Skip to main content

Advertisement

SpringerLink
Log in

Gluten neuropathy: electrophysiological progression and HLA associations

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

Abstract

Objective

Gluten neuropathy (GN) is the term used to describe peripheral neuropathy that occurs in patients with gluten sensitivity (GS) or coeliac disease (CD) in the absence of other risk factors. We aimed to describe the neurophysiological progression rate of GN across time and look into the potential role of genetic susceptibility in its development.

Methods

This is a cohort study of 45 patients with GN with a mean follow-up period of 8 ± 5 years. The assessments included clinical and neurophysiological data and HLA-DQ genotyping.

Results

The mean age at diagnosis was 60 ± 12 years. The majority of patients had a length-dependent neuropathy (75.6%), whereas the rest were diagnosed with sensory ganglionopathy (SG).

DQA1*02-positive patients were more likely to suffer with SG compared to the DQA1*02 negative patients (60% versus 13.8%, p = 0.009). There was also a trend for statistical significance regarding the DQB1*06 allele and the DQA1*01/DQB1*06 haplotype were found more frequently in patients with GN than in healthy controls (p = 0.026 and p = 0.047, respectively). A linear effect of time on the neurophysiological findings was found in radial sensory nerve action potential (1.9% mean annual decrement, p = 0.036), sural sensory nerve action potential (3.3% mean annual decrement, p = 0.013) and tibial nerve motor compound action potential (6.5% mean annual decrement, p < 0.001) amplitudes, independently from age or gender.

Conclusions

GN is a late manifestation of GS and CD. The majority of patients have the length-dependent neuropathy with a linear deterioration over time. HLA genotyping of GS and CD patients who suffer from neuropathic symptoms is recommended as it can help identifying patients at risk for developing SG.

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
Fig. 3

Similar content being viewed by others

References

  1. Brown WC (1908) Sprue and its treatment. Bale and Danielsson

  2. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A (1996) Does cryptic gluten sensitivity play a part in neurological illness? Lancet 347(8998):369–371

    Article  CAS  Google Scholar 

  3. Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D (2010) Gluten sensitivity: from gut to brain. Lancet Neurol 9(3):318–330

    Article  CAS  Google Scholar 

  4. Zis P, Sarrigiannis PG, Rao DG, Hadjivassiliou M (2018) Quality of life in patients with gluten neuropathy: a case-controlled study. Nutrients 10(6)

  5. Hadjivassiliou M, Croall ID, Zis P, Sarrigiannis PG, Sanders DS, Aeschlimann P, Grünewald RA, Armitage PA, Connolly D, Aeschlimann D, Hoggard N (2019) Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6. Clin Gastroenterol Hepatol 17(13):2678–2686

    Article  CAS  Google Scholar 

  6. Zis P, Sarrigiannis PG, Rao DG, Hewamadduma C, Hadjivassiliou M (2016) Chronic idiopathic axonal polyneuropathy: a systematic review. J Neurol 263(10):1903–1910

    Article  Google Scholar 

  7. Zis P, Hadjivassiliou M, Rao DG, Sarrigiannis PG (2019) Electrophysiological determinants of the clinical severity of axonal peripheral neuropathy. Muscle Nerve 59(4):491–493

    Article  Google Scholar 

  8. Leis AA, Schenk MP (2013) Atlas of nerve conduction studies and electromyography. Oxford University Press, New York

    Google Scholar 

  9. Esper GJ, Nardin RA, Benatar M, Sax TW, Acosta JA, Raynor EM (2005) Sural and radial sensory responses in healthy adults: diagnostic implications for polyneuropathy. Muscle Nerve 31(5):628–632

    Article  Google Scholar 

  10. Camdessanché JP, Jousserand G, Ferraud K, Vial C, Petiot P, Honnorat J, Antoine JC (2009) The pattern and diagnostic criteria of sensory neuronopathy: a case-control study. Brain 132(Pt 7):1723–1733

    Article  Google Scholar 

  11. Zis P, Hadjivassiliou M, Sarrigiannis PG, Barker AStJE, Rao DG (2017) Rapid neurophysiological screening for sensory ganglionopathy: a novel approach. Brain Behav 7(12):e00880. https://doi.org/10.1002/brb3.880

