Skip to main content

First report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin: a case report



Diseases caused by nontyphoid Salmonella can range from mild, to self-limiting gastroenteritis and severe invasive infection. Relatively rarely, Salmonella may cause severe encephalopathy.

Case presentation

We report a suspected case of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin. A young man presented with impaired consciousness, ataxia, dysarthria, limb weakness, and restricted eyeball abduction. His clinical symptoms were consistent with Bickerstaff’s brainstem encephalitis.


This is the first case report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin in the literature. After treatment, he recovered and was discharged. Early antibiotic treatment of sepsis may control the disease and avoid serious encephalopathy.

Peer Review reports


Most Salmonella species that are pathogenic in humans belong to Salmonella Enteritidis. Salmonella Typhi and Salmonella Typhi A are the pathogens that cause typhoid fever, a potentially fatal disease. Diseases caused by nontyphoid Salmonella can range from mild to self-limiting gastroenteritis and severely invasive infections. Salmonella may cause severe encephalopathy, though it is relatively rare. We report a case of Bickerstaff’s brainstem encephalitis (BBE) caused by Salmonella Dublin. Cerebrospinal fluid (CSF) examination on admission was normal, as was a brain magnetic resonance imaging (MRI) scan. An anti-GQ1b antibody test was negative, and CSF protein/cell dissociation occurred 20 days after admission. During hospitalization, the patient was treated with intravenous immunoglobulin (IVIg) therapy and then discharged.

Case presentation

A 33-year-old man developed diarrhoea 1 day after eating fried pork with chili and fever the next day, with a body temperature of 40 °C. The results of blood and faecal cultures were positive for Salmonella Dublin. Influenza A virus, influenza B virus, Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory syncytial virus, Haemophilus influenzae, varicella-zoster virus, Legionella, Campylobacter and SARS-CoV-2 tests were all negative. The patient developed drowsiness after 3 days, with gradual weakening of the limbs, dysarthria, binocular abduction paralysis, and ataxia. His brain MRI scan was normal. After 5 days, the patient could not raise his limbs. These symptoms were accompanied by liver function damage and myocardial damage. After 7 days, the patient still had weakness of the limbs and dysarthria. However, as other indicators improved, he was transferred from the Intensive Care Unit ward to the Neurology ward. Physical examination of the nervous system mainly showed flaccid paralysis of the limbs, disappearance of the bilateral tendon reflex, inability to speak, ataxia (bilateral limb paralysis limited the ability to assess gait), and positive bilateral Babinski signs. At that time, lumbar puncture results for intracranial pressure, CSF protein, and CSF cell number were normal, and the CSF was cultured for 3 days with no bacterial growth. On re-examination, the brain MRI and cervical MRI were normal. As BBE was suspected clinically, IVIg therapy (0.4 g/kg) was given for 5 days, but the patient’s symptoms did not improve significantly. Twenty days after admission, lumbar puncture examination showed that the protein content had increased by 0.86 g/L (the normal range is 0.08–0.43 g/L); the cell number was normal (the number of nucleated cells was 6, normal range 0–8; the red blood cell count was 0), CSF and serum anti-GQ1b antibody was negative, and CSF anti-MOG, anti-AQP4, and anti-MBP antibodies were all negative. The results of electrophysiological examination were normal (14 days and 60 days after onset). Considering no obvious improvement, at 21 days, he was given IVIg again at the same dose for 5 days. The patient’s symptoms gradually improved, and he was able to start walking on his own. His limb collateral movement was significantly better than before, his eye movement was normal, and his voice was low. The patient’s speech could be heard clearly, and he was given speech rehabilitation training. After 3 months, the patient could walk 10 m without assistance but was unable to run (the grade of the GBS disability scale was 2) [1]. His speech also returned to normal.

Discussion and conclusion

Salmonella causes a tremendous global burden of disease [2]. It is estimated that 535,000 cases of invasive nontyphoid Salmonella infection occur globally each year [3]. The clinical manifestations caused by human salmonellosis are complicated; they can be divided according to severity into gastroenteritis, typhoid fever, sepsis, local purulent infection, and asymptomatic infection. Nontyphoid Salmonella mainly causes self-limiting diarrhoea in healthy individuals, with mild symptoms; blood-borne or focal infections are rare and mostly occur in individuals with specific risk factors [4]. Salmonella Dublin is the main pathogen causing Salmonella disease in sheep, cattle, and other animals, though it rarely causes severe symptoms in humans [5]. Salmonella Dublin belongs to Group D. Clinically, only 1% of isolates are isolated from faeces; approximately 40% are isolated from blood. The mortality rate is 20% [6]. This case is the first report of BBE caused by Salmonella Dublin. There is a previous report of BBE caused by typhoid fever and Salmonella Paratyphi A [7, 8].

