Clinical correlates of serum anti-GT1a IgG antibodies

https://doi.org/10.1016/j.jns.2004.01.005Get rights and content

Abstract

Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain–Barré syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Fisher syndrome (FS) or Bickerstaff's brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The nosological relationship between these conditions has yet to be established. To investigate the relationships between each manifestation and between clinical features and the coexistence of anti-GQ1b IgG, we reviewed neurological signs present during illnesses of 140 patients who had anti-GT1a IgG. Based on our criteria, FS was diagnosed for 64 (46%) patients, GBS for 22 (16%), BBE for 14 (10%), and PCB for 6 (4%). Overlapping conditions were diagnosed for some patients: FS and GBS (5%), PCB and FS (5%), BBE and GBS (4%), and PCB and BBE (1%). Patients who initially had bulbar palsy developed not only PCB but FS or BBE. The population of anti-GT1a-positive patients frequently had ophthalmoplegia, ataxia, and areflexia, whereas the subpopulation who had anti-GT1a IgG without GQ1b reactivity frequently had preceding diarrhea as well as oropharyngeal, neck, and limb weakness. Patients with anti-GT1a IgG presented a variety of clinical conditions, indicative of a continuous clinical spectrum. A major part of this clinical variation was due to the coexistence of anti-GQ1b IgG. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to FS and BBE as well.

Introduction

Guillain–Barré syndrome (GBS) is characterized by the acute onset of limb weakness. Bulbar palsy, which causes respiratory failure or aspiration and occasionally may require intubation, has been reported in two-fifths of GBS patients studied [1]. Ropper [2] described three patients, in whom oropharyngeal, neck, and shoulder weaknesses progressed acutely. He called this regional variant “pharyngeal-cervical-brachial weakness resembling botulism or diphtheria” and, elsewhere, proposed diagnostic criteria [1].

Cumulative evidence supports the speculation that anti-ganglioside antibodies function in the development of GBS and its variants [3]. A patient developed the pharyngeal-cervical-brachial variant (PCB) after an intramuscular injection of bovine ganglioside mixture [4], indicative that anti-ganglioside antibodies also have a pathogenetic role in the development of PCB. Anti-GT1a IgG antibodies with and without GQ1b reactivity have been detected in patients who have acute oropharyngeal palsy [5], [6], PCB [7], [8], [9], or GBS [10], [11], [12]. On the other hand, anti-GQ1b IgG antibody with anti-GT1a reactivity has been found in patients who have Fisher syndrome (FS), Bickerstaff's brainstem encephalitis (BBE), acute ophthalmoparesis (AO) without ataxia, or ataxic GBS [13], [14], [15]. The nosological relationship between PCB and these other conditions, however, has yet to be established. The aim of our study was to clarify the clinical features of anti-GT1a-positive patients who had various neurological disorders and the relationships between PCB and related conditions.

Section snippets

Patients

A sequential retrospective study was made of 2,148 consecutive patients with various neurological disorders. Serum samples were obtained from patients who had been referred to our laboratory for serum anti-ganglioside antibody testing by Japanese university and district general hospitals between August 1999 and November 2001.

Enzyme-linked immunosorbent assay

Serum IgG antibodies to GT1a, GQ1b, GM1, GM1b, GM2, GD1a, GalNAc-GD1a, GD1b, and GT1b were measured routinely by an enzyme-linked immunosorbent assay (ELISA) as reported

Clinical features of patients with anti-GT1a IgG antibodies

Anti-GT1a IgG antibodies were positive in 140 patients (median age, 40; 77 men, 63 women), 12 of whom were reported elsewhere [11]. Table 2 shows the clinical profiles during illness. Eighty-nine percent of the patients had an antecedent illness (upper respiratory tract infectious symptoms alone, 65%; diarrhea alone, 8%; both, 16%). The most frequent initial symptom was diplopia, the second unsteady gait; both cardinal symptoms of FS.

Most patients had muscular weakness of acute and monophasic

Discussion

The 140 patients with anti-GT1a IgG antibodies had a variety of clinical features. The triad of FS, ophthalmoplegia, ataxia, and areflexia were frequent because half the population sample consisted of FS patients. We elsewhere reported the frequencies of neurological signs in patients with anti-GQ1b IgG [15]. They were similar to those in the patients with anti-GT1a IgG in the current study. The GBS population, however, was larger in the anti-GT1a IgG-positive (16%) than in the anti-GQ1b

Acknowledgments

We thank Ms. Y. Tsuchiya (Dokkyo University, Tochigi) for her technical assistance. This study was supported in part by grants-in-aid from the Uehara Memorial Foundation; for Scientific Research (B) (KAKENHI 14370210 to N.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and a Research Grant for Neuroimmunological Diseases from the Ministry of Health, Labour, and Welfare of Japan.

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