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Introduction: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB., Clinical Findings: We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision., Diagnosis: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients., Conclusion: NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella., (© 2024. The Author(s).)

Purpose: Central nervous system involvement by Brucella species is the most morbid form of brucellosis disease. Studies on neurobrucellosis are scarce and limited to case reports and series. Brucella is unable to infect or harm neurons without the assistance of monocytes. This raises the question of whether ceftriaxone-based regimens are effective., Methods: The primary aim of this study was to identify, evaluate, and summarize the findings of all relevant individual studies in the past 30 years to help better understand the disease. To achieve this, a broad systematic search was undertaken to identify all relevant records. Epidemiological and clinical features of the disease were assessed by the pooled analysis of descriptive studies. Through a meta-analysis, the treatment period duration was compared between the ceftriaxone-based and oral regimens using Standardized mean differences to measure effect size., Results: 448 patients were included in the Meta-analyses from 5 studies. A moderate positive effect was found for ceftriaxone-based regimens over oral treatments, and there was a significant difference between these two groups (SMD 0.428, 95% CI -0.63 to -0.22, I 2 = 37.64). Neurobrucellosis has a different clinical picture in pediatric patients. The disease is less chronic in children. Fever, nausea and vomiting, fatigue, and abdominal pain were significantly more prevalent symptoms in children, and Convulsions, ascites, sensorineural hearing loss, and papilledema were significantly more prevalent signs in children than adults., Conclusion: It is recommended to initiate the treatment of neurobrucellosis with IV ceftriaxone therapy in combination with oral therapy.

Introduction: Brucellosis is a zoonotic disease, caused by a Gram-negative coccobacillus of Brucella genus, transmitted to humans by animals, especially cattle. It rarely involves the nervous system (neurobrucellosis); only a few cases present with hearing loss. We report a case of neurobrucellosis, that presented with bilateral sensorineural hearing loss and mild to moderate persistent headache. To the best of our knowledge, this is the first well-documented case from Nepal., Case Presentation: The patient was a 40-year-old Asian male shepherd from the western mountainous region of Nepal who came to the emergency department of Manipal Teaching Hospital, Pokhara in May, 2018 and did a follow-up for 6 months. He presented with high-grade fever, profuse sweating, headache, myalgia, and bilateral sensorineural hearing loss. His history of consuming raw milk of cattle, symptoms including persistent mild to moderate headache, bilateral hearing loss, and serological findings were suggestive of neurobrucellosis. Following treatment, the symptoms improved, including the complete recovery of hearing loss., Conclusion: Hearing loss may be the manifestation of neurobrucellosis. Physicians should know about such presentations in brucella endemic areas., (© 2023. The Author(s).)

Aim: In this study, we aimed to discuss the clinical features, laboratory findings, treatment and outcome of seven cases of neurobrucellosis from a tertiary care center and review the available global literature., Materials and Methods: The diagnosis of neurobrucellosis was established using the following criteria in our setting: (1) signs and symptoms of neurological infection with examination of cerebrospinal fluid (CSF) revealing signs of meningitis, (2) isolation of Brucella spp. from blood and/or CSF and/or antibody titer ≥1:160 in serum using standard agglutination test (SAT) and/or the presence of anti-Brucella antibodies in CSF and/or detection of Brucella spp.-specific DNA from CSF using PCR. A literature search was performed to review previous cases of neurobrucellosis published worldwide during the last 30 years., Results: The proportion of neurobrucellosis was 2.8% in our setting. Fever with headache and altered sensorium were the major presenting complaints. Brucella melitensis was isolated from blood culture in 6 patients. From the literature search, a total of 221 cases of neurobrucellosis were reviewed and analyzed. Meningitis (32.6%), loss of hearing (25.8%) and encephalitis (14.9%) were the most common clinical features. Involvement of cranial nerves, polyradiculopathy and paraplegia were the major complications found in patients with neurobrucellosis., Conclusions: Neurobrucellosis should always be considered in the differential diagnosis of befitting neurological, rheumatological, and neuropsychiatric presentations in endemic regions for brucellosis. To prevent morbidity and mortality associated with neurobrucellosis, a multimodal diagnostic approach is essential for early and accurate diagnosis and effective treatment.

