Angiostrongyliasis in an Infant Presenting as Lymphocytic Meningitis.

An Unusual Case of Meningitis in an Adolescent.

Cryptococcal meningitis (CM) and tuberculous meningitis (TBM) are common in HIV-infected adults in Africa and difficult to diagnose. Inaccurate diagnosis results in adverse outcomes. We describe patterns of meningitis in a Malawian hospital, focusing on features which differentiate CM and TBM with the aim to derive an algorithm using only clinical and basic laboratory data available in this resource-poor setting. Consecutive patients admitted with meningitis were prospectively recruited, clinical features were recorded and cerebrospinal fluid (CSF) was examined. A total of 573 patients were recruited, and 263 (46%) had CSF consistent with meningitis. One hundred and twelve (43%) had CM and 46 (18%) had TBM. CM was associated with high CSF opening pressure and low CSF leukocyte count. Fever, neck stiffness and reduced conscious level were associated with TBM. A diagnostic index was constructed demonstrating sensitivity 83%and specificity 79% for the differentiation of CM and TBM. An algorithm was derived with 92% sensitivity for the diagnosis of CM, but only 58% specificity. Although we demonstrate features associated with CM and TBM, a sufficiently sensitive and specific diagnostic algorithm could not be derived, suggesting that the diagnosis of CM and TBM in resource-limited settings still requires better access to laboratory tools.

62-Year-Old Man With Back Pain and Lower Extremity Weakness

Nosocomial outbreaks of aseptic meningitis: A public health concern

Lymphocytic Choriomeningitis Virus Infections among American Indians

The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n = 23), differential diagnosis of MS (n = 19), and NDCNS (n = 42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n = 19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92−5120.11] pg/mL, p = 0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r = 0.786, p < 0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.

Aseptic meningitis is often reported to be characterized by a mononuclear cell predominance in the cerebrospinal fluid (CSF), whereas bacterial meningitis is characterized by a polymorphonuclear (PMN) cell predominance. In contrast, other studies suggest that PMNs can be the most prevalent cell in early aseptic meningitis followed by a shift to mononuclear cells within 24 hours. These contradictory reports may lead to uncertainty in the diagnosis and treatment of meningitis. To assess 1) the characteristics of the CSF differential in aseptic versus bacterial meningitis, 2) the influence of duration of illness on the CSF differential, and 3) the role of the CSF differential in discriminating between aseptic versus bacterial meningitis. A retrospective chart review was conducted of all cases of meningitis in children >30 days of age hospitalized during the peak months for enteroviral meningitis (April to October) between 1992 to 1997. Cases of aseptic meningitis were defined as having at least 20 white blood cells/mm(3) and the absence of bacterial growth on culture. Patients were excluded if they received antibiotic therapy within the previous 5 days. Cases of bacterial meningitis were defined as having a positive culture of the CSF or the presence of a CSF pleocytosis with positive cultures of the blood. CSF variables including white blood cell differential and time from the onset of symptoms to the performance of a lumbar puncture were analyzed. PMNs were considered to be predominant when the percentage of neutrophils added to juvenile forms was >50% of cells. One hundred fifty-eight cases of meningitis were reviewed: 138 were aseptic and 20 were bacterial. The patients ranged in age from 30 days to 18 years; 61% were male. Fifty-seven percent of cases of aseptic meningitis had a PMN predominance. The percentage of PMNs in the CSF in patients with aseptic meningitis was not statistically different for patients who had a lumbar puncture performed either within or beyond 24 hours of the onset of symptoms. Fifty-one percent of the 53 patients with aseptic meningitis and duration of illness >24 hours had a PMN predominance. The ability of a PMN predominance to differentiate between aseptic and bacterial meningitis was assessed. The sensitivity of a PMN predominance for aseptic meningitis is 57% whereas the specificity is 10%. The positive predictive value of a PMN predominance for aseptic disease is 81% but the negative predictive value is 3%. Alternative definitions of PMN predominance from 60% to 90% were not useful as a clinical indicator of bacterial disease. The majority of children with aseptic meningitis have a PMN predominance in the CSF. The PMN predominance is not limited to the first 24 hours of illness. Because the majority of children with a PMN predominance during enteroviral season will have aseptic disease, a PMN predominance as a sole criterion does not discriminate between aseptic and bacterial meningitis.

