Brucellosis Spinal Epidural Abscess: A Case Series of Fourteen Patients

Objective: In the present study, we aimed to describe the clinical features, diagnosis, treatment and prognosis of Brucellosis spinal epidural abscess (BSEA). Methods: The complete clinical data of 14 BSEA patients who were treated in our hospital system from January 2014 to February 2019 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment and prognosis of 60 BSEA cases collected from the English literature from 1994 to 2019 were also investigated. Results: 3 cases were positive for blood culture, 6 cases were positive for Brucella latex agglutination test, and 9 cases were positive for tissue culture. All 14 cases showed focal spinal pain, 11 cases showed neurological decits, and 7 cases showed fever. Of the 14 cases, 12 involved the lumbosacral spine and 2 involved the cervical spine. 13 cases were cured, 1 case left limb numbness, and the follow-up time was 12-20 months. Conclusion: The classic diagnosis of triad (focal spinal pain, neurological decit and fever) is less specic for the diagnosis of BSEA. MRI examination can nd epidural abscess, brucella latex agglutination test, blood culture, tissue culture and biopsy can be used for etiological diagnosis. Brucellosis early comprehensive


Introduction
Brucellosis caused by the genus Brucella has been recognized as one of the most common zoonotic diseases in the world, affecting multiple organ systems [1]. In China, human brucellosis is still a serious public health problem. From 2007 to 2017, the number of reported cases increased by 7.8% every year [2]. Bone and joint infections are one of the common complications of human brucellosis [3], of which the spine is most commonly involved [4]. Brucella spinal epidural abscess is a rare and serious complication [5]. At present, there are few reports on Brucella spinal epidural abscess in the literature. This study mainly analyzes and discusses the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess caused by Brucella.

Clinical manifestation
This study is a retrospective case analysis. It has been approved by the Ethics Committee of Qingdao University and the patient's informed consent has been obtained. There were 7 males and 7 females, aged 45-73 years old, with an average age of 56 years. 3 cases were positive for blood culture, 6 cases were positive for Brucella latex agglutination test, and 9 cases were positive for tissue culture. 12 cases involved lumbosacral spine and 2 cases of cervical spine. All 14 cases showed different degrees of focal spinal pain, 11 cases had neurological dysfunction, and 7 cases had fever. The course of illness ranges from 7 to 240 days, with an average course of 98 days. Eight cases had a history of contact with cattle and sheep, or consumed unpasteurized dairy products. See Table 1 Table 3.

BSEA in the literature
Among the 60 cases in the literature (see Table 4), 52% were men, aged 35-75 years, with an average age of 56 years. The most common symptom is local spinal pain (100%), followed by fever (57%) and neurological impairment (52%). The most common violation is the lumbosacral spine (55%), followed by the cervical spine (35%) and the thoracic spine (17%). The positive rate of Brucella latex agglutination test was 87%, and the rate of exposure to cattle and sheep or consumption of unsterilized dairy products was 68%. 18% of cases underwent surgery. Symptoms improved 88%.

