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  • Review Article
  • Published:

CIDP and other inflammatory neuropathies in diabetes — diagnosis and management

Key Points

  • The main neuropathy that occurs in diabetes is distal symmetric polyneuropathy (DSPN), but inflammatory neuropathies can also occur

  • Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common and most treatable inflammatory neuropathy in patients with diabetes, although the extent of its occurrence in association with diabetes is debated

  • Other inflammatory neuropathies that occur in diabetes are diabetic radiculoplexus neuropathies and vasculitic multiple mononeuropathy

  • Diagnosis of CIDP in the presence of diabetes can be made mainly on the basis of clinical characteristics and specific electrophysiological criteria; cerebrospinal fluid analysis, imaging and neuropathology are occasionally helpful

  • The amenability of CIDP to treatment makes its identification important

  • First-line treatment options for CIDP in diabetes include intravenous immunoglobulin and corticosteroids; plasma exchange can be used when these treatments are ineffective, and immunosuppression can occasionally be considered in refractory disease

Abstract

Distal symmetric polyneuropathy (DSPN) is the most common neuropathy to occur in diabetes mellitus. However, patients with diabetes can also develop inflammatory neuropathies, the most common and most treatable of which is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Whether diabetes is a risk factor for CIDP remains under debate. Early studies suggested that patients with diabetes were at increased risk of CIDP, but epidemiological studies failed to confirm the association, and subsequent data have re-opened the debate. Inadequate interpretation of investigations and differentials between CIDP and other neuropathies that can occur in diabetes, such as DSPN, diabetic radiculoplexus neuropathies and vasculitic multiple mononeuropathy, might mean that CIDP is under-recognized. Despite a response rate of >80% to first-line therapies for CIDP in patients with or without diabetes, those with diabetes often present with greater disability owing to late referral and axonal pathology attributed to DSPN. The increasing worldwide prevalence of diabetes creates an urgent need to improve identification of potentially treatable neuropathies, such as CIDP. In this Review, we consider the features of CIDP in patients with diabetes, and discuss how these features can be used to differentiate the condition from other neuropathies. We also review the management options for CIDP and other inflammatory neuropathies in patients with diabetes.

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Figure 1: Corneal confocal microscopy images in health, diabetes and CIDP.
Figure 2: Histopathological features in CIDP.
Figure 3: Current model of immunopathogenesis in CIDP.

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References

  1. Albers, J. W. & Pop-Busui, R. Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. Curr. Neurol. Neurosci. Rep. 14, 473 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Callaghan, B. C. et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol. 71, 1143–1149 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dyck, P. J. et al. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab. Res. Rev. 27, 620–628 (2011).

    Article  PubMed  Google Scholar 

  4. Malik, R. et al. Small fibre neuropathy: role in the diagnosis of diabetic sensorimotor polyneuropathy. Diabetes Metab. Res. Rev. 27, 678–684 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Young, M. J., Boulton, A. J., MacLeod, A. F., Williams, D. R. & Sonksen, P. H. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36, 150–154 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) group. Lancet 352, 837–853 (1998).

  7. Malik, R. A. Wherefore art thou, o treatment for diabetic neuropathy? Int. Rev. Neurobiol. 127, 287–317 (2016).

    Article  CAS  PubMed  Google Scholar 

  8. Pop-Busui, R. et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 40, 136–154 (2017).

    Article  CAS  PubMed  Google Scholar 

  9. Van den Bergh, P. Y. et al. 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, 356–363 (2010). Latest version of the EFNS–PNS criteria for CIDP.

    Article  CAS  PubMed  Google Scholar 

  10. Van den Bergh, P. Y. & Rajabally, Y. A. Chronic inflammatory demyelinating polyradiculoneuropathy. Presse Med. 42, e203–e215 (2013).

    Article  PubMed  Google Scholar 

  11. Gorson, K. C. et al. Chronic inflammatory demyelinating polyneuropathy disease activity status: recommendations for clinical research standards and use in clinical practice. J. Peripher. Nerv. Syst. 15, 326–333 (2010).

    Article  PubMed  Google Scholar 

  12. Rajabally, Y. A., Cassereau, J., Robbe, A. & Nicolas, G. Disease status in chronic inflammatory demyelinating polyneuropathy: inter-centre comparative analysis and correlates. Eur. J. Neurol. 22, 1469–1473 (2015).

    Article  CAS  PubMed  Google Scholar 

  13. Viala, K. et al. A current view of the diagnosis, clinical variants, response to treatment and prognosis of chronic inflammatory demyelinating polyradiculoneuropathy. J. Peripher. Nerv. Syst. 15, 50–56 (2010).

    Article  CAS  PubMed  Google Scholar 

  14. Vital, C. et al. Relapsing inflammatory demyelinating polyneuropathy in a diabetic patient. Acta Neuropathol. 71, 94–99 (1986). One of the earliest descriptions of CIDP in a patient with diabetes.

