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Advances in the diagnosis, pathogenesis and treatment of CIDP

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Despite clinical challenges in diagnosis—owing in part to the existence of disease variants, and different views on how many electrophysiological abnormalities are needed to document demyelination—consensus criteria seem to have been reached for research or clinical practice. Current standard of care involves corticosteroids, intravenous immunoglobulin (IVIg) and/or plasmapheresis, which provide short-term benefits. Maintenance therapy with IVIg can induce sustained remission, increase quality of life and prevent further axonal loss, but caution is needed to avoid overtreatment. Commonly used immunosuppressive drugs offer minimal benefit, necessitating the development of new therapies for treatment-refractory patients. Advances in our understanding of the underlying immunopathology in CIDP have identified new targets for future therapeutic efforts, including T cells, B cells, and transmigration and transduction molecules. New biomarkers and scoring systems represent emerging tools with the potential to predict therapeutic responses and identify patients with active disease for enrollment into clinical trials. This Review highlights the recent advances in diagnosing CIDP, provides an update on the immunopathology including new target antigens, and discusses current treatments, ongoing challenges and future therapeutic directions.

Key Points

  • Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired chronic autoimmune neuropathy

  • Despite disease heterogeneity, recently revised diagnostic criteria provide an optimal balance between sensitivity and specificity

  • Molecules within the non-compact myelin and points of Schwann cell–axon interaction, rather than within compact myelin, seem to be the putative target antigens

  • Corticosteroids, intravenous immunoglobulin (IVIg) and plasmapheresis provide short-term benefits; IVIg is used for long-term maintenance

  • Potential new therapeutic approaches involve targeting key factors in the immunopathogenesis of CIDP, including T cells, B cells and complement

  • Progress in clinical trial design is focused on clinically meaningful tools to define therapeutic responses, enrolling only patients with active disease and exploring biomarkers that predict response to therapies

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Figure 1
Figure 2: Scheme depicting the main immunopathogenic network involved in CIDP.

References

  1. Austin, J. H. Recurrent polyneuropathies and their corticosteroid treatment. Brain 81, 11–192 (1958).

    Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Prineas, J. W. & McLeod, J. G. Chronic relapsing polyneuritis J. Neurol. Sci. 27, 427–458 (1976).

    Article  CAS  PubMed  Google Scholar 

  4. Dalakas, M. C. in Clinical Immunology: Principles and Practice 3rd edn (eds Rich, R. R. et al.) 977–994 (Mosby Elsevier, Philadelphia, 2008).

    Book  Google Scholar 

  5. 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 

  6. Lauria, G. et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur. J. Neurol. 17, 903–912 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Dalakas, M. C. & Engel, W. K. Chronic relapsing (dysimmune) polyneuropathy: pathogenesis and treatment. Ann. Neurol. 10, 134–145 (1981).

    Article  Google Scholar 

  8. Hughes, R. A. C., Allen, D., Makowska, A. & Gregson, N. A. Pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy. J. Periph. Nerv. Syst. 11, 30–46 (2006).

    Article  Google Scholar 

  9. Vallat, J. M., Sommer, C. & Magy, L. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol. 9, 402–412 (2010).

    Article  PubMed  Google Scholar 

  10. Said, G. Chronic inflammatory demyelinating polyneuropathy. Neuromuscul. Disord. 16, 293–303 (2006).

    Article  PubMed  Google Scholar 

  11. Dalakas, M. C., Teravinen, H. & Engel, W. K. Tremor as a feature of chronic relapsing and dysgammaglobulinemic polyneuropathies: incidence and management. Arch. Neurol. 41, 711–714 (1984).

    Article  CAS  PubMed  Google Scholar 

  12. Ryan, M. M., Grattan-Smith, P. J., Procopis, P. G., Morgan, G. & Ouvrier, R. A. Childhood chronic inflammatory demyelinating polyneuropathy: clinical course and long-term outcome. Neuromuscul. Disord. 10, 398–406 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Nevo, Y. et al. Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow-up. Neurology 47, 98–102 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Sladky, J. T. & Teasley, J. E. What is the best initial treatment for childhood CIDP: corticosteroids or IVIg? Muscle Nerve 38, 1638–1643 (2008).

