Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

An Adolescent With Neurobrucellosis Caused by Brucella abortus Cattle Vaccine Strain RB51.

We present the case of an 18-year-old female with a 1-month history of fever, headache, and double vision, whose examination revealed papilledema and cranial nerve VI palsy. Blood cultures grew Brucella abortus cattle vaccine strain RB51, which is inherently resistant to rifampin. We discuss the management of the first known case of neurobrucellosis by this strain.

CEREBROSPINAL FLUID SAMPLING IN A BOTTLENOSE DOLPHIN (TURSIOPS TRUNCATUS) UNDER GENERAL ANESTHESIA.

Brucella ceti, associated with neurobrucellosis, has been isolated from cerebrospinal fluid (CSF) of postmortem cetaceans. A 106-kg, stranded female bottlenose dolphin (Tursiops truncatus) presented with serum antibodies to Brucella spp. via competitive enzyme-linked immunosorbent assay and fluorescence polarization assay. Polymerase chain reaction (PCR) and culture of whole blood, bronchoalveolar fluid, and rectal, nasal, and genital swabs for Brucella spp. were consistently negative. Serial computed tomography revealed mild focal dilatation of brain ventricles. CSF sampling was warranted to exclude neurobrucellosis. Sedation was achieved with 30 mg diazepam (0.28 mg/kg) orally 2.5 hours prior to arrival in hospital, followed by 5.3 mg midazolam (0.05 mg/kg) intramuscularly, and anesthetic induction with 2.5 mg midazolam (0.02 mg/kg) and 200 mg propofol (2 mg/kg) administered slowly intravenously, followed by intubation and maintenance on sevoflurane using controlled mechanical and apneustic anesthesia ventilation. The atlanto-occipital joint was opened by flexing the upper cervical region with the animal in left lateral recumbency. A 20-ga × 6-inch spinal needle was advanced into the cisterna magna using radiographic guidance. CSF was collected successfully with no neurological deficits appreciable on recovery. Brucella spp. was not identified via PCR or culture. This represents the first report of an antemortem CSF tap in a cetacean.

A headache with surprising outcome: first case of brucellosis caused by Brucella suis biovar 1 in Germany.

In July 2018, brucellosis was diagnosed in a German patient without a travel history to regions endemic for Brucella. Microbiological analysis, including whole-genome sequencing, revealed Brucella suis biovar 1 as the etiologic agent. Core-genome-based multilocus sequence-typing analysis placed the isolate in close proximity to strains originating from Argentina. Notably, despite a strong IgM response, the patient did not develop Brucella-specific IgG antibodies during infection. Here, we describe the clinical course of infection, the extensive epidemiological investigations, and discuss possible routes of transmission.

Next-generation sequencing of the cerebrospinal fluid in the diagnosis of neurobrucellosis.

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.

Neurobrucellosis: Unexpected Answer From Metagenomic Next-Generation Sequencing.

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.

[Ocular syndromes in patients with neurobrucellosis].

OBJECTIVE: To investigate the clinical features of ocular syndromes in patients with neurobrucellosis. METHOD: This is a retrospective series case study. The clinical data of 5 patients with neurobrucellosis, who were treated in Department of Neurology, Beijing Tongren Hospital, Captical Medical Uinversity, from May 2009 to January 2015, were collected. Their epidemiological information, clinical manifestation, laboratory and radiologic examination, therapy and prognosis were analyzed. RESULTS: Among the five patients, there were 3 males and 2 females, and their ages ranged from 20 to 67 years. The median age was 25 years. All patients had ever exposed to sheep. 1 patient lived close to a slaughterhouse and 2 patients lived in epidemic areas of brucellosis. 5 patients presented with binocular vision loss, 8 eyes with fundus edema, 3 patients with ophthalmoplegia;4 patients with fever,4 patients with headache,3 patients with neck stiffness,1 patient with movement and sensation disorders. Cerebrospinal fluid (CSF) pressure elevated, white cell number and protein increased with glucose reduction were detected respectively in 3 cases. While, CSF chloride decreased in 2 cases. Serum agglutination test for brucella was positive in 5 patients. Serum brucella culture was positive in 1 patient and CSF brucella culture was positive in 1 patient. Brain magnetic resonance imaging (MRI) showed that the optic nerve was involved in 3 patients,the meninges were involved in 1 patient and the brain white matter was involved in 1 patient. The combination of rifamycin, tetracycline, ceftriaxone sodium or quinolone were given to all patients and showed appreciated effects. CONCLUSIONS: The clinical features of ocular syndromes are atypical in patients with neurobrucellosis. Vision loss and ophthalmoplegia are more common to be seen. Neurobrucellosis should be considered when patients with ocular signs and other system symptoms without a definite diagnosis.

