A Faster, Cheaper Diagnostic Test for MS?

Pauline Anderson

April 08, 2022

A test that measures kappa immunoglobulin free light chains in cerebrospinal fluid (KCSF) is a valid option for diagnosing multiple sclerosis (MS), new research suggests.

Results showed that compared with a commonly used test that detects oligoclonal bands (OCBs) in CSF, the kappa test was similar in efficacy but was much easier to run in the laboratory, was less expensive, and results were available faster.

Dr Maria Willrich

"We would like clinicians to feel comfortable with this test," co-investigator Maria Willrich, PhD, lab director, Immunology Laboratories, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.

However, changing practice habits is a "challenge," as the kappa test is so new, Willrich said. "We're trying to offer education to neurologists so they understand how the test performs," she added.

The findings were published in the April issue of Mayo Clinic Proceedings.

Old Test Labor Intensive

MS triggers the immune system to attack the protective coating on nerve fibers, which disrupts signals between the brain and spinal cord and can lead to permanent nerve damage.

The condition is typically diagnosed using the OCB test, with two or more bands being considered a positive result for MS, Willrich said.

She added that over the years, the OCB test has been "in and out" of the McDonald criteria, the guidelines for clinical, radiographic, and laboratory measures used to diagnose MS. The test was again included as part of the McDonald criteria in the most recent update in 2017.

However, this test requires about 4 hours of analytic processing, is labor-intensive, and involves subjective visual interpretation by trained technologists, Willrich noted.

"We see a lot of variation between readers. For example, one person will count eight bands and the next person will count 10 bands and another 12 bands," she said.

Only approximately 100 labs in the country currently perform the OCB test. In addition, with the COVID pandemic, labs are "super short staffed" and very busy, causing an increase in turnaround time, said Willrich.

This can mean a delay for patients and their doctors in getting a confirmed MS diagnosis or having the condition ruled out.

The kappa CSF test could offer an alternative, Willrich noted. Kappa is one of two light chains in antibodies, which also consist of two immunoglobulin heavy chains.

Instead of measuring the entire antibody, as is done with the OCB test, with this kappa test, "we are measuring a fraction of that; we're measuring the kappa light chain concentration in CSF," said Willrich.

Cheaper, Quicker Turnaround

The current study included more than 1300 patients. Of these, 12% were diagnosed with MS. Researchers divided these individuals into two groups.

In a retrospective cohort of 702 individuals, both OCB and KCSF tests were performed.

Results showed the KCSF level of ≥0.1 mg/dL had a sensitivity of 68.2% and a specificity of 86.1% in detecting patients with MS ― which was not significantly different from the sensitivity and specificity of detecting two OCBs (75.0% and 87.6%, respectively; P >.08).

In the prospective cohort of 657 individuals, researchers validated the cutoff value of 0.1 mg/dL found in the retrospective cohort.

"In that second cohort, the tests performed exactly the same ― we found the same number of positives for MS with the two tests," with no statistical difference, said Willrich.

In a separate cost analysis, the "Medicare reimbursement rates for 2018 (cost to the payor) were used as the standardized cost for the OCB ($27.39) and KCSF tests ($16.79)," the investigators report.

The total cost for all the members of this subgroup for the OCB test, which would "traditionally" be the only test performed, was $36,784.77.

A "reflex algorithm" showed that 73% of the group needed only the KCSF test and that 27% needed both tests, which resulted in a total cost of $32,575.49. This represented "a relative cost reduction for Medicare of approximately 11%," the researchers write.

In addition, estimates showed that the average turnaround time for delivery of test results was 4 hours for the OCB, vs 20 minutes for the KCSF

Willrich noted that she hopes the study results will lead to consideration of the KCSF test for inclusion in the McDonald MS diagnostic criteria as an alternative to the OCB test.

"Diagnostic Gray Zone"

Commenting on the study for Medscape Medical News, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, Massachusetts, said this validation of the kappa test is good news.

"We neurologists are often faced with the diagnostic gray zone when considering MS, and more objective and cost-effective measures are most welcome," said Lakhan, who was not involved with the research.

"I have pleaded for more investigations that mine big datasets such as electronic health records to generate actionable insights and challenge the conventional 'gold standard' assessments in brain health," he said.

However, neurologists "tend to stick with" the McDonald criteria for MS diagnosis and initiation of disease-modifying therapies, Lakhan noted.

Until this kappa test is incorporated into the "formal" criteria, it may remain "a useful supplement to diagnosis," he added.

The study was funded in part by the Department of Laboratory Medicine and Pathology at the Mayo Clinic. The investigators and Lakhan have reported no relevant financial relationships.

Mayo Clin Proc. April 2022;97:738-751. Full article

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