    Article  PubMed  Google Scholar 

  15. Saperstein, D. S. et al. Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis–Sumner syndrome. Muscle Nerve 22, 560–566 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. Lewis, R. A., Sumner, A. J., Brown, M. J. & Asbury, A. K. Multifocal demyelinating neuropathy with persistent conduction block. Neurology 32, 958–964 (1982).

    Article  CAS  PubMed  Google Scholar 

  17. Sabatelli, M. et al. Pure motor chronic inflammatory demyelinating polyneuropathy. J. Neurol. 248, 772–777 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Oh, S. J., Joy, J. L. & Kuruoglu, R. “Chronic sensory demyelinating neuropathy”: chronic inflammatory demyelinating polyneuropathy presenting as a pure sensory neuropathy. J. Neurol. Neurosurg. Psychiatry 55, 677–680 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sinnreich, M. et al. Chronic immune sensory polyradiculopathy: a possibly treatable sensory ataxia. Neurology 63, 1662–1669 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Katz, J. S., Saperstein, D. S., Gronseth, G., Amato, A. A. & Barohn, R. J. Distal acquired demyelinating symmetric neuropathy. Neurology 54, 615–620 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Lunn, M. P., Manji, H., Choudhary, P. P., Hughes, R. A. & Thomas, P. K. Chronic inflammatory demyelinating polyradiculoneuropathy: a prevalence study in south east England. J. Neurol. Neurosurg. Psychiatry 66, 677–680 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Laughlin, R. S., Dyck, P. J., Melton, L. J. 3rd, Leibson, C. & Ransom, J. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology 73, 39–45 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mygland, A. & Monstad, P. Chronic polyneuropathies in Vest-Agder, Norway. Eur. J. Neurol. 8, 157–165 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Iijima, M. et al. Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population. J. Neurol. Neurosurg. Psychiatry 79, 1040–1043 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. 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 

  26. Chiò, A. et al. Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy. J. Neurol. Neurosurg. Psychiatry 78, 1349–1353 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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 

  28. Chiò, A. et al. Comorbidity between CIDP and diabetes mellitus: only a matter of chance? Eur. J. Neurol. 16, 752–754 (2009).

    Article  PubMed  Google Scholar 

  29. Sharma, K. R. et al. Demyelinating neuropathy in diabetes mellitus. Arch. Neurol. 59, 758–765 (2002).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  31. Mendell, J. R. et al. Evidence for central nervous system demyelination in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 37, 1291–1294 (1987).

    Article  CAS  PubMed  Google Scholar 

  32. Sharma, K. R. et al. Chronic inflammatory demyelinating polyradiculoneuropathy associated with multiple sclerosis. J. Clin. Neuromuscul. Dis. 9, 385–396 (2008).

    Article  PubMed  Google Scholar 

  33. Dyck, P. J., Swanson, C. J., Low, P. A., Bartleson, J. D. & Lambert, E. H. Prednisone-responsive hereditary motor and sensory neuropathy. Mayo Clin. Proc. 57, 239–246 (1982).

    CAS  PubMed  Google Scholar 

  34. Notturno, F. et al. Susceptibility to chronic inflammatory demyelinating polyradiculoneuropathy is associated to polymorphic GA repeat in the SH2D2A gene. J. Neuroimmunol. 197, 124–127 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Neurology 41, 617–618 (1991).

  36. Odaka, M., Yuki, N. & Hirata, K. Patients with chronic inflammatory demyelinating polyneuropathy initially diagnosed as Guillain–Barré syndrome. J. Neurol. 250, 913–916 (2003).

