Lucien M. Levy, MD, PhD; Marinos C. Dalakas, MD; Mary Kay Floeter, MD, PhD
An edited summary of a Clinical Staff Conference held on 28 October 1998 at the National Institutes of Health in Bethesda, Maryland.
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Floeter MK. Inhibitory pathways defined by electrophysiology. In: Levy LM, moderator. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of γ-aminobutyric acid. Ann Intern Med. 1999;131:523-524.
Acknowledgments: The authors thank major collaborators, including Drs. Mavis Fujii, David Jacobowitz, Mian Li, Sherry Thomas-Vorbach, Joan Kyhos, and Beverly McElroy. They also thank Dr. Mark Hallett for his support and Dr. Giovanni Di Chiro for setting up the new spectroscopy program at the National Institutes of Health.
Requests for Reprints: Lucien M. Levy, MD, PhD, Neuroimaging Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N226, Bethesda, MD 20892; e-mail, email@example.com. For reprint orders in quantities exceeding 100, please contact the Reprints Coordinator; phone, 215-351-2657; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Levy: National Institutes of Health, Building 10, Room 5N226, Bethesda, MD 20892.
Dr. Dalakas: National Institutes of Health, Building 10, Room 4N248, Bethesda, MD 20892.
Dr. Floeter: National Institutes of Health, Building 10, Room 5C101, Bethesda, MD 20892.
The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal.
The cause of the stiff-person syndrome is unknown; however, an autoimmune pathogenesis is suspected because of 1) the presence of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid [GABA]; 2) the association of the disease with other autoimmune conditions; 3) the presence of various autoantibodies; and 4) a strong immunogenetic association. Anti-GAD antibodies, which are found in high titers in most patients, seem to be directed against conformational forms of GAD. New evidence suggests that these antibodies may be pathogenic because they interfere with the synthesis of GABA. In addition, a reduction in brain levels of GABA, which is prominent in the motor cortex, has been demonstrated with magnetic resonance spectroscopy in patients with the stiff-person syndrome.
The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin, and baclofen, provide mild to modest relief of clinical symptoms. Immunomodulatory agents, such as steroids, plasmapheresis, and intravenous immunoglobulin, seem to offer substantial improvement. Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease.
Proposed mechanism of development of stiffness in the stiff-person syndrome.abcd
Cross-section of rat cerebellum immunostained with serum from a patient who has the stiff-person syndrome and with fluorescence-conjugated antihuman IgG.
Conventional axial and sagittal magnetic resonance images of an unaffected person's brain. A.B.C.GABA
Two-dimensional J-resolved spectroscopy plot of the sensorimotor cortex of a patient with the stiff-person syndrome.N
Levy LM, Dalakas MC, Floeter MK. The Stiff-Person Syndrome: An Autoimmune Disorder Affecting Neurotransmission of γ-Aminobutyric Acid. Ann Intern Med. 1999;131:522–530. doi: https://doi.org/10.7326/0003-4819-131-7-199910050-00008
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Published: Ann Intern Med. 1999;131(7):522-530.
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