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Test ID: SPPC Stiff-Person Spectrum Disorders Evaluation, including Progressive Encephalomyelitis with Rigidity and Myoclonus, Spinal Fluid

Ordering Guidance

This test should not be requested for patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed or canceled if radioactivity remains.

Necessary Information

Provide the following information:

-Relevant clinical information

-Ordering provider name, phone number, mailing address, and e-mail address

Specimen Required

Container/Tube: Sterile vial

Preferred: Vial number 1

Acceptable: Any vial

Specimen Volume: 4 mL

Useful For

Evaluating patients with suspected stiff-person syndrome (classical or focal forms, such as stiff-limb or stiff-trunk) and progressive encephalomyelitis with rigidity and myoclonus using spinal fluid specimens

Profile Information

Test ID Reporting Name Available Separately Always Performed
SPPCI Stiff-Person/PERM Interp, CSF No Yes
AMPHC Amphiphysin Ab, CSF No Yes
GD65C GAD65 Ab Assay, CSF Yes Yes
GLYCC Glycine Alpha1 LCBA, CSF Yes Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AMIBC Amphiphysin Immunoblot, CSF No No
APHTC Amphiphysin Ab Titer, CSF No No

Testing Algorithm

If the indirect immunofluorescence assay (IFA) pattern suggests amphiphysin antibody, then amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.


If the dipeptidyl-peptidase-like protein-6 (DPPX) cell bound assay is positive, then DPPX antibody IFA titer will be performed at an additional charge.

Method Name

AMPHC, APHTC, DPPTC: Indirect Immunofluorescence Assay (IFA)

AMIBC: Immunoblot (IB)

DPPCC: Cell-Binding Assay (CBA)

GD65C: Radioimmunoassay (RIA)

GLYCC: Live Cell-Binding Assay (LCBA)

Reporting Name

Stiff-Person/PERM Eval, CSF

Specimen Type


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
CSF Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Clinical Information

Stiff-person spectrum disorders 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). Paraneoplastic and idiopathic autoimmune causes may be differentiated by a neuronal IgG antibody profile. The unifying clinical and electrophysiologic characteristic is central nervous system hyperexcitability. Clinical manifestations include stiffness, spasms, heightened startle responses, and falls. For the classical stiff-person form, the low back and lower extremities are principally affected. The stiff-limb phenotype may affect one or more limbs without truncal involvement. Truncal manifestations include low back spasms and deformity, with sudden chest wall spasms and breathing difficulties. In addition, patients with PERM have encephalopathy (often with seizures), myoclonus (muscle jerking), and dysautonomia. The most common IgG biomarker detected in stiff-person spectrum is glutamic acid decarboxylase 65 (GAD65) antibody. These patients generally have a classical or limited stiff-person form, almost always have antibody values above 20.0 nmol/L, have accompanying non-neurological autoimmune disease in 50% (type 1 diabetes and thyroid disease being most common), and almost always without accompanying cancer. Amphiphysin-IgG positivity is most frequently encountered in patients with occult breast adenocarcinoma presenting with limb stiffness and spasms; neurogenic changes are usually detectable on clinical exam and electromyography. Glycine receptor (GlyR [alpha1 1 subunit]) autoimmunity patients present more commonly with PERM or stiff-limb phenotype rather than the classical stiff-person form. Associated neoplasms in GlyR antibody positive patients include thymoma, but a general search for age- and sex-pertinent cancers should also be undertaken. Dipeptidyl-peptidase-like protein-6 (DPPX) antibody is associated with diverse central and autonomic presentations, including PERM. B-cell blood dyscrasias should be tested for in DPPX-IgG positive cases. All stiff-person spectrum patients, both seropositive and seronegative, may be immune therapy responsive. GlyR-IgG may be predictive of immune therapy response, including in patients with coexisting GAD65 antibody.

Reference Values

Test ID

Reporting Name


Reference Value


Stiff-Person/PERM Interp, CSF

Medical interpretation



Amphiphysin Ab, CSF








GAD65 Ab Assay, CSF


≤0.02 nmol/L


Glycine Alpha1 LCBA, CSF



Reflex information

Test ID

Reporting Name


Reference Value


Amphiphysin Immunoblot, CSF




Amphiphysin Ab Titer, CSF








*Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Radioimmunoassay (RIA)

Live Cell-Binding Assay (LCBA)

Immunoblot (IB)


Neuron-restricted patterns of IgG staining that do not fulfill criteria for amphiphysin antibody may be reported as "unclassified antineuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."


Spinal fluid antibody positivity supports the clinical diagnosis of stiff-person spectrum disorder (classical stiff-person, stiff-limb, stiff-trunk, or progressive encephalomyelitis with rigidity and myoclonus). A paraneoplastic basis should be considered.

Clinical Reference

1. Hinson SR, Lopez-Chiriboga AS, Bower JH, et al: Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2018 Jan;5:e438

2. Hutchinson M, Waters P, McHugh J, et al: Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology. 2008 Oct;71(16):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 Jun;73(6):714-720

4. McKeon A, Martinez-Hernandez E, Lancaster E, et al: Glycine receptor autoimmune spectrum with stiff-man syndrome phenotype. JAMA Neurol. 2013 Jan;70(1):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):230-238

6. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005 Jun;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 Sep;81(9):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 Nov;83(20):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 Dec;73(12):1161-1166

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

5 to 10 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

86255 x 3


84182-AMIBC (if appropriate)
86256 APHTC (if appropriate)

86256-DPPTC (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SPPC Stiff-Person/PERM Eval, CSF 94712-7


Result ID Test Result Name Result LOINC Value
5906 Amphiphysin Ab, CSF 94354-8
21702 GAD65 Ab Assay, CSF 94359-7
64934 DPPX Ab CBA, CSF 94283-9
606973 Glycine Alpha1 LCBA, CSF 96497-3
614602 Stiff-Person/PERM Interp, CSF 69048-7
618909 IFA Notes 48767-8


If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

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