BBE comprises a group of autoimmune diseases characterized by acute ophthalmoplegia, ataxia, disturbance of consciousness and/or pyramidal tract signs, with an annual incidence rate of less than 0.1 per 100,000 [9]. Although the pathogenesis is still not fully understood, most patients have a history of pre-infection with Guillain–Barré syndrome and Miller-Fisher syndrome, with symptoms such as upper respiratory tract infection and diarrhoea. It has been reported that the main pathogenic microorganisms of BBE are Mycoplasma pneumoniae [10,11,12], Campylobacter jejuni [13, 14], cytomegalovirus [15], varicella-zoster virus [7], and Epstein-Barr virus [8] (Table 1). As no evidence of Campylobacter infection was found in our patient’s blood or faeces during hospitalization, we excluded BBE caused by Campylobacter infection. The results of blood culture and faecal culture in our case indicated Salmonella Dublin infection. The patient was admitted to the hospital to consider sepsis caused by Salmonella Dublin, after which symptoms of encephalopathy appeared. The patient’s typical clinical manifestations and CSF protein/cell dissociation supported the diagnosis of BBE.

Table 1 Summary of the characteristics of Bickerstaff’s brainstem encephalitis-related cases reported in the literature

Studies have found that anti-GQlb IgG antibodies with the same specificity are prevalent in the serum of BBE patients, and approximately 66% of patients test positive for anti-GQlb IgG antibodies [18]. The titre typically reaches its peak at the beginning of the disease and decreases over time. Notably, there may be other unknown mechanisms or autoimmune targets responsible [18]. Nevertheless, the anti-GQlb IgG antibody test was negative in our case, which may be related to the late examination of the patient.

In most cases of BBE, CSF protein/cell dissociation occurs within 4 weeks of disease development. However, in a small number of cases, the disease is not accompanied by elevated protein levels [12, 13, 15,16,17]. Brain MRI examination reveals abnormal findings in approximately one-third of BBE patients, with long T2 signal lesions in the brainstem, thalamus, cerebellum, and white matter [18]. Studies have shown that abnormal MRI results are due to vasogenic cerebral oedema [19]. However, the MRI examination in the present case showed no abnormalities.

In our case, the results of blood and stool cultures indicated Salmonella Dublin infection, and the patient was admitted to the hospital to consider sepsis caused by this organism. Encephalopathy symptoms appeared days later. The current research mechanism include destruction of the blood–brain barrier via upregulated expression of autocrine MMP-9 in human brain microvascular endothelial cells [20].

Effective treatment for BBE involves immunotherapy, such as steroids, plasma exchange, and IVIg [18, 21]. However, dexamethasone is the first choice for neurological complications caused by Salmonella and Salmonella encephalopathy. Therefore, the clinical recognition of BBE and Salmonella encephalopathy is particularly important, which determines the different treatment options. In this case, the patient’s symptoms gradually improved after IVIg therapy.

In conclusion, we report a case of BBE caused by Salmonella Dublin, which needs to be brought to the attention of clinicians. When a patient is suspected of BBE caused by Salmonella Dublin,proper immunotherapy is particularly important. Of course, early antibiotic treatment of sepsis may control the disease and avoid severe encephalopathy .

Availability of data and materials

All data analysed during this study are included in this manuscript.



Bickerstaff’s brainstem encephalitis


Intravenous immunoglobulin


Magnetic resonance imaging


Cerebrospinal fluid


  1. 1.

    Hughes RA, Newsom-Davis JM, Perkin GD, Pierce JM. Controlled trial prednisolone in acute polyneuropathy. Lancet. 1978;2:750–3.

    CAS  Article  Google Scholar 

  2. 2.

    Feasey NA, Dougan G, Kingsley RA, et al. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet. 2012;379(9835):2489–3499.

    Article  Google Scholar 

  3. 3.

    GBD 2017. Non-Typhoidal Salmonella Invasive Disease Collaborators. The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019;19(12):1312–24.

    Article  Google Scholar 

  4. 4.

    Gordon MA. Salmonella infections in immunocompromised adults. J Infect. 2008;56(6):413–22.

    Article  Google Scholar 

  5. 5.

    Selander RK, Smith NH, Li J, et al. Molecular evolutionary genetics of the cattle-adapted serovar Salmonella Dublin. J Bacteriol. 1992;174(11):3587–92.

    CAS  Article  Google Scholar 

  6. 6.

