Brucellosis is one of the most common zoonotic diseases worldwide. It is typically transmitted through direct contact with infected animals or consumption of unpasteurized products. Since 1993, there have been continuous studies reporting neurological complications of brucellosis, collectively referred to as neurobrucellosis, but only approximately 5% of brucellosis patients experience nervous system involvement (1). The pathogenesis of neurobrucellosis involves the invasion of Brucella bacteria into the blood, reaching the meninges and nervous system. The damage to both the peripheral and central nervous systems is predominantly attributed to indirect immune mechanisms (2–4). Frequent complications involving the central nervous system include acute meningitis, myelitis, strokes, subarachnoid hemorrhages, seizures, and cranial nerve involvement, especially the vestibulocochlear nerve (3, 5, 6). Cognitive disorders, psychiatric symptoms, and pituitary region involvement are rare but documented manifestations (6, 7). Complications involving the peripheral nervous system include Guillain Barre syndrome, sciatica, and polyradiculopathy (8–11). Clinical manifestations of neurobrucellosis vary widely, including headaches, vision and hearing impairments, confusion, incontinence, behavioral changes, muscle weakness, and neck rigidity (3, 12, 13). Diagnosis relies on a combination of suggestive symptoms, positive cerebrospinal fluid (CSF) culture or Brucella IgG agglutination in blood, lymphocytic pleocytosis, increased CSF protein, and response to specific antibiotics (2). Although there are many detection methods, the diagnosis is challenging due to its variable manifestations and delayed clinical recognition. Neurobrucellosis is usually diagnosed within 2–12 months after the symptom onset (6, 12).

Most existing articles on neurobrucellosis are primarily case reports, and the sample sizes are generally small, with the majority not exceeding 10 cases (14–16). These articles typically study manifestations, diagnosis, and treatment therapy of neurobrucellosis. There are also a few articles that focus on the immunopathology of neurobrucellosis, which provide valuable insights into the disease’s pathophysiology, diagnostic biomarkers, and therapeutic strategies (17–19). However, there are virtually no comprehensive reviews that integrate and analyze these case studies statistically to track advancements in specific areas such as pathophysiology, diagnostic biomarkers, and treatment therapies. This lack of detailed synthesis contributes to a limited understanding of the existing research gaps in neurobrucellosis.

Web of Science Core Collection Database provides a comprehensive view of scholarly literature. Using this database can ensure the comprehensiveness of literature searches. CiteSpace is a software used for the visualization and analysis of trends and patterns in scientific literature. This study will use CiteSpace and VOSviewer to conduct a bibliometric analysis of the articles related to neurobrucellosis within the Web of Science Core Collection. The aim is to systematically review the existing literature on neurobrucellosis, providing a comprehensive overview that identifies current research trends and gaps. This will guide future studies and provide guidance for the diagnosis and clinical treatment of neurobrucellosis, ultimately aiming to improve the quality of life of patients.

Neurobrucellosis is a neurological complication of brucellosis and demonstrates diverse neurological manifestations. The most common presentation is acute meningitis, with symptoms such as headache, fever, and neck stiffness (6, 25, 34). Meningoencephalitis is also frequently observed, involving prolonged inflammation of the brain and its membranes (25, 35). Chronic radiculoneuropathy, another syndrome of neurobrucellosis, involves inflammation of the nerve roots and peripheral nerves, leading to pain and sensory disturbances (36). Less common but notable presentations include pseudotumor cerebri, where increased intracranial pressure mimics symptoms of a brain tumor, and myelopathy, which affects the spinal cord leading to motor and sensory impairments (37, 38). These syndromes emphasize the complexity of neurobrucellosis, requiring prompt and effective management strategies.

This research focused on the statistical analysis of the 438 articles from Web of Science Core Collaboration. The existing articles in this field predominantly consist of case reports and most of them have relatively small sample sizes (14–16, 39). Researchers found a general upward trend in the articles about neurobrucellosis during the past 30 years. Turkey leads in the number of publications on neurobrucellosis, contributing over 30% of the total articles, with nine out of the top 10 institutions in this field also based in Turkey. However, despite the high volume of research, these Turkish institutions have not conducted in-depth studies in this field. In contrast, the University of Buenos Aires in Argentina has been conducting significant immunopathological research, accounting for 10 of the 11 articles from Argentina (18, 40–43). They shed light on neurobrucellosis and contributed valuable insights to the field. Author collaborations, with two or more articles, were mostly concentrated around 2010, with few collaborations in the past decade. The journal “Neurology” published the highest number of articles related to brucellosis and neurological disease. From the analysis of co-citations, articles related to neurobrucellosis are generally categorized into three main groups: therapy methods, diagnosis of neurobrucellosis, and overview of Brucellosis and its complications, which indicated the past research directions. “Diagnosis,” “meningitis,” and “features” are the most frequently occurring keywords, indicating that articles in this field predominantly focus on case reports, and the most frequently reported neurological complication is meningitis. Researchers conducted a cluster analysis of the keywords and found that “Cerebrospinal Fluid and Antibiotic” and “Antibiotic Therapy” have research value, as they have been consistently appearing in recent years, whereas there was no sustained outbreak of these topics in the earlier years. The burst analysis of the keywords also indicated that “cerebrospinal fluid” may become a prominent keyword in future research. The term emerged as early as 1993 but only began to gain prominence in 2018, indicating its research significance.