    Article  CAS  PubMed  Google Scholar 

  15. Stewart, J. D., McKelvey, R., Durcan, L., Carpenter, S. & Karpati, G. Chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetics. J. Neurol. Sci. 142, 59–64 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Uncini, A. et al. Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy. Clin. Neurophysiol. 110, 705–711 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Rotta, F. T. et al. The spectrum of chronic inflammatory demyelinating polyneuropathy. J. Neurol. Sci. 173, 129–139 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Lozeron, P. et al. Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients. J. Neurol. 249, 569–575 (2002).

    Article  PubMed  Google Scholar 

  19. Sharma, K. R. et al. Demyelinating neuropathy in diabetes mellitus. Arch. Neurol. 59, 758–765 (2002). Study describing an 11-fold increased risk of CIDP in patients with diabetes.

    Article  PubMed  Google Scholar 

  20. Rajabally, Y. A., Simpson, B. S., Beri, S., Bankart, J. & Gosalakkal, J. A. Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population. Muscle Nerve 39, 432–438 (2009).

    Article  PubMed  Google Scholar 

  21. Mahdi-Rogers, M. & Hughes, R. A. Epidemiology of chronic inflammatory neuropathies in southeast England. Eur. J. Neurol. 21, 28–33 (2014).

    Article  CAS  PubMed  Google Scholar 

  22. Public Health England South East. Clinical standards indicators in south central — report 1: diabetes mellitus. The Health Well http://www.thehealthwell.info/node/29470 (2008).

  23. Bril, V. et al. The dilemma of diabetes in chronic inflammatory demyelinating polyneuropathy. J. Diabetes Compl. 30, 1401–1407 (2016). Analysis of a health insurance database from the USA that described a ninefold increased risk of CIDP in patients with diabetes.

    Article  Google Scholar 

  24. Chio, A. et al. Comorbidity between CIDP and diabetes mellitus: only a matter of chance? Eur. J. Neurol. 16, 752–754 (2009). Italian epidemiological study that did not find an association of CIDP with diabetes.

    Article  CAS  PubMed  Google Scholar 

  25. Laughlin, R. S. et al. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology 73, 39–45 (2009). Epidemiological study from the USA, which failed to identify diabetes as a major covariate for CIDP.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Breiner, A, Brannagan, T. H. III. Comparison of sensitivity and specificity among 15 criteria for chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 50, 40–46 (2014).

    Article  PubMed  Google Scholar 

  27. Rajabally, Y. A., Nicolas, G., Pieret, F., Bouche, P. & Van den Bergh, P. Y. Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study. J. Neurol. Neurosurg. Psychiatry 80, 1364–1368 (2009). A multicentre study that demonstrated a high sensitivity of the EFNS–PNS criteria for CIDP.

    Article  CAS  PubMed  Google Scholar 

  28. Rajabally, Y. A., Fowle, A. J. & Van den Bergh, P. Y. Which criteria for research in chronic inflammatory demyelinating polyradiculoneuropathy? An analysis of current practice. Muscle Nerve 51, 932–933 (2015).

    Article  PubMed  Google Scholar 

  29. Rajabally, Y. A. & Chavada, G. Lewis–Sumner syndrome of pure upper-limb onset: diagnostic, prognostic, and therapeutic features. Muscle Nerve 39, 206–220 (2009).

    Article  PubMed  Google Scholar 

  30. Barohn, R. J., Kissel, J. T., Warmolts, J. R. & Mendell, J. R. Chronic inflammatory demyelinating polyradiculoneuropathy. Clinical characteristics, course, and recommendations for diagnostic criteria. Arch. Neurol. 46, 878–884 (1989).

    Article  CAS  PubMed  Google Scholar 

  31. Kobessho, H., Oishi, K., Hamaguchi, H. & Kanda, F. Elevation of cerebrospinal fluid protein in patients with diabetes mellitus is associated with duration of diabetes. Eur. Neurol. 60, 132–136 (2008).

    Article  PubMed  Google Scholar 

  32. Rajabally, Y. A., Adams, D., Latour, P. & Attarian, S. Hereditary and inflammatory neuropathies: a review of reported associations, mimics and misdiagnoses. J. Neurol. Neurosurg. Psychiatry 87, 1051–1060 (2016).

    Article  PubMed  Google Scholar 

  33. Shibuya, K. et al. Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy. Ann. Neurol. 77, 333–337 (2015).

    Article  PubMed  Google Scholar 

  34. Rajabally, Y. A., Knopp, M. J., Martin-Lamb, D. & Morlese, J. Diagnostic value of MR imaging in the Lewis–Sumner syndrome: a case series. J. Neurol. Sci. 342, 182–185 (2014).

    Article  PubMed  Google Scholar 

  35. Duggins, A. J. et al. Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy. Brain 122, 1383–1390 (1999).

    Article  PubMed  Google Scholar 

  36. Pham, M. et al. Magnetic resonance neurography detects diabetic neuropathy early and with proximal predominance. Ann. Neurol. 78, 939–948 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Thakkar, R. S. et al. Spectrum of high-resolution MRI findings in diabetic neuropathy. AJR Am. J. Roentgenol. 199, 407–412 (2012).

