Characterizing Combined Central and Peripheral Demyelination—Insights From a Multimodal Comparison With Chronic Inflammatory Demyelinating Polyneuropathy and Multiple Sclerosis

Introduction/Aims: Combined central and peripheral demyelination (CCPD) is a rare dysimmune disorder sharing features with multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Direct comparisons of central and peripheral diagnostic findings across these entities remain limited. We, therefore, performed a systematic study assessing nervous system involvement in CCPD, using magnetic resonance imaging (MRI), nerve ultrasound (US), and nerve conduction study (NCS) and compared findings to MS and CIDP controls. Methods: We conducted a descriptive case study including 4 CCPD patients, 13 CIDP patients, and 10 MS controls. All subjects underwent a standardized protocol of NCS and US. In addition, MS and CCPD patients also underwent brain and spinal cord MRI. Cerebrospinal fluid testing was performed in 20/27 patients. Results: NCS revealed electrodiagnostic features suggestive of demyelination in all CCPD and CIDP patients, fulfilling the electrodiagnostic criteria for CIDP. We found motor conduction abnormalities in two MS patients, not fulfilling criteria for demyelination. US showed a similar pattern of multifocal nerve enlargement in CCPD and CIDP patients, while three MS patients also demonstrated mild proximal median nerve enlargement. Finally, CSF oligoclonal bands were only found in MS patients. Discussion: Peripheral diagnostic tools reveal strikingly similar electrophysiological and morphologic features in CCPD and CIDP, underscoring a potential overlap in their disease mechanisms and the challenges of distinguishing these entities based on peripheral nerve assessment alone. Our findings further suggest that US could serve as a potentially useful screening tool in patients with predominantly central nervous system demyelinating syndromes and suspected peripheral involvement, helping to guide subsequent electrophysiological testing.