    Article  PubMed  Google Scholar 

  37. Ruts, L., van Koningsveld, R. & van Doorn, P. A. Distinguishing acute-onset CIDP from Guillain–Barré syndrome with treatment related fluctuations. Neurology 65, 138–140 (2005).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  39. Alshekhlee, A., Basiri, K., Miles, J. D., Ahmad, S. A. & Katirji, B. Chronic inflammatory demyelinating polyneuropathy associated with tumor necrosis factor-α antagonists. Muscle Nerve 41, 723–727 (2010).

    Article  PubMed  Google Scholar 

  40. Bromberg, M. B. Review of the evolution of electrodiagnostic criteria for CIDP. Muscle Nerve 43, 780–794 (2011).

    Article  PubMed  Google Scholar 

  41. Brannagan, T. H. 3rd. The current diagnosis of CIDP: the need for biomarkers. J. Peripher. Nerv. Syst. 16, 3–13 (2011).

    Article  PubMed  Google Scholar 

  42. Lewis, R. A. & Sumner, A. J. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology 32, 592–596 (1982).

    Article  CAS  PubMed  Google Scholar 

  43. 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 

  44. Vital, C. et al. Chronic inflammatory demyelinating polyneuropathy: immunopathological and ultrastructural study of peripheral nerve biopsy in 42 cases. Ultrastruct. Pathol. 24, 363–369 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Adachi, Y. et al. Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient. Neuroradiology 53, 3–11 (2011).

    Article  PubMed  Google Scholar 

  46. Nicolas, G. et al. Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 25, 26–30 (2002).

    Article  PubMed  Google Scholar 

  47. Van den Bergh, P. Y. & Pieret, F. Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 29, 565–574 (2004).

    Article  PubMed  Google Scholar 

  48. Magda, P. et al. Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with CIDP. Arch. Neurol. 60, 1755–1759 (2003).

    Article  PubMed  Google Scholar 

  49. Chan, Y. C. et al. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy. J. Neurol. Neurosurg. Psychiatry 77, 114–116 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Haq, R. U. et al. Chronic inflammatory demyelinating polyradiculoneuropathy—a study of proposed electrodiagnostic and histologic criteria. Arch. Neurol. 57, 1745–1750 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Thaisetthawatkul, P., Logigian, E. L. & Herrmann, D. N. Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy. Neurology 59, 1526–1532 (2002).

    Article  PubMed  Google Scholar 

  52. De Sousa, E. A, Chin, R. L., Sander, H. W., Ltob, N. & Brannagean, T. H. 3rd. Demyelinating findings in typical and atypical CIDP: sensitivity and specificity. J. Clin. Neuromusc. Dis. 10, 163–169 (2009).

    Article  Google Scholar 

  53. Rajabally, Y. A. et al. Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study. J. Neurol. Neurosurg. Psychiatry. 80, 1364–1368 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. 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 

  55. Bird, S. J., Brown, M. J., Shy, M. E. & Scherer, S. S. Chronic inflammatory demyelinating polyneuropathy associated with malignant melanoma. Neurology 46, 822–824 (1996).

    Article  CAS  PubMed  Google Scholar 

  56. Tsuchida, T., Saxton, R. E., Morton, D. L. & Irie, R. F. Gangliosides of human melanoma. Cancer 63, 1166–1174 (1989).

    Article  CAS  PubMed  Google Scholar 

  57. Weiss, M. D. et al. Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma. Neurology 51, 1738–1741 (1998).

    Article  CAS  PubMed  Google Scholar 

  58. Kiefer, R. et al. Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies. J. Neurol. Neurosurg. Psychiatry 69, 362–368 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Murata, K. & Dalakas, M. C. Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and their mRNAs in chronic inflammatory demyelinating polyneuropathy. Brain 123, 1660–1666 (2000).

