Skip to main content

Advertisement

SpringerLink
Log in

Respiratory dysfunction in Charcot–Marie–Tooth disease type 1A

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

An Erratum to this article was published on 23 April 2015

Abstract

We aimed to investigate the relationship between neurological compromise, respiratory parameters in wakefulness and in sleep, physiology, and morphology of phrenic nerves in patients with Charcot–Marie–Tooth disease type 1A (CMT1A). Sixteen patients with CMT1A were evaluated by spirometry, maximal expiratory and maximal inspiratory pressures (MEP, MIP), polysomnography, phrenic nerve compound muscle action potential (CMAP), and ultrasonography (roots C3,C4,C5 and phrenic nerves). Clinical disability was measured with Charcot–Marie–Tooth neuropathy score (CMT-NS; range 0–36). Two control groups, comprising 30 individuals matched for age, sex, and body mass index, were used for comparison. Ten patients were female (62 %), mean age was 37.88 years (range 24–76); and CMT-NS range was 7–34. MIP was reduced in five (31 %) and MEP in 12 patients (75 %), although only one had restrictive respiratory dysfunction in spirometry. Apnoea–hypopnea index (AHI) was significantly higher in patients (12.01 ± 11.57/h × 5.89 ± 8.36/h; p value = 0.05) and increased in REM sleep compared with NREM (9.94 ± 10.96/h × 19.13 ± 19.93/h; p value = 0.01). There were significant correlations between CMT-NS and AHI (Pearson = 0.69; p value = 0.03); CMT-NS and MIP (Pearson = −0.691, p value = 0.003); and CMT-NS and MEP (Pearson = −0.603, p value = 0.013). Also, AHI showed negative correlation with MIP (Pearson = −0.52, p value = 0.036) and MEP (Pearson = −0.55, p value = 0.026). Phrenic nerves were enlarged in ultrasonography in all patients and presented significant correlations with CMAPs (right: Pearson = −0.554, p value = 0.026; left: Pearson = −0.558, p value = 0.025). We suggest that axonal degeneration of nerves directed to muscles of respiration might explain the high prevalence of respiratory weakness in patients with CMT1A. Clinical manifestations are frequent during sleep, where the diaphragm alone can only partially surpass the overload in breathing apparatus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Braathen GJ (2012) Genetic epidemiology of Charcot–Marie–Tooth disease. Acta Neurol Scand 126(Suppl. 193):1–22

    Google Scholar 

  2. Lupski JR, Montes de Oca-Luna R, Slaugenhaupt S, Pentao L, Guzetta V, Trask BJ, Saucedo-Cardenas O, Baker DF, Killian JM, Garcia CA, Chakravarti A, Patel PL (1991) DNA duplication associated with Charcot–Marie–Tooth disease type 1A. Cell 66:219–232

    Article  CAS  PubMed  Google Scholar 

  3. Hoogendijk JE, De Visser M, Bour LJ, Ongerboer BW (1992) Conduction block in hereditary motor and sensory neuropathy type 1. Muscle Nerve 15:520–521

    CAS  PubMed  Google Scholar 

  4. Thomas PK, Marques W Jr, Davis MB, Sweeney MG, King RHM, Bradley JL, Muddle JR, Tyson J, Malcolm S, Harding AE (1997) The phenotypic manifestations of chromosome 17p11.2 duplication. Brain 120:465–478

    Article  PubMed  Google Scholar 

  5. Marques WJR, Freitas MR, Nascimento OJ, Oliveira AB, Calia L, Melo A, Lucena R, Rocha V, Barreira AA (2005) 17p duplicated Charcot–Marie–Tooth 1A: characteristics of a new population. J Neurol 252(8):972–979

    Article  CAS  PubMed  Google Scholar 

  6. Saporta ASD, Sottile SL, Miller LJ, Feely SME, Siskind CE, Shy ME (2011) Charcot–Marie–Tooth disease subtypes and genetic testing strategies. Ann Neurol 69:22–33

    Article  PubMed Central  PubMed  Google Scholar 

  7. Reilly MM, Murphy SM, Laurá M (2011) Charcot–Marie–Tooth disease. J Peripher Nerv Syst 16:1–14

    Article  PubMed  Google Scholar 

  8. Birouk N, Gouider R, Le Guern E, Gugenheim M, Tardieu S, Maisonobe T, Forestier LEN, Agid Y, Brice A, Bouche P (1997) Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain 120:813–823

    Article  PubMed  Google Scholar 

  9. Garcia CM, Malamut RE, England JD, Parry GS, Liu P, Lupski JR (1995) Clinical variability in two pairs of identical twins with the Charcot–Marie–Tooth disease type 1A duplication. Neurology 45:2090–2093

