Neurobrucellosis.

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

Neurobrucellosis Presenting with Features of Demyelinating Disorder in a Pediatric Patient.

Brucellosis is an endemic disease in Saudi Arabia, which can present with variable clinical manifestations. It is a zoonotic disease transmitted from animals to humans. Brucellosis is a multisystemic disease that can present with any system involvement; and neurobrucellosis is a serious complication, sometimes leading to permanent neurological deficit, if treatment is not started promptly. Herein, we present a 6-year boy with neurobrucellosis, who developed demyelination of cerebral white matter and presented with fever and seizures. Key Words: Neurobrucellosis, Demyelination, White matter.

Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections.

The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (n = 32), viral meningitis/encephalitis (n = 34), and noninflamed controls (n = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (p = 1.2 × 10-25-1.5 × 10-4) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood-CSF barrier dysfunction and CSF lactate (r = 0.73-0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

BACKGROUND: Rapid and accurate diagnosis of central nervous system (CNS) infections is important, and laboratory tests help diagnose CNS infections. Even when the patient has symptoms, laboratory tests often do not reveal any specific findings. The potential of vitamin D-binding protein (VDBP) to be used as a biomarker for viral and bacterial CNS infections was studied. METHODS: A total of 302 subjects with suspected CNS infection who underwent lumbar puncture were included. Clinical and laboratory data were collected retrospectively. VDBP levels were measured in the cerebrospinal fluid (CSF) samples. Genotyping for the GC gene encoding VDBP was also performed. VDBP levels were analyzed and compared by CNS infection, pathogen, CSF opening pressure, and GC genotype. RESULTS: A CNS infection group (n = 90) and a non-CNS infection group (n = 212) were studied. In terms of its receiver operating characteristic, CSF VDBP showed an area under the curve of 0.726 for the diagnosis of CNS infection. CSF VDBP levels were significantly different between the CNS infection and non-infection groups. The CNS infection group with enterovirus showed a statistically lower distribution of CSF VDBP levels than the other virus groups. The group with CSF opening pressure > 25 cmH2O showed higher CSF VDBP levels than the other groups. There was no significant difference in GC gene allele distribution between the CNS infection and non-infection groups. CONCLUSIONS: CSF VDBP levels were increased in patients with CNS infection. The CSF VDBP showed potential as a new biomarker for viral and bacterial CNS infections.

Brain Abscess in a Patient with Osteopetrosis: A Rare Complication

Brain abscess formation is extremely rare in patients with osteopetrosis. Herein, we report a case of viridans streptococci brain abscess in an immunocompromised child diagnosed with osteopetrosis. The patient presented with a sudden change in mental status and convulsions. Radiological evaluation revealed a temporal lobe brain abscess, and intravenous antibiotherapy was started immediately. The patient underwent abscess drainage, and laboratory investigation of pus material revealed viridans streptococci.

A Rare Presentation of Neurobrucellosis in a 6-Year-Old Pediatric Patient with Sagittal Sinus Thrombosis.

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.

Central Nervous System Infections in the Immunocompromised Adult Presenting to the Emergency Department.

Over the past 2 decades, the population of immunocompromised patients has increased dramatically in the United States. These patients are at elevated risk for both community-acquired and opportunistic central nervous system infections. We review the most common and serious central nervous system pathogens affecting these patients and outline a diagnostic and therapeutic approach to their management in the emergency department. We recommend a broad diagnostic evaluation, including neuroimaging and cerebrospinal fluid studies where appropriate, empiric antimicrobial therapy, and early involvement of subspecialists to provide comprehensive care for these complex patients.

Central nervous system Cryptococcoma mimicking demyelinating disease: a case report.

BACKGROUND: Cerebral cryptococcomas is a rare form of central nervous system cryptococcosis. Most previous cases were mistaken for neoplasm before surgery. We present a case of cerebral cryptococcomas whose radiological profiles resembled demyelinating disease, especially tumefactive demyelinating lesion. CASE PRESENTATION: A 40-year-old male was admitted for 1-week-long unconsciousness. Brain MRI revealed a rim-enhanced mass within the corpus callosum body. Central nervous system demyelinating disease was suspected. Empirical corticosteroid treatment led to some improvement, but his condition deteriorated 2 months later. Brain MRI revealed punctate new foci. Cryptococcus neoformans was detected in cerebrospinal fluid. Cryptococcus antigen test was positive in his current and previous cerebrospinal fluid samples. The patient died despite standard antifungal treatment. CONCLUSION: Diagnosis of cerebral cryptococcomas is challenging. It may mimic demyelinating diseases.

Molecular and Histologic Diagnosis of Central Nervous System Infections.

