Bound and Free Light Chains in Subacute Sclerosing Panencephalitis and Multiple Sclerosis Serum and Cerebrospinal Fluid

A 49-year-old woman sought care for a 9-month history of gait difficulty. She was dragging her right foot when walking and could not walk more than 3 blocks because of right leg weakness. Physical examination showed right-sided weakness of hip flexion and foot dorsiflexion and symmetrical hyperreflexia at the knees and ankles. Magnetic resonance imaging of the brain showed multiple foci of T2 hyperintensity throughout the white matter in both cerebral and cerebellar hemispheres, predominantly in a periventricular distribution. Several small enhancing lesions and mild generalized cerebral volume loss were seen. The appearance and distribution were consistent with a demyelinating process such as multiple sclerosis. Magnetic resonance imaging of the cervical and thoracic spine showed multiple small T2 hyperintensities, including 1 enhancing lesion in the cervical spinal cord. Oligoclonal bands were positive, with 11 unique bands in the cerebrospinal fluid. The concentration of cerebrospinal fluid kappa free light chains was increased, at 0.314 mg/dL. The patient was diagnosed with relapsing-remitting multiple sclerosis. A 5-day course of intravenous corticosteroids was started, after which she noted clinical improvement. At her last follow-up 2 years after initial evaluation, the patient has been stable with no new clinical multiple sclerosis episodes and stable magnetic resonance imaging disease burden with no new lesions. The diagnosis of multiple sclerosis incorporates clinical, imaging, and laboratory evidence. The 2017 revised McDonald criteria state that a finding of cerebrospinal fluid -specific oligoclonal bands can replace the criterion for dissemination in time to make a diagnosis of definitive multiple sclerosis. The standard test for oligoclonal bands is performed using isoelectric focusing electrophoresis and takes more than 3 hours to complete. The case patient had 11 unique cerebrospinal fluid bands. The number of bands is not correlated with disease severity or prognosis.

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Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0285 ◽

2018 ◽

Vol 56 (4) ◽

pp. 609-613 ◽

Cited By ~ 13

Author(s):

Estefania Valencia-Vera ◽

Ana Martinez-Escribano Garcia-Ripoll ◽

Alfredo Enguix ◽

Carmen Abalos-Garcia ◽

Maria Jesus Segovia-Cuevas

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

High Sensitivity ◽

Demyelinating Diseases ◽

Oligoclonal Bands ◽

Light Chains ◽

Moderate Increase ◽

Free Light Chains ◽

Cross Sectional ◽

Significant Difference

Abstract Background: The determination of κ free light chains (KFLC) in cerebrospinal fluid (CSF) by nephelometry is a feasible alternative to immunoglobulin G oligoclonal bands (OCB) in the evaluation of intrathecal synthesis of immunoglobulin in multiple sclerosis (MS) and other demyelinating diseases. The aim of this study was to assess the diagnostic value of KFLC and its inclusion in a procedure algorithm along with OCB interpretation. Methods: A cross-sectional study, which included 123 patients with a CSF OCB request, was carried out. Isoelectric focusing followed by immunofixation was used to detect OCB, and nephelometry was used to analyze KFLC. The KFLC index was calculated using CSF/serum quotient of KFLC and albumin. The KFLC index was compared with MS diagnosis to find the optimal cutoff. It was obtained from the receiver operating characteristic (ROC) curves and the Youden method. Results: The CSF KFLC median was 1.66 mg/L in the MS group, whereas in other central nervous system diseases, KFLC showed generally no or only moderate increase in CSF (median 0.10 mg/L). KFLC index showed a significant difference between groups. ROC analysis for CSF KFLC concentration, and KFLC indexes were 91.88% and 93.94%, respectively. The best cutoff for the KFLC index was 2.91 for MS diagnosis (sensitivity: 83.78%; specificity: 85.88%). The proposed algorithm showed high sensitivity (89.19%) and specificity (84.71%). Conclusions: KFLC determination is rapid and automatized, but it has no higher sensitivity and specificity than OCB in MS diagnosis. Nevertheless, when used in screening, it could reduce the number of manual OCB tests.

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