Abstract
Anti-GQ1b antibodies can be detected in the serum of patients with Miller Fisher syndrome (MFS) and its incomplete forms such as acute ophthalmoparesis (AO), acute ptosis, acute mydriasis, acute oropharyngeal palsy and acute ataxic neuropathy (AAN), as well as in pharyngeal–cervical–brachial weakness, Bickerstaff brainstem encephalitis (BBE) and in overlap syndromes with Guillain–Barré syndrome (MFS–GBS, BBE–GBS). We searched the laboratory medicine database at University Hospitals Leuven between 2002 and 2017 for serum samples with anti-GQ1b IgG antibodies. We identified eight patients with anti-GQ1b antibodies: 4 MFS, 2 AO, 1 MFS–GBS and 1 AAN. Mean age was 57 years and five patients were males. Preceding illness was present in all patients. At nadir, we observed most frequently gait disturbance, external ophthalmoplegia and absent/decreased reflexes. Albumino-cytological dissociation was present in four patients. Mean time between onset and nadir was 4 days, between onset and recovery 2.5 months. Five patients recovered completely and three had minor residual symptoms. Interestingly, one patient with AO experienced a second identical episode, approximately 1 year after the first one. Our data confirm the broad clinical spectrum associated with the presence of anti-GQ1b IgG antibodies. Incomplete MFS subtypes such as AO are a challenge for diagnosis, because of the limited (though invalidating) clinical presentation and the lack of confirming ancillary tests. Subacute onset of ophthalmoplegia and/or ataxia should urge the clinician to include the anti-GQ1b antibody syndrome in the differential diagnosis.
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References
Fisher M (1956) An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 255(2):57–65. https://doi.org/10.1056/NEJM195607122550201
Bickerstaff ER (1957) Brainstem encephalitis. Br Med J 1(5032):1384–1387
Chiba A, Kusunoki S, Shimizu T, Kanazawa I (1992) Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 31:677–679. https://doi.org/10.1002/ana.410310619
Yuki N, Sato S, Tsuji S, Hozumi I, Miyatake T (1993) An immunologic abnormality common to Bickerstaff’s brain stem encephalitis and Fisher’s syndrome. J Neurol Sci 118:83–87. https://doi.org/10.1016/0022-510X(93)90250-3
Yuki N (1996) Acute paresis of extraocular muscles associated with IgG anti-GQ1b antibody. Ann Neurol 39:668–672. https://doi.org/10.1002/ana.410390517
Jindal G, Parmar VR, Gupta VK (2009) Isolated ptosis as acute ophthalmoplegia without ataxia, positive for anti-GQ1b immunoglobulin G. Pediatr Neurol 41:451–452. https://doi.org/10.1016/j.pediatrneurol.2009.07.008
Yuki N, Koga M, Hirata K (1998) Isolated internal ophthalmoplegia associated with immunoglobulin G anti-GQ1b antibody. Neurology 51:1515–1516
O’Leary CP, Veitch J, Durward WF, Thomas AM, Rees JH, Willison HJ (1996) Acute oropharyngeal palsy is associated with antibodies to GQ1b and GT1a gangliosides. J Neurol Neurosurg Psychiatry 61:649–651. https://doi.org/10.1136/jnnp.61.6.649
Yuki N, Susuki K, Hirata K (2000) Ataxic Guillain–Barré syndrome with anti-GQ1b antibody: relation to Miller Fisher syndrome. Neurology 54:1851–1853. https://doi.org/10.1212/WNL.54.9.1851
Odaka M, Yuki N, Hirata K (2001) Anti-GQ1b IgG antibody syndrome: clinical and immunological range. J Neurol Neurosurg Psychiatry 70:50–55. https://doi.org/10.1136/jnnp.70.1.50
Yuki N, Taki T, Takahashi M, Saito K, Yoshino H, Tai T, Handa S, Miyatake T (1994) Molecular mimicry between GQ1b ganglioside and lipopolysaccharides of Campylobacter jejuni isolated from patients with Fisher’s syndrome. Ann Neurol 36(5):791–793. https://doi.org/10.1002/ana.410360517
Houliston RS, Koga M, Li J, Jarrell HC, Richards JC, Vitiazeva V, Schweda EK, Yuki N, Gilbert M (2007) A Haemophilus influenzae strain associated with Fisher syndrome expresses a novel disialylated ganglioside mimic. Biochemistry 46(27):8164–8171. https://doi.org/10.1021/bi700685s
Koga M, Takahashi M, Masuda M, Hirata K, Yuki N (2005) Campylobacter gene polymorphism as a determinant of clinical features of Guillain–Barré syndrome. Neurology 65:1376–1381. https://doi.org/10.1212/01.wnl.0000176914.70893.14
Fukami Y, Wong A, Funakoshi K, Safri A, Shahrizaila N, Yuki N (2016) Anti-GQ1b antibody syndrome: anti-ganglioside complex reactivity determines the clinical spectrum. Eur J Neurol 23(2):320–326. https://doi.org/10.1111/ene.12769
Van den Bergh PY, Piéret F (2004) Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 29(4):565–574. https://doi.org/10.1002/mus.20022
Koga M, Gilbert M, Li J, Koike S, Takahashi M, Furukawa K, Hirata K, Yuki N (2005) Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry. Neurology 64(9):1605–1611. https://doi.org/10.1212/01.WNL.0000160399.08456.7C
Koga M, Yuki N, Tai T, Hirata K (2001) Miller Fisher syndrome and Haemophilus influenzae infection. Neurology 57:686–691. https://doi.org/10.1212/WNL.57.4.686
Yuki N, Hartung HP (2012) Guillain–Barré syndrome. N Engl J Med 366(24):2294–2304. https://doi.org/10.1056/NEJMra1114525
Kashihara K, Shiro Y, Koga M, Yuki N (1998) IgG Anti-GT1a antibodies which do not cross react with GQ1b ganglioside in a pharyngeal–cervical–brachial variant of Guillain–Barré syndrome. J Neurol Neurosurg Psychiatry 65(5):799. https://doi.org/10.1136/jnnp.65.5.799
Kim YK, Kim JS, Jeong SH, Park KS, Kim SE, Park SH (2009) Cerebral glucose metabolism in Fisher syndrome. J Neurol Neurosurg Psychiatry 80(5):512–517. https://doi.org/10.1136/jnnp.2008.154765
Kuwabara S, Sekiguchi Y, Misawa S (2017) Electrophysiology in Fisher syndrome. Clin Neurophysiol 128(1):215–219. https://doi.org/10.1016/j.clinph.2016.11.009
Kuwabara S, Asahina M, Nakajima M, Mori M, Fukutake T, Hattori T, Yuki N (1999) Special sensory ataxia in Miller Fisher syndrome detected by postural body sway analysis. Ann Neurol 45:533–536. https://doi.org/10.1002/1531-8249(199904)45:4%3C533::AID-ANA19%3E3.0.CO;2-H
Liu JX, Willison HJ, Pedrosa-Domellöf F (2009) Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles. Investig Ophthalmol Vis Sci 50(7):3226–3232. https://doi.org/10.1167/iovs.08-3333
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We would like to thank the technical personnel of the Laboratory Medicine department at UZ Leuven for their technical support. PVD holds a senior clinical investigatorship of FWO-Vlaanderen.
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de Bruyn, A., Poesen, K., Bossuyt, X. et al. Clinical spectrum of the anti-GQ1b antibody syndrome: a case series of eight patients. Acta Neurol Belg 119, 29–36 (2019). https://doi.org/10.1007/s13760-019-01093-8
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DOI: https://doi.org/10.1007/s13760-019-01093-8