Infections of the central nervous system cause significant morbidity and mortality in immunocompetent and immunocompromised individuals. A wide variety of microorganisms can cause infections, including bacteria, mycobacteria, fungi, viruses, and parasites. Although less invasive testing is preferred, surgical biopsy may be necessary to collect diagnostic tissue. Histologic findings, including special stains and immunohistochemistry, can provide a morphologic diagnosis in many cases, which can be further classified by molecular testing. Correlation of molecular, culture, and other laboratory results with histologic findings is essential for an accurate diagnosis, and to minimize false positives from microbial contamination.

Central nervous system infections in renal transplant recipients.

BACKGROUND: The aim of this study is to determine the incidence, etiology, clinical characteristics, and outcomes of renal transplant recipients diagnosed and treated for central nervous system (CNS) infection at our institution. METHODS: We analyzed data from all renal transplant recipients between January 2007 and December 2019 that were diagnosed and treated for CNS infections at our institution. RESULTS: Of 1374 patients who received renal allografts, 13 were diagnosed with CNS infections (9 males), with a mean age of 53.5 years. Patients were diagnosed with CNS infections between 2 months and 11 years after the transplantation. Causative agents included JC virus, Streptococcus pneumoniae, Cryptococcus neoformans, Herpes zoster virus, Mycobacterium tuberculosis, Listeria monocytogenes, and West Nile virus. One patient had concomitant Nocardia and Neisseria infection. Immunosuppression was reduced in all patients. The patient with JC encephalitis and the patient with concomitant Neisseria and Nocardia meningitis died. One patient was returned to dialysis. Other patients recovered with differing levels of neurologic sequelae. CONCLUSION: Central nervous system infections in renal transplant recipients are rare. However, they are associated with significant morbidity and mortality. A high level of awareness is needed: neurological symptoms may be nonspecific and caused by non-infectious conditions related to the underlying disease, or side-effects of immunosuppressive drugs.

Evaluation of a micro/nanofluidic chip platform for diagnosis of central nervous system infections: a multi-center prospective study.

Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients with negative microbial cultures were evaluated using the MNCP-II platform for the identification of microorganism and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. The LOD of the various microbes tested with the MNCP-II was found to be in the range of 250-500 copies of DNA. For the 180 CSF microbe-positive cultures, the concordance rate between the platform and the conventional identification method was 90.00%; eight species attained 100% consistency. In the detection of 9 kinds of antibiotic resistance genes, including carbapenemases, ESBLs, aminoglycoside, vancomycin-related genes, and mecA, concordance rates with the conventional antimicrobial susceptibility testing methods exceeded 80.00%. For carbapenemases and ESBLs-related genes, both the sensitivity and positive predictive values of the platform tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. MNCP-II is a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.

Multicenter Evaluation of the Implementation Status of Laboratory Tests in Korea and the Potential Usefulness of a Multiplex PCR Assay in Patients with Suspected Central Nervous System Infections.

BACKGROUND: The rapid diagnosis and treatment of central nervous system (CNS) infections are critical to minimizing morbidity and mortality. We evaluated the implementation status of laboratory tests in patients with suspected CNS infection, and the potential usefulness of a multiplex PCR assay for rapid and simultaneous detection in cerebrospinal fluid (CSF) of 14 targets capable of causing CNS infections. METHODS: The study was conducted at 5 hospitals located in Daegu and Gyeongju over a period of 6 months. A total of 140 patients with suspected CNS infection were included. CSF samples were tested for 6 bacteria, 7 viruses, and 1 yeast using multiplex PCR (FilmArray Meningitis/Encephalitis Panel, BioFire Diagnostics/Biomerieux, Salt Lake City, UT, USA) and conventional diagnostic testing including chemistry tests, cell count, bacterial culture, antigen detection assay, and pathogen-specific PCR. RESULTS: The five conventional tests most commonly performed were the chemistry and cell count (100%), bacterial culture (94.3%), enterovirus PCR (52.9%), and herpes simplex virus PCR (25.7%). Among the 140 CSF samples, 27 (19.3%) and 42 (30.0%) tested positive by conventional and the FilmArray ME panel testing, respectively. CONCLUSIONS: The detection rate of pathogens for CNS infections increased using only one FilmArray test compared to all of the conventional methods actually performed in patients with suspected CNS infection.

[Evaluation of the epidemiological and clinical characteristics of central nervous system infections in adults in the West Pannonian region]. / A felnottkori neuroinfekciók epidemiológiai és klinikai jellemzoinek vizsgálata a nyugat-dunántúli régióban.