    Article  PubMed  Google Scholar 

  38. Vaeggemose, M., Ringgaard, S., Ejskjaer, N. & Andersen, H. Magnetic resonance imaging may be used for early evaluation of diabetic peripheral polyneuropathy. J. Diabetes Sci. Technol. 9, 162–163 (2015).

    Article  PubMed  Google Scholar 

  39. Vaeggemose, M. et al. Magnetic resonance neurography visualizes abnormalities in sciatic and tibial nerves in patients with type 1 diabetes and neuropathy. Diabetes 66, 1779–1788 (2017).

    Article  CAS  PubMed  Google Scholar 

  40. Markvardsen, L. H., Vaeggemose, M., Ringgaard, S. & Andersen, H. Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin. 58, 745–752 (2016).

  41. Breiner, A. et al. Peripheral nerve high-resolution ultrasound in diabetes. Muscle Nerve 55, 171–178 (2017).

    Article  PubMed  Google Scholar 

  42. Kang, S., Kim, S. H., Yang, S. N. & Yoon, J. S. Sonographic features of peripheral nerves at multiple sites in patients with diabetic polyneuropathy. J. Diabetes Complications 30, 518–523 (2016).

    Article  PubMed  Google Scholar 

  43. Di Pasquale, A. et al. Peripheral nerve ultrasound changes in CIDP and correlations with nerve conduction velocity. Neurology 84, 803–809 (2015).

    Article  PubMed  Google Scholar 

  44. Goedee, H. S. et al. Diagnostic value of sonography in treatment-naive chronic inflammatory neuropathies. Neurology 88, 143–151 (2017).

    Article  PubMed  Google Scholar 

  45. Zaidman, C. M. & Pestronk, A. Nerve size in chronic inflammatory demyelinating neuropathy varies with disease activity and therapy response over time: a retrospective ultrasound study. Muscle Nerve 50, 733–738 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Dyck, P. J. et al. Chronic inflammatory polyradiculoneuropathy. Mayo Clin. Proc. 50, 621–637 (1975).

    CAS  PubMed  Google Scholar 

  47. Sommer, C. & Toyka, K. Nerve biopsy in chronic inflammatory neuropathies: in situ biomarkers. J. Periph. Nerv. Syst. 16 (Suppl. 1), 24–29 (2011).

    Article  Google Scholar 

  48. Vallat, J. M. et al. Diagnostic value of nerve biopsy for atypical chronic inflammatory demyelinating polyneuropathy: evaluation of eight cases. Muscle Nerve 27, 478–485 (2003).

    Article  PubMed  Google Scholar 

  49. Ryan, M. M., Jones, H. R. Jr. CMTX mimicking childhood chronic inflammatory demyelinating neuropathy with tremor. Muscle Nerve 31, 528–530 (2005).

    Article  PubMed  Google Scholar 

  50. Tabaraud, F. et al. Demyelinating X-linked Charcot–Marie–Tooth disease: unusual electrophysiological findings. Muscle Nerve 22, 1442–1447 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Bosboom, W. M. et al. Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy. Brain 124, 2427–2438 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Kiefer, R., Kieseier, B. C., Bruck, W., Hartung, H. P. & Toyka, K. V. Macrophage differentiation antigens in acute and chronic autoimmune polyneuropathies. Brain 121, 469–479 (1998).

    Article  PubMed  Google Scholar 

  53. Sommer, C. et al. Macrophage clustering as a diagnostic marker in sural nerve biopsies of patients with CIDP. Neurology. 65, 1924–1929 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Uceyler, N., Necula, G., Wagemann, E., Toyka, K. V. & Sommer, C. Endoneurial edema in sural nerve may indicate recent onset inflammatory neuropathy. Muscle Nerve 53, 705–710 (2016).

    Article  CAS  PubMed  Google Scholar 

  55. Jann, S. et al. Diagnostic value of sural nerve matrix metalloproteinase-9 in diabetic patients with CIDP. Neurology 61, 1607–1610 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Tavakoli, M. & Malik, R. A. Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. J. Vis. Exp. 47, e2194 (2011).

    Google Scholar 

  57. Petropoulos, I. N. et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care 36, 3646–3651 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Tavakoli, M. et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes 62, 254–260 (2013).

    Article  CAS  PubMed  Google Scholar 

  59. Stettner, M. et al. Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy. Ann. Clin. Transl. Neurol. 3, 88–100 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Baron, R., Tolle, T. R., Gockel, U., Brosz, M. & Freynhagen, R. A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: differences in demographic data and sensory symptoms. Pain 146, 34–40 (2009).

    Article  PubMed  Google Scholar 

  61. Freeman, R., Baron, R., Bouhassira, D., Cabrera, J. & Emir, B. Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs. Pain 155, 367–376 (2014).

    Article  PubMed  Google Scholar 

  62. Boulton, A. J., Malik, R. A., Arezzo, J. C. & Sosenko, J. M. Diabetic somatic neuropathies. Diabetes Care 27, 1458–1486 (2004).

