Neuropathic pain in Charcot-Marie-Tooth disease: A clinical and laser-evoked potential study.
Journal
European journal of pain (London, England)
ISSN: 1532-2149
Titre abrégé: Eur J Pain
Pays: England
ID NLM: 9801774
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
12
02
2022
received:
15
08
2021
accepted:
06
02
2022
pubmed:
8
2
2022
medline:
5
4
2022
entrez:
7
2
2022
Statut:
ppublish
Résumé
Pain, either nociceptive or neuropathic (NP), is a common symptom in Charcot-Marie-Tooth (CMT) disease. We investigated small fibers involvement and its correlation with pain in different CMT subtypes through a systematic clinical and neurophysiological study. We enrolled 50 patients: 19 with duplication of PMP22 (CMT1A), 11 with mutation of MPZ (CMT1B, CMT2I/J, or CMTDID), 12 with mutation of GJB1 (CMTX1), and 8 with mutation of MFN2 (CMT2A and CMT2A2B). Pain was rated with the 11-point Numerical Rating Scale and characterized through Neuropathic Pain Symptoms Inventory. Laser-evoked potentials (LEPs) were recorded after right foot and hand stimulation and N2-P2 complex amplitude and latency were compared with those of 41 controls. Overall pain prevalence was 36%. NP was present in 14.6% of patients, with a length-dependent distribution in 85.7% of cases, and it was significantly more frequent in CMT1A (p < 0.001). Aδ fibers involvement greatly varies between CMT subtypes, reflecting differences in molecular pathology and pathophysiologic mechanisms. Prolonged N2 latency from foot stimulation was noted in 11 CMT1A patients, 5 of which report NP. MPZ-CMTs displayed different neurophysiological phenotypes and a very low prevalence of NP. LEPs were normal in all but one CMTX1 patients, although lower limbs N2-P2 amplitude was significantly reduced in males (p = 0.043). MFN2-CMTs were NP free and LEPs recordings were all normal. NP strictly correlated with LEPs alterations (p = 0.017). NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment. Neuropathic pain is a frequent finding in Charcot-Marie Tooth disease and is related to Aδ fibers impairment. Patients at higher risk are those belonging to certain genetic subtypes (i.e. CMT1A and CMT2J) or with laser-evoked potentials abnormalities. While managing this disease, clinicians should be aware of this symptom in order to offer best treatment options to their patients.
Sections du résumé
BACKGROUND
Pain, either nociceptive or neuropathic (NP), is a common symptom in Charcot-Marie-Tooth (CMT) disease.
METHODS
We investigated small fibers involvement and its correlation with pain in different CMT subtypes through a systematic clinical and neurophysiological study. We enrolled 50 patients: 19 with duplication of PMP22 (CMT1A), 11 with mutation of MPZ (CMT1B, CMT2I/J, or CMTDID), 12 with mutation of GJB1 (CMTX1), and 8 with mutation of MFN2 (CMT2A and CMT2A2B). Pain was rated with the 11-point Numerical Rating Scale and characterized through Neuropathic Pain Symptoms Inventory. Laser-evoked potentials (LEPs) were recorded after right foot and hand stimulation and N2-P2 complex amplitude and latency were compared with those of 41 controls.
RESULTS
Overall pain prevalence was 36%. NP was present in 14.6% of patients, with a length-dependent distribution in 85.7% of cases, and it was significantly more frequent in CMT1A (p < 0.001). Aδ fibers involvement greatly varies between CMT subtypes, reflecting differences in molecular pathology and pathophysiologic mechanisms. Prolonged N2 latency from foot stimulation was noted in 11 CMT1A patients, 5 of which report NP. MPZ-CMTs displayed different neurophysiological phenotypes and a very low prevalence of NP. LEPs were normal in all but one CMTX1 patients, although lower limbs N2-P2 amplitude was significantly reduced in males (p = 0.043). MFN2-CMTs were NP free and LEPs recordings were all normal. NP strictly correlated with LEPs alterations (p = 0.017).
CONCLUSIONS
NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment.
SIGNIFICANCE
Neuropathic pain is a frequent finding in Charcot-Marie Tooth disease and is related to Aδ fibers impairment. Patients at higher risk are those belonging to certain genetic subtypes (i.e. CMT1A and CMT2J) or with laser-evoked potentials abnormalities. While managing this disease, clinicians should be aware of this symptom in order to offer best treatment options to their patients.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
929-936Informations de copyright
© 2022 European Pain Federation - EFIC®.
