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Corneal nerve fiber involvement in chronic inflammatory demyelinating polyneuropathy

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A Correction to this article was published on 09 March 2023

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Abstract

Background

Despite the primary myelin-related pathophysiology, small fiber neuropathy (SFN) and axonal degeneration are also considered to be involved and associated with disabling symptoms and impaired quality of life in chronic inflammatory demyelinating polyneuropathy (CIDP). Demonstration of SFN usually requires complex or invasive investigations.

Objects

In vivo corneal confocal microscopy (IVCCM) has evolved as a non-invasive, easily applied method for quantification of small fiber involvement in peripheral nerve disorders. We aimed to investigate the potential role of IVCCM in CIDP.

Methods

In this cross-sectional study, 15 patients with CIDP underwent assessment with clinical disability scales, neuropathic pain (NP) and autonomic symptom questionnaires, nerve conduction studies, and IVCCM. IVCCM parameters were analyzed and compared to those from 32 healthy controls.

Results

Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were significantly decreased in the CIDP group, compared to those in controls (p = 0.03 and p = 0.024, respectively). Langerhans cells and fiber tortuosity were increased in CIDP patients (p = 0.005 and p = 0.001, respectively). IVCCM parameters were significantly lower in patients with NP compared to those in patients without NP.

Conclusion

IVCCM shows promise as a non-invasive complementary biomarker in the assessment of demyelinating polyneuropathies, providing insights into the potential pathophysiology of these non-length-dependent neuropathies.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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References

  1. Jani-Acsadi A, Lewis RA (2013) Evaluation of a patient with suspected chronic demyelinating polyneuropathy. Handb Clin Neurol 115:253–264

    Article  PubMed  Google Scholar 

  2. Figueroa JJ, Dyck PJ, Laughlin RS, Mercado JA, Massie R, Sandroni P et al (2012) Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 78(10):702–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Manganelli F, Nolano M, Pisciotta C, Provitera V, Fabrizi GM, Cavallaro T et al (2015) Charcot-Marie-Tooth disease: new insights from skin biopsy. Neurology 85(14):1202–1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nolano M, Manganelli F, Provitera V, Pisciotta C, Stancanelli A, Caporaso G et al (2015) Small nerve fiber involvement in CMT1A. Neurology 84(4):407–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Barnett MH, Mathey E, Kiernan MC, Pollard JD (2016) Axonal damage in central and peripheral nervous system inflammatory demyelinating diseases: common and divergent pathways of tissue damage. Curr Opin Neurol 29(3):213–221

    Article  CAS  PubMed  Google Scholar 

  6. Rajabally YA, Narasimhan M (2011) Distribution, clinical correlates and significance of axonal loss and demyelination in chronic inflammatory demyelinating polyneuropathy. Eur J Neurol 18(2):293–299

    Article  CAS  PubMed  Google Scholar 

  7. Celiker H, Erekul G, Turhan SA, Kokar S, Yavuz DG, Gunduz OH et al (2021) Early detection of neuropathy in patients with type 2 diabetes with or without microalbuminuria in the absence of peripheral neuropathy and retinopathy. J Fr Ophtalmol 44(4):485–493

    Article  PubMed  Google Scholar 

  8. Perkins BA, Lovblom LE, Bril V, Scarr D, Ostrovski I, Orszag A et al (2018) Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study. Diabetologia 61(8):1856–1861

    Article  PubMed  PubMed Central  Google Scholar 

  9. Petropoulos IN, Ponirakis G, Ferdousi M, Azmi S, Kalteniece A, Khan A et al (2021) Corneal confocal microscopy: a biomarker for diabetic peripheral neuropathy. Clinical Therapeutics 43(9):1457–1475

  10. Pitarokoili K, Sturm D, Labedi A, Greiner T, Eitner L, Kumowski N et al (2019) Neuroimaging markers of clinical progression in chronic inflammatory demyelinating polyradiculoneuropathy. Ther Adv Neurol Disord 12:1756286419855485

    Article  PubMed  PubMed Central  Google Scholar 

  11. Schneider C, Bucher F, Cursiefen C, Fink GR, Heindl LM, Lehmann HC (2014) Corneal confocal microscopy detects small fiber damage in chronic inflammatory demyelinating polyneuropathy (CIDP). J Peripher Nerv Syst 19(4):322–327

    Article  PubMed  Google Scholar 

  12. Stettner M, Hinrichs L, Guthoff R, Bairov S, Petropoulos IN, Warnke C et al (2016) Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy. Ann Clin Transl Neurol 3(2):88–100

    Article  CAS  PubMed  Google Scholar 

  13. Tavakoli M, Marshall A, Banka S, Petropoulos IN, Fadavi H, Kingston H et al (2012) Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth disease type 1A patients. Muscle Nerve 46(5):698–704

    Article  PubMed  PubMed Central  Google Scholar 

  14. Van den Bergh PY, Hadden RD, Bouche P, Cornblath DR, Hahn A, Illa I et al (2010) European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision. Eur J Neurol 17(3):356–363

    Article  PubMed  Google Scholar 

  15. Van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA et al (2021) European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force-second revision. Eur J Neurol 28(11):3556–3583

    Article  PubMed  Google Scholar 

  16. Merkies IS, Schmitz PI, van der Meche FG, Samijn JP, van Doorn PA, Inflammatory Neuropathy C et al (2002) Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies. J Neurol Neurosurg Psychiatry 72(5):596–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W (2012) COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc 87(12):1196–1201

