Inhibitory synaptic transmission is mediated by gamma-aminobutyric acid (GABA) and glycinergic spinal interneurons, which regulate motor neuron excitability in the brain stem and spinal cord. Autoimmune central nervous system disorders include classic stiff-man syndrome (also known as stiff-person syndrome), limited stiff-man forms (e.g., stiff-limb syndrome), and a severe (and sometimes fatal) encephalomyelitic variant known as progressive encephalomyelitis with rigidity and myoclonus (PERM). These disorders are unified clinically by exaggerated startle, stiffness, and spasms of the axis and/or limbs. Characteristic electrophysiologic findings include continuous motor unit activity by unipolar EMG recording, and exaggerated and non-habituating acoustic startle responses. Eighty percent of patients are seropositive for antibody targeting the 65 kDa isoform of glutamic acid decarboxylase (GAD65).
The alpha 1 subunit of the glycine receptor (GlyRα1), which is enriched in brain stem and spinal cord, has emerged as an antigenic target with specificity for the autoimmune stiff-person spectrum, and is particularly useful for diagnostics among patients who are seronegative for GAD65-IgG. GlyRα1-IgG has been described among patients with PERM (33%), classic stiff-man syndrome (9%), and limited stiff-man forms (17%). Seropositivity for GlyRα1-IgG is detected in 19% of patients from the stiff-man spectrum who are GAD65-IgG seronegative.
Andrew McKeon, M.B., B.Ch., M.D, gives an overview of this test available through Mayo Clinic Laboratories. He discusses when this testing should be ordered, how this testing compares to other testing approaches, and what clinical action can be taken due to the results of this testing.
CSF - Specimen Volume: 2 mL
Serum - Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1 mL
Thursday; 6 p.m.