Discussion
Human brucellosis is one of the most common zoonotic infectious diseases [6,7]. It is more common among animal breeders, those who consume unpasteurized dairy products, farmers, veterinarians, and laboratory workers [8,9]. In China, human brucellosis is still a serious public health problem. From 2007 to 2017, the number of reported cases increased by 7.8% every year, and the natural foci were also more widespread [2,7,10]. Spinal epidural abscesses caused by brucellosis are rare [9,[11][12][13][14][15][16][17][18]. Among the 14 cases in this group, 8 cases had a history of contact with cattle and sheep and a history of eating unpasteurized dairy products. Among the 60 cases in the literature, 28 cases had a history of contact with cattle and sheep, and a history of eating non-pasteurized dairy products.
In this group of cases and literature, the most common clinical manifestations of SEA are focal spinal pain, neurological dysfunction, and fever, that is, the typical SEA diagnosis of triad [19]. Some patients have arthritis, low-grade fever, night sweats, fatigue, loss of appetite, hepatosplenomegaly, etc. [18,20].
The clinical symptoms of SEA are often not typical enough, with poor speci city [14], and clinical diagnosis is often delayed [21]. SEA often invades the lumbar spine, followed by the cervical and thoracic spine [5]. The most common in this group and literature review is the lumbar spine, followed by the cervical and thoracic spine. SEA requires early diagnosis and appropriate treatment to improve the prognosis [22]. CRP and ESR can be increased in the early stage of infection, and have a high speci city for the diagnosis of infection [23].
The etiological diagnosis of Brucella usually requires Brucella latex agglutination test, blood culture, tissue culture, etc. [24]. Brucella species can be cultured in blood or tissue samples to authoritatively diagnose brucellosis, but the positive rate is low. Most reports in the literature are diagnosed by brucella serology [12,25,26]. Magnetic resonance imaging (MRI) is the gold standard for diagnosis of SEA [15,27,28]. X-ray and CT are convenient and quick, and can better show the condition of bone involvement, but the diagnosis of SEA is not as good as MRI. The typical manifestations of MRI are: low signal on T1WI, high signal on T2WI, heterogeneous signal and enhanced thick-walled abscess (ring enhancement) on T1WI enhanced image [25]. Research by Xinxin Liu et al. [29] showed that, compared with tuberculous spondylitis, brucellosis spondylitis can be observed on MRI with complete vertebral height and more uniform high signal intensity.
At present, there is no guideline to guide the standardized treatment of SEA, and there are still great differences in the best clinical treatment of SEA [30]. The decision to choose non-surgical or surgical treatment for spinal epidural abscesses depends to a large extent on whether the patient has a movement disorder and whether it is at risk of developing a movement disorder [31]. Pourtaheri S et al [32]found that compared with the use of antibiotics alone, SEA patients undergoing surgery or drainage can obtain greater infection clearance and lower mortality. Historically, early surgery combined with antibacterial therapy has always been the mainstream treatment for SEA [30]. In the past 10 years, SEA medical management has been chosen by more and more people [33,34], that is, when there is no neurological dysfunction or mild neurological dysfunction, conservative treatment can be performed rst, and conservative treatment is not good. Or when the condition deteriorates, surgery is performed again; patients with mild or more neurological dysfunction should be treated immediately. In this group of cases, 11 patients (11/14) underwent surgery combined with anti-bruchella treatment. Since our hospital is a large regional tertiary medical diagnosis and treatment center and teaching hospital, most of the patients admitted are di cult and severe patients and referrals from lower-level hospitals Most of them cannot be improved with conservative treatment, so multiple operations are combined with anti-brucella treatment.
Regardless of whether it is associated with epidural abscess, Brucella infection must be treated with antibiotics once it is diagnosed [18]. The ideal antibiotic treatment plan and duration of treatment for brucella spinal abscess are still controversial [12]. The WHO recommends combining doxycycline (also known as doxycycline) and streptomycin for at least 12 weeks as the rst-line treatment [35]. Stahl JP and others recommended the use of doxycycline combined with rifampicin for antibacterial therapy [24]. Tan Hu et al. [17] recommended the use of doxycycline, rifampicin and levo oxacin for 8-12 weeks, but the speci c duration depends on the clinical response (including blood routine, ESR, CRP, renal and liver function, X-ray Film or even MRI etc.). Most cases in this group were treated with doxycycline, rifampicin and levo oxacin for 12 weeks or more. ESR, CRP, renal and liver function, and Brucella latex agglutination test titers were reviewed regularly.

Conclusions
Brucella spinal epidural abscess is clinically rare and easy to be misdiagnosed and missed. Early diagnosis, early treatment, comprehensive evaluation and comprehensive evaluation are needed to select the most suitable treatment to avoid serious complications. The classic diagnosis of triad (focal spinal pain, neurological dysfunction, and fever) has poor speci city for diagnosis of SEA. MRI is highly speci c to SEA. Blood culture and Brucella latex agglutination test are widely used in the diagnosis of Brucella. When necessary, tissue culture and biopsy can be used to assist in the diagnosis. The medical management of SEA is gradually being applied. Antibiotic therapy is still the basic treatment. For patients with progressive neurological dysfunction and those who have failed conservative treatment, surgery combined with anti-brucella therapy is feasible.

Limitation
The number of cases in this group is small, and the research design is a retrospective study. More accurate research conclusions still need prospective, multi-center randomized controlled trials.

Declarations Ethics approval
This study was approved by the ethics committees of A liated Hospital of Qingdao University.

Con ict of interest
The authors declare that they have no con ict of interest.

Informed consent
All patients involved gave written informed consent to review their medical records. All personal details were erased before analysis to cover patient data con dentiality and comply with the Declaration of Helsinki.

Consent for publication
Written informed consent was obtained from all of the patients for publication of this research and any accompanying images.