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J Clin Pathol. 2007 October; 60(10): 1161–1162.
Published online 2007 May 18. doi:  10.1136/jcp.2006.046284
PMCID: PMC2014832

Bickerstaff's brainstem encephalitis related to Campylobacter jejuni gastroenteritis

Campylobacter species are microaerophilic spiral‐shaped Gram‐negative bacilli which cause diarrhoeal and systemic illness in humans and animals. They are the most commonly identified cause of bacterial intestinal disease in the UK and elsewhere in the developed world. The bacterial cell wall of the organism contains an endotoxin which, when released, can result in acute enteritis and complications such as reactive arthritis, erythema nodosum, peripheral neuropathy, haemolytic uraemic syndrome and Bickerstaff's brain stem encephalitis (BBE). Here we report a case of BBE following a gastrointestinal infection with Campylobacter jejuni. The patient presented with acute onset of confusion and ophthalmoplegia. The cerebrospinal fluid (CSF) showed lymphocytic pleocytosis and raised protein. This acute presentation was preceded by an episode of Campylobacter‐related diarrhoea as confirmed by high titres of Campylobacter‐specific IgM antibodies.

Over 50 000 laboratory confirmed cases of Campylobacter intestinal disease are reported annually in England and Wales.1Campylobacter jejuni is the most common species of the genus Campylobacter identified in clinical samples.1 Transmission occurs throughout the year but rises in late spring and early summer, and requires only small inoculums.2 Clinical features of C jejuni infection range from an absence of symptoms to fulminant sepsis and death. In rare cases a potentially life threatening form of post‐infectious encephalitis affecting the brainstem can arise.3 Initial colonisation occurs in the jejenum and ileum, which spreads distally to involve the colon and rectum. After a prodromal illness, the patient may develop abdominal pain and bloodstained diarrhoea. Other common complications include septic polyarthritis and peripheral polyneuropathy.

In 1957 Bickerstaff described eight patients with brainstem encephalitis presenting with ophthalmoplegia, ataxia and a reduced level of consciousness. Our extensive literature search has revealed only a few documented cases of BBE secondary to intestinal infection with Campylobacter.4

Case report

A 54‐year‐old man presented with a 1‐week history of fever, anorexia and vomiting. On arrival at hospital he was febrile, confused and slightly dysarthric but there were no signs of meningism. Neurological examination showed a generalised weakness of all four limbs. He had absent lower limb reflexes and diminished reflexes in the upper limbs. The right plantar response was extensor while the left was equivocal. Owing to his confusion, adequate sensory testing could not be performed.

Initial investigations were unremarkable. In view of a working diagnosis of encephalitis, a lumbar puncture was performed following a normal CT brain scan. Laboratory examination of the CSF showed 270 white blood cells/mm3 (66% lymphocytes, 34% neutrophils) with a protein level of 0.79 g/l. In view of the clinical presentation and CSF findings, treatment was aimed at a presumptive diagnosis of meningoencephalitis with a combination of ceftriaxone and aciclovir. Serum and CSF samples were sent for herpes simplex virus (HSV) and Epstein‐Barr virus (EBV) titres and PCR, which were later reported as negative.

On transfer to the intensive care unit he was electively intubated and ventilated. Treatment with intravenous piperacillin‐tazobactam and ionotropes was commenced. Elective surgical tracheostomy was performed on day 8 and sedation ceased to allow for regular neurological examination. By day 11 there had been no neurological improvement, with no response to deep pain stimuli and hypotonia. The Glasgow Coma Score was estimated to be 7/15 at this point. An MRI scan of the brain revealed an ill‐defined T2 hyperintense area in the brainstem which was reported as an area of infarction secondary to cerebrovascular ischaemia. An MRI scan of the spine also showed mild degenerative changes. An EEG was performed which excluded non‐convulsive status epilepticus.

On day 13 he was noted to be more responsive to stimuli but remained quadriplegic. By day 15 he was alert, obeyed commands, and had begun to recover some upper limb control. By day 18 his upper limbs continued to improve although his lower limbs remained paralysed. Electromyography on day 22 revealed mild subacute axonal loss, no evidence of demyelination and absent F‐waves. On day 30 he was weaned off positive pressure ventilation.

The laboratory reported a high titre of C jejuni IgM on day 37. Because detection of the IgM antibody response to C jejuni could be unreliable,5 we confirmed the diagnosis of C jejuni infection by demonstrating a significant rise and subsequent fall in the titres of IgM, IgG and IgA antibodies (table 11).). After careful consideration, a 5‐day course of immunoglobulin was commenced to treat possible BBE. Before starting this treatment, serum for anti GQ1b antibodies was sent to the laboratory which was later found to be negative. Although many features of this case fit into the classical description of BBE, there were a number of atypical findings such as a CSF pleocytosis and a negative anti GQ1b. Other conditions mimicking the presentation of BBE such as multiple sclerosis, acute disseminated encephalomyelitis, brainstem tumour, myasthenia gravis, botulism, Wernicke's encephalopathy and vasculitis were excluded. On day 52 the patient was transferred to the local brain injury unit where he continued to display neurological recovery with intensive rehabilitation. The patient has now regained most of his neurological function.

