REVIEW

C URRENT
OPINION Neurobrucellosis
Cristiane N. Soares a, Marcus Tulius T. da Silva b and Marco Antonio Lima c

Purpose of review
Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually.
Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no
typical clinical features, its diagnosis is frequently misdiagnosing by other infections.
Recent findings
Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies,
intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and
psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of
neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive
Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of
cerebrospinal fluid parameters.
Summary
Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently
goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease
in humans, as well as the disease control in animals and prevention based on occupational hygiene and
food hygiene.
Keywords
brucellosis, chronic meningitis, neurobrucellosis

INTRODUCTION 100 000 habitants [6]. However, true incidence is

Human brucellosis, also known as ‘‘undulant fever,’’ unknown and can be bigger, mainly attributable
‘‘Mediterranean fever,’’ or ‘‘Malta fever,’’ is caused to foodborne illness.
by one of the three main species of the genus Brucella Endemic areas for brucellosis include countries
sp., namely B. melitensis, B. suis, and B. abortus. of the Mediterranean basin, Middle East, Central
Worldwide, most human cases are caused by B. Asia, China, the Indian subcontinent, sub-Saharan
melitensis [1]. Africa, and parts of Mexico and Central and South
Brucella sp. are small, nonmotile, facultative America [6].
intracellular aerobic rods that in Gram staining dem- Brucellosis has also been seen among wildlife
onstrates single, tiny, gram-negative coccobacilli. animals in some regions, such as Australia and in the
Complete analysis of Brucella spp. genomes has failed USA. Brucella suis has been observed in approxi-
to identify any of the classic virulence factors [2]. mately 20% of wild swine and are associated with
It is the most common bacterial zoonosis and almost all of the human brucellosis cases reported
has a special scientific interest both as an important annually among hunters in the USA [7,8].
public health problem in many resource-limited
settings and class B bioterrorist agent [3].
This study will discuss the main aspects of Neu-
a
robrucellosis, focusing on its neurological manifes- Infectious Diseases Department (DIP 1) - Hospital Federal dos Servi-
dores do Estado, bLaboratory of Clinical Research in Neuroinfections-
tations and diagnosis, which are always challenging.
Evandro Chagas National Institute of Infectious Diseases (INI) – FIOC-
RUZ and cFundação Oswaldo Cruz, Universidade Federal do Rio de
Janeiro, RJ, Brazil
EPIDEMIOLOGY Correspondence to Cristiane N. Soares, Rua Santa Clara, 50, 1217,
Approximately 500 000 human brucellosis cases are Copacabana, 22041-012, RJ, Brazil. Tel: +55 21 3208 2084;
reported annually, and 2.4 billion people are at e-mail: [email protected]
potential risk of infection [4,5]. In some countries, Curr Opin Infect Dis 2023, 36:192–197
the prevalence rates could exceed 10 cases per DOI:10.1097/QCO.0000000000000920

www.co-infectiousdiseases.com Volume 36  Number 3  June 2023

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Neurobrucellosis Soares et al.

presentation system, avoiding attack and killing

KEY POINTS of the infected cell by the immune system [12].
 Ingestion of unpasteurized or raw dairy products is the
main source of brucellosis infection in most populations.
CLINICAL MANIFESTATIONS
 NB can affect either central or peripheral nervous Brucellosis is a multisystemic disease that may
systems at any stage of the disease.
involve joints, eyes, skin, heart, genitourinary,
 NB diagnosis is based on a combination of two and neurologic systems. According to a recent
different serological tests. Culture is the gold standard, meta-analysis, the incidence of neurological mani-
but its sensitivity is low. festations in brucellosis is 4% [13]. Neurobrucellosis
 A triple-drug regimen of antibiotics for at least 6--8 has no typical clinical features, and it may attack
weeks is recommended. either central and/or peripheral nervous systems at
any stage of the disease [14]. Meningitis, encepha-
litis, cerebrovascular disease, brain or spinal cord
abscess, myelitis, peripheral neuropathy, psychiatric
Brucellosis infection can be transmitted by sev- manifestations, and demyelinating disorders have
eral ways, including person-to-person transmission been reported (Table 1) [15–17].
(mainly by blood donation or tissue transplanta- The most common syndrome is meningitis or
tion), infection from a contaminated environment, meningoencephalitis, occurring in up to half of the
occupational exposure usually resulting from direct patients with neurological complaints (Fig. 1) [18].
contact with infected animals, and foodborne trans- Headache, fever, nausea and vomiting are frequent,
mission (by eating or drinking unpasteurized or raw and meningeal signs are observed in one-third of
dairy products, such as fresh milk, butter, and cases, but the full meningitis triad is seen in only
&
cheese) [9]. 13% [19 ]. Cranial neuropathies occurred in 19% of
Some knowledge about the means of preserving 187 patients, being the VIII nerve the most affected,
food is important for the prevention of human infec- followed by VI and VII nerves [16]. Papilledema can
tion. For instance, Brucella sp can survive up to 2 days occur either by papillitis secondary to inflammatory
in milk at 88C, up to 3 weeks in frozen meat, and up and vascular changes at optic nerves or by pseudo-
to 3 months in goat cheese. It is sensitive to heat, tumor cerebri, when raised CSF pressure is observed
ionizing radiation, and pasteurization [10]. in association with minimal or absent disturbance of
other parameters (cells, protein, and glucose levels)
[20]. Seizures are uncommon and occur in 3–11% of
PATHOGENESIS &
patients [16,19 ,21].
Brucella sp. may enter the host via ingestion or Cerebrovascular complications include ische-
inhalation, or through conjunctiva or skin abra- mic strokes, brain and subarachnoid hemorrhages,
sions. It is transmitted to humans from infected subdural hematomas, and cerebral venous throm-
animals (cattle, sheep, goats, camels, pigs, or other bosis [22]. In a group of 263 patients enrolled in the
animals) by ingestion of food or by contact with Istanbul-3 study, the prevalence of vascular compli-
tissue or fluids. cations detected on imaging was 16%, ischemic
Although rarely fatal in humans, brucellosis lesions being the most common [23]. Possible mech-
could be a disabling disease, especially if the central anisms include vasculitis leading to development of
nervous system (CNS) is affected. Typically, the
disease has a tendency to chronicity and persistence,
and can affect any organ system. The osteoarticular Table 1. Prevalence of neurological manifestations caused
system is the most involved and the nervous system by neurobrucellosis
is the second one [11]. After human being infection,
Neurological complications Prevalence
the pathogen is sequestered into the reticuloendo-
thelial system. Then, it reaches the blood stream and Behavioral changes 60% [29]
later the meninges. Lipopolysaccharides covering Meningitis 50% [18]
Brucella sp. and some bacterial proteins are probably Peripheral neuropathy 18--35.2% [33,34]
involved in the virulence and severity of disease as a
Cranial neuropathies 19% [16]
consequence [2]. Both innate and specific human
immunity are blocked by nonendotoxic lipopoly- Myelopathy 5--17% [16,31,32]
saccharides. Furthermore, these lipopolysaccharides Cerebrovascular complications 16% [23]
modify the ability of the infected cells to present Seizures
&
3--11% [16,19 ,21]
foreign antigens to the MHC class II antigen

0951-7375 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-infectiousdiseases.com 193

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

CNS infections

FIGURE 1. Leptomeningitis in a patient with neurobrucellosis. (a) Diffuse leptomeningeal thickening along the surface of the
spine cord and brain stem (T1-weighted fat suppressed). (b) Linear hyperintensity along the surface of the pons indicating
leptomeningeal thickening (Axial FLAIR). Source: [36 ].
&

mycotic aneurysms or thrombotic obliteration or language, and memory may be affected in different
septic emboli from endocarditis [16,24,25]. Most degrees [14,17,30]. Agitation, apathy, psychosis,
importantly, brucellosis should be considered in depression, and anxiety have been recorded in a
the differential diagnosis of acute vascular lesions significant percentage of patients. Scales for cogni-
in endemic areas [16]. tive assessment such as MMSE and MoCA as well as
Neurobrucellosis may present as a demyelinat- Hamilton Depression Rating Scale and Beck’s inven-
ing disorder, mimicking multiple sclerosis or acute tories for Depression and Anxiety showed abnormal
disseminated encephalomyelitis [26]. Headache, scores more frequently in patients with neurobru-
confusion, and long-tract signs are common. The cellosis when compared with patients with brucel-
nature of these lesions is not completely under- losis with no evidence of CNS invasion [14,21].
stood, but possible explanations are direct bacterial Interestingly, improvement in the neuropsycholog-
invasion or an autoimmune reaction [26]. Improve- ical tests was observed weeks after proper antibiotic
ment is usually observed after proper antibiotic treatment.
treatment and steroids [15,27,28]. Myelopathy occurs due to several mechanisms,
Psychiatric and cognitive disturbances are fre- including transverse myelitis, arachnoiditis, infarc-
quent in patients with neurobrucellosis. In a study tion, intramedullary abscess, or epidural com-
with 48 patients, 60% had behavioral changes in pression from spondylitis [18,31,32]. Prevalence
the last month prior to clinical evaluation [29]. in different studies was between 5 and 17%
Executive function, visual orientation, attention, [16,31,32]. Clinical manifestations include back

194 www.co-infectiousdiseases.com Volume 36  Number 3  June 2023

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Neurobrucellosis Soares et al.

pain, ataxia, tetraplegia or paraplegia, sphincteric Culture is the gold standard, but its sensitivity is
symptoms, paresthesia, radicular pain, and sensory low. Among 187 patients, blood cultures were pos-
level [16]. itive in 28%, while only 14% had positive CSF
Clinical or subclinical peripheral neuropathy of culture [16]. Real-time CSF PCR can be useful in
axonal type was observed in 18% of 60 patients with difficult cases but is not easily available and sensi-
acute brucellosis using nerve conduction studies tivities vary between 50 and 100% in different stud-
[33]. In another study, 12 of 34 patients (35.2%) ies [39,41]. Recently, next-generation sequencing
had clinical and electrophysiological evidence of using CSF was performed in the diagnosis of neuro-
sensorimotor neuropathy. Clinically, most patients brucellosis, providing fast results and being useful in
had absent tendon reflexes and distal hypoesthesia puzzling cases with atypical presentation or in non-
and mild to moderate weakness in the extremities endemic areas [42].
[34]. Guillain-Barre syndrome has been described in CSF abnormalities were detected in more than
&
association with brucellosis. Classical albuminocy- 90% of patients with neurobrucellosis [19 ]. Mild to
tological dissociation is present in two-thirds of moderate lymphocytic pleocytosis was frequent
patients and nerve conduction studies revealed [37]. High protein and reduced glucose levels are
demyelinating pattern in 42.1% and axonal in also observed, but severe hypoglycorrhachia is
&
31.6%. Treatment included antibiotics, plasma unusual [19 ]. CSF oligoclonal bands may be present
exchange, and intravenous immunoglobulin [35]. in some patients [27,38].
Imaging findings are diverse and frequently
mimic other neurological conditions [18]. Tuber-
DIAGNOSIS culosis, mycoses, sarcoidosis, and other granulom-
There are no typical clinical picture or CSF profile in atous diseases have similar radiological patterns and
neurobrucellosis. Diagnosis is based on the presence are more prevalent in several regions of the world,
of neurological symptoms not explained by any other making the diagnosis of neurobrucellosis challeng-
&
disease; isolation of Brucella in culture or positive ing [36 ]. Among 263 patients with neurobrucello-
serological tests in blood or CSF; abnormal CSF sis, imaging abnormalities were detected in 45% [23]
parameters (cellularity, protein, and glucose) and and can be divided into four categories: inflamma-
&
clinical response after antibiotic treatment [36 ]. tory, vascular, white matter changes, and hydro-
Serology assays are crucial for diagnosis of bru- cephalus/brain edema [18,23]. Inflammatory
cellosis. There are several methods, including Rose lesions are the most frequent and include contrast
Bengal slide agglutination test, Serum agglutination enhancement of leptomeninges, cranial nerves, spi-
test (SAT), Microagglutination test (MAT), Indirect nal roots, arachnoiditis, brain and spinal cord gran-
Coombs (antihuman globulin) test, ELISA, indirect ulomas and abscess. Lacunar infarcts, small brain
fluorescent antibody test (IFA), and immunochro- hemorrhages, venous thrombosis, mycotic aneur-
matographic lateral flow assay [37–39]. The inter- isms, and subarachnoid hemorrhage occur due to
pretation of the results should contemplate vessel inflammation or septic emboli. Demyelina-
epidemiological aspects and chronicity of infection. tion in neurobrucellosis is not frequent but occurs in
Individuals from endemic areas may have persistent three distinct patterns: diffuse, periventricular, and
low titers of antibodies against Brucella antigens due focal [18].
to past exposure and not current infection. The most Nonspecific electroencephalographic abnor-
used nowadays are SAT and ELISA. SAT has been malities were observed in 20% of neurobrucellosis
used for years and titers more than 1 : 160 are con- patients; however, these findings have disappeared
sidered positive in nonendemic areas, while titers after treatment [29].
more than 1 : 320 are positive in endemic zones [1].
This test is not suitable for diagnosis of B. canis
infection [1]. In suspected cases, wherein initial test TREATMENT
was negative, it should be repeated in 2–3 weeks. Neurobrucellosis treatment consists of a combina-
Seroconversion or at least four-fold increase in anti- tion of antibiotics. A triple-drug regimen is the best
bodies titer is diagnostic [40]. ELISA has good sensi- choice, as monotherapy and a dual antibiotics regi-
tivity and specificity and provides rapid diagnosis. It men were associated with a higher risk of failure,
reveals total and specific immunoglobulin types when administered for a similar duration [43]. The
(IgG, IgA, and IgM) and is particularly useful for antibiotics selection should regard its permeability
chronic cases and in the diagnosis of neurobrucel- to CSF. Therefore, the third-generation cephalospor-
losis [39,40]. In order to improve diagnostic accu- ins (such as ceftriaxone and cefotaxime), rifampicin,
racy, combination of serological tests (STA and and co-trimoxazole have a good penetration in CNS
&
Coombs or STA and ELISA) can be used [36 ]. and should be combined [44]. Ceftriaxone (4 g/day)