Fatal meningoencephalitis due to Brucella ceti infection has been described in striped dolphins (Stenella coeruleoalba), Atlantic white-sided dolphins (Lagenorhynchus acutus), short-beaked common dolphins (Delphinus delphis) and long-finned pilot whales (Globicephala melas), which are all within the family Delphinidae. We report B. ceti-associated neurobrucellosis in three juvenile male Sowerby's beaked whales (Mesoplodon bidens) that all had typical lesions of lymphocytic meningoencephalitis, which increased in severity from rostral to caudal regions of the brain. In two cases there was loss of ependymal cells lining the cerebral ventricular system, with large numbers of lymphocytes in the underlying neuropil. This finding suggests that B. ceti gains access to, and multiplies in, the cerebrospinal fluid, and confirms that this is the sample of choice for bacteriological recovery of the causative organism. These findings expand the increasing range of cetaceans susceptible to neurobrucellosis to members of the family Ziphiidae., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Neurobrucellosis is the most serious complication of brucellosis with neither a typical clinical manifestations nor a specific cerebrospinal fluid (CSF) picture and mimics other neurological disorders leading to diagnostic dilemma. The prevalence of Neurobrucellosis ranges from 1.7 to 10% of brucellosis worldwide. This present study highlights the integrated diagnostic and clinical approaches in the diagnosis of neurobrucellosis. Cases with neurological abnormalities associated with abnormal CSF findings were included in the study. Serum and CSF samples were subjected to Rose Bengal Plate Test (RBPT), standard tube agglutination test (STAT), indirect Enzyme linked immunosorbent assay (iELISA) for IgM & IgG antibodies and polymerase chain reaction (PCR) to detect BCSP31 gene. Out of 473 cases, 278 (58.8%) were positive in serum and/or CSF by any of the methods. Out of 278, Only IgM anti-brucella antibody was positive in 105 (22.19%) cases. 122 (25.79%) cases were positive by any of the diagnostic methods in serum and not in CSF whereas 51(10.78%) cases were positive in serum and CSF and these 51 cases were considered as Neurobrucellosis among patients presenting with neurological illness. Chronic meningitis was the most common form of presentation. Multimodal differential diagnostic approaches are crucial for accurate diagnosis, effective treatment and to prevent morbidity and mortality associated with neurobrucellosis., Competing Interests: Declaration of Competing Interest We declare that we have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bacteria of the genus Brucella cause brucellosis, an infectious disease common to humans as well as to terrestrial and aquatic mammals. Since 1994 several cases of Brucella spp. infection have been reported in marine mammals worldwide. While sero-epidemiological data suggest that Brucella spp. infection is widespread globally, detecting Brucella spp.-associated antigens by immunohistochemistry (IHC) in tissues from infected animals is often troublesome. The present study was aimed at investigating, by means of IHC based upon the utilization of an anti-Brucella LPS monoclonal antibody (MAb), the central nervous system (CNS) immunoreactivity shown by B. ceti-infected, neurobrucellosis-affected striped dolphins. The aforementioned MAb, previously characterized by means of ELISA and Western Blotting techniques, was able to immunohistochemically detect smooth brucellae both within the CNS from B. ceti-infected striped dolphins and within a range of tissues from Brucella spp.-infected domestic ruminants. In conclusion, the results of the present study are of relevance both from the B. ceti infection's diagnostic and pathogenetic standpoints.

Background: Brucellosis is the most common zoonotic infection in the world. Brucellosis with nervous system involvement is known as 'neurobrucellosis' (NB). The diagnosis of NB is difficult because its clinical manifestations are non-specific and the sensitivity of routine culture tests is low., Methods: Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) was used to detect pathogens in patients with clinically suspected central nervous system (CNS) infections at a tertiary referral center in China between June 1, 2016 and June 1, 2017. The clinical characteristics and NGS results of patients with the diagnosis of NB were reviewed in this study., Results: Four patients were rapidly diagnosed with NB using NGS of the CSF in patients with clinically suspected CNS infections, although the clinical manifestations varied dramatically between these patients. NGS of the CSF revealed that the sequence reads identified that corresponded to Brucella species ranged from 11 to 104, with genomic coverage ranging from 0.043% to 0.4%. Rapid diagnosis led to prompt treatment with the appropriate antibiotics., Conclusions: This study demonstrates the power of NGS of the CSF coupled with a bioinformatic pipeline in the diagnosis of NB., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen.

Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed.

Background: Brucellosis is a zoonotic disease caused by Brucella infection, which is common in pastoral areas. Neurological involvement in brucellosis is relatively rare. But since 1993, continuous studies have been reporting neurological complications of brucellosis, collectively referred to as neurobrucellosis. A bibliometric analysis of existing literature outlines current research progress and gaps and provides guidance for the clinical treatment of neurobrucellosis, promoting patient health in the process of guiding clinical practice, and improving their quality of life. Methods: CiteSpace and VOSviewer are software tools to visualize research trends and networks. By selecting specific areas of interest and configuring the right parameters, the tools can visualize past research data. The study retrieved the literature from the Web of Science Core Collection Database and downloaded it in plain text file format. Citespace6.1.6, VOSviewer v1.6.20, and Microsoft Excel 16.59 were used for analyzing the following terms: countries, institutions, authors' cooperation, journals, keywords, and co-citation. Results: There are eight key results. (1) The publication volume shows a general upward trend. (2) Turkey is the country with the highest publication volume and contributing institutions. (3) Giambartolomei GH, Gul HC, and Namiduru M are the authors with the highest number of publications. (4) Neurology is the journal that published the highest number of related articles (n = 12). (5) "Diagnosis," "meningitis," and "features" are the top three frequently occurring keywords. (6) Keyword clusters show "antibiotic therapy" and "cerebrospinal fluid" have future study value. (7) The burst analysis of the keywords also indicates that "cerebrospinal fluid" may become a prominent keyword in future research. (8) The co-citation analysis concludes three categories of the cited articles, which are diagnosis, therapy, and complications, indicating the past research direction. Conclusion: This study highlights the complexity of neurobrucellosis, presenting the need for advanced diagnostic techniques and multifaceted treatment approaches. While antibiotics remain the cornerstone of therapy, the use of corticosteroids to mitigate inflammatory responses shows promise, albeit with concerns about potential sequelae and relapse. Future research should focus on refining therapeutic strategies that address both the direct effects of infection and the broader immunological impacts to improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Brucellosis, a zoonotic disease caused by Brucella species, poses a significant global health concern. Among its diverse clinical manifestations, neurobrucellosis remains an infrequent yet debilitating complication. Here, we present a rare case of neurobrucellosis with unusual presentations in a 45-year-old woman. The patient's clinical course included progressive lower extremity weakness, muscle wasting, and double vision, prompting a comprehensive diagnostic evaluation. Notable findings included polyneuropathy, elevated brucella agglutination titers in both cerebrospinal fluid and blood, abnormal EMG-NCV tests, and resolving symptoms with antibiotic therapy. The clinical presentation, diagnostic challenges, and differentiation from other neurological conditions are discussed. This case underscores the importance of considering neurobrucellosis in regions where brucellosis is prevalent and highlights this rare neurological complication's distinctive clinical and radiological features. Early recognition and appropriate treatment are crucial to mitigate the significant morbidity associated with neurobrucellosis. [ABSTRACT FROM AUTHOR]

