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Are muscle cramps in Isaacs' syndrome triggered by human immunoglobulin?

Ishii et al reported the clinical evaluation of plasma exchange and treatment with high dose intravenous immunoglobulin (IVIg) in a patient with Isaacs' syndrome.' The rationale for either treatment in this syndrome was a possible autoimmune aetiology.2 The differential treatment response was remarkable: after plasma exchange the symptoms of continuous muscle activity almost disappeared, whereas after IVIg treatment muscle cramps gradually increased. The authors state that the reason for this divergence is unclear, and suggest that IVIg may have a similar adverse effect in Isaacs' syndrome as has recently been reported in patients with Guillain-Barre syndrome.' We would like to draw attention to another explanation for the differential treatment response of plasma exchange and IVIg, and propose the possibility of a direct effect of IVIg on muscle cells, causing muscle cramps in the patient with Isaacs' syndrome. Supplying IgG molecules by IVIg administration may induce effects that disappear with IgG elimination by plasma exchange. Recently we investigated the effect of IVIg on normal human muscle cells in culture, and found a dose dependent release of calcium from the sarcoplasmic reticulum (van Engelen, BGM, Benders AAGM, Veerkamp JH, et al. Unpublished data). Because of these in vitro results, we suggest that in vivo the differential effect of plasma exchange and IVIg in Isaacs' syndrome may also be the result of a direct effect of IVIg on muscle, by an TIVIg mediated increase of intracellular calcium and subsequent muscle cramps. Although muscle cramps are generally not reported as adverse effects of IVIg treatment, myalgia, which is difficult to distinguish from muscle cramps, is one of the most frequent side effects of such treatment.4 In addition, in Isaacs' syndrome the increase of muscle cramps after treatment with IVIg might be due to an altered excitability of motor terminals in this syndrome.2 BAZIEL G M VAN ENGELEN AD A GM BENDERS FONS J M GABREELS JACQUES H VEERKAMP Departments ofNeurology and Biochemistry, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands