Skip to main content
SpringerLink
Log in

Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy?

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Carpal tunnel syndrome (CTS) and spinal canal stenosis can be frequently observed in the medical history of patients with transthyretin amyloidosis (ATTR), both in the hereditary (mt-ATTR) and wild-type (wt-ATTR) form. The aim of this retrospective single-center analysis was to determine the prevalence of these findings, delay to diagnosis of systemic amyloidosis and the prognostic value in a large cohort of patients with wt-ATTR and mt-ATTR amyloidosis.

Methods

Medical records of 253 patients diagnosed with wt-ATTR, 136 patients with mt-ATTR and 77 asymptomatic gene carriers were screened for history of CTS and spinal canal stenosis and laboratory analysis, electrocardiography and echocardiographic results, respectively. Clinical follow-up was performed by phone assessment.

Results

History of CTS was present in 77 patients (56%) with mt-ATTR, in 152 patients (60%) with wt-ATTR and even in 10 of the asymptomatic gene carriers (13%). Latency between carpal tunnel surgery and first diagnosis of systemic amyloidosis was significantly longer in wt-ATTR compared to mt-ATTR (117 ± 179 months vs. 66 ± 73 months; p = 0.02). In total, 36 patients (14%) with wt-ATTR and 7 patients (5%) with mt-ATTR had a history of clinically significant spinal canal stenosis. In the subgroup of mt-ATTR, patients with CTS had thicker IVS (19 ± 5 mm vs. 16 ± 5 mm, p < 0.05), higher LV mass index (225 ± 78 g vs. 193 ± 98 g, p < 0.05), lower Karnofsky index (78 ± 15% vs. 83 ± 17%, p < 0.05), and lower mitral annular plane systolic excursion (MAPSE; 9 ± 4 mm vs. 11 ± 5 mm, p < 0.05) compared to patients without CTS, whereas in wt-ATTR no significant differences could be observed. No significant difference in survival was observed between patients with and without CTS (wt-ATTR: 67 vs. 63 months, p = 0.45; mt-ATTR: 74 vs. 63 months, p = 0.60). A combination of CTS and spinal stenosis was present in 32 wt-ATTR patients (12%) and 3 mt-ATTR patients (2.2%).

Conclusions

The prevalence of CTS is high and the latency between CTS surgery and diagnosis of amyloidosis is long among patients with wt-ATTR and mt-ATTR. CTS might be predictive for future occurrence of systemic (predominantly cardiac) ATTR amyloidosis.

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

Similar content being viewed by others

References

  1. Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosen I (1999) Prevalence of carpal tunnel syndrome in a general population. JAMA 282:153–158

    Article  CAS  Google Scholar 

  2. Bickel KD (2010) Carpal tunnel syndrome. J Hand Surg Am 35:147–152

    Article  Google Scholar 

  3. Gioeva Z, Urban P, Meliss RR, Haag J, Axmann HD, Siebert F, Becker K, Radtke HG, Rocken C (2013) ATTR amyloid in the carpal tunnel ligament is frequently of wildtype transthyretin origin. Amyloid 20:1–6

    Article  CAS  Google Scholar 

  4. De Villiers PD, Booysen EL (1976) Fibrous spinal stenosis. A report on 850 myelograms with a water-soluble contrast medium. Clin Orthop Relat Res. 115:140–144

    Google Scholar 

  5. Roberson GH, Llewellyn HJ, Taveras JM (1973) The narrow lumbar spinal canal syndrome. Radiology 107:89–97

    Article  CAS  Google Scholar 

  6. Fanuele JC, Birkmeyer NJ, Abdu WA, Tosteson TD, Weinstein JN (2000) The impact of spinal problems on the health status of patients: have we underestimated the effect? Spine (Phila Pa 1976) 25:1509–1514

    Article  CAS  Google Scholar 

  7. Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, Ando Y, Mizuta H (2011) Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol 42:1259–1264