Brucellosis is the most common bacterial zoonosis and it causes approx half million human infections per year worldwide. Neurobrucelosis should be considered as possible differential diagnosis when a patient presents with symptomps of neruropasychiatric spectrum and fever. We report a case of neurobrucellosis in a patient who presented with headache, vomiting and an episode of generalized tonic clonic seizure.

Inflammation plays a key role in the pathogenesis of neurobrucellosis where glial cell interactions are at the root of this pathological condition. In this study, we present evidence indicating that soluble factors secreted by Brucella abortus-infected astrocytes activate microglia to induce neuronal death. Culture supernatants (SN) from B. abortus-infected astrocytes induce the release of pro-inflammatory mediators and the increase of the microglial phagocytic capacity, which are two key features in the execution of live neurons by primary phagocytosis, a recently described mechanism whereby B. abortus-activated microglia kills neurons by phagocytosing them. IL-6 neutralization completely abrogates neuronal loss. IL-6 is solely involved in increasing the phagocytic capacity of activated microglia as induced by SN from B. abortus-infected astrocytes and does not participate in their inflammatory activation. Both autocrine microglia-derived and paracrine astrocyte-secreted IL-6 endow microglial cells with up-regulated phagocytic capacity that allows them to phagocytose neurons. Blocking of IL-6 signaling by soluble gp130 abrogates microglial phagocytosis and concomitant neuronal death, indicating that IL-6 activates microglia via trans-signaling. Altogether, these results demonstrate that soluble factors secreted by B. abortus-infected astrocytes activate microglia to induce, via IL-6 trans-signaling, the death of neurons. IL-6 signaling inhibition may thus be considered a strategy to control inflammation and CNS damage in neurobrucellosis. [ABSTRACT FROM AUTHOR]

Brucellosis, caused by Brucella, dominates in the Middle East. Acute or chronic brucellosis can involve any organ system, and the involvement of the central nervous system leads to encephalitis, called neurobrucellosis (NB). We report a rare case from north India where a variant of Brucella caused NB led to progressive labyrinthine dysfunction; who developed vertigo, disequilibrium, and gradual progressive sensorineural (SN) hearing loss. Audiological tests pure-tone audiometry (PTA), otoacoustic emissions (OAE), stapedial muscle reflexes, auditory evoked brainstem responses (ABR), and vestibular evoked myogenic potentials (VEMPs) were conducted on the patients. PTA showed a bilateral profound SN hearing loss, an absent OAE, and ABR suggestive of cochlear dysfunction. The cervical and ocular VEMP showed delayed n1 and p1 latencies, suggesting superior and inferior nerve branch involvement. Vertigo or disequilibrium and SN hearing loss can be the late-onset manifestations of labyrinthine dysfunction in chronic Brucella-induced encephalitis. [ABSTRACT FROM AUTHOR]

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Neurobrucellosis is a serious focal brucella infection. Ventriculitis is a special form of central nervous infection where pyogenic infection of the ependymal linings hinders antibiotics' accessibility to the cerebrospinal fluids and leads to protracted infection. We present a case of a 37-year-old Shepherd who had low-grade fever for 5 months followed by a brief history of vomiting, abdominal pain, and gait imbalance. Investigations showed neutrophilic leukocytosis, high titers of serum anti-brucella antibodies, and lymphocytic pleocytosis. Mycobacterial tuberculosis workup was negative. Magnetic resonance imaging of the brain revealed cervical and spinal meningeal enhancement in addition to mild hydrocephalus. The patient was presumptively diagnosed with neurobrucellosis. He received treatment with ceftriaxone-based combination antibiotics therapy for 6 months with complete resolution of his symptoms. Central nervous infection by brucella is a challenging diagnosis. The possibility of primary ventriculitis due to Brucella infection mandates early recognition and prolonged antimicrobial therapy to achieve full recovery. [ABSTRACT FROM AUTHOR]

Background: Neurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF. Methods: Between August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed. Results: Among the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1–4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1. Conclusion: NGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice. [ABSTRACT FROM AUTHOR]

In India, brucellosis is an often neglected zoonotic disease. Consumption of unpasteurized milk causes transmission of this infection to humans. Brucellosis can affect any organ in the body including the brain. However, the diagnosis is often missed as the clinical presentation of neurobrucellosis is atypical and can be confused with other diseases such as tuberculosis and Lyme disease. Therefore, laboratory investigations are critical for the diagnosis of this infection. Drugs such as doxycycline, rifampicin, and ceftriaxone are useful in the treatment of neurobrucellosis as it penetrates well into the central nervous system (CNS). We report a case of a 45-year-old man presenting with meningitis caused by Brucella melitensis because of the relative rarity of the neurobrucellosis in India. [ABSTRACT FROM AUTHOR]

