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Show Anti-asialo-GM1 and GD1a Variant of Miller Fisher Variant of Guillain-Barré Syndrome Michael L. Morgan, MD, PhD, Nathan Law, BA, Angelina Espino Barros Palau, MD, Umair Saeed, MD, Sushma Yalmanchili, MD, Andrew G. Lee, MD Abstract: We present a woman with acute onset of bilateral ophthalmoparesis and ataxia occurring 4 weeks after gastroenteritis. Serum antibody titers against asialo-GM1 and GD1a, typically associated with inflammatory axonal neuropathies, were elevated but titers against anti-GQ1b, the most commonly found antibody found in the Miller Fisher variant of Guillain-Barre syndrome were not. No other etiology for ophthalmoparesis was found despite extensive patient evaluation. Intravenous immunoglobulin was admin-istered, and the patient gradually improved over subsequent months. This case is unique for its antiganglioside antibody profile associated with Miller Fisher syndrome. Journal of Neuro-Ophthalmology 2014;34:377-379 doi: 10.1097/WNO.0000000000000156 © 2014 by North American Neuro-Ophthalmology Society Miller Fisher syndrome, atypical Miller Fisher Syn-drome, Guillain-Barre syndrome with ophthalmo-plegia, and Bickerstaff encephalitis have been considered collectively as anti-GQ1b syndromes because patients with these disorders have related clinical features (1-4). Ophthal-moplegia, areflexia, and ataxia comprise the classic triad of Miller Fisher syndrome (5). Approximately 83% of patients harbor anti-GQ1b antibodies (6,7). However, variants of these syndromes have been shown to be associated with other antibodies besides anti-GQ1b, and the full triad need not be present. We believe that our patient with postinfec-tious acute ophthalmoparesis and antibodies against asialo- GM1 and GD1a, but not GQ1b, is unique. CASE REPORT A 33-year-old woman reported 4 days of painless binocular horizontal diplopia that she initially noted on waking from a nap. She also complained of an unsteady gait. Four weeks before presentation, she and her family suffered gastroen-teritis while traveling in Europe. Her children had bloody stools and required brief hospitalization for intravenous fluid resuscitation, but no specific organism was identified. Her gastrointestinal symptoms lingered until a week before the onset of frontal headache and diplopia. Treatment with methylprednisolone, 125 mg intravenously every 8 hours for 2 days, failed to improve the patient's diplopia, and she was transferred to our institution. Her medical history included irritable bowel syndrome, allergic rhinitis, and surgery for cesarean section, exploratory laparotomy with laser ablation for endometriosis, tonsillec-tomy/ adenoidectomy, and nasal septal alignment. Her medications were cetirizine and a nasal steroid, and she had allergies to penicillin and latex. Initial examination was remarkable for limitation of abduction and elevation of each eye with mild right ptosis. Ptosis enhanced with contralateral lid elevation was not fatigable, and Cogan lid twitch was absent. The remainder of the ophthalmic examination was normal, and all other cranial nerves were intact. Neurologically, motor strength was 5/5 throughout, and sensation was intact to all modalities including vibratory testing in the extremities. Gait was broad-based and ataxic. Reflexes were 2+ and symmetric throughout. Four days later, ductional deficits involved all directions except depression, and right ptosis had worsened. Routine laboratory testing was normal except for mild normocytic anemia. Serum levels were normal for thiamine, vitamin B12, thyroid-stimulating hormone, triiodothyrorine, Department of Ophthalmology (MLM, AEBP, US, SY, AGL), Houston Methodist Hospital, Houston, Texas; Baylor College of Medicine (NL, AGL), Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medical College, Houston, Texas; UTMB (AGL), Galveston, Texas and the UTMD Anderson Cancer Center (AGL), Houston, Texas; and University of Iowa Hospitals and Clinics (AGL), Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to: Andrew G. Lee, MD, Department of Oph-thalmology, Houston Methodist Hospital, 6560 Fannin Street, Scurlock 450, Houston, Texas 77030; E-mail: aglee@houstonmethodist.org Morgan et al: J Neuro-Ophthalmol 2014; 34: 377-379 377 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. free thyroxine, erythrocyte sedimentation rate, C-reactive protein, angiotensin converting enzyme, antinuclear antibody, antineutrophilic cytoplasmic antibody, anti-Ro (SSA), anti-La (SSB), HIV, and rapid plasma reagin. Thyroid peroxidase antibody titer was elevated at 24.1 IU/mL (normal, 0.0-9.0 IU/mL), and thyroid-stimulating immunoglobulin was nor-mal at 97% (normal #122%). Opening pressure on lumbar puncture was 18 cm H20 with 1 RBC/mL, 1 WBC/mL, glucose 57 mg/dL (normal, 40-70 mg/dL), and protein 18 mg/dL (normal, 10-50 mg/dL). Additional CSF studies for Cryptococcal antigen, West Nile virus PCR, Tropheryma whipplei PCR and Borrelia burgdorferi antibodies were nega-tive. Electromyography and nerve conduction studies were within normal limits. Brain magnetic resonance imaging was normal. Chest computed tomography (CT) revealed an incidental left apical nodule, a reactive left hilar lymph node, and atelectasis. Four-vessel cerebral angiography showed no evidence of carotid-cavernous fistula. IgG/IgM titers for asialo-GM1 were elevated at 170 index value (IV) (ranges, #29 IV negative, 30-50 IV equiv-ocal, 51-100 IV positive, $101 IV strongly positive) as were GD1a antibodies at 77 IV. Titers against