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A 42-year-old immunocompetent man presented with subacute onset unilateral headache and associated lower cranial nerve palsies. Cranial magnetic resonance imaging showed enhancing thickened tentorium cerebelli and subtentorial dura mater. Cerebrospinal fluid examination revealed lymphocytic pleocytosis and positive polymerase chain reaction assay of Aspergillus DNA. While on voriconazole treatment a progressive increase was noted in subtentorial pachymeningeal hypertrophy, which was excised because of critical compression of the medulla. The excision material showed extensive fibrosis, cellular infiltrates and no organisms. With combination therapy with anti-fungal agents and corticosteroids, pachymeningitis showed regression. We hypothesised that intact immune status and less burden of Aspergillus infection in this patient may have resulted in a chronic progressive hypertrophic pachymeningitis.

Objectives: To evaluate accuracy of physical signs for detecting meningitis., Patients and Methods: We enrolled patients aged 12 years or more, admitted with acute encephalitis syndrome (fever, headache, altered mental status, vomiting, seizures, neurodeficit) to a rural teaching hospital. The design was a double-blind, cross-sectional analysis of consecutive patients, independently comparing signs of meningeal inflammation (nuchal rigidity, head jolt accentuation of headache, Kernig's sign and Brudzinski's sign) elicited by internal medicine residents against an established reference standard (cerebrospinal fluid white cell count >5 white cells/μL). Diagnostic accuracy was measured by computing sensitivity, specificity and likelihood ratios (LRs) and their 95% confidence interval (CI) values., Results: Of 190 patients (119 men, 71 women; ages 13-81 years; mean 38(SD 18) years) CSF analysis identified meningitis in 99 (52%; 95% CI 44, 59%) patients. No physical sign of meningeal irritation could accurately distinguish those with and without meningitis: nuchal rigidity (LR+ 1.33 (0.89, 1.98) and LR- 0.86 (0.70, 1.06)), head jolt accentuation of headache (LR+ 5.52 (0.67, 44.9) and LR- 0.95(0.89, 1.00)), Kernig's sign (LR+ 1.84 (0.77, 4.35) and LR- 0.93(0.84, 1.03)) and Brudzinski's sign (LR+ 1.69 (0.65, 4.37) and LR- 0.95 (0.87, 1.04))., Conclusion: Physical signs of meningeal inflammation do not help clinicians rule in or rule out meningitis accurately. Patients suspected to have meningitis should undergo a lumbar puncture regardless of the presence or absence of physical signs., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: A 55-year-old man presented with 4 months of chronic meningitis, neutrophilic pleocytosis and extreme hypoglycorrhachia-an abnormally low concentration of glucose in the cerebrospinal fluid (CSF). A previous neurological work-up had revealed no noteworthy abnormalities. Despite the brief improvements that were seen after numerous trials of antibiotics and corticosteroids, the symptoms relapsed soon after corticosteroids were discontinued. Lumbar puncture revealed cholesterol crystals in the CSF and imaging studies revealed a sickle-shaped sacrum, partial rectal stenosis, and a communicating presacral meningocele with an epidermoid-dermoid mass. Extreme hypoglycorrhachia seems almost always to be bacterial in origin, but its differential diagnosis is, nevertheless, extensive. The definition, physiology, pathophysiology and differential diagnosis of hypoglycorrhachia are reviewed here., Investigations: Physical examination, laboratory testing, multiple imaging studies including CT and MRI of the brain and spinal cord, as well as myelography and CSF analysis., Diagnosis: Cholesterol-induced leptomeningitis in a patient with Currarino syndrome, a triad that consists of sacral bone defects, congenital hindgut anomaly, and a presacral tumor., Management: The patient was initially treated with multiple antimicrobials and steroids. However, once the cholesterol crystals and communicating presacral cyst were identified, the condition was successfully managed with surgically resection of the cyst.