Brucellosis is one of the most frequent zoonotic diseases worldwide. Central nervous system (CNS) involvment has been reported among approximately 5% of patients. Sensorineural hearing loss (SNHL) has been considered as a popular clinical consequence of brucellosis and neurobrucellosis (NB). In this study, we present two cases of neurobrucellosis with bilateral SNHL who were succesfully managed by cochlear implantation (CI). case 1 was 52 year-old woman was admitted to another hospital 10 years ago with diagnosis of neurobrucellosis then she developed bilateral severe SNHL. There was no benefit of using hearing aid and she was found to be suitable for cochlear implantation. After the operation her audiological evaluation reflected aided Pure Tone Average (PTA) of 15 dB HL and Word recognition Score (WRS) in quiet (at 65 dB HL) was 80%. Case 2 A 48 year-old woman was admitted to our center and diagnosed as a case of neurobrucellosis. Two months later she had suffered from bilateral progressive hearing loss. Her hearing assessment showed bilateral profound SNHL and she used hearing aids but without benefit. After successful treatment of her illness, she was accepted for unilateral cochlear implant and underwent right CI. The most recent audiological evaluation reflected aided PTA of 27.5 dB HL. WRS in quiet (at 65 dB HL) was 84%.conclusion: cochlear implantation may be considered as good alternative for hearing rehabilitation in neurobrucellosis patients. Further research is warranted to build standard approach. [ABSTRACT FROM AUTHOR]

A zoonotic disease called brucellosis can cause flu-like symptoms and heart inflammation. The bacteria responsible for this disease can also enter the brain, causing a condition called neurobrucellosis that can result in long-term neurological problems. In this study, researchers aimed to determine the changes in the hippocampal cells of rats infected with Brucella. For the study, 24 adult male albino rats were inoculated with 1 × 106 CFU Brucella abortus 544. The rats were then deeply anesthetized, and their hippocampus samples were taken for stereological, histological, and molecular studies. The results showed that the infected rats had increased microgliosis and astrogliosis. Furthermore, a high level of caspase-3 in their hippocampal tissue indicated their susceptibility to apoptosis. Additionally, there was a decrease in expression of Ki67, which further supported this. Sholl's analysis confirmed a significant failure in glial morphology. The study demonstrated that the pathogen has the ability to destroy the hippocampus and potentially affect its normal physiology. However, more research is needed to clarify various aspects of neurobrucellosis. • Brucella increases astrogliosis and changes the morphological characteristics of astrocytes in the hippocampus. • Brucella Increases microgliosis in rats' hippocampus and alters microglia cells' morphological characteristics. • Brucella infection induces the expression of caspase-3 in Pyramidal cells and reduces neurogenesis in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: Brucellosis is among the most widespread zoonotic diseases worldwide. Although rare, nervous system involvement due to Brucella infection is a major diagnostic challenge in endemic regions. Patients and methods: This study was a cross-sectional investigation of hospitalized adults with neurobrucellosis from March 2007 to February 2017. We described the clinical characteristics, radiographical and laboratory features, and clinical outcomes of patients with neurobrucellosis. Results: Fifty-four patients with neurobrucellosis were included. The median age was 35 (interquartile range, 25–50) years, and 32 (59%) cases were male. Thirty-four (63%) patients were stockmen or shepherds. The most common clinical manifestations were fever in 49 (91%) cases, headache in 47 (87%), decreased consciousness in 12 (22%), and seizures in 6 (11%). Meningeal signs were detected in 36 (67%) cases. Brucella species were isolated in five cases from blood or cerebrospinal fluid (CSF). The median of CSF leukocytes was 75 per µL, CSF protein 83 mg/dL, and CSF glucose 39 mg/dL. Only two cases had severe hypoglycorrhachia and one CSF protein ≥ 500 mg/dL. No patient died during hospitalization. Conclusions: The symptoms of neurobrucellosis could be mild and nonspecific and the classic triad of meningitis is uncommon. Mild CSF pleocytosis of fewer than 50 leukocytes per microliter of CSF was common but severe hyperproteinorrhachia and severe hypoglycorrhachia were rare in neurobrucellosis. Differentiation between neurobrucellosis and systemic brucellosis is important, because more prolonged treatment is indicated for neurobrucellosis, and it could be associated with a broad spectrum of complications that require close follow-up. [ABSTRACT FROM AUTHOR]

Brucellosis is a multisystemic disease that can present with multiple signs and symptoms. Rarely, brucellosis can manifest as neurobrucellosis, with central or peripheral nervous system involvement. Guillain‐Barré syndrome (GBS) is a post‐infectious autoimmune disease that progresses rapidly, causing ascending muscle weakness, and is accompanied by areflexia/hyporeflexia. Regarding GBS etiology, it is thought to be an autoimmune disease, triggered by a previous bacterial or viral infection. There are a few Brucella‐associated GBS case reports in the literature and in our opinion, only one of them is a pediatric patient. Herein we reported a case of GBS associated with neurobrucellosis, who was successfully treated with therapeutic plasmapheresis (TP) due to poor response to IVIG treatment. [ABSTRACT FROM AUTHOR]