    Article  PubMed  Google Scholar 

  63. Tan, L. S. The clinical use of the 10 g monofilament and its limitations: a review. Diabetes Res. Clin. Pract. 90, 1–7 (2010).

    Article  PubMed  Google Scholar 

  64. Boulton, A. & Malik, R. Endocrinology: Adult and Pediatric 7th edn Vol. 1 Ch. 53 (eds Jameson J. L & De Groot, L. J) 920–933 (Saunders Elsevier, 2015).

    Google Scholar 

  65. Boulton, A. J. et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care 31, 1679–1685 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Boulton, A. J. et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28, 956–962 (2005).

    Article  PubMed  Google Scholar 

  67. Andersen, H. Motor neuropathy Handb. Clin. Neurol. 126, 81–95 (2014).

    Article  PubMed  Google Scholar 

  68. Almurdhi, M. M. et al. Reduced lower-limb muscle strength and volume in patients with type 2 diabetes in relation to neuropathy, intramuscular fat, and vitamin D levels. Diabetes Care 39, 441–447 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Almurdhi, M. M. et al. Distal lower limb strength is reduced in subjects with impaired glucose tolerance and is related to elevated intramuscular fat level and vitamin D deficiency. Diabet. Med. 34, 356–363 (2017).

    Article  CAS  PubMed  Google Scholar 

  70. Boukhris, S. et al. Fatigue as the main presenting symptom of chronic inflammatory demyelinating polyradiculoneuropathy: a study of 11 cases. J. Periph. Nerv. Syst. 10, 329–337 (2005).

    Article  Google Scholar 

  71. Boukhris, S., Magy, L., Khalil, M., Sindou, P. & Vallat, J. M. Pain as the presenting symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). J. Neurol. Sci. 254, 33–38 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Rajabally, Y. A., Jacob, S. & Abbott, R. J. Clinical heterogeneity in mild chronic inflammatory demyelinating polyneuropathy. Eur. J. Neurol. 13, 958–962 (2006).

    Article  CAS  PubMed  Google Scholar 

  73. Uncini, A., Di Muzio, A., De Angelis, M. V., Gioia, S. & Lugaresi, A. Minimal and asymptomatic chronic inflammatory demyelinating polyneuropathy. Clin. Neurophysiol. 110, 694–698 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Dunnigan, S. K. et al. Conduction slowing in diabetic sensorimotor polyneuropathy. Diabetes Care 36, 3684–3690 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Herrmann, D. N., Ferguson, M. L. & Logigian, E. L. Conduction slowing in diabetic distal polyneuropathy. Muscle Nerve 26, 232–237 (2002).

    Article  PubMed  Google Scholar 

  76. Dunnigan, S. K. et al. Comparison of diabetes patients with “demyelinating” diabetic sensorimotor polyneuropathy to those diagnosed with CIDP. Brain Behav. 3, 656–663 (2013). Study showing more severe neuropathy but better glycaemic control in patients with CIDP and diabetes, compared with patients with 'demyelinating' DSPN.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Mitsuma, S. et al. Effects of low frequency filtering on distal compound muscle action potential duration for diagnosis of CIDP: a Japanese–European multicenter prospective study. Clin. Neurophysiol. 126, 1805–1810 (2015).

    Article  PubMed  Google Scholar 

  78. Rajabally, Y. A., Martin-Lamb, D. & Nicolas, G. Compound muscle action potential amplitude and distal potential duration in axonal neuropathy. Muscle Nerve 49, 146–147 (2014).

    Article  PubMed  Google Scholar 

  79. Lotan, I., Hellman, M. A. & Steiner, I. Diagnostic criteria of chronic inflammatory demyelinating polyneuropathy in diabetes mellitus. Acta Neurol. Scand. 132, 278–283 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Dyck, P. J. & Windebank, A. J. Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. Muscle Nerve 25, 477–491 (2002).

    Article  PubMed  Google Scholar 

  81. Laughlin, R. S. & Dyck, P. J. Electrodiagnostic testing in lumbosacral plexopathies. Phys. Med. Rehabil. Clin. N. Am. 24, 93–105 (2013).

    Article  PubMed  Google Scholar 

  82. Massie, R. et al. Diabetic cervical radiculoplexus neuropathy: a distinct syndrome expanding the spectrum of diabetic radiculoplexus neuropathies. Brain 135, 3074–3088 (2012).

    Article  PubMed  Google Scholar 

  83. Chan, Y. C., Lo, Y. L. & Chan, E. S. Immunotherapy for diabetic amyotrophy. Cochrane Database Syst. Rev. 6, CD006521 (2012).

    Google Scholar 

  84. Dyck, P. J. et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43, 817–824 (1993).

    Article  CAS  PubMed  Google Scholar 

  85. Gorson, K. C., Ropper, A. H., Adelman, L. S. & Weinberg, D. H. Influence of diabetes mellitus on chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 23, 37–43 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Haq, R. U., Pendlebury, W. W., Fries, T. J. & Tandan, R. Chronic inflammatory demyelinating polyradiculoneuropathy in diabetic patients. Muscle Nerve 27, 465–470 (2003).