We analyzed the frequency of neoplastic meningitis in patients with acute myeloid leukemia prior to allogeneic hematopoietic stem cell transplantation at our institution. Between 1996 and 2009, cerebrospinal fluid samples of 204 adult patients were examined during pre-transplant work-up for cell counts and, if abnormal, morphologically. We found blasts in cerebrospinal fluid samples of 17 patients with either persistent (n=9) or newly diagnosed (n=8) neoplastic meningitis. All patients proceeded to transplant. The proportion of patients with central nervous system involvement was significantly higher in patients with refractory disease at the time of transplantation compared with patients responding to prior systemic therapy (19% vs. 4.6%; P=0.003). Since most of the patients with central nervous system involvement were asymptomatic, cerebrospinal fluid evaluation should be considered at least in patients with refractory acute myeloid leukemia.

Background: The term "surface epithelium" is used to describe cells, including meningeal, choroid plexus, ependymal, and endothelial cells, that are found in human cerebrospinal fluid (CSF) and are difficult to distinguish cytologically. We hypothesized that the presence of surface epithelial cells in canine CSF was associated with specific diseases of the central nervous system (CNS)., Objectives: In this retrospective study the frequency of surface epithelial cells in CSF from dogs with neurologic disease was investigated along with the potential association with age, specific type of CNS disease, and CSF total nucleated cell count (TNCC) and protein concentration., Methods: The frequency of surface epithelial cells in 359 canine CSF samples was analyzed for 5 disease groups: CNS neoplasia, CNS compression, CNS inflammation, idiopathic epilepsy, and miscellaneous diseases. Groups were also combined into those with and without expected meningeal involvement. Association of the presence of surface epithelial cells in CSF with age, disease type, and CSF TNCC and protein concentration was investigated., Results: Surface epithelial cells were found in 27 of 359 (7.5%) CSF samples: CNS neoplasia 2/30 (6.7%), CNS compression 7/64 (10.9%), CNS inflammation 1/39 (2.6%), idiopathic epilepsy 8/124 (6.5%), and miscellaneous diseases 9/102 (8.8%). Significant associations between surface epithelial cell presence in CSF and age, disease type, CSF TNCC, and CSF protein concentration were not found., Conclusions: The presence of surface epithelial cells was not related to a specific disease group or CSF changes in the studied population. Thus, the presence of surface epithelial cells should be interpreted carefully, as it could represent an incidental finding in CSF specimens., (©2010 American Society for Veterinary Clinical Pathology.)

Cerebrospinal fluid (CSF) urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) levels were measured in patients with eosinophilic meningitis associated with angiostrongyliasis (EOMA) by quantitative sandwich enzyme immunoassays. The CSF concentrations of uPA and MMP-9 were evaluated in 30 EOMA patients and 10 controls. The CSF uPA and MMP-9 levels of the EOMA patients were significantly higher than those of the controls (p<0.001). The positive detection values were 73% (22/30) and 86.7% (26/30) for uPA and MMP-9, respectively. The uPA detection was in correlation with headache duration (p=0.008) and stiff neck (p=0.048), while the MMP-9 was in correlation with CSF total protein (p=0.006), CSF leukocytosis (p=0.004) and CSF eosinophil numbers (p=0.02). CSF uPA and MMP-9 levels are potentially useful for the understanding of immunologic pathogenesis, for therapeutic targets, for the diagnosis of EOMA and for monitoring treatment efficacy., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Despite the advent of new antifungal agents, coccidioidal meningitis (CM) remains a difficult-to-treat condition with significant morbidity and mortality. In this study we directly compare the clinical presentation and management of patients with Coccidioides immitis meningitis in the azole era (after 1980) to that of a cohort of patients from the pre-azole era. We reviewed 30 CM cases seen at 3 Los Angeles hospitals between the years 1993 to 2008 ("2008 cohort") and compared them to 31 patients ("1980 cohort") described by Bouza et al in a previous study. The demographics and clinical presentation of patients in the 2008 cohort were similar to those of the 1980 cohort except for a higher incidence of Hispanic patients (2008: 53% vs. 1980: 6%) and a greater percentage of patients with underlying, predisposing clinical conditions (2008: 66% vs. 1980: 32%). Ten patients in the 2008 cohort had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a condition not reported in the earlier study. Laboratory findings were similar between the 2 groups except for a lower incidence of peripheral leukocytosis and eosinophilia in the 2008 group.There were marked differences in drug treatment between the 2 eras. In the 2008 cohort, 29 patients received fluconazole therapy: 13 were treated with fluconazole monotherapy, and 16 received a combination of fluconazole and intravenous amphotericin B. Although almost all patients (29/31) in the 1980 cohort received intrathecal amphotericin B, only 3 patients in the 2008 study received amphotericin B via this route. With respect to complications of CM, a similar percentage of patients in each cohort developed complications such as stroke and hydrocephalus. The 2008 cohort (40%) had similar mortality compared to patients in the 1980 study (39%); survivors in both groups experienced significant impairment of activities of daily living. Although recommended as first-line therapy for CM, azole-based therapies are not curative and do not necessarily prevent complications associated with the disease.CM remains a serious illness with a high rate of morbidity and mortality. Immunocompromised individuals, especially those with HIV/AIDS, are at special risk for CM and represent a greater share of the overall population with this condition. Despite the clear advantages of azole treatment in CM, new therapeutic approaches are needed to provide definitive cure and to reduce the need for long-term suppressive therapy.