Since the introduction of the varicella-zoster virus (VZV) vaccine in the United States in 1995, there has been a dramatic decrease in both the number and severity of varicella cases. However, VZV surveillance data and information on the VZV clade distribution in central nervous system (CNS) disease and non-CNS disease in New York State is not available. To investigate this, cerebrospinal fluid (CSF) samples from patients with encephalitis or meningitis and non-CSF samples from patients with non-CNS disease manifestations consistent with VZV, collected from 2004 to 2019, were tested with molecular VZV assays. A total of 341 CSF and 1,398 non-CSF samples that tested positive by a VZV-specific real-time PCR assay were further characterized as wild-type or vaccine strain by 3 biallelic real-time PCR assays targeting single nucleotide polymorphism (SNP) markers in open reading frame (ORF) 62. Genotyping was then performed on wild-type strains by conventional PCR and sequencing of 500-bp regions in ORFs 21, 22, and 50. Sequence analysis identified clades 1 to 5 in both sample types with a virtually identical clade distribution between CSF and non-CSF samples. In addition, 19 clade 6 and 13 clade 9 samples were detected in non-CSF samples after implementation of an expanded genotyping scheme, including ORF 29, 38, and 67. These clades were not detected in any CSF samples. Finally, a total of 28 vaccine strains were detected, 25 in the non-CSF samples and 3 in the CSF samples. All three cases of vaccine strain with CNS involvement experienced relatively minor symptoms of aseptic meningitis and fully recovered. These results support the evidence that while the VZV vaccine is capable of causing CNS disease, it is still a rare event and symptoms are typically less severe than those caused by wild-type infection.

Clinical manifestations of eosinophilic meningitis caused by Angiostrongylus cantonensis: 18 years’ experience in a medical center in southern Taiwan

Different intra-cerebrospinal distribution of linezolid in patients with inflammatory meningitis

Cerebrospinal fluid (CSF) is a potential source of biomarkers for many disorders of the central nervous system, including Alzheimer disease (AD). Prior to comparing CSF samples between individuals to identify patterns of disease-associated proteins, it is important to examine variation within individuals over a short period of time so that one can better interpret potential changes in CSF between individuals as well as changes within a given individual over a longer time span. In this study, we analyzed 12 CSF samples, composed of pairs of samples from six individuals, obtained 2 weeks apart. Multiaffinity depletion, two-dimensional DIGE, and tandem mass spectrometry were used. A number of proteins whose abundance varied between the two time points was identified for each individual. Some of these proteins were commonly identified in multiple individuals. More importantly, despite the intraindividual variations, hierarchical clustering and multidimensional scaling analysis of the proteomic profiles revealed that two CSF samples from the same individual cluster the closest together and that the between-subject variability is much larger than the within-subject variability. Among the six subjects, comparison between the four cognitively normal and the two very mildly demented subjects also yielded some proteins that have been identified in previous AD biomarker studies. These results validate our method of identifying differences in proteomic profiles of CSF samples and have important implications for the design of CSF biomarker studies for AD and other central nervous system disorders.

Correlation Of Cryptococcal Antigen Assay With C-reactive Protein As Serum And Urine Biomarker In Cryptococcal Meningitis: Experience In A Tertiary Hospital

Leptomeningeal metastasis (LM) is a devastating complication that occurs in 5% of patients with breast cancer. Early diagnosis and initiation of treatment are essential to prevent neurological deterioration. However, early diagnosis of LM remains challenging because 25% of cerebrospinal fluid (CSF) samples produce false-negative results at first cytological examination. We developed a new, MS-based method to investigate the protein expression patterns present in the CSF from patients with breast cancer with and without LM. CSF samples from 106 patients with active breast cancer (54 with LM and 52 without LM) and 45 control subjects were digested with trypsin. The resulting peptides were measured by MALDI-TOF MS. Then, the mass spectra were analyzed and compared between patient groups using newly developed bioinformatics tools. A total of 895 possible peak positions was detected, and 164 of these peaks discriminated between the patient groups (Kruskal-Wallis, p<0.01). The discriminatory masses were clustered, and a classifier was built to distinguish patients with breast cancer with and without LM. After bootstrap validation, the classifier had a maximum accuracy of 77% with a sensitivity of 79% and a specificity of 76%. Direct MALDI-TOF analysis of tryptic digests of CSF gives reproducible peptide profiles that can assist in diagnosing LM in patients with breast cancer. The same method can be used to develop diagnostic assays for other neurological disorders.

Adrenomedullin (ADM) is a potent hormone-like peptide rapidly induced by hypoxia and inflammatory cytokines in the early stages of sepsis. For this reason, the dosage of its more stable precursor fragment called mid-regional (MR)-proADM is currently recommended to assist in triaging patients in the emergency department. Since MR-proADM dosage is currently only approved for use in plasma, we validated its dosage in cerebrospinal fluid (CSF) samples to improve the diagnosis of central nervous system (CNS) diseases. MR-proADM concentrations were measured in samples using a fully automated platform (Brahms Kryptor Gold Analyzer, Thermo Scientific, Germany), applying the same analytical conditions in plasma and CSF samples, to finally set up an accurate laboratory protocol to validate its dosage in CSF. MR-proADM is highly stable in CSF samples stored at room temperature for up to 48 h, allowing it to be measured with confidence also in CSF samples that may be left on the bench for several hours. In addition, the repeatability and within-laboratory precision of the MR-proADM assay using CSF samples appeared equal to or better than those obtained by the manufacturer using plasma samples, allowing the use of this assay, with high precision, also for CSF samples. The reliable measure of MR-proADM in CSF and the role of this molecule in CNS will allow its introduction in the diagnostic process of infectious, inflammatory, and degenerative neurological diseases.

64-Year-Old Man With Subacute Altered Mental Status and Headache