Nodopathy: clinic, diagnosis, treatment. Clinical description

Abstract

AIM: Evaluation of the significance and possibilities of laboratory-instrumental diagnostic methods in establishing the diagnosis and selection of targeted therapy in patients with nodopathies.

MATERIALS AND METHODS: System analysis of data from foreign and domestic literature with the presentation of a clinical case.

RESULTS: Polyneuropathies are classified as demyelinating or axonal based on electrophysiological studies. However, in 2015, in addition to axonal and demyelinating neuropathies, it was proposed to distinguish a separate pathophysiological group — nodopathies. The pathogenesis of nodopathies may differ depending on the type of ion channels involved in the process, but always leads to a loss of excitability of the axon membrane; in the nodal region the membrane becomes inexcitable. Such neuropathies are characterized by transient conduction blocks followed by the development of axonal degeneration. Typical examples of nodopathies are acute motor axonal neuropathy, as well as multifocal motor neuropathy. Current pathophysiological understanding of specialized nodal regions (nodes of Ranvier) and associated axoglial proteins is growing. Hypotheses have been put forward about their role in the pathogenesis of immune-mediated attack on the peripheral myelinated axon. Recently, high titers of antibodies directed against a number of key adhesion molecules have been identified in both acute and chronic inflammatory neuropathies. These facts add to the differences in differential diagnosis between axonal and demyelinating peripheral neuropathies. New disease classification schemes based on seropositivity, improved electrophysiological and ultrasound classification, and identification of putative underlying pathological targets and mechanisms are being rapidly developed.

CONCLUSION: Using our clinical example, we demonstrated the capabilities of laboratory and instrumental diagnostic methods in establishing a diagnosis in a patient with one of the forms of nodopathies — multifocal motor neuropathy.

Keywords

ENMG / nodopathy / nod of Ranvier / sonography of nerves / NF155 / NF184 / paranodopathy

References

[1] 1.Uncini A, Kuwabara S. Nodopathies of the peripheral nerve: an emerging concept. J Neurol Neurosurg Psychiatry. 2015;86(11): 1186–1195. DOI: 10.1136/jnnp-2014-310097

[2] Uncini A., Kuwabara S. Nodopathies of the peripheral nerve: an emerging concept // J. Neurol. Neurosurg. Psychiatry. 2015. Vol. 86, No. 11. P. 1186–1195. DOI: 10.1136/jnnp-2014-310097

[3] 2.Kira J, Yamasaki R, Ogata H. Anti-neurofascin autoantibody and demyelination. Neurochem. Int. 2019;130:104360. DOI: 10.1016/j.neuint.2018.12.011

[4] Kira J., Yamasaki R., Ogata H. Anti-neurofascin autoantibody and demyelination // Neurochem. Int. 2019. Vol. 130. P. 104360. DOI: 10.1016/j.neuint.2018.12.011

[5] 3.Nikitin SS, Murtazina AF, Druzhinin DS. Block of excitation conduction along the peripheral nerve as an electrophysiological phenomenon: a review of the literature. Neuromuscular diseases. 2019;9(1):12–23.

[6] Никитин С.С., Муртазина А.Ф., Дружинин Д.С. Блок проведения возбуждения по периферическому нерву как электрофизиологический феномен: обзор литературы // Нервно-мышечные болезни. 2019. Т. 9, № 1. С. 12–23.

[7] 4.Fehmi J, Scherer SS, Willison HJ, Rinaldi S. Nodes, paranodes and neuropathies. J Neurol Neurosurg Psychiatry. 2018;89(1):61–71. DOI: 10.1136/jnnp-2016-315480

[8] Fehmi J., Scherer S.S., Willison H.J., Rinaldi S. Nodes, paranodes and neuropathies // J. Neurol. Neurosurg. Psychiatry. 2018. Vol. 89, No. 1. P. 61–71. DOI: 10.1136/jnnp-2016-315480

[9] 5.Koike H, Kadoya M, Kaida KI, et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies. J Neurol Neurosurg Psychiatry. 2017;88(6):465–473. DOI: 10.1136/jnnp-2016-314895

[10] Koike H., Kadoya M., Kaida K.I., et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies // J. Neurol. Neurosurg. Psychiatry. 2017. Vol. 88, No. 6. P. 465–473. DOI: 10.1136/jnnp-2016-314895

[11] 6.Kira J. Anti-neurofascin 155 antibody-positive chronic inflammatory demyelinating polyneuropathy/combined central and peripheral demyelination: Strategies for diagnosis and treatment based on the disease mechanism. Front Neurol. 2021;12:12. DOI: 10.3389/fneur.2021.665136

[12] Kira J. Anti-neurofascin 155 antibody-positive chronic inflammatory demyelinating polyneuropathy/combined central and peripheral demyelination: Strategies for diagnosis and treatment based on the disease mechanism // Front. Neurol. 2021. Vol. 12. P. 12. DOI: 10.3389/fneur.2021.665136

[13] 7.Roggenbuck JJ, Boucraut J, Delmont E, et al. Diagnostic insights into chronic-inflammatory demyelinating polyneuropathies. Ann Transl Med. 2018;6(17):337. DOI: 10.21037/atm.2018.07.34

[14] Roggenbuck J.J., Boucraut J., Delmont E., et al. Diagnostic insights into chronic-inflammatory demyelinating polyneuropathies // Ann. Transl. Med. 2018. Vol. 6 (17). P. 337. DOI: 10.21037/atm.2018.07.34

[15] 8.Vizcarra J, Harrison T, Garcia-Santibanez R. Update on Nodopathies of the Peripheral Nerve. Current Treatment Options in Neurology. 2021;23(8):25. DOI: 10.1007/s11940-021-00683-3

[16] Vizcarra J., Harrison T., Garcia-Santibanez R. Update on Nodopathies of the Peripheral Nerve // Current Treatment Options in Neurology. 2021. Vol. 23, No. 8. P. 25. DOI: 10.1007/s11940-021-00683-3

[17] 9.Sokmen O, Demirci M, Tan E. A case with Neurofascin-155 IgG antibody-associated combined central and peripheral demyelination: Successfully treated with anti-CD20 monoclonal antibody. Clin Neurol Neurosurg. 2021;210:106961. DOI: 10.1016/j.clineuro.2021.106961

[18] Sokmen O., Demirci M., Tan E. A case with Neurofascin-155 IgG antibody-associated combined central and peripheral demyelination: Successfully treated with anti-CD20 monoclonal antibody // Clin. Neurol. Neurosurg. 2021. Vol. 210. P. 106961. DOI: 10.1016/j.clineuro.2021.106961

[19] 10.Kerasnoudis A, Pitarokoili K, Haghikia A, et al. Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies. Muscle & Nerv. 2016;54(5):864–871. DOI: 10.1002/mus.25138

[20] Kerasnoudis A., Pitarokoili K., Haghikia A., et al. Nerve ultrasound protocol in differentiating chronic immune-mediated neuropathies // Muscle & Nerv. 2016. Vol. 54, No. 5. P. 864–871. DOI: 10.1002/mus.25138

[21] 11.Naumova ES, Nikitin SS, Druzhinin DS. Quantitative sonographic characteristics of peripheral nerves in healthy subjects. Annals of Clinical and Experimental Neurology. 2017;11(1):55–61. (In Russ.)

[22] Наумова Е.С., Никитин С.С., Дружинин Д.С. Количественные сонографические характеристики периферических нервов у здоровых людей // Анналы клинической и экспериментальной неврологии. 2017. Т. 11, № 1. С. 55–61.

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