Cetacean neurobrucellosis is a common cause of strandings in Costa Rica diagnosed by serology, bacteriology, and histopathology. Pathological studies were performed on 18 dolphins. Twelve were scanned by postmortem computed tomography (PMCT) as a complementary tool for describing neurobrucellosis and osteoarticular alterations associated with Brucella ceti infections. The central nervous system (CNS) and the skeleton of five dolphins not infected with B ceti did not reveal alterations by PMCT scanning. Seven Brucella-infected dolphins showed at least bilateral ventriculomegaly associated with hydrocephalus and accumulation in CSF in the lateral ventricles. We performed semiquantitative grading of the inflammatory process in the different areas of the CNS and evaluated the thickness of the cellular infiltrate in the meninges and the perivascular cuffs. The results for the severity grading were graphed to provide an injury profile associated with each area of the CNS. Age is not a decisive factor regarding neurobrucellosis presentation. The severity of ventriculomegaly by PMCT does not directly correlate with the severity of the inflammatory index determined by histopathological parameters of the brain cortex and other CNS regions, suggesting that these processes, although linked, are multifactorial and need further characterization and validation to establish better cutoffs on the PMCT. [ABSTRACT FROM AUTHOR]

A diagnosis of brucellosis can be difficult because routine culture and serological methods exhibit variable sensitivity and specificity. We present the use of a metagenomic next- generation sequencing assay to diagnose a case of neurobrucellosis from cerebrospinal fluid, resulting in the institution of appropriate antibiotic treatment and a favorable clinical outcome.

Simple Summary: Brucella ceti, a zoonotic bacterial pathogen, is known to exhibit a strong neurotropism and neuropathogenicity for striped dolphins (Stenella coeruleoalba), often leading to their stranding and death. Given the lack of information on B. ceti infection's neuropathogenesis, we investigated, for the first time, cellular prion protein (PrPc) expression in the brain tissue from B. ceti-infected, neurobrucellosis-affected striped dolphins. Our study was inspired by previous work, reporting PrPc as the host cell receptor for B. abortus on the surface of murine macrophages. Immunohistochemistry (IHC) and Western blot (WB) analyses were carried out on brain tissues from 12 striped dolphins found stranded along the coasts of Italy (11 specimens) and the Canary Islands (one individual), five of which served as negative controls. While PrPc IHC yielded inconclusive results, WB analyses showed a clear-cut PrPc expression, albeit of different intensity, in the brain tissue of all the herein investigated, B. ceti-infected and neurobrucellosis-affected individuals. In this respect, the aforementioned PrPc expression patterns could be influenced by a number of intrinsic host-related factors, as well as by several extrinsic factors including simultaneously occurring neuropathies and/or coinfections by other neurotropic pathogens. Additionally, an upregulation of PrPc mRNA in the brain tissue of striped dolphins could be also hypothesized during the different stages of B. ceti infection, in a similar fashion to what is already shown in murine bone marrow cells challenged with Escherichia coli. In conclusion, much more work is needed in order to properly assess the role of PrPc, if any, as a host cell receptor for B. ceti in striped dolphins. Brucella ceti, a zoonotic pathogen of major concern to cetacean health and conservation, is responsible for severe meningo-encephalitic/myelitic lesions in striped dolphins (Stenella coeruleoalba), often leading to their stranding and death. This study investigated, for the first time, the cellular prion protein (PrPc) expression in the brain tissue from B. ceti-infected, neurobrucellosis-affected striped dolphins. Seven B. ceti-infected, neurobrucellosis-affected striped dolphins, found stranded along the Italian coastline (6) and in the Canary Islands (1), were investigated, along with five B. ceti-uninfected striped dolphins from the coast of Italy, carrying no brain lesions, which served as negative controls. Western Blot (WB) and immunohistochemistry (IHC) with an anti-PrP murine monoclonal antibody were carried out on the brain parenchyma of these dolphins. While PrPc IHC yielded inconclusive results, a clear-cut PrPc expression of different intensity was found by means of WB analyses in the brain tissue of all the seven herein investigated, B. ceti-infected and neurobrucellosis-affected cetacean specimens, with two dolphins stranded along the Italian coastline and one dolphin beached in Canary Islands also exhibiting a statistically significant increase in cerebral PrPc expression as compared to the five Brucella spp.-negative control specimens. The significantly increased PrPc expression found in three out of seven B. ceti-infected, neurobrucellosis-affected striped dolphins does not allow us to draw any firm conclusion(s) about the putative role of PrPc as a host cell receptor for B. ceti. Should this be the case, an upregulation of PrPc mRNA in the brain tissue of neurobrucellosis-affected striped dolphins could be hypothesized during the different stages of B. ceti infection, as previously shown in murine bone marrow cells challenged with Escherichia coli. Noteworthy, the inflammatory infiltrates seen in the brain and in the cervico-thoracic spinal cord segments from the herein investigated, B. ceti-infected and neurobrucellosis-affected striped dolphins were densely populated by macrophage/histiocyte cells, often harboring Brucella spp. antigen in their cytoplasm, similarly to what was reported in macrophages from mice experimentally challenged with B. abortus. Notwithstanding the above, much more work is needed in order to properly assess the role of PrPc, if any, as a host cell receptor for B. ceti in striped dolphins. [ABSTRACT FROM AUTHOR]