    Article  PubMed  Google Scholar 

  60. Hu, W. et al. Expression of CD28-related costimulatory molecule and its ligand in inflammatory neuropathies. Neurology 68, 277–282 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Salomon, B. et al. Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice. J. Exp. Med. 194, 677–684 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chi, L. J. et al. Distribution of Th17 cells and Th1 cells in peripheral blood and cerebrospinal fluid in chronic inflammatory demyelinating polyradiculoneuropathy. J. Peripher. Nerv. Syst. 15, 345–356 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Chi, L. J., Wang, H. B. & Wang, W. Z. Impairment of circulating CD4+CD25+ regulatory T cells in patients with chronic inflammatory demyelinating polyradiculoneuropathy. J. Peripher. Nerv. Syst. 13, 54–63 (2008).

    Article  CAS  PubMed  Google Scholar 

  64. Sanvito, L., Makowska, A., Gregson, N., Nemni, R. & Hughes, R. A. Circulating subsets and CD4+CD25+ regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy. Autoimmunity 42, 667–677 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. 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 

  66. 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 

  67. Mahad, D. J., Howell, S. J. & Woodroofe, M. N. Expression of chemokines in cerebrospinal fluid and serum of patients with chronic inflammatory demyelinating polyneuropathy. J. Neurol. Neurosurg. Psychiatry 73, 320–323 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Maimone, D., Annunziata, P., Simone, I. L., Livrea, P. & Guazzi, G. C. Interleukin-6 levels in the cerebrospinal fluid and serum of patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J. Neuroimmunol. 47, 55–61 (1993).

    Article  CAS  PubMed  Google Scholar 

  69. Oka, N. et al. Expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) in chronic inflammatory demyelinating polyneuropathy. Neurology 44, 946–950 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Renaud, S. et al. Gene expression profiling in chronic inflammatory demyelinating polyneuropathy. J. Neuroimmunol. 159, 203–214 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Lee, G., Xiang, Z., Brannagan, T. H. 3rd, Chin, R. L. & Latov, N. Differential gene expression in chronic inflammatory demyelinating polyneuropathy (CIDP) skin biopsies. J. Neurol. Sci. 290, 115–122 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Yan, W. X., Taylor, J., Andrias-Kauba, S. & Pollard, J. D. Passive transfer of demyelination by serum or IgG from chronic inflammatory demyelinating polyneuropathy patients. Ann. Neurol. 47, 765–775 (2000).

    Article  CAS  PubMed  Google Scholar 

  73. Dalakas, M. C. & Engel, W. K. Immunoglobulin and complement deposits in nerves of patients with chronic relapsing polyneuropathy. Arch. Neurol. 37, 637–640 (1980).

    Article  CAS  PubMed  Google Scholar 

  74. Ilyas, A. A., Mitchen, F. A., Dalakas, M. C., Chen, Z. W. & Cook, S. D. Antibodies to acidic glycolipids in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy. J. Neurol. Sci. 107, 1111–1121 (1992).

    Article  Google Scholar 

  75. Tagawa, Y., Yuki, N. & Hirata, K. Anti-SGPG antibody in CIDP: a nosological position of IgM anti-MAG/SGPG antibody-associated neuropathy. Muscle Nerve 23, 895–899 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Yan, W. X., Archelos, J. J., Hartung, H. P. & Pollard, J. D. P0 protein is a target antigen in chronic inflammatory demyelinating polyradiculoneuropathy. Ann. Neurol. 50, 286–292 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Dalakas, M., Houff, S. A., Engel, W. K., Madden, D. L. & Sever, J. L. CSF monoclonal bands in chronic relapsing polyneuropathy. Neurology 30, 864–867 (1980).

    Article  CAS  PubMed  Google Scholar 

  78. Tackenberg, B. et al. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc. Natl Acad. Sci. USA 106, 4788–4792 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Cifuentes-Diaz, C. et al. Nodes of Ranvier and paranodes in chronic acquired neuropathies. PLoS ONE 6, e14533 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lonigro, A. & Devaux, J. J. Disruption of neurofascin and gliomedin at nodes of Ranvier precedes demyelination in experimental allergic neuritis. Brain 132, 260–273 (2009).