The clinical and diagnostic characteristics and treatment of the most severe and frequent community-acquired infections in the Intensive Care Units are analyzed. These are serious community-acquired pneumonias, meningitis, encephalitis and urinary tract infections. Regarding the pneumonias, emphasis is placed on the use of the severity scales to evaluate admission in the critical units, on evolutive monitoring using biological markers and on the importance of initiating adequate early antibiotic treatment. The importance of the Gram staining of the cerebral spinal fluid in the etiological diagnosis of meningitis, of the polymerase chain reaction amplification techniques in real time and of the magnetic resonance imaging in the etiological diagnosis of the encephalitis. Furthermore, concern is expressed regarding the increase of the percentage of the strains of extended spectrum betalactamase-producing Escherichia coli and Klebsiella pneumoniae in our country., (Copyright © 2010 Elsevier España, S.L. y SEMICYUC. All rights reserved.)

Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinal fluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinal fluid of affected patients.

Background: Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated., Methods: The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2-->87.0 (SA) and m/z 311.2--> 90.0 ((13)C(3)-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients' samples with known differences in SA metabolites like meningitis (n=6), brain tumour (n=2), leukaemia (n=5), and Salla disease (n=1)., Results: Limit of detection (LOD) was 0.54 microM for FSA and 0.45 mM for TSA. Intra- and inter-assay variation for FSA (21.8 microM) were 4.8% (n=10) and 10.4% (n=40) respectively. Intra- and inter-assay variation for TSA (35.6 microM) were 9.7% (n=10) and 12.8% (n=40) respectively. Tested patients showed values of TSA above established reference value., Conclusion: The validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses., (2010 Elsevier B.V. All rights reserved.)

A 75-year-old man presented with headache, right facial palsy, and left hemiparesis. Because of elevated myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers and findings from magnetic resonance imaging (MRI) which were compatible with hypertrophic pachymeningitis (HP), he was diagnosed with MPO-ANCA-positive HP. He was treated with the combination therapy of steroid and cyclophosphamide (CY), leading to good prognosis. We present a case of HP associated with MPO-ANCA-positive vasculitis and emphasize the importance of MPO-ANCA tests as a predictable factor for relapse of the disease in order to start earlier treatment for the disease.

We conducted a prospective survey from January 2001 to March 2002. Our objective was to study etiologic, clinic, and prognostic aspect of lymphocytic meningitis in hospital of Point G to Bamako. We included 35 patients with 25 male (71. 4%) and 10 female (28. 6%), sex - ratio (M / F) equal 2. 5. The median age was of 35 ± 25.4 years (range, 16 - 66 years). HIV serology was positive 26 cases (83. 9%). Clinical presentations were different. We observed 15 cases of encephalitis, 12 cases of meningoencephalitis, 2 cases of meningitis and 6 cases of febrile syndrome. Mean duration of hospitalization was 32. 6 ± 68 days. Mean of lymphocyte was 85.3 ± 25.9% among leukocytes in cerebrospinal fluid of 31 patients. Analysis of cerebrospinal fluid (CSF) identified in 9 cases Cryptococcocus neoformans. In 16 cases etiology was determination based on indirect arguments. In 9 cases viral meningoencephalitis diagnosis was made by exodiagnosis. It concerned 2 cases of TB meningitis, 1 case of cerebral toxoplasmosis, 1 case of decapitate bacterial meningitis and 1 case of cerebral tumor. Malaria thick smear permits to diagnosticate 1 case of cerebral malaria and 1 case of uncomplicated malaria. There are still 10 cases in which the cause remained unknown during study. HIV infection provides principally lymphocytic meningitis. Co morbidity with HIV is associated to lethality at 75%. But no statistical difference with patients without HIV (p = 0.52). Our work puts in exergue all problematic and hold correct of lymphocytic meningitis in our country.