    Article  PubMed  PubMed Central  Google Scholar 

  18. Alkan H, Ardic F, Erdogan C, Sahin F, Sarsan A, Findikoglu G (2013) Turkish version of the painDETECT questionnaire in the assessment of neuropathic pain: a validity and reliability study. Pain Med 14(12):1933–1943

    Article  PubMed  Google Scholar 

  19. Kimura J (2013) Electrodiagnosis in diseases of nerve and muscle: principles and practice 4th edn. Oxford University Press, New York

  20. Dabbah MA, Graham J, Petropoulos I, Tavakoli M, Malik RA (2010) Dual-model automatic detection of nerve-fibres in corneal confocal microscopy images. Med Image Comput Comput Assist Interv 13(Pt 1):300–307

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Petropoulos IN, Alam U, Fadavi H, Marshall A, Asghar O, Dabbah MA et al (2014) Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci 55(4):2071–2078

    Article  PubMed  PubMed Central  Google Scholar 

  22. Alam U, Jeziorska M, Petropoulos IN, Asghar O, Fadavi H, Ponirakis G et al (2017) Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy. Plos One 12(7):e0180175

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chen X, Graham J, Dabbah MA, Petropoulos IN, Ponirakis G, Asghar O et al (2015) Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density. Diabetes Care 38(6):1138–1144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ferrari G, Nallasamy N, Downs H, Dana R, Oaklander AL (2013) Corneal innervation as a window to peripheral neuropathies. Exp Eye Res 113:148–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gemignani F, Ferrari G, Vitetta F, Giovanelli M, Macaluso C, Marbini A (2010) Non-length-dependent small fibre neuropathy. Confocal microscopy study of the corneal innervation. J Neurol Neurosurg Psychiatry 81(7):731–733

  26. Kemp HI, Petropoulos IN, Rice ASC, Vollert J, Maier C, Strum D et al (2017) Use of corneal confocal microscopy to evaluate small nerve fibers in patients with human immunodeficiency virus. JAMA Ophthalmol 135(7):795–800

    Article  PubMed  PubMed Central  Google Scholar 

  27. Klitsch A, Evdokimov D, Frank J, Thomas D, Saffer N, Meyer ZU, Altenschildesche C et al (2020) Reduced association between dendritic cells and corneal sub-basal nerve fibers in patients with fibromyalgia syndrome. J Peripher Nerv Syst 25(1):9–18

    Article  CAS  PubMed  Google Scholar 

  28. Rousseau A, Cauquil C, Dupas B, Labbe A, Baudouin C, Barreau E et al (2016) Potential role of in vivo confocal microscopy for imaging corneal nerves in transthyretin familial amyloid polyneuropathy. JAMA Ophthalmol 134(9):983–989

    Article  PubMed  Google Scholar 

  29. Hanemann CO, Gabreels-Festen AA (2002) Secondary axon atrophy and neurological dysfunction in demyelinating neuropathies. Curr Opin Neurol 15(5):611–615

    Article  PubMed  Google Scholar 

  30. Leppin K, Behrendt AK, Reichard M, Stachs O, Guthoff RF, Baltrusch S et al (2014) Diabetes mellitus leads to accumulation of dendritic cells and nerve fiber damage of the subbasal nerve plexus in the cornea. Invest Ophthalmol Vis Sci 55(6):3603–3615

    Article  PubMed  Google Scholar 

  31. Fleischer M, Lee I, Erdlenbruch F, Hinrichs L, Petropoulos IN, Malik RA et al (2021) Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy. J Neuroinflammation 18(1):89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kalteniece A, Ferdousi M, Azmi S, Mubita WM, Marshall A, Lauria G et al (2020) Corneal confocal microscopy detects small nerve fibre damage in patients with painful diabetic neuropathy. Sci Rep 10(1):3371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Marmara University School of Medicine, Muhsin Yazıcıoğlu Street, No:10, Kaynarca/Pendik, 34899, Istanbul, Turkey

    Ezgi Keskiner-Ozturk

  2. Department of Ophthalmology, Marmara University School of Medicine, Istanbul, Turkey

    Semra Akkaya-Turhan & Ebru Toker

  3. Department of Neurology, Acibadem Health Group, Istanbul, Turkey

    Kayihan Uluc & Pinar Kahraman-Koytak

  4. Department of Neurology, Erenkoy Mental Health Education and Research Hospital, Istanbul, Turkey

    Hande Alibas

  5. Department of Neurology, Academic Hospital, Istanbul, Turkey

    Tulin Tanridag

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  1. Ezgi Keskiner-Ozturk
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Contributions

K.U., E.T., and P.K.K. contributed to the conception and design of the study; E.K.O., S.A.T., H.A., and P.K.K. contributed to the acquisition and analysis of the data; E.K.O., S.A.T., E.T., K.U., H.A., T.T., and P.K.K. contributed to drafting the text or preparing the figures.

Corresponding author

Correspondence to Ezgi Keskiner-Ozturk.

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Written informed consent was obtained from all participants.

Ethical approval

The study was approved by the Institutional Ethics Committee and conformed to the Declaration of Helsinki.

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The authors declare no competing interests.

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The original online version of this article was revised: The original article contains an error during online publication:

1. Changing the keywords from 'confocal confocal microscopy' to 'corneal confocal microscopy'.

2. Deletion of Fig.3 caption in the body text.

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Keskiner-Ozturk, E., Akkaya-Turhan, S., Toker, E. et al. Corneal nerve fiber involvement in chronic inflammatory demyelinating polyneuropathy. Neurol Sci 44, 2509–2516 (2023). https://doi.org/10.1007/s10072-023-06711-1

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