Table thumbnail
Table 1 Serological markers of Campylobacter jejuni infection

Discussion

BBE is a rare complication of Campylobacter food poisoning7 resulting in an ascending polyneuropathy.8 It may be related to certain genetic polymorphisms in the host which can be correlated with the severity of the disease. A high incidence of autoantibodies against glycoconjugates such as GM, GD1a and GD1b is found among these patients.9 Similar epitopes have been shown to occur in the lipopolysaccharide antigens of C jejuni which may represent the immunogenic stimulus. In addition, there is cross‐reactivity between antigens from C jejuni and the P2 protein of the myelin sheath which may explain the pathogenetic connection between C jejuni infection and brainstem encephalitis.8

The lymphocytic pleocytosis and raised protein level in the CSF led us to start empirical treatment for both bacterial and viral meningitis. However, the acute onset of ophthalmoplegia, generalised limb weakness and reduced level of consciousness suggested BBE (table 22).). Campylobacter was considered as an aetiological agent after a detailed history revealed that the patient had suffered an episode of diarrhoea a week before becoming acutely unwell. Subsequent serological examination confirmed the diagnosis of C jejuni infection. Although C jejuni infection can lead to a wide spectrum of neurological complications, this case did not display features consistent with a classical presentation of Miller Fisher syndrome or Guillain‐Barré syndrome.

Table thumbnail
Table 2 Diagnostic criteria of Bickerstaff's brainstem encephalitis

Further investigations of these patients include neuroimaging and electrophysiological studies. High‐intensity areas on T2‐weighted images of the brainstem, thalamus, cerebellum and cerebrum on MRI are present in approximately one‐third of patients, and these lesions can be erroneously reported as infarcts.7 EEG studies may show slow wave activity in the θ to δ range. Electromyography may reveal decreased motor nerve conduction studies, prolonged distal latency, reduced compound muscle action potential and absent or prolonged F‐waves. As in this case, these findings are highly suggestive of axonal loss. Patients may have raised levels of anti‐GQ1b IgG antibody, which is strongly associated with ophthalmoplegia.

Most patients can be managed by immunotherapy, using plasmapheresis or intra‐venous immunoglobulin either singly or in combination. Those patients who fulfil the diagnostic criteria of BBE usually have a good prognosis. Optimal effective treatment has not been established. Intravenous immunoglobulin has proved as effective as plasma exchange, while combined treatment with methylprednisolone and intravenous immunoglobulin is controversial.10,11

Take‐home messages

  • Bickerstaff's brainstem encephalitis is a rare but potentially life threatening complication of Campylobacter jejuni gastroenteritis.
  • A high index of clinical suspicion and a close liaison with laboratory staff can facilitate an early diagnosis.
  • For confirmation of the diagnosis it is essential to test sequential serum samples to demonstrate a significant rise and subsequent decline of IgM, IgG and IgA antibodies to C jejuni.

BBE is a rare but important complication of C jejuni gastroenteritis. A high index of suspicion together with a detailed history and examination are essential in making an accurate diagnosis.

Footnotes

Competing interests: None declared.

References

1. Anon Campylobacter sp. Laboratory reports of faecal isolates England & Wales, 1986–2005. http://www.hpa.org.uk/infections/topics_az/campy/data_ew.htm (accessed 30 July 2006)
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6. Winer J B. Nosological entities? Bickerstaff's encephalitis and the Miller Fisher syndrome. J Neurol Neurosurg Psychiatry 2001. 71433–435.435 [PMC free article] [PubMed]
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8. Odaka M, Yuki N, Yamada M. et al Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Gullain‐Barré syndrome. Brain 2003. 1262279–2290.2290 [PubMed]
9. Yuki N. Infectious origins of, and molecular mimicry in, Gullain‐Barré and Fisher syndromes. Lancet Infect Dis 2001. 129–37.37 [PubMed]
10. Odaka M, Tatsumoto M, Hoshiyama E. et al Side effects of combined therapy of methylprednisolone and intravenous immunoglobulin in Gullain‐Barré syndrome. Eur Neurol 2005. 53194–196.196 [PubMed]
11. Hughes R A C, Swan A V, von Koningsveld R. et al Corticosteroids for Guillain‐Barré syndrome (review). The Cochrane Library. Issue 3 2006

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