy
    • Physical therapy and occupational therapy are critical to the recovery of the patient under treatment. Medical treatment may make the patient feel weak, a feeling that may respond well to therapy.
    • The patient may also have a great deal of problems with voluntary movement and fine motor skills.

Consultations

Psychiatry may be consulted especially when symptoms of depression or anxiety are prominent. The psychiatrist should be made aware of the pathophysiology of stiff person syndrome and that the anxiety symptoms may be directly related to the presence of glutamic acid decarboxylase antibodies in the central nervous system. If possible, consult a psychiatrist that has shown interest in the disease.

Activity

Exercise or physical therapy may be helpful in preserving range of motion and in relieving symptoms related to prolonged muscle tension. In addition, muscular biofeedback may be helpful, although careful studies of physical therapy treatments have not been done. Keep in mind that activity or exercise may exacerbate spasms.

Medication

The goals of pharmacotherapy are to reduce symptoms, reduce morbidity, and prevent complications.

Benzodiazepines

Most frequently cited as useful in the treatment of stiff person syndrome. Activate the GABA-A receptor to enhance central inhibitory circuits. Benzodiazepines include diazepam (Valium) or lorazepam (Ativan).


Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Individualize dosage and increase cautiously to avoid adverse effects.

Adult

Mild spasms: 5-10 mg PO q4-6h prn
Moderate spasms: 5-10 mg IV prn
Severe spasms: Mix 50-100 mg IV in 500 cc D5W and infuse at 40 mL/h

Pediatric

Mild spasms: 0.1-0.8 mg/kg/d PO divided tid/qid
Moderate or severe spasms: 0.1-0.3 mg/kg IV q4-8h

Increased toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs

Documented hypersensitivity; narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity)


Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

Adult

1-10 mg/d PO divided bid/tid

Pediatric

Not established

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease

Immune modulators

These agents alter immune response to antigens. IVIG can be used.


Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin)

Neutralizes circulating antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Adult

2 g/kg total dose administered at 0.4 g/kg IV qd for 5 d or 1 g/kg for 2 d

Pediatric

Administer as in adults

Increases toxicity of live virus vaccine (MMR); do not administer within 3 mo of vaccine

Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly individuals and in those with diabetes, volume depletion, and preexisting kidney disease; laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Skeletal muscle relaxants

These agents increase activity of central inhibitory systems. Theoretically less sedating in relationship to GABA-A agonists such as benzodiazepines. Baclofen can be used.


Baclofen (Lioresal)

May induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level.

Adult

5 mg PO tid for 3 d; 10 mg tid for 3 d; 15 mg tid for 3 d; 20 mg tid for 3 d; thereafter, additional increases may be necessary; not to exceed 80 mg/d PO divided qid

Pediatric

Not established

Opiate analgesics, benzodiazepines, alcohol, TCAs, guanabenz, MAOIs, clindamycin, and hypertensive agents may increase baclofen effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with history of autonomic dysreflexia and when spasticity is used to obtain increased function; autonomic dysreflexia can result from withdrawal of this medication

More on Stiff Person Syndrome

Overview: Stiff Person Syndrome
Differential Diagnoses & Workup: Stiff Person Syndrome
Treatment & Medication: Stiff Person Syndrome
Follow-up: Stiff Person Syndrome
References
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Further Reading

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Keywords

stiff person syndrome, SPS, stiff man syndrome, SMS, stiff baby syndrome, SBS, hyperekplexia, Moersch-Woltmann syndrome, stiff woman syndrome, stiff limb syndrome, spasticity, GABA, muscle rigidity, axial muscle rigidity, proximal limb muscle rigidity, muscle stiffness, muscle spasm, intermittent rigidity, autoimmune disease, glutamic acid decarboxylase, GAD, GAD antibodies, glycine, spinal motor neurons, motor pathway inhibitor, GABA, motor neurons, motor neuron dysfunction, glutamate, baclofen pump failure, upright posture, posture discomfort, spasm, intermittent spasm, startle syndrome, lumbar lordosis, spastic, stiff encephalomyelitis, paraneoplastic hypertonic syndrome, paraneoplastic syndrome, PNS, myoclonic seizure, seizure

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Contributor Information and Disclosures

Author

Nancy Theresa Rodgers-Neame, MD, Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida; Director, Florida Comprehensive Epilepsy and Seizure Disorders Program
Nancy Theresa Rodgers-Neame, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Women's Association, Society for Neuroscience, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Paul E Barkhaus, MD, Professor, Department of Neurology, Medical College of Wisconsin; Director of Neuromuscular Diseases, Milwaukee Veterans Administration Medical Center
Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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