# B-Cell Depletion as Evidence for Shared Neuroimmune Pathways in Combined Central and Peripheral Demyelination: A Case Report and Literature Review

## TL;DR

This case report explores a rare condition where both the central and peripheral nervous systems are affected by demyelination, suggesting a shared immune mechanism involving B cells.

## Contribution

The study provides evidence for B-cell involvement in combined central and peripheral demyelination through antibody-independent pathways.

## Key findings

- B-cell depletion with anti-CD20 therapy stabilized the patient's condition, supporting a B-cell-driven model.
- Shared immune mechanisms, including cytokine production and barrier dysfunction, may explain parallel inflammation in both nervous systems.
- No unifying autoantibody was identified, emphasizing the role of immune pathways beyond antibody-mediated mechanisms.

## Abstract

Combined central and peripheral demyelination (CCPD) is a rare neuroimmunological condition involving inflammatory demyelination of both the central nervous system (CNS) and peripheral nervous system (PNS). We report a chronic progressive CCPD case initially diagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) and treated with conventional CIDP-directed immunotherapies, with subsequent development of multiple sclerosis (MS)-like CNS demyelination. An extensive diagnostic evaluation excluded alternative infectious, metabolic, paraneoplastic, and antibody-mediated etiologies affecting either compartment. In the absence of a unifying pathogenic autoantibody, the combined clinical, radiological, cerebrospinal fluid, and electrophysiological findings support a shared immune-mediated process. Within this framework, B cells are implicated through antibody-independent mechanisms, including antigen presentation, pro-inflammatory cytokine production (e.g., IL-6), and amplification of Th1/Th17-driven inflammation. Interactions between B cells and the complement system via CR1 (CD35) and CR2 (CD21), together with dysfunction of the blood–brain barrier (BBB) and blood–nerve barrier (BNB), may facilitate parallel immune activation across both compartments. In this case, the observed radiological and electrophysiological stabilization under anti-CD20 therapy is consistent with a B-cell-driven pathogenic model in CCPD.