The Stiff-Person Syndrome: An Autoimmune Disorder Affecting Neurotransmission of γ-Aminobutyric Acid

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   Figure 1. Impairment of intracortical inhibitory neurons causes corticospinal neurons in the motor cortex to discharge heavily to the α motor neurons. The increased excitation to the spinal cord causes excessive firing by α motoneurons ( ). The loss of spinal inhibitory circuits, represented by two inhibitory motor neurons (illustrated with solid dots in center), enhances the motoneuron hyperexcitability and may increase discharges from γ motor neurons to the muscle spindles ( ). Excessive responses to afferent impulses from muscle spindles ( ) and skin afferents ( ), caused by impaired inhibitory interneurons, may explain the increased stiffness after sudden tactile stimuli. Proposed mechanism of development of stiffness in the stiff-person syndrome.abcd
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   Figure 2. Intense and specific staining of the Purkinje cells and γ-aminobutyric acidergic synapses can be seen. Cross-section of rat cerebellum immunostained with serum from a patient who has the stiff-person syndrome and with fluorescence-conjugated antihuman IgG.
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   Figure 3. Placement of selected regions of interest in motor cortex. Placement of selected regions of interest in posterior occipital cortex. Additional regions of interest in the putamen. Average γ-aminobutyric acid ( ) levels (expressed as ratios to creatine), obtained by magnetic resonance spectroscopy in unaffected persons, are displayed by using a color scale. Conventional axial and sagittal magnetic resonance images of an unaffected person's brain. A.B.C.GABA
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   Figure 4. The signal profile represents the magnitude of the metabolite peaks occurring in a two-dimensional J-resolved spectrum along the J = 0 axis, where J is the decoupling dimension variable. Decoupling of peaks by introduction of a second dimension improves separation and identification of metabolite peaks. GABA = γ-aminobutyric acid; NAA = -acetylaspartate. Two-dimensional J-resolved spectroscopy plot of the sensorimotor cortex of a patient with the stiff-person syndrome.N

• Copyright ©2004 by the American College of Physicians