Differential diagnosis of chronic acquired demyelinating polyneuropathies

Introduction. The rarity of chronic acquired polyneuropathies (PNP) with the demyelinating nature of peripheral nerve damage causes the difficulties of their differential diagnosis that persist in our country and abroad. Objective: to identify significant clinical, neurophysiological and sonographic differential diagnostic markers in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and non-IgM paraproteinemic demyelinating polyneuropathies (PDP).

Material and methods: 80 patients were included in the study: 30 with CIDP, 30 with non-IgM-PDP associated with monoclonal gammapathy of unclear significance (PDP-MGUS), and 20 with non-IgM-PDP associated with lymphoproliferative disease (PDP-LPD). The patients included in the study underwent clinical evaluation of neurological disorders according to the MRC, NIS, VAS, INCAT, IRODS, SARA scales; ENMG and ultrasound studies of peripheral nerves.

Results. The predominance of men in all groups was noted (p > 0.05). Compared with patients with CIDP, patients with PDP were significantly older, they were more likely to have neuropathic pain syndrome and trophic disorders (p < 0.05). In patients with PDP-LPD, in contrast to CIDP and PDP-MGUS, there was a predominance of the distal pattern of muscle weakness distribution and a greater severity of sensitive ataxia (p < 0.05). During NCV studies in patients with CIDP, compared with patients with PDP, blocks of conduction and dispersion of M-waves were signifi -cantly more often recorded in the study of motor fibers of the nerves of the hands (p < 0.05); and in the study of motor nerves of the legs, non-excitability of motor fibers was significantly less often noted (p < 0.05). Ultrasound examination of peripheral nerves showed no significant differences between patients (p > 0.05).

Conclusion. Clinical phenotype, neurophysiological and sonographic changes in patients with CIDP and PDP do not have highly specific differences. Electrophoresis of serum proteins with immunofixation makes it possible to differentiate CIDP and PDP, and further examination by an oncohematologist with paraproteinemia makes it possible to distinguish MGUS from LPD.

1. Lehmann H.C., Wunderlich G., Fink G.R., Sommer C. Diagnosis of peripheral neuropathy. Neurol Res Pract. 2020;2:20. https://doi.org/10.1186/s42466-020-00064-2 PMID: 33324924; PMCID: PMC7650053.

2. Van den Bergh P.Y.K., van Doorn P.A., Hadden R.D.M., Avau B., Vankrunkelsven P., Allen J.A. et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision. J Peripher Nerv Syst. 2021;26(3):242–268. https://doi.org/10.1111/jns.12455 PMID: 34085743.

3. Allen J.A., Gorson K.C., Gelinas D. Challenges in the diagnosis of chronic inflammatory demyelinating polyneuropathy. Brain Behav. 2018;8(3):e00932. https://doi.org/10.1002/brb3.932 PMID: 29541543; PMCID: PMC5840455.

4. Grishina D.A., Suponeva N.A., Arestova A.S., Melnik E.A., Tumilovich T.A., Sinkova V.V., Piradov M.A. Chronic inflammatory demyelinating polyradiculoneuropathy overdiagnosis in Russia. Annals of Clinical and Experimental Neurology. 2023;17(3):5–12. (In Russ.) https://doi.org/10.54101/ACEN.2023.3.1

5. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2006;11(1):9–19. doi: 10.1111/j.1085-9489.2006.00059.x PMID: 16519778.

6. Karam C., Moshe-Lilie O., Chahin N., Ragole T., Medvedova E., Silbermann R. Diagnosis of paraproteinemic neuropathy: Room for improvement. J Neurol Sci. 2020;415:116902. doi: 10.1016/j.jns.2020.116902 Epub 2020 May 18. PMID: 32497875.

7. Alkhawajah N.M., Dunnigan S.K., Bril V. Comparison of monoclonal gammopathy of undetermined significance-associated neuropathy and chronic inflammatory demyelinating polyneuropathy patients. J Neurol. 2014;261(8):1485–91. doi: 10.1007/s00415-014-7357-0 Epub 2014 May 7. PMID: 24801490; PMCID: PMC4119250.

8. Ginsberg M.A., Varlamova E.Y., Ryzhko V.V., Suponeva N.А., Piradov M.A. Clinical and neurophysiological studies of chronic demyelinating polyneuropathy associated with monoclonal secretion. Meditsinskiy sovet=Medical Council. 2015;(10):93–99. (In Russ.) https://doi.org/10.21518/2079-701X-2015-10-93-99].

9. Gorson K.C., Allam G., Ropper A.H. Chronic inflammatory demyelinating polyneuropathy: clinical features and response to treatment in 67 consecutive patients with and without a monoclonal gammopathy. Neurology. 1997;48(2):321–8. doi: 10.1212/wnl.48.2.321. PMID: 9040714.

10. Campo E., Jaffe E.S., Cook J.R., Quintanilla-Martinez L., Swerdlow S.H., Anderson K.C. et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229– 1253. doi: 10.1182/blood.2022015851 Erratum in: Blood. 2023 Jan 26;141(4):437. PMID: 35653592; PMCID: PMC9479027.

