Abstract
The inflammatory neuropathies (chronic inflammatory demyelinating polyradiculoneuropathy [CIDP], Guillain-Barré syndrome [GBS] and multifocal motor neuropathy [MMN]) affect only one to two individuals per 100 000 of the population, but result in major disability and impairment.
Intravenous immunoglobulin (IVIg) can be used as an initial treatment for CIDP, GBS and MMN. While plasma exchange and corticosteroids can also be used initially, they are not as uniformly effective for each of these disorders as IVIg. Substituting corticosteroids, plasma exchange or immunosuppressants may be appropriate for patients not responding to initial IVIg therapy, and combination therapy may be needed in some patients.
There are no data from controlled clinical trials of long-term management strategies for CIDP and MMN; however, empirical evidence suggests that a positive long-term response to IVIg can be achieved by increasing the initial dose or its frequency of administration. Corticosteroids and immunosuppressants may be appropriate in some patients with CIDP. Adverse events with IVIg are usually mild and not treatment limiting; however, patients do need to be monitored for uncommon, but serious, adverse events such as renal insufficiency, stroke and thromboembolic events. Nevertheless, the safety profile of IVIg is exceptional relative to the potential complications of other long-term treatments for CIDP and MMN, especially corticosteroids and immunosuppressants.
Predictors of response have been reported for each of the neuropathies, and until controlled clinical trials provide evidence on which to base treatment strategies, effective management will require individualising therapy according to patient response.
Similar content being viewed by others
Notes
1. The GBS disability scale is: 0 = healthy; 1 = minor symptoms and signs, capable of running; 2 = able to walk 10 metres across an open space without assistance, walking frame or stick, but unable to run; 3 = able to walk 10 metres across an open space with the help of one person and waist-level walking frame, sticks or stick; 4 = chair-bound, bedbound, unable to walk as in 3; 5 = requiring assisted ventilation.
2 The modified Rankin scale score is: 0 = no symptoms at all; 1 = no significant disability despite symptoms, able to carry out all usual duties and activities; 2 = slight disability, unable to carry out all previous activities but able to look after own affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance; 5 = severe disability, bedridden, incontinent and requiring constand nursing care and attention; 6 = dead.
References
Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular disease. JAMA 2004; 291: 2367–75
Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001; 345: 747–55
Rees JH, Thompson RD, Smeeton NC, et al. Epidemiological study of Guillain-Barre syndrome in southeast England. J Neurol Neurosurg Psychiatry 1998; 64: 74–7
Hughes RAC, Wijdicks EFM, Barohn R, et al. Practice parameter: Immunotherapy for Guillain-Barré syndrome. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003; 61: 736–40
Hughes RAC, Raphael JC, Swan AV, et al. Intravenous immunoglobulin for Guillain-Barré syndrome (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2003
Kleyweg RP, van der Meche FG, Schmitz PI. A randomized trial comparing intravenous immunoglobulin and plasma exchange in Guillain-Barre syndrome. Transfus Sci 1994; 15: 389–92
Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of plasma exchange, i.v. immunoglobulin and combined treatments in Guillain-Barré syndrome. Lancet 1997; 349: 225–30
Hughes RAC, van der Meche FGA. Corticosteroids for treating Guillain-Barré syndrome (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2001
van Koningsveld R, Schmitz PI, Meche FG, et al. Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomized trial. Lancet 2004; 363: 192–6
