Paraneoplastic neurological syndromes (PNS) are diseases that occur due to the remote effects of tumors (usually malignant). The most common tumors associated with PNS include small cell lung cancer (SCLC), thymoma, neuroblastoma, ovarian, breast, testicular, and Hodgkin lymphoma. Researchers believe PNS is caused by cancer-fighting abilities of the immune system, in particular antibodies and specific white blood cells, known as T-cells. Instead of attacking only the cancer cells, these immune agents also attack the normal cells of the nervous system and cause neurological disorders.

Test Information

When to Order Testing

  • Neurologic disease of unknown etiology without evidence of malignancy
  • Neurologic disease with high suspicion of malignancy or known risk factors for malignancy

Why is Testing Important?

  • Aids in the diagnosis of paraneoplastic neurological disease associated with certain cancers (carcinoma of lung, breast, ovary, thymoma, or Hodgkin’s lymphoma) and/or related disorders such as autoimmune encephalitis
  • Directs a focused search for cancer
  • Differentiates autoimmune neuropathies from neurotoxic effects of chemotherapy
  • Monitors the immune response of seropositive patients in the course of cancer therapy
  • Can detect early evidence of cancer recurrence in previously seropositive patients

Benefits of PNS Testing at ARUP

  • ARUP offers a comprehensive list of tests that represent the autoantibodies found in about 85–90% of patients with PNS or other autoimmune neurologic disorder (as standalone or in panels).
  • ARUP Panels are directed at specific syndromes, allowing for more targeted testing than the large panels offered by competitors.
  • Smaller directed panels and individual tests are more cost effective.

Additional Resources

Guidelines

FAQ

How does ARUP testing compare to the extensive panels performed at other laboratories?

ARUP offers a comprehensive list of tests that represent the autoantibodies found in about 85-90% of patients with PNS or other autoimmune neurologic disorders (as standalone or in panels). Of the tests not offered by ARUP, the N-type VGCC which overlaps with the P/Q-type VGCC and the ganglionic AChR antibody assays are the most prevalent. Assays for detecting both of these antibodies are currently under development. While other laboratories may offer more tests than ARUP, most of these are very rare and significantly overlap with the readily available tests1,2.

Clinically, what does the ARUP test not provide and how do the missing pieces impact the clinical assessment of the patient?

ARUP Laboratories offers a significant number of the same tests as our competitors and they are offered as standalone tests or in limited panels. The majority of these have significant clinical impact and may cover 85-90% of the disease cases (unique antibodies). Of the tests not offered by ARUP, the N-type VGCC which overlaps with the P/Q-type VGCC and the ganglionic AChR antibody assays are the most prevalent. Assays for detecting both of these antibodies are currently under development. In addition, there are two categories of tests that cannot be offered by ARUP. The first due to patent issues and the second because of negligible or questionable clinical significance, or they are extremely rare and should only be ordered in limited cases. These include:

  1. Under development (<5% of unique cases)
    • N-Type Calcium Channel Ab
    • AChR Ganglionic Neuronal Ab, S
  2. Restricted by license (<5% of unique cases)
    • Anti-Glial Nuclear Ab, Type 1
  3. Negligible clinical significance or extremely rare (likely less than 1% of unique cases)
    • Anti-Neuronal Nuclear Ab, Type 3
    • Purkinje Cell Cytoplasmic Ab Type 2
    • Purkinje Cell Cytoplasmic Ab Type 3
    • AMPA-R Ab CBA, S
    • GABA-B-R Ab CBA, S
  4. Additional:
    • The N-type VGCC antibody significantly overlaps with the P/Q-type.
    • PCCA-2 and ANNA-3 are both extremely rare with limited clinical relevance.
    • GABA-B-R Ab, AMPA-R Ab, and PCCA-3 assays are not currently offered in the ARUP panel. These markers are also very rare with very few cases described since their discovery.
    • ARUP offers VGKC with reflex to LGI1 and CASPR2. This panel is very important, more so than the GABA and AMPA, which are less common.

Panels offered by ARUP :

Panel Test Panel Includes
Autoimmune Encephalitis Reflexive Panel 2013601 N-methyl-D-Aspartate Receptor Antibody, IgG, Serum with Reflex to Titer 2004221
Glutamic Acid Decarboxylase Antibody 2001771
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Aquaporin-4 Receptor Antibody, IgG by IFA with Reflex to Titer, Serum 2013320
Aquaporin-4 Receptor Antibody 203036
Leucine-Rich, Glioma-Inactivated Protein 1 Antibody, IgG with Reflex to Titer 2009456
Contactin-Associated Protein-2 Antibody, IgG with Reflex to Titer 2009452
Autoimmune Neuromuscular Junction Reflective Panel 2005640 Acetylcholine Receptor Binding Antibody 0080009
Acetylcholine Receptor Blocking Antibody 0099580
Acetylcholine Receptor Modulating Antibody 0099521
Voltage-Gated Calcium Channel (VGCC) Antibody 0092628
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Striated Muscle Antibodies, IgG with Reflex to Titer 0050746
Titin Antibody 2005636
Leucine-Rich, Glioma-Inactivated Protein 1 Antibody, IgG and Contactin-Associated Protein-2 Antibody, IgG with Reflex to Titers 2009460
Paraneoplastic Reflexive Panel 2013955 Paraneoplastic Antibodies (PCCA/ANNA) by IFA with Reflex to Titer and Immunoblot 2007961 (immunoblot tests for Hu, Ri and Yo)
Amphiphysin Antibody, IgG 2008893
CV2.1 Screen by IFA with Reflex to Titer 2013956
Autoimmune Neurologic Disease Comprehensive Panel 2013944 Paraneoplastic Antibodies (PCCA/ANNA) by IFA with Reflex to Titer and Immunoblot 2007961 (immunoblot tests for Hu, Ri and Yo)
Amphiphysin Antibody, IgG 2008893
CV2.1 Antibody, IgG, Serum with Reflex to Titer 2013956
N-methyl-D-Aspartate Receptor Antibody, IgG, Serum with Reflex to Titer 2004221
Glutamic Acid Decarboxylase Antibody 2001771
Voltage-Gated Potassium Channel (VGKC) Antibody with Reflex to LGI1 and CASPR2 Screen and Titer 2009463
Aquaporin-4 Receptor Antibody by ELISA with Reflex to Aquaporin-4 Antibody, IgG by IFA 2013327
Acetylcholine Receptor Binding Antibody 0080009 (If Acetylcholine Receptor Binding Antibody result is greater than 0.4 nmol/L then Acetylcholine Receptor Modulating Antibody will be added)
Voltage-Gated Calcium Channel (VGCC) Antibody 0092628
Striated Muscle Antibodies, IgG with Reflex to Titer 0050746
Titin Antibody 2005636

References

Associated Disorders