GM1 and GD1b were equivocal at 33 IV and 45 IV, respectively, and titers against GQ1b and GM2 were negative. The patient was treated with intravenous immunoglobulin 0.5 gm/kg daily for 4 days, and her symptoms gradually improved with diplopia only at extremes of gaze by 2 months. DISCUSSION We present the case of a woman with bilateral ophthalmo-paresis and elevated antibody titers against asialo-GM1 and GD1a after an episode of acute gastroenteritis. Classic Miller Fisher syndrome consists of ophthalmoplegia, ataxia, and areflexia (5). However, the presentation can be limited to ophthalmoplegia alone. Our patient presented with only ophthalmoparesis and ataxia. Miller Fisher syndrome is most often associated with anti-GQ1b antibodies (1-4). These antibodies are often detected in a group of related syndromes including Miller Fisher syndrome, atypical Miller Fisher Syndrome, Guillain-Barre syndrome with ophthalmoplegia, and Bickerstaff encephalitis. These disor-ders frequently have a preceding infection, with Campylo-bacter jejuni, Hemophilus influenza, and enterovirus often implicated. The pathoetiology presumably is due to molec-ular mimicry between the infectious agent and endogenous gangliosides (2-6,8-13). Chiba et al (1) demonstrated that 28 of 30 patients with either Miller Fisher syndrome, atyp-ical Miller Fisher Syndrome, or Guillain-Barre syndrome with ophthalmoplegia tested positive for anti-GQ1b antibodies, whereas zero out of 107 patients with other neurologic or nonneurologic disorders, including 23 Guillain-Barre patients without ophthalmoplegia, tested positive. They also showed that human ocular motor nerves contain a larger amount of GQ1b than the ventral and dorsal roots of the spinal cord, indicating a possible etiology of the ophthalmoplegia. Koga et al (8) analyzed the sero-logical antibodies in 207 patients with Miller Fisher syn-drome and found that the majority (88%) were positive for anti-GQ1b. However, the remaining 12% were anti-GQ1b negative and tested positive for a variety of other antibodies including GM1b, GD1a, and GT1a. Antiganglioside antibodies, asialo-GM1, and GD1a, present in our patient are most often associated with axonal autoimmune neuropathies. Asialo-GM1 antibodies have been detected in patients with multifocal motor neuropathy (MMN), and GD1 antibodies with MMN and the axonal variant of Guillain-Barre syndrome, also known as acute motor axonal neuropathy (9-11). However, our patient showed no evidence of peripheral neuropathy on examina-tion or electrophysiological testing. There are few reports of patients with a constellation of antibodies similar to our case. Fusco et al (12) evaluated a 6-year-old child with acute ophthalmoparesis after entero-virus infection. The child was positive for anti-GM1, GD1a, and GD1b and negative for anti-GQ1b. Paine et al (13) reported a case of Miller Fisher syndrome in which the patient was positive for both anti-GQ1b anti-bodies and anti-asialo-GM1 antibodies. Lavallée et al (14) described a 30-year-old woman who developed a left abduc-tion defect and right ptosis with spontaneous recovery and persistent hyporeflexia after an upper respiratory illness, who was positive for anti-GM1, but negative for anti- GQ1b. Fusco et al (12) hypothesized that a regionally restricted axonal acute immune neuropathy developed in their patient. We presume a similar etiology in our case. Although our patient harbored antibodies more often tar-geted toward noncranial peripheral nerves, ophthalmopare-sis was her dominant finding. In the case reported by Fusco et al (12), enterovirus was identified as the preceding infec-tion. No such causative agent was tested for in our patient or her family; enterovirus and Campylobacter infections remain potential etiologies. This case provides a unique presentation of acute ophthalmoplegia with a previously unreported combina-tion of antiganglioside antibodies and contributes to the spectrum of presentations and serologies in acute oph-thalmoplegic syndromes. Although the majority of Miller Fisher syndromes are associated with anti-GQ1b anti-bodies, other antiganglioside antibodies should be consid-ered, particularly when clinical presentation raises suspicion of Miller Fisher syndrome and anti-GQ1b antibodies are absent. REFERENCES 1. Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies. Neurology. 1993;43:1911-1917. 378 Morgan et al: J Neuro-Ophthalmol 2014; 34: 377-379 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 2. Odaka M, Yuki N, Hirata K. Anti-GQ1b IgG antibody syndrome: clinical and immunological range. J Neurol Neurosurg Psychiatry. 2001;70:50-55. 3. Saul RF. Neuro-ophthalmology and the anti-GQ1b antibody syndromes. Curr Neurol Neurosci Rep. 2009;9:379-383. 4. Chiba A, Kusunoki S, Shimizu T, Kanazawa I. Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol. 1992;31:677-679. 5. Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med. 1956;255:57-65. 6. Ito M, Kuwabara S, Odaka M, Misawa S, Koga M, Hirata K, Yuki N. Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum: clinical analysis of 581 cases. J Neurol. 2008;255:674-682. 7. 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Atypical Miller Fisher syndrome with GQ1b antibodies. J Clin Neurosci. 1996;3:268-271. 14. Lavallée P, Vidailhet M, Dussaule JC, Derkinderen P. Post-infectious ophtalmoparesis associated with anti-GM1 but not with anti-GQ1b antibodies. Eur J Neurol. 2001;8:475-476. Morgan et al: J Neuro-Ophthalmol 2014; 34: 377-379 379 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
