Accelerating the field of autoimmune neurological testing

Improved diagnosis through expanded antibody analysis

Mayo Clinic Laboratories has met the challenge of identifying stiff-person spectrum disorders through the development and implementation of the world’s first commercially available evaluation that includes all relevant biomarkers for the disorder. Available exclusively at Mayo Clinic Laboratories, this assay allows physicians to more efficiently evaluate patients suspected of stiff-person disorder, enabling faster diagnosis and treatment to maximize recovery of this rare and oftentimes serious illness.

While disease presentation varies, the unifying clinical and electrophysiologic characteristic of stiff-person spectrum disorders — which include classical stiff-person syndrome, focal stiff-person forms (stiff-limb and stiff-trunk), and a severe encephalomyelitic form known as progressive encephalomyelitis with rigidity and myoclonus (PERM) — is central nervous system hyperexcitability.

The most common IgG biomarker detected in the stiff-person spectrum is GAD65 antibody; however, glycine receptor (GlyRα1), DPPX, and amphiphysin antibodies are also found. Since each biomarker is associated with a unique prognosis and treatment plan, antibody detection is integral to enabling the best therapeutic response.

By the numbers


89%

of GLYRα1 positive patients were immunotherapy responsive (compared to 40% for general stiff-person syndrome)


33%

of GLYα1 positive patients have PERM and can be treated accordingly

Data-driven, phenotypic testing

Our stiff-person spectrum disorders evaluation detects GAD65, GlyRα1, DPPX, and amphiphysin antibodies in one assay. This unique test is part of an evolving approach to testing for autoimmune neurological disorders using phenotypic-specific evaluations that include multiple antibodies known for their disease association.

When to consider testing

Consider testing for patients with subacute onset and a family/personal history of autoimmune disease. This testing would be appropriate if the patient shows one or more of the following symptoms:

  • Stiffness and spasms
  • Exaggerated startle
  • Rigidity in one or more limbs

Which test should I order?


A Test in Focus

Andrew McKeon, M.B., B.Ch., M.D., discusses Mayo Clinic Laboratories' stiff-person spectrum disorders assay, which includes evaluating for the four known antibodies that can be present in individuals on the spectrum — including patients with the severe PERM phenotype.

Learn more about how to order this evaluation at your institution.


Clinical references

  1. Hinson SR, Lopez-Chiriboga AS, Bower JH, et al: Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2018;5:e438.
  2. Hutchinson M, Waters P, McHugh J, et al: Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology. 2008;71:1291-1292.
  3. Martinez-Hernandez E, Arino H, McKeon A, et al: Clinical and immunologic investigations in patients with stiff-person spectrum disorder. JAMA Neurol. 2016;73:714-720.
  4. McKeon A, Martinez-Hernandez E, Lancaster E, et al: Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol. 2013;70:44-50.
  5. McKeon A, Robinson MT, McEvoy KM, et al: Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012 Feb;69(2):230-8.
  6. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005;58(1):96-107.
  7. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc. 2006;81:1207-1214.
  8. Tobin WO, Lennon VA, Komorowski L, et al: DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology. 2014;83:1797-1803.
  9. Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc. 1998 December;73(12):1161-1166.