Brucellosis is an infectious disease seen particularly in developing countries with a high rate of morbidity. It can affect any system in the body and lead to different clinical presentations. The patients presented here draw attention because they were different presentations of rarely encountered central nervous system involvement. Case 1, a 17-year-old male patient was referred to our hospital with symptoms including sudden-onset fever, headache, vomiting, and being unable to speak and walk. On physical examination, the patient had a fever of 37.5 °C, he was lethargic and had no orientation and cooperation. Lumbar puncture was performed. Cerebrospinal fluid (CSF) findings were consistent with purulent meningitis. Case 2, it was learned that a 34-year-old male patient went to a physician two weeks ago due to a decrease in hearing. He was brought to the emergency room because of the deterioration in his time and place orientation and his symptoms of agitation gradually increased after a headache that started in the morning. It was learned from his relatives that similar symptoms happened again about a month ago, but he did not consult a physician because it resolved spontaneously within a few hours and he had been using depression treatment for more than a year. In the physical examination, his temperature was 37.2 °C, the patient was unconscious, his orientation and cooperation were limited. There was no neck stiffness, and Brudzinski’s neck phenomenon and Kernig’s sign were negative. Both patients were diagnosed as having neurobrucellosis through blood and CSF examinations and they both recovered with appropriate treatment. Here, we report and discuss two patients with neurobrucellosis with different clinical features.

Brucella melitensis is the main cause of human brucellosis worldwide and is considered the most virulent and neurotropic species. In Mexico, this species is considered endemic, being reported since the first decade of the 20th century. Here we present a case of subacute transverse myelitis with the isolation and identification of B. melitensis as the causative agent of Neurobrucellosis in a female patient from the coastal state of Guerrero, Mexico. [ABSTRACT FROM AUTHOR]

Abstract When a patient presents with undulating fever and neuropsychiatric features, neurobrucellosis should be considered as a differential diagnosis. If diagnosed early, neurobrucellosis is a treatable disease with a favorable outcome.

When a patient presents with undulating fever and neuropsychiatric features, neurobrucellosis should be considered as a differential diagnosis. If diagnosed early, neurobrucellosis is a treatable disease with a favorable outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Brucella spp. isolation is increasingly reported in cetaceans, although associated pathologies, including lesions of the musculoskeletal and nervous systems, are less frequently described. Concerning the nervous system, Brucella sp. infection causing meningitis, meningoencephalitis or meningoencephalomyelitis have been extensively reported in striped dolphins (Stenella coeruleoalba), and less frequently in other cetacean species. Case presentation A juvenile female common bottlenose dolphin (Tursiops truncatus) was found stranded alive in Lanzarote (Canary Islands, Spain) in 2005, but died shortly after. On physical examination, the dolphin showed a moderate body condition and was classified as code 2 (fresh dead) at the time of necropsy. The main gross findings were severe multiorgan parasitism, thickened and congested leptomeninges, and (sero)fibrino-suppurative and proliferative arthritis of the shoulder joint. Histopathological examination revealed the distinct features of a sub-acute systemic disease associated with Cetacean Morbillivirus (CeMV) infection. However, brain lesions diverged from those reported in systemic CeMV infection. This led to suspect that there was a coinfecting pathogen, based on the characteristics of the inflammatory response and the lesion distribution pattern in the central nervous system. Brucella sp. was detected in the brain tissue by PCR and Brucella antigen was demonstrated by immunohistochemistry in the brain and shoulder joint lesions. Conclusions The zoonotic potential of marine mammal strains of Brucella has been demonstrated both in natural and laboratory conditions. In this study, PCR detected Brucella sp. in the brain of a common bottlenose dolphin stranded in the Canary Islands; the dolphin was also co-infected with CeMV. This is the first detection of Brucella sp. infection in a stranded cetacean in this archipelago. Therefore, we stress the importance of taking adequate measures during the handling of these species to prevent the transmissions of the infection to humans.

Neurobrucellosis is a chronic complication of human brucellosis that is caused by the presence of Brucella spp in the central nervous system (CNS) and the inflammation play a key role on the pathogenesis. Doxycycline (Dox) is a widely used antibiotic that induces apoptosis of bacteria-infected cells. However, the mechanisms of Brucella inhibition of microglial apoptosis and Dox induction of apoptosis are still poorly understood. In this study, we found that Brucella suis S2 strain (B. suis S2) increased calreticulin (CALR) protein levels and inhbited HMC3 cell apoptosis. Hence, we constructed two HMC3 cell line variants, one with stable overexpression (HMC3-CALR) and one with low expression of CALR (HMC3-sh-CALR). CALR was found to decrease levels of p-JNK and p-p53 proteins, as well as suppress apoptosis in HMC3 cells. These findings suggest that CALR suppresses apoptosis by inhibiting the JNK/p53 signaling pathway. Next, we treated HMC3, HMC3-CALR and HMC3-sh-CALR cell lines with B. suis S2 or Dox. Our results demonstrate that B. suis S2 restrains the JNK/p53 signaling pathway to inhibit HMC3 cell apoptosis via increasing CALR protein expression, while Dox plays the opposite role. Finally, we treated B. suis S2-infected HMC3 cells with Dox. Our results confirm that Dox induces JNK/p53-dependent apoptosis in B. suis S2-infected HMC3 cells through inhibition of CALR protein expression. Taken together, these results reveal that CALR and the JNK/p53 signaling pathway may serve as novel therapeutic targets for treatment of neurobrucellosis. [ABSTRACT FROM AUTHOR]

