Abstract
Objectives—To report the long term effect of the combined treatment with high dose intravenous immunoglobulins (IVIg) and oral cyclophosphamide (CTX) in patients with multifocal motor neuropathy, and to determine whether the association of oral CTX in these patients may help to delay and, possibly, suspend IVIg infusions. METHODS—Six patients with multifocal motor neuropathy responding to an initial course of IVIg (0.4 g/kg/day for five consecutive days) were followed up for 37 to 61 (mean 47) months. All patients were subsequently treated with periodic IVIg infusions (0.4 g/kg/day for two days at clinical worsening) and oral CTX (1-3 mg/kg/day). Improvement was assessed using the Rankin disability scale, a functional impairment scale for upper and lower limbs, and the MRC rating scale on the 20 most affected muscles. Electrophysiological and antiglycolipid antibody studies were performed before treatment, then yearly during follow up. RESULTS—All patients improved during treatment and, by the end of follow up or before worsening after therapy suspension, the median Rankin (P=0.0335) and upper (P=0.0015) and lower limb (P=0.0301) impairment scores and the mean MRC (P=0.0561) score were improved. By that time the number of nerves with partial motor conduction block was reduced (P=0.0197) and antiglycolipid antibody titres had decreased in all but one patient. All patients required periodic IVIg infusions to maintain improvement but, after three to seven months of oral CTX, the interval between IVIg infusions could be progressively prolonged until, in three patients, both treatments could be stopped for up to two years before clinical worsening. The main complications, both related to oral CTX, were haemorrhagic cystitis in two patients and persistent amenorrhea in one patient. Conclusions—IVIg can induce and maintain improvement in multifocal motor neuropathy but does not eradicate the disease. Oral CTX may help to induce a sustained remission but it is not devoid of side effects and might therefore be reserved for patients with multifocal motor neuropathy who require frequent IVIg infusions to maintain improvement.
Full Text
The Full Text of this article is available as a PDF (128.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Azulay J. P., Blin O., Pouget J., Boucraut J., Billé-Turc F., Carles G., Serratrice G. Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study. Neurology. 1994 Mar;44(3 Pt 1):429–432. doi: 10.1212/wnl.44.3_part_1.429. [DOI] [PubMed] [Google Scholar]
- Bouche P., Moulonguet A., Younes-Chennoufi A. B., Adams D., Baumann N., Meininger V., Léger J. M., Said G. Multifocal motor neuropathy with conduction block: a study of 24 patients. J Neurol Neurosurg Psychiatry. 1995 Jul;59(1):38–44. doi: 10.1136/jnnp.59.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cappellari A., Nobile-Orazio E., Meucci N., Scarlato G., Barbieri S. Multifocal motor neuropathy: a source of error in the serial evaluation of conduction block. Muscle Nerve. 1996 May;19(5):666–669. doi: 10.1002/(SICI)1097-4598(199605)19:5<666::AID-MUS19>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
- Chad D. A., Hammer K., Sargent J. Slow resolution of multifocal weakness and fasciculation: a reversible motor neuron syndrome. Neurology. 1986 Sep;36(9):1260–1263. doi: 10.1212/wnl.36.9.1260. [DOI] [PubMed] [Google Scholar]
- Chaudhry V., Corse A. M., Cornblath D. R., Kuncl R. W., Drachman D. B., Freimer M. L., Miller R. G., Griffin J. W. Multifocal motor neuropathy: response to human immune globulin. Ann Neurol. 1993 Mar;33(3):237–242. doi: 10.1002/ana.410330303. [DOI] [PubMed] [Google Scholar]