    Article  PubMed  Google Scholar 

  87. Garces-Sanchez, M. et al. Painless diabetic motor neuropathy: a variant of diabetic lumbosacral radiculoplexus neuropathy? Ann. Neurol. 69, 1043–1054 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Said, G., Goulon-Goeau, C., Lacroix, C. & Moulonguet, A. Nerve biopsy findings in different patterns of proximal diabetic neuropathy. Ann. Neurol. 35, 559–569 (1994).

    Article  CAS  PubMed  Google Scholar 

  89. Llewelyn, J. G., Thomas, P. K. & King, R. H. Epineurial microvasculitis in proximal diabetic neuropathy. J. Neurol. 245, 159–165 (1998).

    Article  CAS  PubMed  Google Scholar 

  90. Coppack, S. W. & Watkins, P. J. The natural history of diabetic femoral neuropathy. Q. J. Med. 79, 307–313 (1991).

    CAS  PubMed  Google Scholar 

  91. Vrancken, A. F., Said, G. Vasculitic neuropathy. Handb. Clin. Neurol. 115, 463–483 (2013).

    Article  PubMed  Google Scholar 

  92. Dionne, A., Nicolle, M. W. & Hahn, A. F. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy. Muscle Nerve 41, 202–207 (2010).

    PubMed  Google Scholar 

  93. Ruts, L., Drenthen, J., Jacobs, B. C. & van Doorn, P. A. Distinguishing acute-onset CIDP from fluctuating Guillain–Barré syndrome: a prospective study. Neurology 74, 1680–1686 (2010).

    Article  CAS  PubMed  Google Scholar 

  94. Bosboom, W. M. et al. The diagnostic value of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy. Neurology 53, 837–845 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Hartung, H. P., Reiners, K., Schmidt, B., Stoll, G. & Toyka, K. V. Serum interleukin-2 concentrations in Guillain–Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis. Ann. Neurol. 30, 48–53 (1991).

    Article  CAS  PubMed  Google Scholar 

  96. Kieseier, B. C. et al. Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. Brain 125, 823–834 (2002).

    Article  PubMed  Google Scholar 

  97. Schmidt, B. et al. Inflammatory infiltrates in sural nerve biopsies in Guillain–Barré syndrome and chronic inflammatory demyelinating neuropathy. Muscle Nerve 19, 474–487 (1996).

    Article  CAS  PubMed  Google Scholar 

  98. Kiefer, R., Kieseier, B. C., Stoll, G. & Hartung, H. P. The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog. Neurobiol. 64, 109–127 (2001).

    Article  CAS  PubMed  Google Scholar 

  99. Hughes, R. J. Chronic inflammatory demyelinating polyradiculoneuropathy J. Clin. Immunol. 30 (Suppl. 1), S70–S73 (2010).

    Article  PubMed  Google Scholar 

  100. Koller, H., Kieseier, B. C., Jander, S. & Hartung, H. P. Chronic inflammatory demyelinating polyneuropathy. N. Engl. J. Med. 352, 1343–1356 (2005).

    Article  PubMed  Google Scholar 

  101. Mathey, E. K. et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J. Neurol. Neurosurg. Psychiatry 86, 973–985 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Eftimov, F., Winer, J. B., Vermeulen, M., de Haan, R. & van Schaik, I. N. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst. Rev. 12, CD001797 (2013).

    Google Scholar 

  103. Press, R., Hiew, F. L. & Rajabally, Y. A. Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice. Acta Neurol. Scand. 133, 228–238 (2016).

    Article  CAS  PubMed  Google Scholar 

  104. Mehndiratta, M. M., Hughes, R. A. & Pritchard, J. Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst. Rev. 8, CD003906 (2015).

    Google Scholar 

  105. Rajabally, Y. A. & Kearney, D. A. Thromboembolic complications of intravenous immunoglobulin therapy in patients with neuropathy: a two-year study. J. Neurol. Sci. 308, 124–127 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. Ramirez, E. et al. Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins: results from a retrospective cohort study. Thromb. Res. 133, 1045–1051 (2014).

    Article  CAS  PubMed  Google Scholar 

  107. Donaghy, M. et al. Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin. J. Neurol. Neurosurg. Psychiatry 57, 778–783 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nobile-Orazio, E. et al. Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial. Lancet Neurol. 11, 493–502 (2012).

    Article  CAS  PubMed  Google Scholar 

  109. Nobile-Orazio, E. et al. Frequency and time to relapse after discontinuing 6-month therapy with IVIg or pulsed methylprednisolone in CIDP. J. Neurol. Neurosurg. Psychiatry 86, 729–734 (2015).

    Article  PubMed  Google Scholar 

  110. Rabin, M. et al. Chronic inflammatory demyelinating polyradiculoneuropathy: search for factors associated with treatment dependence or successful withdrawal. J. Neurol. Neurosurg. Psychiatry 85, 901–906 (2014).