11. Mani A.M., Devasia A.J., Nair A., Benjamin R.N., Prabhakar A.T., Sivadasan A. et al. Monoclonal Gammopathies of ‘Neurological Significance’: Paraproteinemic Neuropathies. Can J Neurol Sci. 2021;48(5):616–625. doi: 10.1017/cjn.2020.278 Epub 2021 Jan 5. PMID: 33397535.

12. Khwaja J., D’Sa S., Minnema M.C., Kersten M.J., Wechalekar A., Vos J.M. IgM monoclonal gammopathies of clinical significance: diagnosis and management. Haematologica. 2022;107(9):2037– 2050. doi: 10.3324/haematol.2022.280953 PMID: 35770530; PMCID: PMC9425303.

13. Suponeva N.A., Arestova А.S., Melnik Е.А. et al. Validation of the Medical Research Council sum score (MRCss) for use in Russian-speaking patients with chronic inflammatory demyelinating polyneuropathy. Neuromuscular Diseases 2023;13(1):68–74. (In Russ.) doi: 10.17650/2222-8721-2023-13-1-68-74

14. Arestova А.S., Melnik Е.А., Zaytsev A.B., Zimin A.A., Yakubu А., Sherbakova E.S., Yusupova D.G., Grishina D.A., Suponeva N.A., Piradov M.A. Inflammatory Neuropathy Cause and Treatment (INCAT) Scale for the assessment of disability level in patients with chronic inflammatory demyelinating polyneuropathy: linguocultural ratification in Russia. Neuromuscular Diseases. 2021;11(4):26–33. (In Russ.) https://doi.org/10.17650/2222-8721-2021-11-4-26-33

15. Kimura J. Electrodiagnosis in diseases of nerve and muscle: principles and practice. 4rd edn. Oxford University Press, 2013:1176.

16. Goedee H.S., van der Pol W.L., van Asseldonk J.H., Franssen H., Notermans N.C., Vrancken A.J. et al. Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies. Neurology. 2017;88(2):143–151. doi: 10.1212/WNL.0000000000003483 Epub 2016 Dec 7. PMID: 27927940.

17. Bromberg M.B., Feldman E.L, Albers J.W. Chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients with and without an associated monoclonal gammopathy. Neurology. 1992;42(6):1157–63. doi: 10.1212/wnl.42.6.1157 PMID: 1603342.

18. Simmons Z., Albers J.W., Bromberg M.B., Feldman E.L. Presentation and initial clinical course in patients with chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients without and with monoclonal gammopathy. Neurology. 1993;43(11):2202–9. doi: 10.1212/wnl.43.11.2202 PMID: 8232929.

19. Notermans N., Franssen H., Eurelings M., Van der Graaf Y., Wokke J.H. Diagnostic criteria for demyelinating polyneuropathy associated with monoclonal gammopathy. Muscle Nerve. 2000;23:73–79.

20. Cocito D., Isoardo G., Ciaramitaro P., Migliaretti G., Pipieri A., Barbero P. et al. Terminal latency index in polyneuropathy with IgM paraproteinemia and anti-MAG antibody. Muscle Nerve. 2001;24(10):1278–82. doi: 10.1002/mus.1145 PMID: 11562906.

21. Radziwill A.J., Steck A.J., Renaud S., Fuhr P. Distal motor latency and residual latency as sensitive markers of anti-MAG polyneuropathy. J Neurol. 2003;250(8):962–6. doi: 10.1007/s00415-003-1128-7 PMID: 12928916.

22. Lupu V.D., Mora C.A., Dambrosia J., Meer J., Dalakas M., Floeter M.K. Terminal latency index in neuropathy with antibodies against myelin-associated glycoproteins. Muscle Nerve. 2007;35(2):196–202. doi: 10.1002/mus.20678 PMID: 17068765.

23. Niu J., Ding Q., Fan J., Zhang L., Liu J., Guan Y. et al. Nerve Ultrasound Performances in Differentiating POEMS Syndrome from CIDP. Neurotherapeutics. 2022;19(2):455–463. doi: 10.1007/s13311-022-01209-8 Epub 2022 Mar 7. PMID: 35257327; PMCID: PMC9226218.

24. Dörner M., Ceanga M., Schreiber F., Stahl J.H., Kronlage C., Wittlinger J. et al. High-Resolution Nerve Ultrasound Abnormalities in POEMS Syndrome-A Comparative Study. Diagnostics (Basel). 2021;11(2):264. doi: 10.3390/diagnostics11020264 PMID: 33572067; PMCID: PMC7915164.

25. Zhu S., Li W., Lin M., Li T. Serum Protein Electrophoresis and Immunofixation Electrophoresis Detection in Multiple Myeloma. J Coll Physicians Surg Pak. 2021;30(7):864-–867. doi: 10.29271/jcpsp.2021.07.864 PMID: 34271795