- Chaudhry V., Corse A. M., Cornblath D. R., Kuncl R. W., Freimer M. L., Griffin J. W. Multifocal motor neuropathy: electrodiagnostic features. Muscle Nerve. 1994 Feb;17(2):198–205. doi: 10.1002/mus.880170211. [DOI] [PubMed] [Google Scholar]
- Elliott J. L., Pestronk A. Progression of multifocal motor neuropathy during apparently successful treatment with human immunoglobulin. Neurology. 1994 May;44(5):967–968. doi: 10.1212/wnl.44.5.967. [DOI] [PubMed] [Google Scholar]
- Feldman E. L., Bromberg M. B., Albers J. W., Pestronk A. Immunosuppressive treatment in multifocal motor neuropathy. Ann Neurol. 1991 Sep;30(3):397–401. doi: 10.1002/ana.410300312. [DOI] [PubMed] [Google Scholar]
- Kaji R., Shibasaki H., Kimura J. Multifocal demyelinating motor neuropathy: cranial nerve involvement and immunoglobulin therapy. Neurology. 1992 Mar;42(3 Pt 1):506–509. doi: 10.1212/wnl.42.3.506. [DOI] [PubMed] [Google Scholar]
- Kornberg A. J., Pestronk A. Chronic motor neuropathies: diagnosis, therapy, and pathogenesis. Ann Neurol. 1995 May;37 (Suppl 1):S43–S50. doi: 10.1002/ana.410370706. [DOI] [PubMed] [Google Scholar]
- Lange D. J., Trojaborg W., Latov N., Hays A. P., Younger D. S., Uncini A., Blake D. M., Hirano M., Burns S. M., Lovelace R. E. Multifocal motor neuropathy with conduction block: is it a distinct clinical entity? Neurology. 1992 Mar;42(3 Pt 1):497–505. doi: 10.1212/wnl.42.3.497. [DOI] [PubMed] [Google Scholar]
- Levine L. A., Richie J. P. Urological complications of cyclophosphamide. J Urol. 1989 May;141(5):1063–1069. doi: 10.1016/s0022-5347(17)41173-6. [DOI] [PubMed] [Google Scholar]
- Nobile-Orazio E., Carpo M., Legname G., Meucci N., Sonnino S., Scarlato G. Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. Neurology. 1990 Nov;40(11):1747–1750. doi: 10.1212/wnl.40.11.1747. [DOI] [PubMed] [Google Scholar]
- Nobile-Orazio E., Meucci N., Barbieri S., Carpo M., Scarlato G. High-dose intravenous immunoglobulin therapy in multifocal motor neuropathy. Neurology. 1993 Mar;43(3 Pt 1):537–544. doi: 10.1212/wnl.43.3_part_1.537. [DOI] [PubMed] [Google Scholar]
- Nobile-Orazio E. Multifocal motor neuropathy. J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):599–603. doi: 10.1136/jnnp.60.6.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parry G. J., Clarke S. Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease. Muscle Nerve. 1988 Feb;11(2):103–107. doi: 10.1002/mus.880110203. [DOI] [PubMed] [Google Scholar]
- Pestronk A., Cornblath D. R., Ilyas A. A., Baba H., Quarles R. H., Griffin J. W., Alderson K., Adams R. N. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol. 1988 Jul;24(1):73–78. doi: 10.1002/ana.410240113. [DOI] [PubMed] [Google Scholar]
- Roth G., Rohr J., Magistris M. R., Ochsner F. Motor neuropathy with proximal multifocal persistent conduction block, fasciculations and myokymia. Evolution to tetraplegia. Eur Neurol. 1986;25(6):416–423. doi: 10.1159/000116045. [DOI] [PubMed] [Google Scholar]
- Van den Berg L. H., Franssen H., Wokke J. H. Improvement of multifocal motor neuropathy during long-term weekly treatment with human immunoglobulin. Neurology. 1995 May;45(5):987–988. doi: 10.1212/wnl.45.5.987. [DOI] [PubMed] [Google Scholar]
- Van den Berg L. H., Kerkhoff H., Oey P. L., Franssen H., Mollee I., Vermeulen M., Jennekens F. G., Wokke J. H. Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry. 1995 Sep;59(3):248–252. doi: 10.1136/jnnp.59.3.248. [DOI] [PMC free article] [PubMed] [Google Scholar]