    Article  PubMed  Google Scholar 

  111. van Schaik, I. N. et al. Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial. Lancet Neurol. 9, 245–253 (2010).

    Article  CAS  PubMed  Google Scholar 

  112. Rajabally, Y. A. Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 51, 657–661 (2015).

    Article  CAS  PubMed  Google Scholar 

  113. Dunnigan, S. K. et al. The characteristics of chronic inflammatory demyelinating polyneuropathy in patients with and without diabetes — an observational study. PLoS ONE 9, e89344 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Iijima, M. et al. Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. Neurology 64, 1471–1475 (2005).

    Article  CAS  PubMed  Google Scholar 

  115. Chan, Y. C., Allen, D. C., Fialho, D., Mills, K. R. & Hughes, R. A. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy. J. Neurol. Neurosurg. Psychiatry 77, 114–116 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Abraham, A. et al. Treatment responsiveness in CIDP patients with diabetes is associated with unique electrophysiological characteristics, and not with common criteria for CIDP. Expert Rev. Clin. Immunol. 11, 537–546 (2015).

    Article  CAS  PubMed  Google Scholar 

  117. Abraham, A. et al. Treatment responsiveness in CIDP patients with diabetes is associated with higher degrees of demyelination. PLoS ONE 10, e0139674 (2015). Study suggesting that among patients with CIDP, more demyelinating features are required to enable prediction of treatment response in those with diabetes than in those without diabetes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cocito, D. et al. A nationwide retrospective analysis on the effect of immune therapies in patients with chronic inflammatory demyelinating polyradiculoneuropathy. Eur. J. Neurol. 17, 289–294 (2010).

    Article  CAS  PubMed  Google Scholar 

  119. Mahdi-Rogers, M., van Doorn, P. A. & Hughes, R. A. Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst. Rev. 6, CD003280 (2013).

    Google Scholar 

  120. Oaklander, A. L. et al. Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews. Cochrane Database Syst. Rev. 1, CD010369 (2017).

    PubMed  Google Scholar 

  121. RMC Trial Group. Randomised controlled trial of methotrexate for chronic inflammatory demyelinating polyradiculoneuropathy (RMC trial): a pilot, multicentre study. Lancet Neurol. 8, 158–164 (2009).

  122. Dyck, P. J., O'Brien, P., Swanson, C., Low, P. & Daube, J. Combined azathioprine and prednisone in chronic inflammatory-demyelinating polyneuropathy. Neurology 35, 1173–1176 (1985).

    Article  CAS  PubMed  Google Scholar 

  123. Hadden, R. D., Sharrack, B., Bensa, S., Soudain, S. E. & Hughes, R. A. Randomized trial of interferon β-1a in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 53, 57–61 (1999).

    Article  CAS  PubMed  Google Scholar 

  124. Hughes, R. A. et al. Intramuscular interferon β-1a in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 74, 651–657 (2010).

    Article  CAS  PubMed  Google Scholar 

  125. Matsuda, M., Hoshi, K., Gono, T., Morita, H. & Ikeda, S. Cyclosporin A in treatment of refractory patients with chronic inflammatory demyelinating polyradiculoneuropathy. J. Neurol. Sci. 224, 29–35 (2004).

    Article  CAS  PubMed  Google Scholar 

  126. Odaka, M., Tatsumoto, M., Susuki, K., Hirata, K. & Yuki, N. Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin. J. Neurol. Neurosurg. Psychiatry 76, 1115–1120 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Radziwill, A. J., Schweikert, K., Kuntzer, T., Fuhr, P. & Steck, A. J. Mycophenolate mofetil for chronic inflammatory demyelinating polyradiculoneuropathy: an open-label study. Eur. Neurol. 56, 37–38 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. Vallat, J. M. et al. Natalizumab as a disease-modifying therapy in chronic inflammatory demyelinating polyneuropathy — a report of three cases. Eur. Neurol. 73, 294–302 (2015).

    Article  CAS  PubMed  Google Scholar 

  129. Hirst, C., Raasch, S., Llewelyn, G. & Robertson, N. Remission of chronic inflammatory demyelinating polyneuropathy after alemtuzumab (Campath 1H). J. Neurol. Neurosurg. Psychiatry 77, 800–802 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Marsh, E. A. et al. Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating polyneuropathy. J. Neurol. 257, 913–919 (2010).

    Article  CAS  PubMed  Google Scholar 

  131. Gladstone, D. E., Prestrud, A. A. & Brannagan, T. H. III. High-dose cyclophosphamide results in long-term disease remission with restoration of a normal quality of life in patients with severe refractory chronic inflammatory demyelinating polyneuropathy. J. Peripher. Nerv. Syst. 10, 11–16 (2005).

    Article  CAS  PubMed  Google Scholar 

  132. Good, J. L., Chehrenama, M., Mayer, R. F. & Koski, C. L. Pulse cyclophosphamide therapy in chronic inflammatory demyelinating polyneuropathy. Neurology 51, 1735–1738 (1998).