Cerebrospinal fluid (CSF) is emerging as a focal point for future research, with a primary focus on the detection of neurobrucellosis. Neurobrucellosis poses diagnostic challenges due to non-specific clinical manifestations and inefficient routine culture tests (44). Traditional approaches to detecting neurobrucellosis, such as microbial culture and serological tests, have limitations in application due to low sensitivity or specificity, along with the requirement for a long sample-to-answer turnaround time (45–47). Serological tests include RBPT (Rose Bengal plate agglutination tests), STAT (Standard tube agglutination test), and ELISA (Enzyme-linked immunosorbent assay) to identify antibodies in serum and CSF (1, 2). PCR (Polymerase chain reaction) for specific DNA sequences and oligoclonal immunoglobulin G (IgG) tests in cerebrospinal fluid are also traditional methods to confirm neurobrucellosis (48–50). Using a combination of diagnostic and clinical methods is recommended for accurate brucellosis detection. Recent research found that Next-generation sequencing (NGS) is a rising method for identifying pathogenic microorganisms based on sequencing, and its utilization is growing in the diagnosis of infectious diseases affecting the central nervous system (CNS) (46, 51). Next-generation sequencing (NGS) is also recommended to be used in diagnosing neurobrucellosis due to its Enhanced Sensitivity and rapid Diagnosis (44, 45, 52). Other research proposed that Metabolites of cerebrospinal fluid (CSF) are biomarkers for neurobrucellosis, representing a potential diagnostic modality for neurobrucellosis (53, 54). CSF samples from neurobrucellosis patients and normal controls were analyzed using liquid chromatography-mass spectrometry (LC–MS) to detect metabolites. The results showed differences in metabolite profiles between neurobrucellosis patients and normal controls, and elevated inflammatory cytokines in CSF further support the utility of metabolomics for diagnosis and treatment insights (53). Although the effectiveness of Next-Generation Sequencing (NGS) and the identification of metabolites of cerebrospinal fluid using LC–MS for detecting neurobrucellosis has been proven, large-scale studies with expanded sample sizes are crucial for further validation (44). Further research into the diagnosis of neurobrucellosis is expected to lead to earlier and more precise identification of the condition, which enables timely and appropriate therapeutic interventions. It is also crucial to validate the efficacy of these diagnostic methods and establish standardized protocols for their use in clinical settings.

Magnetic Resonance Imaging (MRI) can be also instrumental in diagnosing neurobrucellosis. A study classified the MRI features of neruobrucellosis into five types: In meningitis (Type I), MRI often displays equal T1 and high T2 signal intensities, accompanied by meningeal-like enhancement, primarily affecting the frontal and temporal lobes (55). Meningoencephalitis (Type II) is characterized by abnormal signal intensities in the meninges and submeningeal brain regions, presenting with similar T1 and elevated T2 signals. The presence of subtle meningeal enhancements without significant submeningeal tissue alteration further aligns with findings from specialized case studies (55). Inflammatory demyelinating (Type III) features diffuse myelitis, increased intensity in the cerebral white matter, and localized white matter changes (55, 56). These alterations are typically found around critical structures such as the lateral ventricles and spinal cord (55–57). Ata et al. (58) also reported that MRI characteristics of demyelination include meningeal enhancement, particularly around the brainstem and along cranial nerves and the lower cranial nerves. The Abscess (Type IV) presents enhancement both in the brain and spinal cord similar to the typical abscess. Pseudotumor (Type V) mimics neoplastic processes with well-defined, enhancing lesions that exhibit low T1 and high T2 signals, demanding meticulous differential diagnosis (55).