Background: Brucellosis is a common zoonotic disease that may have a variety of clinical manifestations when it affects the nervous system. Ischemic stroke is a rare clinical symptom, but if it is not diagnosed and treated early, it may cause more severe consequences.Case Presentation: We report a 38-year-old man presenting with hearing impairment for four years and sudden weakness of the right limb for two years, recurrent aphasia, and gradual weakness of bilateral lower limbs for nine months. He had bilateral positive Babinski's sign. Cerebrospinal fluid (CSF) showed raised protein and pleocytosis. Magnetic resonance imaging (MRI) showed ischemic infarcts in the pons and extensive enhancement of spinal meninges combined with spinal cord atrophy and ischemia. The tests revealed Brucella Rose Bengal positive in serum and CSF. Brucella culture in CSF was also positive. Next-generation sequencing (NGS) of CSF revealed positive for Brucella with 105 species were detected. He showed significant improvement with antibiotics at five months follow-up.Conclusions: Neurobrucellosis may mimic stroke and transverse myelitis like syndromes. NB is a treatable infectious condition and should always be considered in the differentials, especially if there are risk factors, as in our case. [ABSTRACT FROM AUTHOR]

Brucellosis is one of the most common zoonosis worldwide. It is still endemic in many regions of the world. A 6-year-old female was admitted to the emergency department (ED) due to a sudden change in consciousness, urinary incontinence, vomiting, and difficulty in walking. Neurological examination demonstrated abducens nerve paralysis, mild-to-moderate motor deficit in hemiparesis in the left arm. Brain magnetic resonance imaging showed a hemorrhagic focus at the right frontal lobe and thrombosis in the superior sagittal sinus of the brain. The diagnosis of neurobrucellosis was confirmed by identifying Brucella spp. in the blood culture on the day 6 of pediatric intensive care unit admission; thus, trimethoprim-sulfamethoxazole and rifampicin, and ceftriaxone were promptly initiated. Despite neuroprotective management and acetazolamide, the patient's neurological problems and high intracranial pressure (ICP) persisted. An external ventricular drainage tube and a Codman ICP monitor were placed to be on the consent vigilance of the patient's neurological condition. The patient's ICP continued to increase despite the current treatment regimen; therefore, a decompressive bitemporal craniectomy was performed. The ICP level of the patient returned to its normal range immediately after the craniectomy. The patient did not have any notable neurologic sequelae at the first-year follow-up. Neurobrucellosis is a rare complication of systemic brucellosis and may present as meningitis, encephalitis, myelitis, radiculitis, and/or neuritis. Herein, we describe a six-year-old girl with brucellosis complicated with cerebral vein thrombosis. This case illustrates the need for close monitoring of patients with unexplained neurological signs or symptoms for brucellosis in endemic areas. [ABSTRACT FROM AUTHOR]

Introduction: Brucellosis is a zoonotic disease that can affect the central and peripheral nervous system and it has variable neurological manifestation. However, brucellosis infection that presents with acute peripheral neuropathy mimicking Guillain-Barre syndrome (GBS) is rarely reported in the literature. Objective and method: We report a 56-year-old man who was initially diagnosed with GBS, and then he was confirmed to have acute Brucella infection. We also did a systematic literature review to study the natural history and management of previously reported cases of brucellosis that presented with manifestations consistent with GBS. Results: We found 19 (including our patient) cases of brucellosis that presented with GBS-like manifestations. The age range was 9-62 years. Eight (42.1%) patients had a history of fever. Seven (36.8%) patients had no constitutional symptoms. Five (26.3%) patients had splenomegaly. Brucella serological tests were positive in all patients, while blood Brucella culture was positive in three (37.5%) out of eight patients. Albuminocytological dissociation was present in nine (64.3%) out of 14 patients. Nerve conduction studies and electromyography were consistent with demyelination polyneuropathy in eight (42.1%) patients, with axonal polyneuropathy in six (31.6) patients, and with mixed axonal and demyelinating polyneuropathy in one (5.3%) patient. Spine MRI showed root enhancement in three (42.9%) patients. Conclusion: In regions endemic with brucellosis, acute peripheral neuropathy presentation may warrant investigations for Brucella infection. [ABSTRACT FROM AUTHOR]

Brucellosis is an infectious disease seen particularly in developing countries with a high rate of morbidity. It can affect any system in the body and lead to different clinical presentations. The patients presented here draw attention because they were different presentations of rarely encountered central nervous system involvement. Case 1, a 17-year-old male patient was referred to our hospital with symptoms including sudden-onset fever, headache, vomiting, and being unable to speak and walk. On physical examination, the patient had a fever of 37.5 °C, he was lethargic and had no orientation and cooperation. Lumbar puncture was performed. Cerebrospinal fluid (CSF) findings were consistent with purulent meningitis. Case 2, it was learned that a 34-year-old male patient went to a physician two weeks ago due to a decrease in hearing. He was brought to the emergency room because of the deterioration in his time and place orientation and his symptoms of agitation gradually increased after a headache that started in the morning. It was learned from his relatives that similar symptoms happened again about a month ago, but he did not consult a physician because it resolved spontaneously within a few hours and he had been using depression treatment for more than a year. In the physical examination, his temperature was 37.2 °C, the patient was unconscious, his orientation and cooperation were limited. There was no neck stiffness, and Brudzinski's neck phenomenon and Kernig's sign were negative. Both patients were diagnosed as having neurobrucellosis through blood and CSF examinations and they both recovered with appropriate treatment. Here, we report and discuss two patients with neurobrucellosis with different clinical features. [ABSTRACT FROM AUTHOR]