    Article  CAS  PubMed  Google Scholar 

  10. Krajewski KM, Lewis RA, Fuerst DR, Turansky C, Hinder SR, Garbern J, Kamholz J, Shy ME (2000) Neurological dysfunction and axonal degeneration in Charcot–Marie–Tooth disease type 1A. Brain 123:1516–1527

    Article  PubMed  Google Scholar 

  11. Verhamme C, Van Schaik IN, Koelman JHTM, De Haan RJ, Vermeulen M, De Visser M (2004) Clinical disease severity and axonal dysfunction in hereditary motor and sensory neuropathy Ia. J Neurol 251:1491–1497

    Article  PubMed  Google Scholar 

  12. Chan CK, Mohsenin V, Loke J, Virgulto J, Sipski L, Ferranti R (1987) Diaphragmatic dysfunction in siblings with hereditary motor and sensory neuropathy. Chest 91(4):567–570

    Article  CAS  PubMed  Google Scholar 

  13. Dyer EL, Callahan AS III (1988) Charcot–Marie–Tooth disease and respiratory failure. Chest 92(1):221

    Article  Google Scholar 

  14. Laroche CM, Carrol N, Moxham J, Stanley NN, Evans RJC, Green M (1988) Diaphragm weakness in Charcot–Marie–Tooth disease. Thorax 143:478–479

    Article  Google Scholar 

  15. Hardie R, Harding AE, Hirsch N, Stanley NN, Evans RJC, Green M (1990) Diaphragmatic weakness in hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry 53:348–350

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Osanai S, Akiba Y, Nakano H, Matsumoto H, Yahara O, Onodera S (1992) Charcot–Marie–Tooth disease with diaphragmatic weakness. Intern Med 31(11):1267–1270

    Article  CAS  PubMed  Google Scholar 

  17. Gilchrist D, Chan CK, Deck JHN (1989) Phrenic involvement in Charcot–Marie–Tooth disease. Chest 96(5):1197–1199

    Article  CAS  PubMed  Google Scholar 

  18. Takakura Y, Furuya H, Yamashita K, Murai H, Araki T, Kikushi H, Ohiagy Y, Yamada T, Kira J (2002) A case of Charcot–Marie–Tooth disease (CMT) type 1 complicated by diabetes mellitus (DM) showing bilateral phrenic nerve palsy. Rinsho Shinkeigaku 42:320–322

    PubMed  Google Scholar 

  19. Carter GT, Kilmer DD, Bonekat HW, Lieberman JS, Fowler WM (1992) Evaluation of phrenic nerve and pulmonary function in hereditary motor and sensory neuropathy, type I. Muscle Nerve 15:459–462

    Article  CAS  PubMed  Google Scholar 

  20. Eichacker PQ, Spiro A, Sherman M, Lazar E, Reichel J, Dodick F (1988) Respiratory muscle dysfunction in hereditary motor sensory neuropathy, type I. Arch Int Med 148:1739–1740

    Article  CAS  Google Scholar 

  21. Maggi G, Bragadin MM, Padua L, Fiorina E, Bellone E, Grandis M, Lizia R, Benicelli A, Grosso M, Saporiti R, Scorsone D, Zuccarino R, Crimi E, Schenone A (2011) Outcome measures and rehabilitation treatment in patients affected by Charcot–Marie–Tooth neuropathy: a pilot study. Am J Phys Med Rehabil 90(8):628–637

    Article  PubMed  Google Scholar 

  22. Cruz-Martinez A, Armijo A, Fermoso A, Moraleda S, Maté I, Marín M (2000) Phrenic nerve conduction study in demyelinating neuropathies and open-heart surgery. Clin Neurophysiol 111:821–825

    Article  CAS  PubMed  Google Scholar 

  23. Sagliocco L, Orlandi G, Calabrese R, Pellegrinetti A, Baglini O, Castelli F, Baldinotti F, Sartucci F (2003) Electrodiagnostic evidence of phrenic nerve demyelination in Charcot–Marie–Tooth disease 1A. Am J Phys Med Rehabil 82(10):754–759

    Article  PubMed  Google Scholar 

  24. Dematteis M, Pépin JL, Jeanmart M, Deschaux C, Labarre-Villa A, Lévi P (2001) Charcot–Marie–Tooth disease and sleep apnoea syndrome: a family study. Lancet 57:267–272

    Article  Google Scholar 

  25. Dziewas R, Waldmann N, Böntert M, Hor H, Müller T, Okegwo A, Ringelstein EB, Young P (2008) Increased prevalence of obstructive sleep apnoea in patients with Charcot–Marie–Tooth disease: a case control study. J Neurol Neurosurg Psychiatry 79:829–831

    Article  CAS  PubMed  Google Scholar 

  26. Boentert M, Knop K, Schuhmacher C, Gess B, Okegwo, Young P (2014) Sleep disorders in Charcot–Marie–Tooth disease type 1. J Neurol Neurosurg Psychiatry 85(3):319–325