Références
Bas, J., Delmont, E., Fatehi, F., Salort-Campana, E., Verschueren, A., Pouget, J., Levebvre, M.-N., Grapperon, A.-M., & Attarian, S. (2018). Motor unit number index correlates with disability in Charcot-Marie-Tooth disease. Clinical Neurophysiology, 129, 1390-1396. https://doi.org/10.1016/j.clinph.2018.04.359
Bjelica, B., Peric, S., Basta, I., Bozovic, I., Kacar, A., Marjanovic, A., Ivanovic, V., Brankovic, M., Jankovic, M., Novakovic, I., & Stojanovic, V. R. (2020). Neuropathic pain in patients with Charcot-Marie-Tooth type 1A. Neurological Sciences, 41, 625-630. https://doi.org/10.1007/s10072-019-04142-5
Briani, C., Adami, F., Cavallaro, T., Taioli, F., Ferrari, S., & Fabrizi, G. M. (2008). Axonal neuropathy due to myelin protein zero mutation misdiagnosed as amyloid neuropathy. Muscle and Nerve, 38, 921-923. https://doi.org/10.1002/mus.21062
Carter, G. T., Jensen, M. P., Galer, B. S., Kraft, G. H., Crabtree, L. D., Beardsleay, R. M., Abresh, R. T., & Birdt, T. D. (1998). Neuropathic pain in Charcot-Marie-Tooth disease. Archives of Physical Medicine and Rehabilitation, 79, 1560-1564. https://doi.org/10.1016/S0003-9993(98)90421-X
Cruccu, G., Sommer, C., Anand, P., Attal, N., Baron, R., Garcia-Larrea, L., Haanpaa, M., Jensen, T. S., Serra, J., & Treede, R.-D. (2010). EFNS guidelines on neuropathic pain assessment: Revised 2009. European Journal of Neurology, 17, 1010-1018. https://doi.org/10.1111/j.1468-1331.2010.02969.x
De Jonghe, P., Timmerman, V., Cauterick, C., Nelis, E., de Vriendt, E., Lőfgren, A., Vercruyssen, A., Verellen, C., Van Maldergem, L., Martin, J. J., & Van Broekhoven, C. (1999). The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype. Brain, 122, 281-290. https://doi.org/10.1093/brain/122.2.281
Devigili, G., Cazzato, D., & Lauria, G.. (2020). Clinical diagnosis and management of small fiber neuropathy: An update on best practice. Expert Review of Neurotherapeutics, 20(9), 967-980. https://doi.org/10.1080/14737175.2020.1794825
Duchesne, M., Danigo, A., Richard, L., Vallat, J.-M., Attarian, S., Gonnaud, P.-M., Lacour, A., Péréon, Y., Stojkovic, T., Nave, K.-A., Bertrand, V., Nabirotchkin, S., Cohen, D., Demiot, C., & Magy, L. (2018). Skin biopsy findings in patients with CMT1A: Baseline data from the CLN-PXT3003-01 study provide new insights into the pathophysiologiy of the disorder. Journal of Neuropathology and Experimental Neurology, 77, 274-281.