    Article  CAS  PubMed  Google Scholar 

  133. Benedetti, L. et al. Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature. J. Neurol. Neurosurg. Psychiatry 82, 306–308 (2011).

    Article  CAS  PubMed  Google Scholar 

  134. Munch, C., Anagnostou, P., Meyer, R. & Haas, J. Rituximab in chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus. J. Neurol. Sci. 256, 100–102 (2007).

    Article  CAS  PubMed  Google Scholar 

  135. Velardo, D. et al. Rituximab in refractory chronic inflammatory demyelinating polyradiculoneuropathy: report of four cases. J. Neurol. 264, 1011–1014 (2017).

    Article  PubMed  Google Scholar 

  136. Axelson, H. W., Oberg, G. & Askmark, H. Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP. J. Neurol. Neurosurg. Psychiatry 612–614 (2008).

  137. Mahdi-Rogers, M. et al. Autologous peripheral blood stem cell transplantation for chronic acquired demyelinating neuropathy. J. Peripher. Nerv. Syst. 14, 118–124 (2009).

    Article  PubMed  Google Scholar 

  138. Oyama, Y. et al. Nonmyeloablative autologous hematopoietic stem celltransplantation for refractory CIDP. Neurology 69, 1802–1803 (2007).

    Article  CAS  PubMed  Google Scholar 

  139. Vermeulen, M. & Van Oers, M. H. Successful autologous stem cell transplantation in a patient with chronic inflammatory demyelinating polyneuropathy. J. Neurol. Neurosurg. Psychiatry 72, 127–128 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Vermeulen, M. & van Oers, M. H. Relapse of chronic inflammatory demyelinating polyneuropathy 5 years after autologous stem cell transplantation. J. Neurol. Neurosurg. Psychiatry 78, 1154 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Press, R. et al. Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP. J. Neurol. Neurosurg. Psychiatry 85, 618–624 (2014).

    Article  CAS  PubMed  Google Scholar 

  142. [No authors listed.] Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP): report from an ad hoc subcommittee of the American Academy Of Neurology Aids Task Force. Neurology 41, 617–618 (1991).

  143. Sharma, K. R., Cross, J., Ayyar, D. R., Martinez-Arizala, A. & Bradley, W. G. Diabetic demyelinating polyneuropathy responsive to intravenous immunoglobulin therapy. Arch. Neurol. 59, 751–757 (2002).

    Article  PubMed  Google Scholar 

  144. Jann, S., Bramerio, M. A., Facchetti, D. & Sterzi, R. Intravenous immunoglobulin is effective in patients with diabetes and with chronic inflammatory demyelinating polyneuropathy: long term follow-up. J. Neurol. Neurosurg. Psychiatry 80, 70–73 (2009). Prospective study describing the effectiveness of intravenous immunoglobulin in CIDP patients with diabetes.

    Article  CAS  PubMed  Google Scholar 

  145. Koski, C. L. et al. Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy. J. Neurol. Sci. 277, 1–8 (2009).

    Article  CAS  PubMed  Google Scholar 

  146. Hughes, R. A. et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 7, 136–144 (2008).

    Article  CAS  PubMed  Google Scholar 

  147. Kuitwaard, K., Hahn, A. F., Vermeulen, M., Venance, S. L. & van Doorn, P. A. Intravenous immunoglobulin response in treatment-naive chronic inflammatory demyelinating polyradiculoneuropathy. J. Neurol. Neurosurg. Psychiatry 86, 1331–1336 (2015).

    Article  PubMed  Google Scholar 

  148. Pascoe, M. K., Low, P. A., Windebank, A. J. & Litchy, W. J. Subacute diabetic proximal neuropathy. Mayo Clin. Proc. 72, 1123–1132 (1997).

    Article  CAS  PubMed  Google Scholar 

  149. Jaradeh, S. S., Prieto, T. E. & Lobeck, L. J. Progressive polyradiculoneuropathy in diabetes: correlation of variables and clinical outcome after immunotherapy. J. Neurol. Neurosurg. Psychiatry 67, 607–612 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Zochodne, D. W., Isaac, D. & Jones, C. Failure of immunotherapy to prevent, arrest or reverse diabetic lumbosacral plexopathy. Acta Neurol. Scand. 107, 299–301 (2003).

    Article  CAS  PubMed  Google Scholar 

  151. Choudhry, M. N., Malik, R. A. & Charalambous, C. P. Blood glucose levels following intra-articular steroid injections in patients with diabetes: a systematic review. JBJS Rev. http://dx.doi.org/10.2106/JBJS.RVW.O.00029 (2016).

  152. Rajabally, Y. A. Tailoring of therapy for chronic inflammatory demyelinating polyneuropathy. Neural Regen. Res. 10, 1399–1400 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Collins, M. P. & Hadden, R. D. The nonsystemic vasculitic neuropathies. Nat. Rev. Neurol. 13, 302–316 (2017).

