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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.

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples ( n  = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples ( P  < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection. Next-generation metagenomic testing increases the accuracy and sensitivity of the etiology of central nervous system infections in hospitalized patients.

Background Central nervous system (CNS) infections in kidney transplant recipients (KTRs) remain poorly characterized, with current evidence largely derived from isolated case reports over the past two decades. This multicenter study aims to systematically delineate the epidemiology, clinical profiles, and outcomes of CNS infections in a large KTR cohort. Methods We conducted a retrospective analysis of 3,602 KTRs across three transplant centers in China (May 2004–July 2024). CNS infections were defined by: 1) neurological symptoms/signs, and 2) microbiological confirmation via cerebrospinal fluid (CSF) analysis, including metagenomic next-generation sequencing (mNGS) and routine microbiologic testing (bacterial and fungal cultures). Results CNS infections were diagnosed in 0.53% of KTRs (19/3602), with symptom onset occurring 2–121 months post-transplantation. Etiologies included bacterial (47%, 9/19), viral (32%, 6/19), and fungal (21%, 4/19) pathogens. Notably, 79% of cases (15/19) were exclusively identified by mNGS, whereas conventional cultures failed detection. Presenting symptoms included headache (79%) and altered mental status (42%). Mortality reached 42% (8/19) within 9–22 days of diagnosis; among survivors, 73% (8/11) exhibited neurological sequelae. Conclusions CNS infections in KTRs are rare but characterized by rapid progression and high fatality rate. While the risk of CNS infections persists throughout the post-transplant period, 1–6 months after transplantation is a higher-incidence period of CNS infections. KTRs with neurological symptoms (particularly headache and elevated CSF pressure) should undergo CSF mNGS which is critical in diagnosing such infections.

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2–7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient’s general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Chinese Clinical Trial Registry, ChiCTR1800020442.

Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or ‘virus spreaders’. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID‐19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.

Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015–16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities.

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.

An increase in the number of herpes zoster patients has been reported since universal varicella immunization was introduced, perhaps because of reduced opportunities for varicella patients to experience the natural booster effect caused by reexposure. We investigated recent trends of varicella zoster virus (VZV)-related central nervous system (CNS) infections at a university hospital in Japan. We enrolled patients with suspected CNS infection during 2013-2022 and tested cerebrospinal fluid samples by real-time PCR for DNA from 7 human herpesviruses. VZV DNA was the most commonly detected in 62 (10.2%) of 615 patients. Kulldorff's circular spatial scan statistics demonstrated a significant temporal cluster of patients with VZV-related CNS infections during 2019-2022 (p = 0.008). Among persons with such infections, the percentage with aseptic meningitis was significantly higher during 2019-2022 (86.8%), when the temporal cluster of cases occurred, than during 2013-2018 (50.0%) (p = 0.0029).

Background In acquired immunodeficiency syndrome patients, Talaromyces marneffei infections are mostly disseminated and may involve the skin, mucosa, respiratory system, digestive system, lymphatic system, and as some reports indicate, the nervous system. Mp1p, a cell wall-specific polysaccharide in Talaromyces marneffei , is used for laboratory diagnosis of Talaromyces marneffei in blood and urine samples. However, Cerebrospinal fluid Mp1p diagnosis of Talaromyces marneffei central nervous system infection has not been reported. Case presentation We present the case of an acquired immunodeficiency syndrome 35-year-old woman who has had dizziness and headache and was infected with central nervous system Talaromycosis.Magnetic resonance imaging scan which showed intracranial infectious lesions, altered brain atrophic, and periventricular demyelination.The Mp1p antigen was positive by using immunofluorescence in the Cerebrospinal fluid. Talaromyces marneffe i was isolated from the Cerebrospinal fluid.After antifungal treatment, her clinical symptoms significantly improved. Conclusions Talaromyces marneffei central nervous system infection is rare. If the patient has symptoms of central nervous system, the Cerebrospinal fluid Mp1p antigen and culture should be performed to make a definitive diagnosis.