Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy—a Prospective Follow-Up
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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 (r2 = 0.397 and r2 = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r2 = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scores INCAT r2 = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r2 = 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.
KeywordsNerve ultrasonography · CIDP · Polyneuropathy · Ultrasound pattern sum score · Nerve ultrasound and therapy.
myelin-associated glycopeptide antibodies
- C5 and 6
cervical roots 5 and 6
chronic inflammatory demyelinating polyradiculoneuritis
treated chronic neuritis
distal acquired demyelinating sensory neuropathy
European Federation of Neurological Societies
inflammatory neuropathy cause and treatment disability score
multifocal acquired demyelinating sensory and motor neuropathy
monoclonal gammopathy of unknown significance
medical research council sum score
nerve conduction studies
positive predictive value
ultrasound pattern sum score
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Florian Härtig, Marlene Ross, Natalie Winter, and Alexander Grimm designed the study and participated in data acquisition, analysis, interpretation, and drafted the manuscript. Nele M. Dammeier, Bianka Heiling, Nadine Fedtke, Antje Bornemann, and Tim W. Rattay participated in data acquisition and were involved in drafting the manuscript. Bernhard F. Décard participated in the acquisition of data. Hubertus Axer and Holger Lerche participated in the design of the study and acquisition of data, were involved in the analysis and interpretation of data, and helped to draft the manuscript. All authors read, critically revised, and approved the final manuscript.
Compliance with Ethical Standards
The study was registered in the German clinical trial registry (DRKS-ID 00005253) and approved by the local ethics committees (Tübingen 702/2015BO2, Basel 2014-230, and Jena 3663-01/13). Written informed consent to study participation was obtained from all patients.
Conflict of Interest
T.W.R. received travel and accommodation costs from Baxalta for a symposium on multifocal motor neuropathy and once from Merz for a botulinum toxin class, both unrelated to this work. A.G. received reimbursement for travel and accommodation costs from Pfizer for a polyneuropathy symposium. F.H. received reimbursement for travel and accommodation costs from Bayer AG. MK reports nonfinancial support from Biogen, personal fees from Roche, grants, personal fees and nonfinancial support from Novartis, and personal fees from Genzyme. H. L. reports grants from German Federal Ministry of Education and Research and grants from Deutsche Forschungsgemeinschaft during the conduct of the study, personal fees and other from UCB, personal fees from Desitin, personal fees and other from BioMarin, personal fees and other from Telethon, personal fees and other from Eisai, and grants, personal fees, and other from Bial, outside the submitted work. There are no conflicts of interest.
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