Do we still need OCBs in MS diagnosis and how many?

Area of Science:

• Neurology
• Immunology
• Diagnostic Medicine

Background:

• Cerebrospinal fluid-specific oligoclonal bands (CSF-OCBs) are crucial for diagnosing multiple sclerosis (MS) via dissemination in time (DIT).
• Current MS diagnostic criteria recommend a cut-off of ≥2 CSF-OCBs, but evidence suggests ≥3 may offer superior diagnostic utility.
• This study evaluates the diagnostic performance of different CSF-OCB cut-offs for MS.

Purpose of the Study:

• To assess the diagnostic utility of ≥2 and ≥3 CSF-OCBs for multiple sclerosis (MS) diagnosis.
• To compare the sensitivity and specificity of these cut-offs in a real-world clinical setting.
• To determine the impact of CSF-OCB analysis on the time to MS diagnosis.

Main Methods:

• Retrospective analysis of paired serum and CSF-OCB samples analyzed between July 2018 and June 2020.
• Isoelectric focusing was used to detect CSF-OCBs, with results reviewed by two blinded raters.
• Clinical data review of 945 patients with sufficient information from 1334 requests.

Main Results:

• Of 945 patients, 28% had more than one CSF-OCB detected.
• The sensitivity and specificity for MS were high for both ≥2 (91.7%, 91.2%) and ≥3 (90.2%, 93.8%) CSF-OCBs.
• A threshold of ≥3 CSF-OCBs showed a slightly better specificity, and only 3 of 22 patients with 2 CSF-OCBs had MS. CSF analysis reduced time to diagnosis by approximately 14 months.

Conclusions:

• While both ≥2 and ≥3 CSF-OCBs show similar performance, ≥3 CSF-OCBs may be more specific for MS diagnosis, as 2 CSF-OCBs were often associated with non-inflammatory conditions.
• Consideration of a ≥3 CSF-OCB cut-off is recommended for improved MS diagnostic accuracy.
• Cerebrospinal fluid analysis significantly expedites the diagnosis of MS, reducing diagnostic delay by an average of 14 months.