    Article  CAS  Google Scholar 

  8. Sueyoshi T, Ueda M, Sei A, Misumi Y, Oshima T, Yamashita T, Obayashi K, Shinriki S, Jono H, Shono M, Ando Y, Mizuta H (2011) Spinal multifocal amyloidosis derived from wild-type transthyretin. Amyloid 18:165–168

    Article  CAS  Google Scholar 

  9. Sekijima Y, Uchiyama S, Tojo K, Sano K, Shimizu Y, Imaeda T, Hoshii Y, Kato H, Ikeda S (2011) High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly. Hum Pathol 42:1785–1791

    Article  Google Scholar 

  10. Takanashi T, Matsuda M, Yazaki M, Yamazaki H, Nawata M, Katagiri Y, Ikeda S (2013) Synovial deposition of wild-type transthyretin-derived amyloid in knee joint osteoarthritis patients. Amyloid 20:151–155

    Article  CAS  Google Scholar 

  11. Yanagisawa A, Ueda M, Sueyoshi T, Okada T, Fujimoto T, Ogi Y, Kitagawa K, Tasaki M, Misumi Y, Oshima T, Jono H, Obayashi K, Hirakawa K, Uchida H, Westermark P, Ando Y, Mizuta H (2015) Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol 28:201–207

    Article  CAS  Google Scholar 

  12. Westermark P, Westermark GT, Suhr OB, Berg S (2014) Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci 119:223–228

    Article  Google Scholar 

  13. Nakagawa M, Sekijima Y, Yazaki M, Tojo K, Yoshinaga T, Doden T, Koyama J, Yanagisawa S, Ikeda S (2016) Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid 23:58–63

    Article  CAS  Google Scholar 

  14. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN (2016) Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 133:2404–2412

    Article  CAS  Google Scholar 

  15. Fernandez Fuertes J, Rodriguez Vicente O, Sanchez Herraez S, Ramos Pascua LR. Early diagnosis of systemic amyloidosis by means of a transverse carpal ligament biopsy carried out during carpal tunnel syndrome surgery. Med Clin (Barc). 2017

  16. Connors LH, Prokaeva T, Lim A, Theberge R, Falk RH, Doros G, Berg A, Costello CE, O’Hara C, Seldin DC, Skinner M (2009) Cardiac amyloidosis in African Americans: comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J 158:607–614

    Article  CAS  Google Scholar 

  17. Jacobson DR, Pastore R, Pool S, Malendowicz S, Kane I, Shivji A, Embury SH, Ballas SK, Buxbaum JN (1996) Revised transthyretin Ile 122 allele frequency in African-Americans. Hum Genet 98:236–238

    Article  CAS  Google Scholar 

  18. Bauer R, Dikow N, Brauer A, Kreuter M, Buss S, Evers C, Rocken C, Schnabel PA, Hinderhofer K, Ehlermann P, Katus HA, Kristen AV (2014) The “Wagshurst study”: p.Val40Ile transthyretin gene variant causes late-onset cardiomyopathy. Amyloid 21:267–275

    Article  CAS  Google Scholar 

  19. Givens RC, Russo C, Green P, Maurer MS (2013) Comparison of cardiac amyloidosis due to wild-type and V122I transthyretin in older adults referred to an academic medical center. Aging Health 9:229–235

    Article  CAS  Google Scholar 

  20. Coelho T, Maurer MS, Suhr OB (2013) THAOS—The transthyretin amyloidosis outcomes survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin 29:63–76

    Article  CAS  Google Scholar 

  21. Quarta CC, Solomon SD, Uraizee I, Kruger J, Longhi S, Ferlito M, Gagliardi C, Milandri A, Rapezzi C, Falk RH (2014) Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation 129:1840–1849

    Article  Google Scholar 

  22. Dungu JN, Valencia O, Pinney JH, Gibbs SD, Rowczenio D, Gilbertson JA, Lachmann HJ, Wechalekar A, Gillmore JD, Whelan CJ, Hawkins PN, Anderson LJ (2014) CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging 7:133–142

