key: cord-0017463-k7st0t7a authors: Xie, Jiangbo; Zhang, Tingting; Liu, Tao title: First report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin: a case report date: 2021-05-15 journal: BMC Neurol DOI: 10.1186/s12883-021-02230-8 sha: f65fdd5213903b88c8b79c0159260f22aa5ba929 doc_id: 17463 cord_uid: k7st0t7a BACKGROUND: 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. CONCLUSIONS: 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. 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 selflimiting 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. 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. 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 preinfection 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] , varicellazoster 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. 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 . Abbreviations BBE: Bickerstaff's brainstem encephalitis; IVIg: Intravenous immunoglobulin; MRI: Magnetic resonance imaging; CSF: Cerebrospinal fluid Controlled trial prednisolone in acute polyneuropathy Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa 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 Salmonella infections in immunocompromised adults Molecular evolutionary genetics of the cattle-adapted serovar Salmonella Dublin Salmonella dublin infections in the United States, 1979-1980 Bickerstaff's brainstem encephalitis associated with shingles Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with Epstein Barr virus Nationwide survey of patients in Japan with Bickerstaff brainstem encephalitis: epidemiological and clinical characteristics Bickerstaff's brainstem encephalitis associated withIgG anti-GQ1b antibody subsequent to Mycoplasmapneumoniae infection: favourable response to immunoadsorption therapy Bickerstaff brainstem encephalitis associated with mycoplasma pneumoniae infection A case of Bickerstaff encephalitis associated with mycoplasma pneumoniae infection Bickerstaff's brainstem encephalitis related to campylobacter jejuni gastroenteritis Bickerstaff's brainstem encephalitis after an outbreak of campylobacter jejuni enteritis Bickerstaff's brain stem encephalitis associated with cytomegalovirus infection Bickerstaff's brainstem encephalitis associated with typhoid fever Bickerstaff's brainstem encephalitis complicating Salmonella Paratyphi an infection Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain-Barré syndrome Vasogenic oedema in Bickerstaff'S brainstem encephalitis:a serial MRI study Blood-brain barrier destruction determines Fisher/ Bickerstaff clinical phenotypes: an in vitro study Treatment for fisher syndrome, bickerstaff's brainstem encephalitis and related disorders Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations We would like to thank the patient for his participation in this study. Authors' contributions 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. None. All data analysed during this study are included in this manuscript. Ethics approval and consent to participate Not applicable. The patient gave written consent for their personal or clinical details along with any identifying images to be published in this study.