Bickerstaff's brainstem encephalitis (BBE) is characterised by acute ophthalmoplegia and ataxia preceded by infection.1BBE rather than Miller Fisher syndrome is usually diagnosed for patients who show drowsiness and have brisk reflexes, extensor plantar responses, and long tract sensory disturbance. Bickerstaff and Cloake1 speculated that the aetiology of BBE is similar to that of Guillain-Barré syndrome (GBS) because areflexia and CSF albuminocytological dissociation was detected in one of their three patients. Because prior infection is frequent in BBE, as in GBS, autoimmune mechanisms produced by microbial infections may function in its pathogenesis. A review of the literature in English turned up eight cases of BBE in which the pathogens of antecedent infection had been identified. The reported antecedent infections in BBE are herpes simplex virus, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, measles virus, Salmonella typhi, andMycoplasma pneumoniae. We here describe a case of BBE subsequent to Campylobacter jejuni enteritis.

A 17 year old youth had fever and diarrhoea that cleared up over a period of 5 days. Eight days after the resolution of this illness, he experienced unsteady gait (day 1), and the next day he required assistance to walk and experienced vertigo. On day 3, he could no longer walk and vomited several times. He was apyrexic but drowsy. The pupils were normal and responded promptly to light. There was no limitation of ocular movement. Bifacial palsy was present, and there was mild weakness in the four limbs. Tendon jerks were brisk. Babinski's sign was negative. Paraesthesias of the glove and stocking type were present. The white blood count, C reactive protein, and erythrocyte sedimentation rate were normal. Protein in CSF was 30 mg/dl with 7 cells/μl. The tentative diagnosis was brainstem encephalitis. Acyclovir was given intravenously for 5 days and methylprednisolone for 3 days. Brain MRI showed no brain abnormality on days 5 and 12. On day 7, the patient became confused. Upward gaze and lateral gaze to the left were impossible, and downward and lateral gaze were moderately impaired. Bell's phenomenon and oculocephalic reflexes were absent. He developed palatal and lingual weakness. Muscular weakness was severe in the distal part of the arms and moderate in the legs. On day 8, motor and sensory nerve conduction velocities were normal, but an EEG showed bilateral diffuse θ and δ activity at rest. He was given 0.2 g/kg human immunoglobulin (Venilon^®, Teijin, Tokyo, Japan) daily for 5 days starting on day 8. Consciousness disturbance lessened from day 9, and he became fully conscious on day 12. Facial and oropharyngeal weakness disappeared on day 13. On day 17, there was no paresis of the extraocular muscles, except for upward gaze limitation of the right eye. Limb power returned to normal on day 19. On day 22, he could walk, but his gait was markedly ataxic. An EEG was normal on day 29. Ataxic gait and gaze limitation disappeared respectively on days 30 and 39. Proprioceptive sensation was not impaired during the course of this illness. Thin layer chromatography with immunostaining showed that on day 3 his serum IgG reacted with GQ1b and GT1a, but not with GM1, GD1a, GD1b, or GT1b. The C jejuniwhich grew from stool cultures taken on day 3 belonged to Penner's serogroup D (corresponding to PEN 4, 13, 16, 43, and 50) in the modified Penner's serotyping system,2 and to LIO 1 in Lior's serotyping scheme. An enzyme linked immunosorbent assay showed strongly positive serum anti-C jejuniantibody on day 3 (IgM, 4000; IgG, 64 000; IgA, 16 000). Viral screening (including herpes simplex virus) of the blood and CSF was unremarkable.

The gram negative bacterium C jejuni, the most often identified trigger pathogen in GBS, may also be a trigger for Miller Fisher syndrome and encephalopathy. Subsequent toC jejuni enteritis, our patient showed consciousness disturbance (drowsiness and confusion), hyperreflexia, and tetraparesis as well as external ophthalmoplegia and ataxia of the cerebellar type. Serology and isolation of the bacterium from his faeces confirmed prior C jejuni infection. BBE was diagnosed because five (cases 6, 7, 8, 13, and 18) of the 18 patients with BBE described by Al-Din et al 3 (Bickerstaff being one of the authors) had limb weakness. This diagnosis was supported by the presence of anti-GQ1b IgG antibody, a serological marker of BBE and Miller Fisher syndrome.4 Overlapping BBE and GBS was another possible diagnosis, and this has been reviewed elsewhere.5 The presence of BBE (or overlapping BBE and GBS) after infection byC jejuni supports the speculation that BBE and GBS are closely related and that BBE is an autoimmune disorder that occurs after microbial infection.

We previously reported the occurrence of GBS in two family members after C jejuni infection.6 The clinical features of that second case are very similar to those of the case reported here; the patient was comatose and showed external ophthalmoplegia. Overlapping GBS and BBE, therefore, could also be diagnosed for that patient. Anti-ganglioside serology testing was not possible because no serum was kept. Aspinall et al 7 proposed that the lipopolysaccharide of the strain OH 4384 isolated from that patient with GBS has a GT1a-like structure. We partially confirmed this using anti-GT1a monoclonal antibody but in addition showed that OH 4384 has lipopolysaccharides that bear GM1, GM2, GD1a, GD2, GD3, GT1b, or GQ1b epitopes.8 Goodyear et al 9 immunised mice with the lipopolysaccharide from OH 4384 and cloned three monoclonal antibodies with GQ1b reactivity. Anti-GQ1b IgG usually cross reacts with GT1a, and GQ1b is abundantly expressed in human ocular motor nerves.10 Infection byC jejuni bearing a GT1a-like or GQ1b-like lipopolysaccharide may induce the production of anti-GQ1b IgG antibody, which then may bind to ocular motor nerves causing paresis of the extraocular muscles in patients with overlapping BBE and GBS.

Effective therapy for BBE has yet to be established. As stated above, BBE and GBS are closely related; therefore, steroids should not be used to treat BBE. Instead, the established treatments for GBS, plasmapheresis and intravenous immunoglobulins (IVIg), should be used. Some patients with BBE have responded favourably to plasmapheresis,4 and the patient in our case responded favourably to IVIg. We recommend not giving steroids, but using IVIg (or plasmapheresis) to treat BBE. Controlled clinical trials are required to establish the efficacy of these procedures as therapeutic for BBE.