Pritchard J, Gray IA, Idrissova ZR, et al. A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barré syndrome. Neurology 2003; 61: 1282–4
Spies JM, Sheikh KA. Management of Guillain-Barré syndrome. Expert Rev Neurother 2001; 1: 119–29
French Cooperative Group on Plasma Exchange in Guillain-Barre Syndrome. Plasma exchange in Guillain-Barre syndrome: one-year follow-up. Ann Neurol 1992; 32: 94–7
van den Bergh PY, Pieret F. Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2004; 29: 565–74
Kaplan RL, Albers JW. Treatment of chronic inflammatory demyelinating polyneuropathy. Expert Rev Neurother 2003; 3: 233–46
Hahn AF, Bolton CF, Zochodne D, et al. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study. Brain 1996; 119 (pt 4): 1067–77
Iijima M, Yamamoto M, Hirayama M, et al. Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. Neurology 2005; 64: 1471–5
van Doorn PA, Dippel DWJ, van Burken MMG, et al. Long-term IV immunoglobulin treatment in CIDP. J Peripher Nerv Syst 2003; 8: S1–78
Isoardo G, Rota E, Ciaramitaro P, et al. Predictive value of clinical, electrophysiological and immunological features for response to IVIg in patients with CIDP [abstract]. J Peripher Nerv Syst 2004; 9: 107
Good JL, Chehrenama M, Mayer RF, et al. Pulse cyclophosphamide therapy in chronic inflammatory demyelinating polyneuropathy. Neurology 1998; 51: 1735–8
Bouchard C, Lacroix C, Plante V, et al. Clinicopathologic findings and prognosis of chronic inflammatory demyelinating polyneuropathy. Neurology 1999; 52: 498–503
Sghirlanzoni A, Solari A, Ciano C, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: long-term course and treatment of 60 patients. Neurol Sci 2000; 21: 31–7
van Schaik IN, Winer JB, de Haan R, et al. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review. Lancet Neurol 2002; 1: 491–8
Mehndiratta MM, Hughes RAC. Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2003
Mendell JR, Barohn RJ, Freimer ML, et al., Working Group on Peripheral Neuropathy. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 2001; 56: 445–9
Thompson N, Choudhary P, Hughes RA, et al. A novel trial design to study the effect of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol 1996; 243: 280–5
Vermeulen M, van Doom PA, Brand A, et al. Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry 1993; 56: 36–9
Kubori T, Mezaki T, Kaji R, et al. The clinical usefulness of high-dose intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. No To Shinkei 1999; 51: 127–35
Venance SL, Koopman WJ, Hahn AF. Treatment approaches and long-term outcome in a Canadian cohort (1972–2002) with chronic inflammatory demyelinating polyneuropathy (CIDP). J Peripher Nerv Syst 2003; 8: S1–78
McCrone P, Chisholm D, Knapp M, et al. Cost-utility analysis of intravenous immunoglobulin and prednisolone for chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol 2003; 10: 687–94
Brannagan III TH, Pradhan A, Heiman-Patterson T, et al. Highdose cyclophosphamide without stem-cell rescue for refractory CIDP. Neurology 2002; 58: 1856–8
Gorson KC, Amato AA, Ropper AH. Efficacy of mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy. Neurology 2004; 63: 715–7
Schweikert K, Radziwill, Fuhr P, et al. Mycophenolate mofetil for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an open-label study. Presented at the 13th Meeting of the European Neurological Society; 2003 Jun 14–18; Istanbul
Umapathi T, Hughes RAC. Mycophenolate in treatment-resistant inflammatory neuropathies. Eur J Neurol 2002; 9: 683–5
Mowzoon N, Sussman A, Bradley WG. Mycophenolate (Cellcept) treatment of myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and inclusion body myositis. J Neurol Sci 2001; 185: 19–22
Spies JM, Pollard JD. Mycophenolate mofetil is effective therapy for refractory CIDP. J Peripher Nerv Syst 2003; 8: S1–78