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lancaster AK, Single RM, Solberg OD et al (2007) PyPop update - a software pipeline for large-scale multilocus population genomics. Tissue Antigens 69(s1):192–197

    Article  CAS  Google Scholar 

  13. González-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, Teles e Silva AL, Ghattaoraya GS, Alfirevic A, Jones AR, Middleton D (2015) Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 43(Database issue):D784–D788

  14. Benjamini Y, Drai D, Elmer G et al (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125:279–284

    Article  CAS  Google Scholar 

  15. Narum SR (2006) Beyond Bonferroni: less conservative analyses for conservation genetics. Conserv Genet 7:783–787

    Article  CAS  Google Scholar 

  16. Hadjivassiliou M, Sanders DD, Aeschlimann DP (2015) Gluten-related disorders: gluten ataxia. Dig Dis 33(2):264–268

    Article  Google Scholar 

  17. Sarrigiannis PG, Hoggard N, Aeschlimann D, Sanders DS, Grünewald RA, Unwin ZC, Hadjivassiliou M (2014) Myoclonus ataxia and refractory coeliac disease. Cerebellum Ataxias 1(1):11

    Article  Google Scholar 

  18. Gordon N (2000) Cerebellar ataxia and gluten sensitivity: a rare but possible cause of ataxia, even in childhood. Dev Med Child Neurol 42(4):283–286

    Article  CAS  Google Scholar 

  19. Hadjivassiliou M, Kandler RH, Chattopadhyay AK, Davies-Jones AG, Jarratt JA, Sanders DS, Sharrack B, Grünewald RA (2006) Dietary treatment of gluten neuropathy. Muscle Nerve 34(6):762–766

    Article  CAS  Google Scholar 

  20. Zis P, Sarrigiannis PG, Rao DG, Hadjivassiliou M (2018) Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet. J Neurol 265(10):2231–2236

    Article  CAS  Google Scholar 

  21. Rouvroye MD, Zis P, Van Dam AM, Rozemuller AJ, Bouma G, Hadjivassiliou M (2020) The neuropathology of gluten-related neurological disorders: a systematic review. Nutrients 12(3):822

    Article  CAS  Google Scholar 

  22. Zis P, Rao DG, Sarrigiannis PG, Aeschlimann P, Aeschlimann DP, Sanders D, Grünewald RA, Hadjivassiliou M (2017) Transglutaminase 6 antibodies in gluten neuropathy. Digest Liver Dis 49(11):1196–1200

  23. Kaukinen K, Partanen J, Mäki M, Collin P (2002) HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol 97(3):695–699

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr Dasappaiah Ganesh Rao for his contribution in the data collection. We would like to thank all participants in the study.

Funding

None.

Author information

Authors and Affiliations

  1. Academic Directorate of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    Panagiotis Zis, Ptolemaios Sarrigiannis & Marios Hadjivassiliou

  2. Medical School, University of Cyprus, Nicosia, Cyprus

    Panagiotis Zis & Artemios Artemiadis

  3. Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    Panagiotis Zis & David S. Sanders

Authors
  1. Panagiotis Zis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ptolemaios Sarrigiannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Artemios Artemiadis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David S. Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marios Hadjivassiliou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.Z.: drafting/revising the manuscript, data collection, statistical analysis, accept responsibility for conduct of research and final approval. M.H., D.S. and P.G.S.: drafting/revising the manuscript, data collection, accept responsibility for conduct of research and final approval. A.A.: drafting/revising the manuscript, statistical analysis, accept responsibility for conduct of research and final approval.

Corresponding author

Correspondence to Panagiotis Zis.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Ethical standards

The study protocol has been approved by the local ethics committee.

Disclosures

Panagiotis Zis, Ptolemaios Georgios Sarrigiannis, Artemios Artemiadis, David Sanders and Marios Hadjivassiliou have nothing to disclose.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (XLS 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zis, P., Sarrigiannis, P., Artemiadis, A. et al. Gluten neuropathy: electrophysiological progression and HLA associations. J Neurol 268, 199–205 (2021). https://doi.org/10.1007/s00415-020-10137-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-10137-6

Keywords

Search

Navigation