    Taylor DN, Bied JM, Munro JS, et al. Salmonella dublin infections in the United States, 1979–1980. J Infect Dis. 1982;146(3):322–7.

    CAS  Article  Google Scholar 

  7. 7.

    Tagawa Y, Yuki N. Bickerstaff's brainstem encephalitis associated with shingles. J Neurol. 2000;247:218–9.

    CAS  Article  Google Scholar 

  8. 8.

    Rho YI. Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with Epstein Barr virus. Korean J Pediatr. 2014;57(10):457–60.

    Article  Google Scholar 

  9. 9.

    Koga M, Kusunoki S, Kaida K, et al. Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis: epidemiological and clinical characteristics. J Neurol Neurosurg Psychiatry. 2012;83:1210–5.

    Article  Google Scholar 

  10. 10.

    Kikuchi M, Tagawa Y, Iwamoto H, Yuki N. Bickerstaff's brainstem encephalitis associated withIgG anti-GQ1b antibody subsequent to Mycoplasmapneumoniae infection: favourable response to immunoadsorption therapy. J Child Neurol. 1997;12(6):403–5.

    CAS  Article  Google Scholar 

  11. 11.

    Steer AC, Starr M, Kornberg AJ. Bickerstaff brainstem encephalitis associated with mycoplasma pneumoniae infection. J Child Neurol. 2006;21(6):533–4.

    Article  Google Scholar 

  12. 12.

    Coriolani G, Ferranti S, Squarci G, et al. A case of Bickerstaff encephalitis associated with mycoplasma pneumoniae infection. Neurol Sci. 2020;41(6):1605–6.

    Article  Google Scholar 

  13. 13.

    Hussain AM, Flint NJ, Livsey SA, Wong R, Spiers P, Bukhari SS. Bickerstaff’s brainstem encephalitis related to campylobacter jejuni gastroenteritis. J Clin Pathol. 2007;60(10):1161–2.

    CAS  Article  Google Scholar 

  14. 14.

    Mori M, Koga M, Yuki N, et al. Bickerstaff's brainstem encephalitis after an outbreak of campylobacter jejuni enteritis. J Neuroimmunol. 2008;196(1–2):143–6.

    CAS  Article  Google Scholar 

  15. 15.

    Kanzaki A, Yabuki S, Yuki N. Bickerstaff's brain stem encephalitis associated with cytomegalovirus infection. J Neurol Neurosurg Psychiatry. 1995;58:260–1.

    CAS  Article  Google Scholar 

  16. 16.

    Wali GM. Bickerstaff's brainstem encephalitis associated with typhoid fever. Postgrad Med J. 1991;67:1011–2.

    CAS  Article  Google Scholar 

  17. 17.

    Sheng B, Ho WS, Lau KK, et al. Bickerstaff's brainstem encephalitis complicating Salmonella Paratyphi an infection. J Neurol Sci. 2011;302:108–11.

    Article  Google Scholar 

  18. 18.

    Odaka M, Yuki N, Yamada M, et al. Bickerstaff’s brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain–Barré syndrome. Brain. 2003;126:2279–90.

    Article  Google Scholar 

  19. 19.

    Weidauer S, Ziemann U, Thomalske C, et al. Vasogenic oedema in Bickerstaff’S brainstem encephalitis:a serial MRI study. Neurology. 2003;61(6):836.

    CAS  Article  Google Scholar 

  20. 20.

    Saito K, Shimizu F, et al. Blood–brain barrier destruction determines Fisher/Bickerstaff clinical phenotypes: an in vitro study. J Neurol Neurosurg Psychiatry. 2013;84:756–65.

    Article  Google Scholar 

  21. 21.

    Overell JR, Hsieh ST, et al. Treatment for fisher syndrome, bickerstaff's brainstem encephalitis and related disorders. Cochrane Database Syst Rev. 2007;24(1):CD004761.

    Google Scholar 

Download references


We would like to thank the patient for his participation in this study.



Author information




J X: case description, acquisition of data, analysis, and interpretation. T Z: acquisition of data, analysis, and interpretation. T L: critical revision of the manuscript for important intellectual content. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Tao Liu.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The patient gave written consent for their personal or clinical details along with any identifying images to be published in this study.

Competing interests

J. Xie reports no disclosures.

T. Zhang reports no disclosures.

T. Liu reports no disclosures.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xie, J., Zhang, T. & Liu, T. First report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin: a case report. BMC Neurol 21, 199 (2021).

Download citation


  • Bickerstaff’s brainstem encephalitis
  • Salmonella Dublin
  • Case report