Antibiotic therapy is commonly used to treat neurobrucellosis. Shaw et al. (59) advocate for multiagent antibiotic protocols, specifically incorporating ceftriaxone, rifampin, and doxycycline, as the preferred therapeutic approach. They also recommended a treatment duration of 4–6 weeks for ceftriaxone and a minimum of 12 weeks for rifampin and doxycycline, underscoring the pivotal role of strict adherence in mitigating the risk of relapse (59) Many studies have also confirmed the efficacy of antibiotic therapy in various neurological complications of brucellosis. For example, protracted polymicrobial antibiotic therapy and heparin are also proven to be effective in achieving a favorable outcome in patients with neurobrucellosis accompanied by cerebral venous sinus thrombosis (CVST) (60). Antibiotic regimen involving rifampicin, doxycycline, and trimethoprim/sulfamethoxazole is effective for neurobrucellosis complicated with sensorineural hearing loss (SNHL) (15). However, antibiotic therapy may not be permanently effective. Mirza et al. (15) mentioned a previous case report where SNHL persisted even after 6 weeks of antibiotic treatment, which suggested future research about the relationship between neurobrucellosis and SNHL. A documented case of neurobrucellosis with clinical manifestations resembling amyotrophic lateral sclerosis (ALC) reported that the disease-specific antibiotic therapy failed to impede the progression of motor neuron disease, suspecting a causal association between systemic neurobrucellosis and ALS (49).

The primary treatment for neurobrucellosis is antibiotics, but corticosteroids are also used in some situations to mitigate the damaging effects of bacterial toxins, potentially reducing the likelihood of enduring complications (6). Evidence from case reports suggests that corticosteroid therapy can effectively alleviate neurological symptoms such as headaches and vision problems and moderate the inflammatory response in neurobrucellosis patients (61). Despite these benefits, the efficacy of corticosteroids has not been conclusively established through large-scale studies or randomized controlled trials. Recent research indicates a significant concern: corticosteroid therapy was associated with a higher risk of sequelae or relapse (62). It contrasts with outcomes in other conditions like Pneumococcal meningitis, where steroid use is associated with a reduced risk of neurological sequelae, including hearing loss (63). Consequently, while corticosteroids can provide symptomatic relief in neurobrucellosis, the potential risks must be carefully weighed against the benefits.

The relationship between neurobrucellosis and neurological conditions arises from the frequent occurrence of neurological diseases among patients with brucellosis (41). The underlying mechanisms of neurobrucellosis involve direct invasion by Brucella abortus into the Central Nervous System (CNS), primarily facilitated through two routes: the “Trojan horse” mechanism and transcellular traversal of the blood–brain barrier (BBB). B. abortus utilizes infected monocytes to cross the BBB, effectively employing these cells as a means to enter the CNS (64, 65). Once inside, the bacteria can infect brain microvascular endothelial cells (HBMEC), as well as resident CNS cells like astrocytes and microglia (65). The presence of the bacteria triggers an inflammatory response, characterized by the production of cytokines and chemokines, which leads to astrogliosis and potentially to the apoptosis of astrocytes, contributing to the pathology observed in neurobrucellosis (42). The hypothesis is that the bacterial antigens may mimic neuronal antigens (molecular mimicry), leading to an autoimmune response that targets the myelin sheath of nerve cells (6). This could explain the demyelinating-like lesions observed in some patients with neurobrucellosis (66). Both neurobrucellosis and demyelinating disorders such as multiple sclerosis (MS) can present with neurological symptoms like headaches, visual disturbances, ataxia, and sensory or motor deficits (6, 12, 67). MRI findings in neurobrucellosis often include meningeal enhancement, white matter lesions, and other signs of inflammation which are also commonly seen in demyelinating disorders (66, 68). These similarities necessitate a careful differential diagnosis to distinguish between infectious causes and primary demyelinating processes. Neurobrucellosis is also reported to potentially link to psychiatric disorders, a connection supported by its inflammatory and systemic impacts on the central nervous system, which may lead to neuropsychiatric symptoms (69). Studies have shown that patients with neurobrucellosis experience significant emotional disturbances, and exhibit severely impaired cognitive functions, such as mental control, logical memory, and visual reproduction, and score higher on measures of depressive symptoms compared to control subjects (1, 70, 71). Further research needs to clarify these associations and understand the underlying pathophysiological processes, although some reports have recently begun to investigate the pathophysiological processes that associate psychiatric disorders with inflammatory responses elicited by the bacterium (72, 73). Understanding the complex interactions between neurobrucellosis and neurological diseases is crucial for improving diagnostic accuracy and patient outcomes.

This study has certain limitations. It exclusively used the Web of Science Core Collection Database for data analysis and focused on English-language articles during the screening process. This approach might lead to the omission of relevant studies. To counteract these limitations and strengthen the validity of our conclusions, we conducted a thorough review of additional key articles from prominent databases such as PubMed and Scopus in the discussion section, which broadened the scope and enhanced the comprehensiveness of the analysis.

This article employed both CiteSpace and VOSviewer software to make a bibliometric analysis of articles related to neurobrucellosis. By identifying the most active regions, leading institutions, and prevalent themes in current research, this analysis outlines the intellectual landscape and gaps, and guides researchers to develop targeted therapies and interventions that address the most pressing needs in the management of Neurobrucellosis, enhancing clinical outcomes and patients’ quality of life.