A Seronegative CCPD Misclassified as MS : A Practical Lesson in B‐Cell‐Driven Disease Stabilized With Rituximab

ABSTRACT Background Combined central and peripheral demyelination ( CCPD ) is a rare immune‐mediated disorder involving both central and peripheral myelin. Recent evidence suggests that CCPD may represent a distinct clinical and immunological entity rather than a coincidental overlap between multiple sclerosis ( MS ) and chronic inflammatory demyelinating polyneuropathy ( CIDP ). Case Presentation We report a 63‐year‐old seronegative female patient who had initially been followed with a diagnosis of MS and was later re‐evaluated as having CCPD after developing new peripheral symptoms. Cerebrospinal fluid analysis revealed elevated protein levels with negative oligoclonal bands. Autoantibody screening, including anti‐MOG, anti‐MAG, AQP4, and NF155, was negative. MRI showed confluent periventricular and juxtacortical lesions consistent with central involvement. The patient showed clinical stability with no further radiological progression after rituximab therapy over an 8‐month follow‐up period. Conclusion This case supports the existence of a seronegative, B‐cell‐mediated variant of CCPD and highlights the potential role of rituximab in achieving disease stabilization. Recognition of CCPD as a distinct diagnostic entity may prevent misclassification as MS and guide appropriate immunotherapy strategies.