    Article  PubMed  Google Scholar 

  27. Shy ME, Blake J, Krajewski K, Fuerst DR, Laura M, Hahn AF, Li J, Lewis RA, Reilly M (2005) Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology 64:1209–1214

    Article  CAS  PubMed  Google Scholar 

  28. American Thoracic Society (1987) Standardization of spirometry: 1987 update. Am Rev Respir Dis 136:1285–1298

    Article  Google Scholar 

  29. ATS/ERS (2002) Joint statement on respiratory muscle testing. Am J Respir Crit Care Med 166:518–624

    Article  Google Scholar 

  30. Costa D, Gonçalves HA, Lima LP, Ike D, Cancelliero KM, Montebelo MI (2010) New reference values for maximal respiratory pressures in the Brazilian population. J Bras Pneumol 36(3):306–312

    Article  PubMed  Google Scholar 

  31. Iber C, Ancoli-Israel, Chesson A et al, for the American Academy of Sleep Medicine (2007) The AASM manual for the scoring of sleep and associated events. Rules, terminology and technical specifications, 1st edn. American Academy of Sleep Medicine, Westchester

  32. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 14(6):540–545

    CAS  PubMed  Google Scholar 

  33. Morélot-Panzini C, Fournier E, Donzel-Raynaud C, Dubourg O, Willer JC, Similowski T (2007) Conduction velocity of the human phrenic nerve in the neck. J Electromyogr Kinesiol 19(1):122–130

    Article  PubMed  Google Scholar 

  34. Bolton CF (2004) Clinical Neurophysiology of Breathing. In Bolton CF, Chen R, Wijdicks EFM, Zifko UA (eds) Neurology of breathing 2004, 1st edn. Butterworth-Heinemann, pp 75–107

  35. Dionne A, Parkes A, Engler B, Watson BV, Nicolle MW (2009) Determination of the best electrode position for recording of the diaphragm compound muscle action potential. Muscle Nerve 40:37–41

    Article  PubMed  Google Scholar 

  36. Fromageot C, Lofaso F, Annane D, Falaize L, Lejaille M, Clair B, Gajdos P, Raphael JC (2001) Supine fall in lung volumes in the assessment of diaphragmatic weakness in neuromuscular disorders. Arch Phys Med Rehabil 82:123–128

    Article  CAS  PubMed  Google Scholar 

  37. Canella C, Demondion X, Delebarre A, Moraux A, Cotten H, Cotten A (2010) Anatomical study of phrenic nerve using ultrasound. Eur Radiol 20(3):659–665

    Article  PubMed  Google Scholar 

  38. Gibson GJ, Pride NB, Newson-Davis J, Loh C (1977) Pulmonary mechanics in patients with respiratory muscle weakness. Am Rev Respir Dis 115:389–395

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Sandra Elizabete Marques for her technical support in our neurogenetic research laboratory (LNAE).

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard statement

All participants individually signed an informed consent. The study has been approved by the Ethics Committee for Medical Research of the University Hospital of Ribeirão Preto Medical School, University of São Paulo, SP, Brazil.

Author information

Authors and Affiliations

  1. Department of Neurosciences and Behaviour Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil

    Wilson Marques Junior, Mônica de Carvalho Alcântara, Regina Maria França Fernandes, Heide H. Sander & Charles Marques Lourenço

  2. Hospital das Clínicas-FMRP/USP, 4º andar-sala 434-Campus Universitario, Ribeirão Preto, SP, 14048-900, Brazil

    Wilson Marques Junior & Mônica de Carvalho Alcântara

  3. Radiology Division, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil

    Marcello H. Nogueira-Barbosa

  4. Hospital das Clínicas-FMRP/USP, Neurofisiologia-1º andar, Ribeirão Preto, SP, 14048-900, Brazil

    Regina Maria França Fernandes & Heide H. Sander

  5. Pneumology Division, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil

    Geruza Alves da Silva

  6. Hospital das Clínicas-FMRP/USP, Neurofisiologia-2º andar, Ribeirão Preto, SP, 14048-900, Brazil

    Charles Marques Lourenço

Authors
  1. Wilson Marques Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mônica de Carvalho Alcântara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcello H. Nogueira-Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Regina Maria França Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Geruza Alves da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Heide H. Sander
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Charles Marques Lourenço
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wilson Marques Junior.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Junior, W.M., de Carvalho Alcântara, M., Nogueira-Barbosa, M.H. et al. Respiratory dysfunction in Charcot–Marie–Tooth disease type 1A. J Neurol 262, 1164–1171 (2015). https://doi.org/10.1007/s00415-015-7677-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7677-8

Keywords

Search

Navigation