Neurobrucellosis: clinical and diagnostic features.

BACKGROUND: We describe the neurological involvement in brucellosis and revisited diagnostic criteria for neurobrucellosis. METHODS: Patients with laboratory-confirmed brucellosis who were consequently hospitalized were observed prospectively in a brucellosis-endemic region. The neurobrucellosis was diagnosed by any one of the following criteria: (1) symptoms and signs consistent with neurobrucellosis; (2) isolation of Brucella species from cerebrospinal fluid (CSF) and/or presence of anti-Brucella antibodies in CSF; (3) the presence of lymphocytosis, increased protein, and decreased glucose levels in CSF; or (4) diagnostic findings in cranial magnetic resonance imaging or CT. RESULTS: Lumbar puncture was performed in 128 laboratory-confirmed brucellosis cases who had neurological symptoms and signs, and 48 (37.5%) were diagnosed as neurobrucellosis. The sensitivity of tube agglutination (TA) in CSF was 0.94, specificity 0.96, positive predictive value 0.94, and negative predictive value 0.96. Brucella bacteria were isolated from CSF in 7 of 48 patients (15%). The mean age of 48 neurobrucellosis patients was 42 years (SD, 19 years), and 16 (33%) were female. The most common neurological findings were agitation (25%), behavioral disorders (25%), muscle weakness (23%), disorientation (21%), and neck rigidity (17%). Cranial nerves were involved in 9 of 48 patients (19%). One patient was left with a sequela of peripheral facial paralysis and 2 patients with sensorineural hearing loss. CONCLUSIONS: Patients with severe and persistent headache and other neurologic symptoms and signs should be considered for neurobrucellosis in endemic regions and to possibly receive longer therapy than 6 weeks. Brucella TA with Coombs test in CSF is sensitive and specific by using a cutoff of ≥1:8.

Comparative analysis of cerebrospinal fluid adenosine deaminase activity in meningitis.

AIM: The purpose is to determine the cut-off value of adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of patients with tuberculous and non-tuberculous meningitis, and to assess its value in differential diagnosis. MATERIAL AND METHODS: This study was conducted in 91 patients with meningitis in two university hospitals in Turkey. 24 patients had tuberculous meningitis (TBM), 25 purulent meningitis (PM), 25 aseptic meningitis (AM) and 17 neurobrucellosis (BM). ADA activity of CSF was quantified by colorimetry. RESULTS: In our study, mean ADA values in CSF were 28.34 ± 14.83 IU/L in TB cases, 8.71 ± 5.83 IU/L in BM, 6.18 ± 2.54 IU/L in PM and 3.43 ± 3.48 U/L in AM cases. If we accept for CSF ADA an activity cut-off value of 12.5 IU/L for differential diagnosis of TBM and BM, its sensitivity was 92% and specificity was 88%. If we accept 12.35 IU/L for differential diagnosis of TBM and PM, its sensitivity was 92% and specificity was 100%. If we accept 6.45 IU/L for differential diagnosis of TBM and AM, its sensitivity was 100% and specificity was 92%. Additionally, we examined the cases after dividing them into two groups, viz. TB and non-TB. If we accept an ADA activity cut-off level of 11 IU/L for differential diagnosis of TB and non-TB by applying ROC analysis, its sensitivity was 92% and specificity was 90%. CONCLUSION: The sensitivity and specificity for CSF ADA activity are markedly high in differential diagnosis of TB from non-TB. Hence CSF ADA activity may be used as a simple, cost-effective and reliable test for early differential diagnosis of TB.

[Progressive paraparesis with sensorineural deafness and leukoencephalopathy revealing neurobrucellosis]. / Paraparésie et surdité progressives avec leuco-encéphalopathie révélant une neurobrucellose chronique.

INTRODUCTION: Brucellosis is a rare disease with variable neurological and imaging manifestations. CASE REPORT: A 54-year-old woman presented with progressive paraparesis and sensorineural hearing loss over 18 months. The presence of diffuse white matter changes on brain magnetic resonance imaging (MRI) and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. Spinal MRI did not show any lesion that could explain the paraparesis that was finally attributed to the leukoencephalopathic lesions. The patient improved clinically after three months of antibiotic treatment but no significant changes were noticed on brain imaging. DISCUSSION AND CONCLUSION: Neurobrucellosis is a treatable disease which should be discussed when a patient presents with the triade progressive paraparesis, sensorineural hearing loss and leukoencephalopathy on MRI. Outcome can be favorable if adapted treatment is given early.

Acute meningoencephalitis due to Brucella: case report and review of neurobrucellosis in children.