    Article  PubMed  Google Scholar 

  81. Pollard, J. D. & Armati, P. J. CIDP—the relevance of recent advances in Schwann cell/axonal neurobiology J. Peripher. Nerv. Syst. 16, 15–23 (2011).

    Article  Google Scholar 

  82. Yan, W. X., Mathey, E., Yiannikas, C. & Pollard, J. Antineurofascin antibodies are present in patients with peripheral demyelinating neuropathies and mediate changes in nerve conduction in animals. J. Peripher. Nerv. Syst. 15, 288–289 (2010).

    Google Scholar 

  83. Iijima, M. et al. Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP. Neurology 73, 1348–1352 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Dyck, P. J. et al. Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment. Ann. Neurol. 11, 136–141 (1982).

    Article  CAS  PubMed  Google Scholar 

  85. Hughes, R. et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann. Neurol. 50, 195–201 (2001).

    Article  CAS  PubMed  Google Scholar 

  86. Muley, S. A., Kelkar, P. & Parry, G. J. Treatment of chronic inflammatory demyelinating polyneuropathy with pulsed oral steroids. Arch. Neurol. 65, 1460–1464 (2008).

    Article  PubMed  Google Scholar 

  87. 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 

  88. Lopate, G., Pestronk, A. & Al-Lozi, M. Treatment of chronic inflammatory demyelinating polyneuropathy with high-dose intermittent intravenous methylprednisolone. Arch. Neurol. 62, 249–254 (2005).

    Article  PubMed  Google Scholar 

  89. Mendell, J. R. et al. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 56, 445–449 (2001).

    Article  CAS  PubMed  Google Scholar 

  90. Hahn, A. F. Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. Neurology 51 (6 Suppl. 5), S16–S21 (1998).

    Article  CAS  PubMed  Google Scholar 

  91. Vermeulen, M. et al. Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study. J. Neurol. Neurosurg. Psychiatry 56, 36–39 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Dyck, P. J. et al. A plasma exchange versus immune globulin infusion trial in chronic inflamatory demyelinating polyradiculoneuropathy. Ann. Neurol. 36, 838–845 (1994).

    Article  CAS  PubMed  Google Scholar 

  93. van Doorn, P. A., Brand, A., Strengers, P. F., Meulstee, J. & Vermeulen, M. High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study. Neurology 40, 209–212 (1990).

    Article  CAS  PubMed  Google Scholar 

  94. Hughes, R. A. C. 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 

  95. Merkies, I. S. et al. Health-related quality-of-life improvements in CIDP with immune globulin IV 10%: the ICE Study. Neurology 72, 1337–1344 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Bril, V. et al. Electrophysiologic correlations with clinical outcomes in CIDP. Muscle Nerve 42, 492–497 (2010).

    Article  PubMed  Google Scholar 

  97. Latov, N. et al. Timing and course of clinical response to intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. Arch. Neurol. 67, 802–807 (2010).

    Article  PubMed  Google Scholar 

  98. Lee, D. H. et al. Subcutaneous immunoglobulin infusion: a new therapeutic option in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 37, 406–409 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. Dyck, P. J. et al. Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy. N. Engl. J. Med. 314, 461–465 (1986).

    Article  CAS  PubMed  Google Scholar 

  100. Hahn, A. F. et al. Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double blind, sham-controlled, cross-over study. Brain 119, 1055–1066 (1996).

    Article  PubMed  Google Scholar 

  101. Hughes, R., Swan, A. & Doorn, P. Cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD003280. doi: 10.1002/14651858.CD003280 (2003).

  102. Mahdi-Rodgers, M., Swan, A. V., van Doorn, P. A. & Hughes, R. A. C. Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for CIDP. Cochrane Database of Systematic Reviews, Issue 11. Art. No.: CD003280. doi: 10.1002/14651858.CD003280.pub3 (2010).

