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Show Journal of Neuro- Ophthalmology 20( 1): 61- 62, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphi; Acute Onset of a Bilateral Areflexical Mydriasis in Miller- Fisher Syndrome: A Rare Neuro- ophthalmologic Disease Antonio Caccavale, MD, and Licia Mignemi, MD Miller- Fisher syndrome ( MFS) is characterized by variable ophthalmoplegia, ataxia, and tendon areflexia. It seems to be a variant of Guillain- Barre syndrome ( GBS), but unlike in GBS, there is a primitive involvement of the ocular motor nerves, and in some cases there is brainstem or cerebellum direct damage. The unusual case of MFS in the current study started with a bilateral areflexical mydriasis and a slight failure of accommodative- convergence. Ocular- movement abnormalities developed progressively with a palsy of the upward gaze and a bilateral internuclear ophthalmoplegia to a complete ophthalmoplegia. In the serum of this patient, high titers of an IgG anti- GQlb ganglioside and IgG anti- cerebellum, anti- Purkinje cells in particular, were found. The former autoantibody has been connected to cases of MFS, of GBS with associated ophthalmoplegia, and with other acute ocular nerve palsies. The anti- cerebellum autoantibody could explain central nervous system involvement in MFS. The role of these findings and clinical implications in MFS and in other neuro-ophthalmologic diseases are discussed. Key Words: Anti- cerebellum antibody- Anti- ganglioside antibody- Miller- Fisher syndrome- Ophthalmoplegia. CASE REPORT A ten- year- old boy experienced acute onset bilateral mydriasis and a slight failure of accommodative-convergence. Visual acuity was 20/ 20 OU; no alterations of fundus oculi or of the optic discs were present. It was also possible to observe a moderate ( about 2 mm) ptosis OS. In the hours following the admission, the patient developed a paralysis of the upward gaze and a horizontal nystagmus in extreme lateral positions. There was a light sleepiness and a low level of psychasthenia. Tendon reflexes were normal, and there were no other abnormal neurologic signs. Hematochemical routine parameters were normal. The patient's medical history was negative for recent infectious disease ( in particular, of viral disease). Pharmacologic and toxicologic history were negative; regardless, blood was tested for the presence of sympathetic-like drugs ( e. g., cocaine, amphetamines). Cerebro- spinal Manuscript received March 25, 1999; accepted November 15, 1999. From the Neuro- Ophthalmology and Retina Service, Magenta General Hospital, Milan, Italy. Address correspondence and reprint requests to Dr. Antonio Caccavale, Via Verga, 4, 20017 Rho ( MI), Italy. fluid analysis did not show any abnormalities. There were no oligoclonal bands, and there were no antibodies against Clostridium botulini or antineurotropic viruses. Results of computed tomography and magnetic resonance imaging did not show pathologic signals from the brain in toto. An electroencephalogram showed small groups of slow, high voltage, delta waves on the parietal-occipital derivations. After 48 hours, the patient developed a complete ophthalmoplegia with an exotropia of about 30° OS and a frozen gaze. A new neurologic examination revealed cerebellar ataxia and tendon areflexia in all limbs. Serum analysis showed high titers of anti- GQlb ganglioside autoantibodies ( 1: 1,200, detected by enzyme- linked immunosorbent assay) and anti- cerebellum autoantibodies. Anti- Purkinje cells were detected with Western blot analysis. No antibody against Campilobacter jejuni was found in the serum. Results of feces analysis were negative for Salmonella species, Shigella species, and C. jejuni. Our diagnosis was of a primitive polineuropafhy, probably in the context of Miller- Fisher syndrome ( MFS). The patient was treated with a high dose of human aspecific Ig, 15 g/ day for 2 weeks, and he received dex-ametazone intravenously, 8 mg/ day for 2 days, in a scaled regimen. Next he underwent two sessions of im-munoadsorption plasmapheresis. During the following days, the patient's neurologic conditions improved. Gradually, ataxia and tendon areflexia disappeared, but ocular movements showed little improvement. After 3 weeks, conjugate horizontal and vertical eye movements were restored, with