Laboratory medicine and neurology textbooks report that about 95 percent of MS cases are positive, Dr. Willrich said. In a study she and colleagues reported, consisting of 325 residual paired CSF and serum specimens obtained after physician-ordered oligoclonal banding isoelectric focusing testing, 67 cases were categorized as demyelination (Gurtner KM, et al. Clin Chem Lab Med. 2018;56[7]:1071–1080). The positivity rate of MS cases was lower than in textbooks. AUC was 0.854, sensitivity 94 percent, and specificity 72.5 percent. “Our control group was from the real world; it was heterogeneous and comprised everyone who had an indication for lumbar puncture. So you lose some of the specificity as a result.”
In another study, she and colleagues had 159 MS cases out of 1,307 samples. “We showed only 74 percent sensitivity with greater specificity [88.6 percent], but it shows how variable this can be, depending on the cohorts,” Dr. Willrich said (Saadeh RS, et al. Mayo Clin Proc. 2022;97[4]:738–751). The same OCB assay was used in this study, she noted, though the patient cohorts were different. “I thought it was important to show this because the test may not always match the textbook sensitivity we’re used to,” she said.
The IgG index, also called the CSF IgG index, is a correction used to determine if the increased IgG in CSF is due to increased permeability, intrathecal synthesis, or both, Dr. Willrich said. Measurement of CSF and serum IgG and albumin is performed by nephelometry or by turbidimetry.
The calculation for the ratio of IgG and albumin is IgG CSF (mg/dL) / albumin CSF (mg/dL). The index uses the four assays to make the calculation: IgG CSF (mg/dL) × albumin serum (g/dL) / albumin CSF (mg/dL) × IgG serum (g/dL).
“This is often performed in combination with oligoclonal banding,” Dr. Willrich said. Some laboratories may offer oligoclonal banding plus IgG index as a panel, “but the IgG index is not part of the MS diagnostic criteria.”
Results greater than 0.7 for the IgG index indicate intrathecal IgG synthesis, she said.
Dr. Willrich and colleagues recently tested the performance of their CSF IgG index using the cohort of 159 positive MS cases from their study published in 2022. “We were very surprised and somewhat disappointed when we learned that our sensitivity was only 49 percent with a cutoff of 0.705 for MS, with a specificity of 92 percent,” she said. The Youden index was 0.42. “This turns out not to be sensitive enough to be part of the McDonald diagnostic criteria for MS.”
The authors of the 2024 McDonald criteria acknowledge the value of CSF-restricted oligoclonal bands as a diagnostic tool, but they note it is time-consuming and rater-dependent and thus limits the assessment to laboratories with specialized expertise. κ-FLC have emerged as another diagnostic biomarker, they write, noting studies that have reported increased intrathecal production of κ-FLC in people with MS compared with controls.
“In contrast to oligoclonal bands, κFLC measurement can be conducted in hospitals and institutions with access to nephelometry or turbidimetry instruments,” the authors write, “which are cost-effective platforms that return objectively quantifiable and rater-independent results.”
Asked about the cost-effectiveness of running two different tests that provide similar utility, Dr. Willrich said in her laboratory, “we would love to run less oligoclonal banding to have more FTEs available for other complex tests.” For that to happen, she said, the neurologists will have to have confidence in the newer testing.
Amy Carpenter is CAP TODAY senior editor.