    Article  Google Scholar 

  23. Pinney JH, Whelan CJ, Petrie A, Dungu J, Banypersad SM, Sattianayagam P, Wechalekar A, Gibbs SD, Venner CP, Wassef N, McCarthy CA, Gilbertson JA, Rowczenio D, Hawkins PN, Gillmore JD, Lachmann HJ (2013) Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc 2:e000098

    Article  Google Scholar 

  24. Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY, Falk RH, Cheung KN, Patel AR, Pano A, Packman J, Grogan DR (2012) Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS). Am Heart J 164:222–228 e1

    Article  CAS  Google Scholar 

  25. Miller SR, Sekijima Y, Kelly JW (2004) Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest 84:545–552

    Article  CAS  Google Scholar 

  26. Tojo K, Sekijima Y, Kelly JW, Ikeda S (2006) Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neurosci Res 56:441–449

    Article  CAS  Google Scholar 

  27. Ferreira N, Cardoso I, Domingues MR, Vitorino R, Bastos M, Bai G, Saraiva MJ, Almeida MR (2009) Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. FEBS Lett 583:3569–3576

    Article  CAS  Google Scholar 

  28. Ferreira N, Saraiva MJ, Almeida MR (2012) Epigallocatechin-3-gallate as a potential therapeutic drug for TTR-related amyloidosis: “in vivo” evidence from FAP mice models. PloS One 7:e29933

    Article  CAS  Google Scholar 

  29. aus dem Siepen F, Bauer R, Aurich M, Buss SJ, Steen H, Altland K, Katus HA, Kristen AV (2015) Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study. Drug Des Dev Ther 9:6319–6325

    Article  CAS  Google Scholar 

  30. Kristen AV, Lehrke S, Buss S, Mereles D, Steen H, Ehlermann P, Hardt S, Giannitsis E, Schreiner R, Haberkorn U, Schnabel PA, Linke RP, Rocken C, Wanker EE, Dengler TJ, Altland K, Katus HA (2012) Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Clinical research in cardiology: official journal of the German Cardiac Society 101:805–813

    Article  CAS  Google Scholar 

  31. Mereles D, Buss SJ, Hardt SE, Hunstein W, Katus HA (2010) Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis. Clinical research in cardiology: official journal of the German Cardiac Society 99:483–490

    Article  CAS  Google Scholar 

  32. Cardoso I, Saraiva MJ (2006) Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J 20:234–239

    Article  CAS  Google Scholar 

  33. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB (2018) Rapezzi C and Investigators A-AS. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. The New England journal of medicine 379:1007–1016

    Article  CAS  Google Scholar 

  34. Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ (2018) Gertz MA and Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. The New England journal of medicine 379:22–31

    Article  CAS  Google Scholar 

  35. Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB (2018) Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. The New England journal of medicine 379:11–21

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Angiology and Respiratory Medicine, Amyloidosis Center, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Fabian aus dem Siepen, Selina Hein, Sofie Prestel, Christian Baumgärtner, Hugo A. Katus & Arnt V. Kristen

  2. Department of Hematology and Oncology, Amyloidosis Center, University Hospital Heidelberg, Heidelberg, Germany

    Stefan Schönland & Ute Hegenbart

  3. Institute of Pathology, Christian-Albrechts-University Kiel, Kiel, Germany

    Christoph Röcken

  4. Partner Site Heidelberg/Mannheim, DZHK (German Center for Cardiovascular Research), University of Heidelberg, Heidelberg, Germany

    Hugo A. Katus

Authors
  1. Fabian aus dem Siepen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Selina Hein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sofie Prestel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Baumgärtner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Schönland
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ute Hegenbart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christoph Röcken
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hugo A. Katus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arnt V. Kristen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabian aus dem Siepen.

Ethics declarations

Conflict of interest

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

aus dem Siepen, F., Hein, S., Prestel, S. et al. Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy?. Clin Res Cardiol 108, 1324–1330 (2019). https://doi.org/10.1007/s00392-019-01467-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-019-01467-1

Keywords

Search

Navigation