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Miller Fisher syndrome (MFS), characterised by the clinical triad of ataxia, ophthalmoplegia, and areflexia, is considered to be a variant form of Guillain-Barré syndrome (GBS). Large studies have shown that plasmapheresis1 and immunoglobulin treatment2 are beneficial for treating GBS. Because of the close relation between GBS and MFS, plasmapheresis may prove efficacious for treating MFS and has actually been tried in some cases. Moreover, because antibody to GQ1b is often present in serum from patients with MFS and is suggested to have a role in the pathophysiology of MFS, removing this antibody through plasmapheresis should have beneficial effects on patients with this syndrome. Although several reports have described possible plasmapheresis benefits in treating MFS,3,4 none has compared its clinical effects in patients treated and not treated with plasmapheresis. We conducted a retrospective analysis of 50 consecutive patients with MFS to clarify whether plasmapheresis enhanced the speed of recovery.
Medical records of 53 patients with MFS, seen at Chiba University Hospital or its affiliated hospitals between 1979 and 1999, were reviewed. These patients were described in our previous investigation of the natural course of MFS.5 Criteria for inclusion in the study were the clinical triad of MFS (ataxia, ophthalmoplegia, and areflexia) and acute onset without major limb weakness or other signs suggestive of central nervous system involvement. Three of the 53 patients who initially had the typical clinical triad of MFS later developed profound limb weakness, and GBS was diagnosed. Clinical data for the remaining 50 patients were therefore analysed. Twenty two patients with MFS underwent plasmapheresis with a second filter (Evaflux 3A (Kurare Co Ltd, Kurashiki, Japan) or Immusorber TR-350 (Asahi Medical Co Ltd, Tokyo, Japan)). They received plasmapheresis every other day two to six times (mean 4.1 times). All had given informed consent to receive the treatments. The other 28 patients did not receive plasmapheresis or an intravenous immunoglobulin infusion. The clinical course was charted monthly until the disappearance of symptoms and signs, with focus on the amelioration of ataxia and ophthalmoplegia. The severity of ataxia was evaluated on the Hughes functional grading scale (0, no ataxia; 1, able to run; 2, able to walk 5 m without assistance; 3, able to walk 5 m with assistance; 4, chair bound or bed bound). The two tailed χ2 or Fisher's exact test was used to test the significance of differences in percentage. The Mann-Whitney U test was used to test the differences in medians. Recoveries were assessed from Kaplan-Meier curves.
At entry, there were no significant differences in age, sex, antecedent events, the frequency of bulbar palsy, inability to walk, total ophthalmoplegia, the Hughes grade, and speed of progression (interval between neurological onset and nadir) between the two patient groups. Whether patients were allocated to plasmapheresis or not depended on the different practice of different neurologists and the different time of diagnosis of MFS. Some patients did not receive plasmapheresis because it was not widely used in the early 1980s.1 The time required to resolve ataxia and ophthalmoplegia did not differ significantly for the patient groups with or without plasmapheresis. The chance of recovery from ataxia and ophthalmoplegia on the Kaplan-Meier curve was not affected by whether or not plasmapheresis was received (fig 1). Of the subgroup of patients who had severe disability (inability to walk because of ataxia or complete total ophthalmoplegia) and those with bulbar palsy, the time required to resolve the ataxia and ophthalmoplegia did not differ significantly between those who received plasmapheresis (all underwent plasmapheresis more than four times) and those who did not. Nor did the interval from onset to the start of plasmapheresis affect the speed of the clinical recovery from ataxia and ophthalmoplegia of the patients with MFS. Six months after the onset of neurological symptoms, except for areflexia, almost all the patients with MFS were free from symptoms and signs, irrespective of whether they received plasmapheresis.
Our findings failed to show that plasmapheresis hastens the amelioration of ataxia and ophthalmoplegia in patients with MFS, whereas some reports have suggested the possible efficacy of plasmapheresis treatment for MFS.3,4 Because MFS is a self limiting disease and recovery is spontaneous, a case-control study is needed to evaluate the effects of plasmapheresis treatment. Our findings do not completely negate the efficacy of plasmapheresis in every instance of MFS. On the basis of two cases, Yeh et al4 reported that plasmapheresis is indicated for the treatment of complicated MFS in which there is profound ataxia, severe bulbar palsy, and respiratory and motor impairment. Although our study excluded patients with MFS who had prominent muscle weakness (Miller Fisher-Guillain-Barré overlap syndrome), plasmapheresis has been established to be an efficacious treatment for GBS.1 Such patients would require immunotherapy. We found that, for patients with typical MFS, plasmapheresis had no effect on recovery speed.
There could be a number of limitations in our study. Firstly, it is a retrospective one and did not involve a large enough number of patients to reach a firm conclusion. Secondly, our plasmapheresis method based on the use of a second filter may have affected the results. In Japan, second filters are often used to reduce the loss of albumin. As a consequence, fewer immunoglobulins would be removed in our method than in simple plasma exchange. Six months after onset, almost all the patients with MFS were symptom free, indicating the naturally good course of the disorder, as described elsewhere.5 Lack of a significant difference in the speeds of recovery of the two patient groups is probably due mainly to good spontaneous recovery from MFS symptoms. Our findings suggest that the indication for the use of immunotherapy may be limited to an MFS subpopulation (those cases overlapped by GBS).