The involvement of the central nervous system (CNS) in brucellosis is rare and has a broad range of presentations. Subacute and chronic meningoencephalitis are described as the most common neurologic manifestations. We report a six-year-old boy with culture-proven neurobrucellosis who presented with an acute picture of meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with slight elevation of protein. The agglutination test titer was elevated in serum and Brucella spp. were isolated from both blood and CSF. He was treated with trimethoprim-sulfamethoxazole plus rifampin and streptomycin. His clinical and laboratory features improved with specific antibiotic therapy and no sequela was observed in the short-term follow-up. Due to protean clinical features, unfamiliarity with the disease can delay the diagnosis in children who are not occupationally exposed. In endemic areas, neurobrucellosis should be considered in the evaluation of patients with unexplained neurologic symptoms.

Neurobrucellosis: an evaluation of a rare presentation of brucellosis from a tertiary care centre in Central Anatolia, Turkey.

Nervous system involvement is a rare manifestation of brucellosis. We describe our experience of the diagnosis, treatment and final outcome of patients with neurobrucellosis at the Erciyes University Gevher Nesibe Hospital, a tertiary referral centre in Central Anatolia, Turkey. Thirty-six adult patients were diagnosed with neurobrucellosis from January 1997 to December 2006. Headache and fever were the most common symptoms. Neck stiffness was present in 25 patients. Brucella spp was isolated from the blood of nine patients and from the cerebrospinal fluid of 11. Doxycycline (by mouth) plus rifampin (by mouth) with ceftriaxone (intravenously) were the most common treatment choices. Three patients died as a result of problems other than neurobrucellosis and relapse occurred in one patient. Neurobrucellosis presents with hetoregenous clinical signs.

Management of neurobrucellosis: an assessment of 11 cases.

OBJECTIVE: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy. PATIENTS AND METHODS: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases. RESULTS: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection. CONCLUSIONS: Parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.

Pseudotumor--like presentation of neurobrucellosis.

Brucellosis is bacterial zoonoses. In endemic areas brucellosis can present with clinical features of nearly any neurological illness. Meningitic presentation is most common, with patient presenting with either acute or chronic meningitis. Pseudotumor--like presentation is also documented and accounts for only 4% of cases of neurobrucellosis. Here we are documenting a case of neurobrucellosis with presentation similar to pseudotumor cerebri but with abnormal CSF. This highlights the fact that being a potentially treatable condition brucellosis should always come in the differential diagnosis of neurotuberculosis especially if there are atypical features e.g. pseudotumor presentation with abnormal CSF.

Acquired progressive spastic paraparesis due to neurobrucellosis: a case report.

A 39-year-old man with a 4-month history of transient pins and needles sensations occurring below the waist while walking and difficulty walking presented to our outpatient clinic. He had an approximate 1-year history of bilateral hearing loss, the etiology of which was unknown. His symptoms had been progressive, and there was no significant family history. He demonstrated a spastic gait and required assistance for walking. Deep tendon reflexes were hypertonic; a sensation deficit was defined as originating from the 12th thoracic vertebra. Babinski's sign was positive bilaterally. Sphincter abnormalities were seen in the patient's bladder and bowel functions. Cerebral and spinal magnetic resonance images with contrast media were unremarkable. An analysis of the patient's cerebrospinal fluid was consistent with neurobrucellosis. Owing to spastic paraparesis and hearing loss, the diagnosis of neurobrucellosis was made. Combined antimicrobial therapy was started and continued 6 months. His neurologic condition improved, and he was able to walk without help after 3 months' treatment. Our case illustrates that acquired progressive spastic paraparesis may occur during the course of neurobrucellosis. Neurobrucellosis should be borne in mind when patients present with spastic paraparesis.

Abducens nerve palsy and optic neuritis as initial manifestation in brucellosis.

Cranial nerve involvement in brucellosis is rare. We present a case of brucellosis presenting with optic neuritis and abducens nerve palsy on the left side. Cerebrospinal fluid findings indicated Brucella meningitis with high protein count, low sugar level and pleocystosis. In addition, Brucella agglutination test (Wright test) was found to be 1/128 in cerebrospinal fluid. Serum agglutination test for Brucella was also positive at 1/1280. This case was diagnosed as brucellosis involving optic and abducens nerves. The patient was treated by ceftriaxone (intravenous), rifampicin (orally) and doxycycline (orally). Two months later the patient's vision acuity in the left eye had moderately improved and the patient's left abducens palsy had almost disappeared. In conclusion, cranial nerve involvement in brucellosis can have good prognosis if anti-Brucella treatment is undertaken early.