Sabatelli M, Quaranta L, Madia F, et al. Interferon alpha may benefit CIDP patients refractory to standard therapies: description of long-term results in 12 patients. Presented at the Peripheral Nerve Society Meeting; 2001 Jun; Tyrol
Cocco E, Mascia MG, Floris GL, et al. CIDP refractory patient treated with interferon beta-1b. Presented at the 13th Meeting of the European Neurological Society; 2003 Jun 14–18; Istanbul
Vallat J-M, Hahn AF, Leger J-M, et al. Interferon beta-1a as an investigational treatment for CIDP. Neurology 2003; 60: S23–8
Ropper AH, Hughes RAC, Cros DP, et al. Design of a dose-ranging study to determine the safety and efficacy of intramuscular interferon beta-1a (Avonex) when used in subjects with chronic inflammatory demyelinating polyradiculoneuropathy. Presented at the American Academy of Neurology Annual Meeting; 2004 Apr 29 San Francisco (CA)
Barnett MH, Pollard JD, Davies L, et al. Cyclosporin A in resistant chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 1998; 21: 454–60
Mahattanakul W, Crawford TO, Griffin JW, et al. Treatment of chronic inflammatory demyelinating polyneuropathy with cyclosporin-A. J Neurol Neurosurg Psychiatry 1996; 60:185–7
Chin RL, Sherman WH, Sander HW, et al. Etanercept (enbrel) therapy for chronic inflammatory demyelinating polyneuropathy. J Neurol Sci 2003; 210: 19–21
Nobile-Orazio E, Cappellari A, Meucci N, et al. Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block. J Neurol Neurosurg Psychiatry 2002; 72: 761–6
Nobile-Orazio E. Multifocal motor neuropathy. J Neuroimmunol 2001; 115: 4–18
van den Berg-Vos RM, Franssen H, Wokke JH, et al. Multifocal motor neuropathy: diagnostic criteria that predict the response to immunoglobulin treatment. Ann Neurol 2000; 48: 919–26
Bouche P, Moulonguet A, Younes-Chennoufi AB, et al. Multifocal motor neuropathy with conduction block: a study of 24 patients. J Neurol Neurosurg Psychiatry 1995; 59: 38–44
Azulay JP, Blin O, Pouget J, et al. Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study. Neurology 1994; 44 (3 pt 1): 429–32
Federico P, Zochodne DW, Hahn AF, et al. Multifocal motor neuropathy improved by IVIg. Randomized, double-blind placebo-controlled, study. Neurology 2000; 55: 1256–62
van den Berg LH, Franssen H, Wokke JHJ. The long-term effect of intravenous immunoglobulin treatment in multifocal motor neuropathy. Brain 1998; 121: 421–8
van den Berg-Vos RM, Franssen H, Visser J, et al. Disease progression in multifocal motor neuropathy. Presented at the Peripheral Nerve Society meeting; 2001 Jun; Tyrol
Leger JM, Chassande B, Musset L, et al. Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study. Brain 2001; 124 (Pt 1): 145–53
van den Berg LH, Kerkhoff H, Oey PL, et al. Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry 1995; 59: 248–52
van den Berg-Vos RM, Franssen H, Visser J, et al. Disease severity in multifocal motor neuropathy and its association with the response to immunoglobulin treatment. J Neurol 2002; 249: 330–6
Leger J-M, Gruwez B, Chassande B, et al. Long-term treatment of multifocal motor neuropathy with persistent conduction blocks: a retrospective study of 43 cases. Presented at the Peripheral Nerve Society Meeting; 2001 Jun; Tyrol
Meucci N, Cappellari A, Barbieri S, et al. Long term effect of intravenous immunoglobulins and oral cyclophosphamide in multifocal motor neuropathy. J Neurol Neurosurg Psychiatry 1997; 63: 765–9
Terenghi F, Cappellari A, Bersano A, et al. How long is IVIg effective in multifocal motor neuropathy? Neurology 2004; 62: 666–8
van den Berg-Vos RM, Franssen H, Wokke JH, et al. Multifocal neuropathy: long-term clinical and electrophysiological assessmnet of intravenous immunoglobulin maintenance treatment. Brain 2002; 125(8): 1875–86
van den Berg-Vos RM, Franssen H, Wokke JH, et al. Multifocal motor neuropathy: four to eight year follow up during maintenance therapy with intravenous immunoglobulins. J Peripher Nerv Syst 2003; 8: S1–78
