below 100 pgiml may be abnormal, w e recommend the use of more sensitive radio- and immunoenzymatic tests, able to detect less than 4 pgiml of TNF-a [e.g., 91. Supplementation of freshly obtained samples with protease inhibitors may also be useful in evaluating levels of circulating human cytokines.

*Clinics Neurologica IV IRCCS San Ragaele Klinica delle Malattie lnfettive Ospedzle L. Sacco Universitridi Milano Milano, Italy $lstituto Neurologico “Fondazione Mondino” DClinica dele Malattie lnfttive Universita‘ di Pavia Pavia, Italy ’Divisione Malattie Infttive Ospedale Regionale Bolzano, Italy

Referencej 1. Grimaldi LME, Martino GV, Franciotta DM, et al. Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1infected patients with central nervous system involvement. Ann Neurol 1991;29:21-25 2. Aulitzky WE, Aulitzky WK, Frick J, et al. Treatment of cancer patients with recombinant interferon-gamma induces release of endogenous tumor necrosis factor-alpha. Immunobiology 1990; 1801385-394 3. Reddy MM, McKinley G, Englard A, Grieco MH. Effect of azidothymidine (AZT) on HIV p24 antigen, beta 2-microglobulin, neopterin, soluble CD8, soluble interleukin-2 receptor and tumor necrosis facror alpha levels in patients with AIDS-related complex or AIDS. Int J Immunopharmacol 1990;12:737-741 4. de la Mata M, Meager A, Rolando N, et al. Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection. Clin Exp Imrnunol 1990;82:479-484 5. Chang HR, Grau GE, Pechere JC. Role of TNF and IL-1 in infections with tomplusma gondii. Immunology 1990;69:33-37 6. Aderka D, Holtman H, Toker L, et al. Tumor necrosis factor induction by Sendai virus. J Immunol 1986;136:2938-2942 7 . Franciotta DM, Grimaldi LME, Martino GV, et al. Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis. Ann Neurol 1989;26:787-789 8. Maimone D, Gregory S , Arnason BGW, Reder AT. Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J Neuroimmunol 1991;32:67-74 9. Tsukada N, Miyagi K, Matsuda M, et al. Tumor necrosis factor and interleukin-1 in the CSF and sera of patients with multiple sclerosis. J Neurol Sci 1991;102:230-234 10. Sharief MK, Henrger R. Association between tumor necrosis factor-u and disease progression in patients with multiple sclerosis. N Engl J Med 1991;325:467-472 11. Gallo P, Piccinno MG, Krzalic L, Tavolato B. Tumor necrosis factor alpha (TNFu) and neurological diseases. Failure in detecting TNFu in the cerebrospinal fluid from patients with rnultiple sclerosis, AIDS dementia complex, and brain tumours. 3 Neuroimmunol 1989;23:41-44 12. Frederiksen JL,Hansen MB. Tumor necrosis factor in patients with multiple sclerosis and/or acute optic neuritis. Cytokine 1991;3: 149

Monoclonal Gammopathy and Neuropathy -

Alan Pestronk, MD There are two oversights that reduce the usefulness of the paper by Gosselin and colleagues (11. First, the paper should contain enough information to allow other investigators t o repeat it. Unfortunately, there is n o description of the technique used or data obtained in measuring M-protein reactivity t o myelin-associated glycoprotein (MAG). Was ELISA, Western blotting, or thin layer chromatography used? Was MAG or sulfated glucuronyl paragloboside (SGPG) used as a substrate? They are not equivalent. What titers were considered positive? How was it determined that the M-protein itself was reactive with MAG or S G P G ? Second, assuming the anti-MAG data are correct, the authors overlook results in their o w n paper in reaching conclusions in the discussion and abstract. The main distinctive feature of anti-MAG neuropathies is demyelination. Several recent studies [2-61 (none of which are cited by the authors) support the association of demyelination with anti-MAG IgM-monoclonal gammopathy of undetermined significance (MGUS). The electrophysiological results of this paper support that conclusion. The median motor conduction velocity ( p = 0.003) and the distal latency ( p = 0.02) correlated with anti-MAG neuropathies. These results are ignored in statements that neuropathies associated with MAG-reactive IgM-MGUS are not significantly different from those without anti-MAG reactivity.

Department of Neurology Washington University St Louis, MO References 1. Gosselin S, Kyle RA, Dyck PJ. Neuropathy associated with monoclonal gammopathies of undetermined significance. Ann Neurol 1991;30:54-6 1 2. Nobile-Orazio E, Francomano E, Daverio R, et al. Anti-myelin associated glycoprotein IgM antibody titers in neuropathy associated with macroglobulinemia. Ann Neurol 1989;26:543-550 3. Kelly JJ Jr. The electrodiagnostic findings in polyneuropathies associated with IgM monoclonal gammopathies. Muscle Nerve 1990;13:1113- 1117 4. Pestronk A, Li F, Griffin J, et al. Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelinassociated glycoprotein. Neurology 1991;41:357-362 5. Y u RK, Ariga T, Kohriyama T, et al. Autoimmune mechanisms in peripheral neuropathies. Ann Neurol l990;27:S30-S35 6. Trojaborg W, Galassi G , Hays AP, et al. Electrophysiologicstudy of experimental demyelination induced by serum of patients with IgM M proteins and neuropathy. Neurology 1989;39:15811586

Annals of Neurology

Vol 31 No 6 June 1992 689