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Test ID: SPPS Stiff-Person Spectrum Disorders Evaluation, including Progressive Encephalomyelitis with Rigidity and Myoclonus, Serum


Ordering Guidance


This test should not be requested in 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:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 2 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 serum specimens

Profile Information

Test ID Reporting Name Available Separately Always Performed
SPPSI Stiff-Person/PERM Interp, S No Yes
AMPHS Amphiphysin Ab, S No Yes
DPPCS DPPX Ab CBA, S No Yes
GD65S GAD65 Ab Assay, S Yes Yes
GLYCS Glycine Alpha1 LCBA, S Yes Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AMIBS Amphiphysin Immunoblot, S No No
DPPTS DPPX Ab IFA Titer, S No No

Testing Algorithm

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

 

If 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

AMPHS, DPPTS: Indirect Immunofluorescence Assay (IFA)

AMIBS: Immunoblot (IB)

DPPCS: Cell-Binding Assay (CBA)

GD65S: Radioimmunoassay (RIA)

GLYCS: Live Cell-Binding Assay (LCBA) 

SPPSI: Medical Interpretation

Reporting Name

Stiff-Person/PERM Eval, S

Specimen Type

Serum

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum 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, and sudden chest wall spasms with breathing difficulties. Patients with PERM, in addition, 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 commonly encountered in patients with occult breast adenocarcinoma presenting with limb stiffness and spasms; neurogenic changes are usually also detectable on clinical exam and electromyography. Glycine receptor (GlyR [alpha1 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

AMPHIPHYSIN ANTIBODY

<1:240

 

DIPEPTIDYL-PEPTIDASE-LIKE PROTEIN-6 ANTIBODY CELL BINDING ASSAY (CBA)

Negative

 

GLUTAMIC ACID DECARBOXYLASE 65 ANTIBODY ASSAY

≤0.02 nmol/L

Reference values apply to all ages.

 

GLYCINE RECEPTOR ALPHA1 IgG, CBA

Negative

 

AMPHIPHYSIN IMMUNOBLOT

Negative

 

DIPEPTIDYL-PEPTIDASE-LIKE PROTEIN IMMUNOFLUORESCENCE TITER

<1:240

Interpretation

Seropositivity 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;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

Day(s) Performed

AMPHS, DPPTS, GD65S:

Monday through Sunday

 

AMIBS:

Monday through Friday

 

DPPCS:

Monday through Thursday, Sunday

 

GLYCS:

Thursday

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

86341

84182-AMIBS (if appropriate)

86256-DPPTS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SPPS Stiff-Person/PERM Eval, S 94701-0

 

Result ID Test Result Name Result LOINC Value
81722 Amphiphysin Ab, S 94340-7
81596 GAD65 Ab Assay, S 94345-6
64933 DPPX Ab CBA, S 94676-4
606972 Glycine Alpha1 LCBA, S 96496-5
614601 Stiff-Person/PERM Interp, S 69048-7

Forms

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

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Movement-Disorders