0951-7375 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-infectiousdiseases.com 195

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

CNS infections

for the first 4–6 weeks, in addition to rifampin and unknown infection should be considered for
at 15 mg/kg/day (600–900 mg) and doxycycline neurobrucellosis investigation, in endemic areas.
(100 mg twice a day), for at least 12 weeks, are
considered the first-line therapy. In cases of ceph- Acknowledgements
alosporins allergy, quinolones could replace it. None.
Another practical regimen is the combination of
doxycycline, rifampin, and trimethoprim/sulfame- Financial support and sponsorship
thoxazole (TMP-SMX). Treatment should be None.
administered for 6–8 weeks or longer, as a relapse
rate is usually high in brucellosis (5–15%) [45]. Conflicts of interest
Hence, patients should be followed up every
There are no conflicts of interest.
3 months, until at least 2 years. Treatment should
remain until the clinical manifestations vanish and
the CSF returns to normal [29]. REFERENCES AND RECOMMENDED
There is no consensus treatment for pregnant READING
women, neonates, and children under eight. For Papers of particular interest, published within the annual period of review, have
been highlighted as:
children, options include trimethoprim/sulfame- & of special interest
thoxazole (co-trimoxazole) combined with an ami- && of outstanding interest

noglycoside (streptomycin, gentamycin) or 1. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med
rifampicin. For pregnancy, co-trimoxazole and 2005; 352:2325–2336.
2. Lapaque N, Moriyon I, Moreno E, Gorvel JP. Brucella lipopolysaccharide acts
rifampicin have been used in brucellosis cases with as a virulence factor. Curr Opin Microbiol 2005; 8:60–66.
some success [10]. 3. Greenfield RA, Drevets DA, Machado LJ, et al. Bacterial pathogens as
biological weapons and agents of bioterrorism. Am J Med Sci 2002;
The effectiveness of corticosteroids in neurobru- 323:299–315.
cellosis was not validated, until nowadays. However, 4. Bosilkovski M, Dimzova M, Grozdanovski K. Natural history of brucellosis in an
endemic region in different time periods. Acta Clin Croat 2009; 48:4.
they have been used in severe presentations such as 5. Jennings GJ, Hajjeh RA, Girgis FY, et al. Brucellosis as a cause of acute febrile
arachnoiditis, cranial nerve involvement, myelop- illness in Egypt. Trans R Soc Trop Med Hyg 2007; 101:707–713.
6. Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human
athy, demyelinating lesions, high intracranial pres- brucellosis. Lancet Infect Dis 2006; 6:91–99.
sure, and optic neuritis/ papilledema [27]. As it 7. Centers for Disease Control (CDC). Brucellosis Reference Guide: exposures,
testing, and prevention. In: Brucellosis Reference Guide. First Edition. Edited
seems to reduce the incidence of long-term compli- by: CDC. Atlanta: 2017. pp. 1–32. https://www.cdc.gov/brucellosis/pdf/
&
cation, we tend to support its use [36 ]. brucellosi-reference-guide.pdf.
8. Eales KM, Norton RE, Ketheesan N. Brucellosis in northern Australia. Am J
Trop Med Hyg 2010; 83:876–878.
9. Zheng N, Wang W, Zhang JT, et al. Neurobrucellosis. Int J Neurosci 2018;
PROGNOSIS 128:55–62.