a slight nystagmus in extreme gaze positions; soon after, exotropia OS disappeared. At the 2- month follow- up examination, there was only a moderate mydriasis OS. Pupillary reflexes were normal, as was accommodative- convergence. After 6 months, there was no recurrence of the disease. DISCUSSION Miller- Fisher syndrome is characterized by ophthalmoplegia, ataxia, and tendon areflexia. It has an acute onset and seems to be like Guillain- Barre syndrome 61 62 A. CACCAVALE AND L. MIGNEMl ( GBS) ( 1). Both diseases are polyneuropathies, but only MFS gives rise to various degrees of external ophthalmoplegia. This symptom is occasionally present in GBS. An important link between these neurologic diseases has been the discovery of a serum anti- ganglioside antibody, an IgG anti- GQlb ganglioside, detected in MFS and in GBS with ophthalmoplegia; in cases of GBS without ocular signs, it is not possible to find IgG anti- GQlb ( 2). There is a close relationship between the presence of anti- GQlb antibodies in the serum and internal and external ophthalmoplegia. Anti- ganglioside IgG is not an exclusive feature of MFS or of GBS with ophthalmoplegia; it has been detected in some patients with acute isolated ophthalmoparesis without any signs of polineuritis. A possible immune mechanism can produce these ocular motor palsies ( 3). In otherwise unexplainable, acute, isolated ophthalmoparesis, it can be helpful to search the anti- GQlb antibody in the serum, especially in young patients. Pathogenesis of ophthalmoplegia in MFS, in GBS with ocular nerve involvement, or in isolated ophthalmoparesis is explained with the presence of a large amount and an almost unique expression of the GQlb ganglioside in the paranodal regions of Schwann cells of the extramedullary regions of the third, fourth, and sixth cranial nerves ( 2). Also interesting is the cross- reaction between the anti- GQlb antibodies, derived from patients with MFS, and the surface epitopes of C. jejuni ( 4). C. jejuni lipopoly-saccharide has a molecular similarity to GQlb ganglioside ( 5). This could explain the link between a previous C. jejuni infection and successive MFS or GBS with ophthalmoplegia ( 6). Our patient's clinical history did not indicate previous infectious disease; examination of the serum and feces did not show the presence of C. jejuni, Salmonella species, or Shigella species. The acute, bilateral, areflexical mydriasis, the only neurologic sign for about 24 hours, is particular to this case. In the early phase of MFS, when only intrinsic third-nerve impairment is present, finding IgG anti- GQlb may facilitate a precise diagnosis. In the serum of our patient, we also found anti-cerebellum autoantibodies, anti- Purkinje cells in particular. This could explain the cerebellar ataxia and, partially, the eye- movement abnormalities described in another study ( 7). As far as we know, this work is the second report of a case of MFS in which anti- cerebellum antibodies have been found ( 8). REFERENCES 1. Fisher CM. An unusual variant of acute idiopathic polyneuritis. N Engl J Med 1956; 255: 57- 65. 2. Chiba A, Kusonoki S, Obata H, et al. Serum anti- GQlb IgG antibody is associated with ophthalmoplegia in Miller- Fisher syndrome and Guillain- Barre syndrome: clinical and immunohisto-chemical studies. Neurology 1993; 43: 1911- 7. 3. Yuki N. Acute paresis of extraocular muscles associated with IgG anti- GQlb antibody. Ann Neurol 1996; 39: 668- 72. 4. Jacobs BC, Endtz H, Van der Meche FGA, et al. Serum anti- GQlb IgG antibodies recognize surface epitopes on Campilobacter jejuni from patients with Miller- Fisher syndrome. Ann Neurol 1995; 37: 26( M. 5. Yuki N, Taki T, Takahashi M, et al. Molecular mimicry between GQ1 b ganglioside and lipopolysaccharides of Campilobacter jejuni isolated from patients with Miller- Fisher syndrome. Ann Neurol 1994; 36: 791- 3. 6. Kohler A, De Torrente A, Inderwildl B. Fisher's syndrome associated with Campilobacter jejuni infection. Eur Neurol 1988; 28: 150- 1. 7. Zasarin NC, Yee RD, Baloh RW. Eye movement abnormalities in ophthalmoplegia, ataxia and areflexia. Arch Ophthalmol 1985; 103: 55- 8. 8. Iwahashi T. The detection of ami cerebellar antibody Western blot analysis in serum from patients with MFS. Arerugi. 1995; 44; 1176- 80. J Neuro- Ophthalmol, Vol. 20, No. I, 2000 |