Terenghi F, Meurcci N, Nobile-Orazio E. Long-term disability in multifocal motor neuropathy and its relation to IVIg therapy. J Peripher Nerv Syst 2003; 8: S1–78
Katz JS, Wolfe GI, Gorson KC. Outcome in multifocal motor neuropathy: what is the risk of developing weakness in new nerve distributions over time? Presented at the American Academy of Neurology Annual Meeting, 2004 Apr 29; San Francisco (CA)
Vucic S, Black KR, Chong PS, et al. Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with long-term IVIg. Neurology 2004; 63: 1264–9
Umapathi T, Hughes RAC, Nobile-Orazio E, et al. Immunosuppressive treatment for multifocal motor neuropathy (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2003
Azulay JP, Rihet P, Pouget J, et al. Long term follw up of multifocal motor neuropathy with conduction block under treatment. J Neurol Neurosurg Psychiatry 1997; 62: 391–4
Estrada-Acosta R, Lestayo-O’Farrill Z, Coba-Morales C. Multifocal motor neuropathy with block of nerve conduction. Report of three cases. Rev Neurol 1999; 29: 130–3
Gutierrez Ronquillo JH, Andrade Machado R, Machado Rojas A, et al. Multifocal motor neuropathy with partial block of nerve conduction. Rev Neurol 2001; 32: 427–30
Koski CL. Therapy of CIDP and related immune-mediated neuropathies. Neurology 2002; 59(12 Suppl. 6): S22–7
Nemni R, Santuccio G, Calabrese E, et al. Efficacy of cyclosporine treatment in multifocal motor neuropathy. J Neurol 2003; 250: 1118–20
van den Berg-Vos RM, van den Berg LH, Franssen H, et al. Treatment of multifocal motor neuropathy with interferon β1A. Neurology 2000; 54: 1518–21
Martina IS, van Doom PA, Schmitz PI, et al. Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies. J Neurol Neurosurg Psychiatry 1999; 66: 197–201
Nobile-Orazio E, Meucci N, Baldini L, et al. Long-term prognosis of neuropathy associated with anti-MAG IgM M-proteins and its relationship to immune therapies. Brain 2000; 123: 710–7
Gorson KC, Ropper AH, Weinberg DH, et al. Treatment experience in patients with anti-myelin-associated glycoprotein neuropathy. Muscle Nerve 2001; 24: 778–86
Dalakas MC, Quarles RH, Farrer RG, et al. A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy. Ann Neurol 1996; 40: 792–5
Levine TD, Pestronk A. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology 1999; 52: 1701–4
Latov N, Sherman WH, Vlahide G. Therapy of neuropathy associated with anti-MAG IgM monoclonal gammopathy with rituxan [abstract]. Neurology 1999; 52: A551
Pestronk A, Florence J, Miller T, et al. Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry 2003; 74: 485–9
Renaud S, Gregor M, Fuhr P, et al. Rituximab in the treatment of polyneuropathy associated with anti-MAG antibodies. Muscle Nerve 2003; 27: 611–5
Eibl MM. Intravenous immunoglobulins in neurological disorders: safety issues. Neurol Sci 2003; 24Suppl. 4: S222–6
Stangel M, Kiefer R, Pette M, et al. Side effects of intravenous immunoglobulins in neurological autoimmune disorders. J Neurol 2003; 250: 818–21
Wittstock M, Benecke R, Zettl WK. Therapy with intravenous immunoglobulins: complications and side effects. Eur Neurol 2003; 50: 172–5
Pierce LF, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfus Med Rev 2003; 17: 241–51
Caress JB, Cartwright MS, Donofrio PD, et al. The clinical features of 16 cases of stroke associated with administration of IVIg. Neurology 2003; 60: 1822–4
Gras V, Andrejak M, Decocq G. Acute renal failure associated with intravenous immunoglobulins. Pharmacoepidemiol Drug Saf 1999; 8(S1): S73–8
Acknowledgements
No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koski, C.L. Initial and Long-Term Management of Autoimmune Neuropathies. CNS Drugs 19, 1033–1048 (2005). https://doi.org/10.2165/00023210-200519120-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-200519120-00005