    Article  PubMed  Google Scholar 

  154. Devaux, J. J. et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 86, 800–807 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Miura, Y. et al. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. Brain 138, 1484–1491 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Querol, L. et al. Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg. Neurology 82, 879–886 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Gibbons, C. H. et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J. Neurol. 264, 1567–1582 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Vinik, A. I. & Erbas, T. Diabetic autonomic neuropathy. Handb. Clin. Neurol. 117, 279–294 (2013).

    Article  PubMed  Google Scholar 

  159. van Dijk, G. W., Notermans, N. C., Franssen, H. & Wokke, J. H. Development of weakness in patients with chronic inflammatory demyelinating polyneuropathy and only sensory symptoms at presentation: a long-term follow-up study. J. Neurol. 246, 1134–1139 (1999).

    Article  CAS  PubMed  Google Scholar 

  160. Malik, R. A. et al. Sural nerve pathology in diabetic patients with minimal but progressive neuropathy. Diabetologia 48, 578–585 (2005).

    Article  CAS  PubMed  Google Scholar 

  161. Llewelyn, J. G. et al. Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy. A clinicopathological study. Brain 114, 867–892 (1991).

    Article  PubMed  Google Scholar 

  162. Khawaja, K. I., Walker, D., Hayat, S. A., Boulton, A. J. & Malik, R. A. Clinico-pathological features of postural hypotension in diabetic autonomic neuropathy. Diabet. Med. 17, 163–166 (2000).

    Article  CAS  PubMed  Google Scholar 

  163. Britland, S. T., Young, R. J., Sharma, A. K. & Clarke, B. F. Association of painful and painless diabetic polyneuropathy with different patterns of nerve fibre degeneration and regeneration. Diabetes 39, 898–908 (1990).

    Article  CAS  PubMed  Google Scholar 

  164. Kanda, T. Morphometric analysis of sural nerve in elderly diabetes mellitus. Bull. Tokyo Med. Dent. Univ. 31, 209–224 (1984).

    CAS  PubMed  Google Scholar 

  165. Tekle Haimanot, R., Abdulkadir, J., Doyle, D. Light and electron microscopic changes in sural nerves in Ethiopian diabetics. Ethiop. Med. J. 27, 1–8 (1989).

    CAS  PubMed  Google Scholar 

  166. Thrainsdottir, S. et al. Endoneurial capillary abnormalities presage deterioration of glucose tolerance and accompany peripheral neuropathy in man. Diabetes 52, 2615–2622 (2003).

    Article  CAS  PubMed  Google Scholar 

  167. Yasuda, H. & Dyck, P. J. Abnormalities of endoneurial microvessels and sural nerve pathology in diabetic neuropathy. Neurology 37, 20–28 (1987).

    Article  CAS  PubMed  Google Scholar 

  168. Malik, R. A. et al. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia 32, 92–102 (1989).

    Article  CAS  PubMed  Google Scholar 

  169. Malik, R. A. et al. Endoneurial capillary abnormalities in mild human diabetic neuropathy. J. Neurol. Neurosurg. Psychiatry 55, 557–561 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Said, G., Goulon-Goeau, C., Slama, G. & Tchobroutsky, G. Severe early-onset polyneuropathy in insulin-dependent diabetes mellitus. A clinical and pathological study. N. Engl. J. Med. 326, 1257–1263 (1992).

    Article  CAS  PubMed  Google Scholar 

  171. Dyck, P. J. et al. Capillary number and percentage closed in human diabetic sural nerve. Proc. Natl Acad. Sci. USA 82, 2513–2517 (1985).

    Article  CAS  PubMed  Google Scholar 

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Y.A.R., B.C.K and R.M. researched data for and wrote the article. All authors made substantial contributions to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Yusuf A. Rajabally.

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Y.A.R. has received speaker and/or consultancy honoraria from CSL Behring, LfB, Grifols, BPL, Octapharma and Kedrion, has received educational sponsorships from LfB, CSL Behring and Baxter, and has obtained research grants from CSL Behring and LfB. M.S. has received honoraria for consulting or lecturing and travel expenses for attending meetings from Biogen Idec, Genzyme, Novartis, Sanofi Aventis, UCB, Grifols and TEVA, and has received financial support for research from Bayer Health Care and UCB. B.C.K. has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen, Genzyme/Sanofi Aventis, Grifols, Merck Serono, Mitsubishi Europe, Novartis, Roche, Talecris and TEVA. He is currently also an employee of Biogen. H.-P.H. has received fees for consulting, speaking and serving on steering committees from Baxelta, CSL Behring, Kedrion, Novartis, Octapharma and LfB. R.A.M. has received honoraria for speaking or consultancy from Pfizer, Lilly and Novo Nordisk.

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Rajabally, Y., Stettner, M., Kieseier, B. et al. CIDP and other inflammatory neuropathies in diabetes — diagnosis and management. Nat Rev Neurol 13, 599–611 (2017). https://doi.org/10.1038/nrneurol.2017.123

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