Introduction: Despite advancements in diagnostic capabilities and the availability of effective antimicrobial agents, community-acquired infections of the central nervous system (CNS) are still associated with high mortality rates. Aim: To assess the epidemiological and clinical characteristics of community-acquired CNS infections treated in the West Pannonian region between 2010 and 2016. Method: Clinical data of 176 patients were retrospectively analysed in two age cohorts: 15 to 65 and more than 65 years of age. Results: Neuroinfections were found to be bacterial in 81, viral in 91, parasitic in 1 and mixed in 3 cases during the observation period. The most frequent bacterial pathogens isolated were Streptococcus pneumoniae (20%) and Borrelia burgdorferi (16%). The most frequent viral pathogens isolated were tick-borne encephalitis virus (37%), herpes simplex virus (10%) and enterovirus (7%). Aetiology was unknown in 40 percent of all cases. The average incidence rate was 9.8/100 000 person/year with a mortality rate of 12%. In the cohort of patients aged >65 years, significantly higher frequencies of immunocompromising factors, lower Glasgow Coma Scale values at admission and confusion were observed (p-values: 0.008, 0.017, and 0.050, respectively). Prognosis was negatively influenced by low Glasgow Coma Scale values at admission (OR = 1.6 CI95%: 1.3-1.9; p<0.001), old age (OR = 6.5 CI95%: 2.5-17.1; p<0.001) and immunodeficiency (OR = 3.1 CI95%: 1.2-8.1; p = 0.019). Conclusions: S. pneumoniae remains the most frequently observed causative bacterial pathogen associated with community-acquired CNS infections. Incidence of tick-borne encephalitis in our county is higher than the national average (2.3 versus 0.35/100 000 person/year). Orv Hetil. 2019; 160(40): 1574-1583.

Factors and measures predicting external CSF drain-associated ventriculitis: A review and meta-analysis.

OBJECTIVE: To determine the diagnostic value of clinical factors and biochemical or microbiological measures for diagnosing a drain-associated ventriculitis, we summarized the available evidence. METHODS: We performed a systematic review and meta-analysis of studies of patients with external ventricular CSF drains who developed drain-associated ventriculitis by searching MEDLINE, EMBASE, and CENTRAL electronic database. We reported the occurrence of abnormal test results in patients with and without drain-associated ventriculitis. For continuous variables, we recalculated mean values presented in multiple studies. RESULTS: We identified 42 articles published between 1984 and 2018 including 3,035 patients with external CSF drains of whom 697 (23%) developed drain-associated bacterial ventriculitis. Indications for drain placement were subarachnoid, intraventricular or cerebral hemorrhage or hemorrhage not further specified (69%), traumatic brain injury (13%), and obstructive hydrocephalus secondary to a brain tumor (10%). Fever was present in 116 of 162 patients with ventriculitis (72%) compared with 80 of 275 (29%) patients without ventriculitis. The CSF cell count was increased for 74 of 80 patients (93%) with bacterial ventriculitis and 30 of 95 patients (32%) without ventriculitis. CSF culture was positive in 125 of 156 episodes classified as ventriculitis (80%), and CSF Gram stain was positive in 44 of 81 patients (54%). In patients with ventriculitis, PCR on ribosomal RNA was positive on 54 of 78 CSF samples (69%). CONCLUSION: Clinical factors and biochemical and microbiological measures have limited diagnostic value in differentiating between ventriculitis and sterile inflammation in patients with external CSF drains. Prospective well-designed diagnostic accuracy studies in drain-associated ventriculitis are needed.

Intracranial actinomycosis of odontogenic origin masquerading as auto-immune orbital myositis: a fatal case and review of the literature.

BACKGROUND: Actinomycetes can rarely cause intracranial infection and may cause a variety of complications. We describe a fatal case of intracranial and intra-orbital actinomycosis of odontogenic origin with a unique presentation and route of dissemination. Also, we provide a review of the current literature. CASE PRESENTATION: A 58-year-old man presented with diplopia and progressive pain behind his left eye. Six weeks earlier he had undergone a dental extraction, followed by clindamycin treatment for a presumed maxillary infection. The diplopia responded to steroids but recurred after cessation. The diplopia was thought to result from myositis of the left medial rectus muscle, possibly related to a defect in the lamina papyracea. During exploration there was no abnormal tissue for biopsy. The medial wall was reconstructed and the myositis responded again to steroids. Within weeks a myositis on the right side occurred, with CT evidence of muscle swelling. Several months later he presented with right hemiparesis and dysarthria. Despite treatment the patient deteriorated, developed extensive intracranial hemorrhage, and died. Autopsy showed bacterial aggregates suggestive of actinomycotic meningoencephalitis with septic thromboembolism. Retrospectively, imaging studies showed abnormalities in the left infratemporal fossa and skull base and bilateral cavernous sinus. CONCLUSIONS: In conclusion, intracranial actinomycosis is difficult to diagnose, with potentially fatal outcome. An accurate diagnosis can often only be established by means of histology and biopsy should be performed whenever feasible. This is the first report of actinomycotic orbital involvement of odontogenic origin, presenting initially as bilateral orbital myositis rather than as orbital abscess. Infection from the upper left jaw extended to the left infratemporal fossa, skull base and meninges and subsequently to the cavernous sinus and the orbits.