10. Corbel MJ. Brucellosis in humans and animals. WHO: Geneva; 2006; 89.
Mortality rates in neurobrucellosis cases have been 11. Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect
Dis 2007; 7:775–786.
reported between 0 and 27% [29]. Neurological 12. Forestier C, Moreno E, Pizarro-Cerda J, Gorvel JP. Lysosomal accumulation
sequelae such as facial palsy, paraparesis, and uri- and recycling of lipopolysaccharide to the cell surface of murine macro-
phages, an in vitro and in vivo study. J Immunol 1999; 162:6784–6791.
nary incontinence have been described, but the 13. Dean AS, Crump L, Greter H, et al. Clinical manifestations of human
most common complication seems to be deafness brucellosis: a systematic review and meta-analysis. PLoS Negl Trop Dis
2012; 6:e1929.
(20–30%) [46]. 14. Esmael A, Elsherif M, Elegezy M, Egilla H. Cognitive impairment and neu-
Prevention of brucellosis is based on surveil- ropsychiatric manifestations of neurobrucellosis. Neurol Res janeiro de 2021;
43:1–8.
lance, and the most effective prevention strategy 15. Abrahão A, de Aquino CCH, Pedroso JL, et al. Teaching NeuroImages:
is the disease elimination in animals. Vaccination brucellosis mimicking demyelinating disease. Neurology 2011; 76:e51.
16. Gul HC, Erdem H, Bek S. Overview of neurobrucellosis: a pooled analysis of
programs of cattle, goats, and sheep and pasteuriza- 187 cases. Int J Infect Dis 2009; 13:e339–e343.
tion of milk should be implanted in endemic 17. Shehata GA, Abdel-Baky L, Rashed H, Elamin H. Neuropsychiatric evaluation
of patients with brucellosis. J Neurovirol 2010; 16:48–55.
areas [10]. 18. Kizilkilic O, Calli C. Neurobrucellosis. Neuroimaging Clin N Am 2011;
21:927–937.
19. Naderi H, Sheybani F, Parsa A, et al. Neurobrucellosis: report of 54 cases.
CONCLUSION Trop Med Health 2022; 50:77.
&

A 10-year cross-sectional study of hospitalized adults with neurobrucellosis.

20. Sharma PP, Murali MV, Hamdi T. Neurobrucellosis presenting as Pseudotu-
Although brucellosis is found globally and consid- mor Cerebri: first report from Oman. Oman Med J 2017; 32:507–509.
ered one of the most common public health prob- 21. Eren S, Bayam G, Ergön€ ul O, et al. Cognitive and emotional changes in
neurobrucellosis. J Infect 2006; 53:184–189.
lems worldwide, its diagnosis remains often 22. Guan Y, Xu N, Yao Y, et al. Subarachnoid hemorrhage secondary to
unrecognized and frequently unreported. Other Brucella-induced cerebral aneurysm: a case report. BMC Infect Dis
2021; 21:720.
chronic infections, such as tuberculosis, are usually 23. Erdem H, Senbayrak S, Meriç K, et al. Cranial imaging findings in neurobru-
confounded by neurobrucellosis, resulting in diag- cellosis: results of Istanbul-3 study. Infection 2016; 44:623–631.
24. Hadjinikolaou L, Triposkiadis F, Zairis M, et al. Successful management of
nostic and treatment delays. Hence, patients with Brucella mellitensis endocarditis with combined medical and surgical ap-
neurological complications coursing with a chronic proach. Eur J Cardiothorac Surg 2001; 19:806–810.

196 www.co-infectiousdiseases.com Volume 36  Number 3  June 2023

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Neurobrucellosis Soares et al.