Ericson, U., & Borg, K. (1999). Analysis of sensory function in Charcot-Marie-Tooth disease. Acta Neurologica Scandinavica, 99, 291-296. https://doi.org/10.1111/j.1600-0404.1999.tb00678.x
Fabrizi, G. M., Pellegrini, M., Angiari, C., Cavallaro, T., Morini, A., Taioli, F., Cabrini, I., Orrico, D., & Rizzuto, N. (2006). Gene dosage sensitivity of a novel mutation in the intracellular domain of P0 associated with Charcot-Marie-Tooth disease type 1B. Neuromuscular Disorders, 16, 183-187. https://doi.org/10.1016/j.nmd.2006.01.006
Fabrizi, G. M., Tamburin, S., Cavallaro, T., Cabrini, I., Ferrarini, M., Taioli, F., Magrinelli, F., & Zanette, G. (2018). The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic, nerve ultrasound and histological study. Clinical Neurophysiology, 129, 21-32. https://doi.org/10.1016/j.clinph.2017.09.117
Finnerup, N. B., Haroutounian, S., Kamerman, P., Baron, R., Bennett, D. L. H., Bouhassira, D., Cruccu, G., Freeman, R., Hansson, P., Nurmikko, T., Raja, S. N., Rice, A. S. C., Serra, J., Smith, B. H., Treede, R.-D., & Jensen, T. S. (2016). Neuropathic pain: An updated grading system for research and clinical practice. Pain, 157(8), 1599-1606. https://doi.org/10.1097/j.pain.0000000000000492
Gemignani, F., Melli, G., Alfieri, S., Inglese, C., & Marbini, A. (2004). Sensory manifestations in Charcot-Marie-Tooth disease. Journal of the Peripheral Nervous System, 9, 7-14. https://doi.org/10.1111/j.1085-9489.2004.09103.x
Hahn, A. F., Ainsworth, P. J., Bolton, C. F., Bilbao, J. M., & Vallat, J. M. (2001). Pathological findings in the X-linked form of Charcot-Marie-Tooth disease: A morphometric and ultrastructural analysis. Acta Neuropathologica, 101, 129-139. https://doi.org/10.1007/s004010000275
Hanemann, C., Gabreȅls-Festen, A. A., & De Jonghe, P. (2001). Axon damage in CMT due to mutation in myelin protein P0. Neuromuscular Disorders, 11, 753-756. https://doi.org/10.1016/S0960-8966(01)00229-2
Hanson, P., & Deltombe, T. (1998). Preliminary study of large and small peripheral nerve fibers in Charcot-Marie-Tooth disease, type I. American Journal of Physical Medicine & Rehabilitation, 77(1), 45-48. https://doi.org/10.1097/00002060-199801000-00008
Hattori, N., Yamamoto, M., Yoshihara, T., Koike, H., Nakagawa, M., Yoshikawa, H., Ohnishi, A., Hayasaka, K., Onodera, O., Baba, M., Yasuda, H., Saito, T., Nakashima, K., Kira, I.-I., Kaji, R., Oka, N., Sobue, G.; Study Group for Hereditary Neuropathy in Japan. (2003). Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): A clinicopathological study of 205 Japanese patients. Brain, 126, 134-151. https://doi.org/10.1093/brain/awg012
Laurà, M., Hutton, E. J., Blake, J., Lunn, P. M. P., Fox, Z., Pareyson, D., Solari, A., Radice, D., Koltzenburg, M., & Reilly, M. M. (2014). Pain and small fiber function in Charcot-Marie-Tooth disease type 1A. Muscle and Nerve, 50, 366-371. https://doi.org/10.1002/mus.24169
Laurà, M., Milani, M., Morbin, M., Moggio, M., Ripolone, M., Jann, S., Scaiokli, V., Taroni, F., & Pareyson, D. (2007). Rapid progression of late onset axonal Charcot-Marie-Tooth disease associated with a novel MPZ mutation in the extracellular domain. Journal of Neurology, Neurosurgery and Psychiatry, 78, 1263-1266. https://doi.org/10.1136/jnnp.2006.112276
Laurà, M., Pipis, M., Rossor, A. M., & Reilly, M. M. (2019). Charcot-Marie-Tooth disease and related disorders: An evolving landscape. Current Opinion in Neurology, 32, 641-650. https://doi.org/10.1097/WCO.0000000000000735
Manganelli, F., Pisciotta, C., Reilly, M. M., Tozza, S., Schenone, A., Fabrizi, G. M., Cavallaro, T., Vita, G., Padua, L., Gemignani, F., Laurà, M., Hughes, R. A. C., Solari, A., Pareyson, D., Santoro, L.; CMT-TRIAAL and CMT-TRAUK Group. (2016) Nerve conduction velocity in CMT1A: What else can we tell? The European Journal of Neurology, 23, 1566-1571.
