Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy—a Prospective Follow-Up

Abstract

As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r = 0.397 and r = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scores INCAT r = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r = 0.272-0.414, p < 0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in > 50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12 months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p < 0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.

Clinical, Sonographic, and Electrophysiologic Longitudinal Features of Chronic Inflammatory Demyelinating Polyneuropathy

“…BUS showed increasing values in progressive CIDP, which were not statistically significant. Härtig et al have recently described that in a larger cohort with 80 patients, changes of UPSS correlated good to clinical disability in a 12‐month follow‐up. A difference in evaluation of results of our study and the one of Härtig et al is that we worked with relative changes of the ultrasound parameters based on the first value to make parameters comparable interindividually.…”

“…Nerve ultrasound is an increasingly used examination for the diagnosis of autoimmune neuropathies, such as CIDP. Recent studies have suggested that nerve ultrasound may also be useful for assessing the clinical course of the disease . The intranerve CSA variability seems reasonable to evaluate the ultrasound data in the disease course, as it reflects the focal inflammation of the nerves .…”

“…A difference in evaluation of results of our study and the one of Härtig et al is that we worked with relative changes of the ultrasound parameters based on the first value to make parameters comparable interindividually. Härtig et al worked with changes in form of a difference (eg, delta‐UPSS). Further studies are needed to explore which method may give more reliable results (relative values vs. differences of the absolute values).…”

“…Kerasnoudis et al described that the intranerve CSA variability of each nerve, but not the CSA alone, correlated with the disability score during a 12‐month follow‐up of 11 CIDP patients. Härtig et al have recently shown that changes of the UPSS correlate to the clinical disability score in a 12‐month follow‐up.…”

“…In CIDP, an enlargement of cross‐sectional‐area (CSA) can be observed by ultrasound. As reason for the enlargement of CSA, a focal edematous inflammation of the nerve is assumed . Not only edema causes nerve enlargement, but also remodeling with fibrous tissue, demyelination and remyelination caused by hereditary motor and sensory neuropathies, etc .…”