Brucellosis may present with a broad spectrum of clinical manifestations. Neurobrucellosis (NB), an uncommon but a serious complication, may occur at any stage of the disease. We aimed to evaluate the clinical, diagnostic, therapeutic, and evolutionary features of NB. We conducted a retrospective study including all patients hospitalized for neurobrucellosis in the infectious diseases department between 1994 and 2018. The diagnosis was based on the association of neurological symptoms with bacteriological and/or serological confirmation of brucellosis in blood or Cerebrospinal Fluid (CSF). There were 16 patients (10 male) with NB. The median (range) age was 35 (24–48) years. The revealing symptoms were fever (n = 15), headache (n = 12), and vomiting (n = 9). CSF analysis showed lymphocytic pleocytosis (n = 9) and a high level of protein (n = 10). Brucella was isolated from the blood and CSF in two and five cases, respectively. All patients had a positive Brucella serological test. Eleven patients received rifampicin, doxycycline, and trimethoprim/sulfamethoxazole. The median (range) duration of treatment was 4.5 (3–5.3) months. The disease evolution was favorable in 13 cases. Sequelae were noted in one case. Two patients died. In cases of unusual neurological disorders, NB should be considered, especially in endemic areas. Prompt diagnosis and treatment are crucial in order to avoid serious complications and sequelae.

Abstract Background Brucellosis is a chronic bacterial disease caused by members of the genus Brucella. Among the classical species stands Brucella neotomae, until now, a pathogen limited to wood rats. However, we have identified two brucellosis human cases caused by B. neotomae, demonstrating that this species has zoonotic potential. Cases presentation Within almost 4 years of each other, a 64-year-old Costa Rican white Hispanic man and a 51-year-old Costa Rican white Hispanic man required medical care at public hospitals of Costa Rica. Their hematological and biochemical parameters were within normal limits. No adenopathies or visceral abnormalities were found. Both patients showed intermittent fever, disorientation, and general malaise and a positive Rose Bengal test compatible with Brucella infection. Blood and cerebrospinal fluid cultures rendered Gram-negative coccobacilli identified by genomic analysis as B. neotomae. After antibiotic treatment, the patients recovered with normal mental activities. Conclusions This is the first report describing in detail the clinical disease caused by B. neotomae in two unrelated patients. In spite of previous claims, this bacterium keeps zoonotic potential. Proposals to generate vaccines by using B. neotomae as an immunogen must be reexamined and countries housing the natural reservoir must consider the zoonotic risk.

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen.

Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed.

Brucellosis (malta fever) is a zoonotic infection caused by a gram-negative coccobacillus which is a facultative intracellular pathogen. It causes a chronic granulomatous infection, similar in histology to tuberculosis. Brucellosis remains a diagnostic dilemma due to misleading, nonspecific manifestations and increasing trend of unusual presentations. In brucellosis, the nervous system involvement occurs in only 5 to 7% of untreated patients, and it may manifest with encephalitis, meningoencephalitis, radiculitis, and peripheral and cranial neuropathies. Transverse myelitis is an unusual occurrence. Here, the authors are reporting an unusual case of neurobrucellosis in an elderly male patient who visited multiple hospitals with recurring febrile encephalopathy and paraparesis. The diagnosis was suspected by his occupational history of working as an abattoir worker and was confirmed by the presence of high titers of Brucella immunoglobulin (Ig) M and IgG antibodies in the serum. The patient was managed with injection gentamicin for 2 weeks along with oral course of doxycycline and rifampicin for 6 weeks. He made a good clinical recovery and went back to work with mild residual deficits. [ABSTRACT FROM AUTHOR]

Neurobrucellosis, which is the most morbid form of brucellosis disease, presents with inflammatory signs and symptoms. Recent experimental evidence clearly indicates that deregulation of astrocytes and microglia caused by Brucella infection creates a microenvironment in the central nervous system (CNS) in which secretion of pro-inflammatory mediators lead to destabilization of the glial structure, the damage of the blood brain barrier (BBB) and neuronal demise. This review of Brucella interactions with cells of the CNS and the BBB is intended to present recent immunological findings that can explain, at least in part, the basis for the inflammatory pathogenesis of the nervous system that takes place upon Brucella infection. Unlabelled Image • Brucella traverses the BBB using infected monocytes as a Trojan horse. • Brucella infection of CNS induces astrogliosis. • Astrogliosis affects the neurovascular unit. • Brucella -activated microglia induce neuronal loss. • Brucella -activated glial cells affect the integrity of the BBB. [ABSTRACT FROM AUTHOR]

Brucellosis is a frequent zoonosis in some regions of the world and may cause various symptoms. Neurobrucellosis is a rare but serious complication of the infection. Our case report describes the course of neurobrucellosis in a patient who had received a ventriculoperitoneal shunt in his native country 13 years prior to diagnosis of brucellosis. He initially presented to us with symptoms of peritonitis, which misled us to perform abdominal surgery first. After the diagnosis of neurobrucellosis was confirmed and appropriate antibiotics were initiated, the symptoms soon disappeared. Although the ventriculoperitoneal shunt was subsequently removed, the patient did not develop a symptomatic hydrocephalus further on. This case displays the challenges in diagnosing an infection that occurred sporadically in Europe and may be missed by currently applied routine microbiological workup. Considering the political context, with increasing relocation from endemic areas to European countries, it is to be expected that the cases of brucellosis and neurobrucellosis will rise. Brucellosis should be considered and adequate investigations should be performed. [ABSTRACT FROM AUTHOR]