25. Altekin RE, Karakas MS, Yanikoglu A, et al. Aortic valve endocarditis and 36. Soares CN, Angelim AIM, Brandão CO, et al. Neurobrucellosis: the great
cerebral mycotic aneurysm due to brucellosis. J Cardiol Cases 2011; 4: & mimicker. Rev Soc Bras Med Trop 2022; 55:e05672021.
e179–e182. A recent review about the main neurobrucellosis topics.
26. Al-Sous MW, Bohlega S, Al-Kawi MZ, et al. Neurobrucellosis: clinical and 37. Erdem H, Kilic S, Sener B, et al. Diagnosis of chronic brucella meningitis and
neuroimaging correlation. AJNR Am J Neuroradiol 2004; 25:395–401. meningoencephalitis: the results of the Istanbul-2 study. Clin Microbiol Infect
27. Ata F, Yousaf Z, Sharif MK, Abdallah A. Demyelinating steroid-responsive 2013; 19:E80–E86.
neurobrucellosis. BMJ Case Rep 2020; 13:e233798. 38. Pascual J, Combarros O, Polo JM, Berciano J. Localized CNS brucellosis:
28. Karaoglan I, Akcali A, Ozkur A, Namýdurua M. Neurobrucellosis mimicking report of 7 cases. Acta Neurol Scand 1988; 78:282–289.
demyelinizating disorders. Ann Saudi Med 2008; 28:148–149. 39. Araj GF. Update on laboratory diagnosis of human brucellosis. Int J Antimicrob
29. Guven T, Ugurlu K, Ergonul O, et al. Neurobrucellosis: clinical and diagnostic Agents 2010; 36(Suppl 1):S12–S17.
features. Clin Infect Dis 2013; 56:1407–1412. 40. Yagupsky P, Morata P, Colmenero JD. Laboratory diagnosis of human
30. Bahemuka M, Shemena AR, Panayiotopoulos CP, et al. Neurological syn- brucellosis. Clin Microbiol Rev 2019; 33:e00073–e19.
dromes of brucellosis. J Neurol Neurosurg Psychiatry 1988; 51:1017–1021. 41. Colmenero J, Queipo-Ortuno M, Reguera J, et al. Real time polymerase chain
31. Turgut M, Turgut AT, Koşar U. Spinal brucellosis: Turkish experience based on reaction: a new powerful tool for the diagnosis of neurobrucellosis. J Neurol
452 cases published during the last century. Acta Neurochir (Wien) 2006; Neurosurg Psychiatry 2005; 76:1025–1027.
148:1033–1044. 42. Fan S, Ren H, Wei Y, et al. Next-generation sequencing of the cerebrospinal
32. G€und€uz T, Tekt€urk PT, Yap̌ˇičˇi Z, et al. Characteristics of isolated spinal cord fluid in the diagnosis of neurobrucellosis. Int J Infect Dis 2018; 67:20–24.
involvement in neurobrucellosis with no corresponding MRI activity: a case 43. Skalsky K, Yahav D, Bishara J, et al. Treatment of human brucellosis:
report and review of the literature. J Neurol Sci 2017; 372:305–306. systematic review and metaanalysis of randomised controlled trials. BMJ
33. Sanivar H, Ozlece HK, Huseyinoglu N, et al. Frequency of subclinical 2008; 336:701–704.
peripheral neuropathy in cases of untreated brucellosis. J Infect Dev Ctries 44. Patra S, Eshwara VK, Pai AR, et al. Evaluation of clinical, diagnostic features
2017; 11:753–758. and therapeutic outcome of neurobrucellosis: a case series and review of
34. Kutlu G, Ertem GT, Coskun O, et al. Brucella: a cause of peripheral neuro- literature. Int J Neurosci 2022; 132:1080–1090.
pathy. Eur Neurol 2009; 61:33–38. 45. Zhao S, Liao YCY, Zhang Z, et al. Treatment efficacy and risk factors of
35. Alanazi A, Al Najjar S, Madkhali J, et al. Acute brucellosis with a Guillain-Barre neurobrucellosis. Med Sci Monit 2016; 22:1005–1012.
syndrome-like presentation: a case report and literature review. Infect Dis Rep 46. Dreshaj S, Shala N, Dreshaj G, et al. Clinical manifestations in 82 neuro-
2021; 13:1–10. brucellosis patients from Kosovo. Mater Sociomed 2016; 28:408–411.

0951-7375 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-infectiousdiseases.com 197

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.