Murphy, S. M., Herrmann, D. N., McDermott, M. P., Scherer, S. S., Shy, M. E., Reilly, M. M., & Pareyson, D. (2011). Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. Journal of the Peripheral Nervous System, 16, 191-198. https://doi.org/10.1111/j.1529-8027.2011.00350.x
Nolano, M., Manganelli, F., Provitera, V., Pisciotta, C., Stancanelli, A., Caporaso, G., Iodice, R., Shy, M. E., & Santoro, L. (2015). Small nerve fiber involvement in CMT1A. Neurology, 84, 407-414. https://doi.org/10.1212/WNL.0000000000001188
Padua, L., Briani, C., Jann, S., Nobile-Orazio, E., Pazzaglia, C., Morini, A., Mondelli, M., Ciaramitaro, P., Cavaletti, G., Cocito, D., Fazio, R., Santoro, L., Galeotti, F., Carpo, M., Plasmati, R., Benedetti, L., Schenone, A., Marchettini, P., & Cruccu, G. (2009). Validation of the Italian version of the Neuropathic Pain Symptom Inventory in peripheral nervous system diseases. Neurological Sciences, 30, 99-106. https://doi.org/10.1007/s10072-009-0025-y
Padua, L., Cavallaro, T., Pareyson, D., Quattrone, A., Vita, G., Schenone, A.; Italian CMT QoL Study group. (2008). Charcot-Marie-Tooth and pain: Correlations with neurophysiological, clinical, and disability findings. Neurological Sciences, 29, 193-194. https://doi.org/10.1007/s10072-008-0935-0
Pazzaglia, C., Vollono, C., Ferraro, D., Virdis, D., Lupi, V., Le Pera, D., Tonali, P., Padua, L., & Valeriani, M. (2010). Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1A: A laser-evoked potential study. Pain, 149, 379-385. https://doi.org/10.1016/j.pain.2010.03.001
Ragé, M., Van Acker, N., Knaapen, M. W. M., Timmers, M., Streffer, J., Hermans, M. P., Sindic, C., Meert, T., & Plaghki, L. (2011). Asymptomatic small fiber neuropathy in diabetes mellitus: Investigations with intraepidermal nerve fiber density, quantitative sensory testing and laser-evoked potentials. Journal of Neurology, 258, 1852-1864. https://doi.org/10.1007/s00415-011-6031-z
Ribiere, C., Bernardin, M., Sacconi, S., Delmont, E., Fourner-Mehouas, M., Rauscent, H., Benchortane, M., Staccini, P., Lanteri-Minet, M., & Desnuelle, C. (2012). Pain assessment in Charcot-Marie-Tooth (CMT) disease. Annals of Physical and Rehabilitation Medicine, 55, 160-173. https://doi.org/10.1016/j.rehab.2012.02.005
Rossor, A. M., Shy, M., & Reilly, M. M. (2020). Are we prepared for clinical trials in Charcot-Marie-Tooth disease? Brain Research, 1729, 146625. https://doi.org/10.1016/j.brainres.2019.146625
Schneider-Gold, C., Kötting, J., Epplen, J. T., Gold, R., & Gerding, W. M. (2010). Unusual Charcot- Marie-Tooth phenotype due to a mutation within the intracellular domain of myelin protein zero. Muscle and Nerve, 41, 550-554. https://doi.org/10.1002/mus.21523
Stojkovic, T., De Seze, J., Dubourg, O., Arne-Bes, M. C., Tardieu, S., Hache, J. C., & Vermesh, P. (2003). Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene. Clinical Neurophysiology, 114, 1609-1614. https://doi.org/10.1016/S1388-2457(03)00159-7
Truini, A., Garcia-Larrea, L., & Cruccu, G.. (2013). Reappraising neuropathic pain in humans-How symptoms help disclose mechanisms. Nature Reviews Neurology, 9(10), 572-582. https://doi.org/10.1038/nrneurol.2013.180
Turri, M., Teatini, F., Donato, F., Zanette, G., Tugnoli, V., Deotto, L., Bonetti, B., & Squintani, G. (2018). Pain modulation after oromucosal cannabinoid spray (SATIVEX®) in patients with multiple sclerosis: A study with quantitative sensory testing and laser-evoked potentials. Medicines, 5, 59. https://doi.org/10.3390/medicines5030059
Van Hecke, O., Austin, S. K., Khan, R. A., Smith, B. H., & Torrance, N. (2014). Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain, 155, 654-662. https://doi.org/10.1016/j.pain.2013.11.013
Weis, J., Caeys, K. G., Roos, A., Azzedine, A., Katona, I., Schrőder, J. M., & Senderek, J. (2017). Towards a functional pathology of hereditary neuropathies. Acta Neuropathologica, 133, 493-515. https://doi.org/10.1007/s00401-016-1645-y
Zambelis, T. (2009). Small fiber neuropathy in Charcot-Marie-Tooth disease. Acta Neurologica Belgica, 109, 294-297.