  103. 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 

  104. Brannagan, T. H. 3rd et al. High-dose cyclophosphamide without stem-cell rescue for refractory CIDP. Neurology 58, 1856–1858 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Gladstone, D. E., Prestrud, A. A. & Brannagan, T. H. 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 

  106. 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 

  107. Gorson, K. C., Amato, A. A. & Ropper, A. H. Efficacy of mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy. Neurology 63, 715–717 (2004).

    Article  CAS  PubMed  Google Scholar 

  108. 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 

  109. Barnett, M. H., Pollard, J. D., Davies, L. & McLeod, J. G. Cyclosporin A in resistant chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 21, 454–460 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  111. 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).

  112. Dalakas, M. C. Therapeutic targets in patients with inflammatory myopathies: present approaches and a look to the future. Neuromuscul. Disord. 16, 223–236 (2006).

    Article  PubMed  Google Scholar 

  113. 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 

  114. Kazmi, M. A., Mahdi-Rogers, M. & Sanvito, L. Chronic inflammatory demyelinating polyradiculoneuropathy: a role for haematopoietic stem cell transplantation? Autoimmunity 41, 611–615 (2008).

    Article  CAS  PubMed  Google Scholar 

  115. 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 

  116. Dalakas, M. C. B cells as therapeutic targets in autoimmune neurological disorders. Nat. Clin. Pract. Neurol. 4, 557–567 (2008).

    Article  CAS  PubMed  Google Scholar 

  117. Dalakas, M. C. Inhibition of B cell functions: implications for neurology. Neurology 70, 2252–2260 (2008).

    Article  CAS  PubMed  Google Scholar 

  118. 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 

  119. Münch, 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  PubMed  CAS  Google Scholar 

  120. Briani, C. et al. Rituximab-responsive CIDP. Eur. J. Neurol. 11, 788 (2004).

    Article  CAS  PubMed  Google Scholar 

  121. Kosmidis, M. & Dalakas, M. C. Practical considerations on the use of rituximab in autoimmune neurological disorders. Ther. Adv. Neurol. Disord. 3, 93–105 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Fitzpatrick, A. M. et al. An open label clinical trial of complement inhibition in multifocal motor neuropathy. J. Peripher. Nerv. Syst. 16, 84–91 (2011).

    Article  PubMed  Google Scholar 

  123. Wolf, C. et al. Natalizumab treatment in a patient with chronic inflammatory demyelinating polyneuropathy. Arch. Neurol. 67, 881–883 (2010).

    Article  PubMed  Google Scholar 

  124. Dalakas, M. C. Advances in chronic inflammatory demyelinating polyneuropathy: disease variants and inflammatory response mediators and modifiers. Curr. Opin. Neurol. 12, 403–409 (1999).

    Article  CAS  PubMed  Google Scholar 

  125. Dalakas, M. C. Potential biomarkers for monitoring therapeutic responses to IVIg and other therapies in CIDP. J. Peripher. Nerv. Syst. 16, 63–67 (2011).

    Article  PubMed  Google Scholar 

  126. Comi, C. et al. Fas-mediated T-cell apoptosis is impaired in patients with chronic inflammatory demyelinating polyneuropathy. J. Peripher. Nerv. Syst. 11, 53–60 (2006).

    Article  CAS  PubMed  Google Scholar 

  127. Tanighuchi, J. et al. Inflammatory demyelinating polyneuropathy sera inhibit axonal growth of mouse dorsal root ganglion neurons by activation of Rho-kinase. Ann. Neurol. 66, 694–697 (2009).

    Article  Google Scholar 

  128. 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 

  129. Hartung, H. P., Lehmann, H. C. & Willison, H. G. Establishing common clinical research standards for CIDP. Nat. Rev. Neurol. 7, 250–251 (2011).

    Article  PubMed  Google Scholar 

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Acknowledgements

L. Barclay, freelance writer and reviewer, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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The author has received speaking honoraria or consulting fees for serving on the steering committees of the following companies: Biogen, Novartis, Octapharma, Talecris/Grifol.

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Dalakas, M. Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol 7, 507–517 (2011). https://doi.org/10.1038/nrneurol.2011.121

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