We report a rare cause of sub acute meningitis in a 15-yr-old immunocompetent female child with successful outcome. The etiological agent was Acanthamoeba. The child was successfully treat with combination of Ketoconazole. Rifampicin, cotrimoxa zole and for a period of 9 month.

Background: Breast cancer, lung cancer and melanoma metastasize to the meninges in 5-15% of patients. The identification of specific biomarkers of disease may allow for earlier diagnosis and treatment. Preclinical evidence suggests the possible relevance of SDF-1 and VEGF in the homing and neoangiogenesis of metastases. We chose to measure these molecules in the cerebrospinal fluid (CSF) of melanoma, breast, and lung cancer patients being evaluated for neoplastic meningitis (NM)., Materials and Methods: We collected CSF from patients with these cancers who were being evaluated for possible NM. CSF was assayed for SDF-1 and VEGF levels using Enzyme-linked Immunosorbent Assay (ELISA) assays., Results: CSF samples from 89 patients met criteria for analysis, including 41 with breast cancer, 35 with lung cancer and 13 with melanoma. Twenty-five percent (22/89) of all samples were positive for malignant cells; 8/41 (20%) from breast cancer, 10/35 (29%) from lung cancer and 4/13 (31%) from melanoma. CSF VEGF levels were available from 83 patients, and were elevated (>20 pg/ml) in 15/22 (68%) of patients with positive CSF cytology and normal (<20 pg/ml) in 59/61 (97%) of patients with negative CSF cytology. The two patients with negative CSF cytology who also had elevated CSF VEGF levels had MRI evidence of NM. CSF SDF-1 levels were available from 81 patients, and were elevated (>950 pg/ml) in 11/18 (61%) of patients with positive CSF cytology and normal (<950 pg/ml) in 57/63 (90%) of patients with negative CSF cytology., Conclusions: Elevated CSF levels of VEGF are sensitive and highly specific for the diagnosis of NM from breast cancer, lung cancer and melanoma, and may serve as a useful biomarker of NM in high risk patients. CSF SDF-1 levels add little to the diagnostic information provided by CSF VEGF. Evaluation of CSF VEGF levels as a trigger for early treatment in high risk breast cancer, lung cancer and melanoma patients at risk for NM, is warranted.

The aim of the present study was to reveal some etio-pathogenetic aspects of bacterial meningitis in children. The complex clinical and microbiological investigation of 14 year old 66 children with meningeal and infectious syndromes was conducted. Bacterial meningitis was diagnosed in 90,9% patients. The meningococcal meningitis was diagnosed in 18 (30%) patients, H.influenzae meningitis--in 9 (15%), S.pneumoniae--in 8 (13,3%). Meningitis as a monoinfection was revealed in 85% cases; mixed infection--in 15%. In 28 patients the etiologic agents of disease were gram-negative bacteria, in 16 children--gram-positive.

Background: Previous multidrug studies have identified the value of prednisolone in treating steroid responsive meningitis-arteritis (SRMA) and the potential value of acute phase proteins (APPs) and immunoglobulin A (IgA) in diagnosis and monitoring., Hypothesis: (1) Prednisolone monotherapy is a successful immunosuppressive modality in the treatment of SRMA; (2) protein markers are useful in identifying the potential for relapse., Animals: Twenty client-owned dogs with SRMA presented to the University of Glasgow Small Animal Hospital between May 2006 and May 2008., Methods: A prospective, observational study: CBC, biochemistry, and cerebrospinal fluid (CSF) analyses were performed. C-reactive protein (CRP), serum amyloid-A, alpha-1-acid glycoprotein, and haptoglobin (Hp) were assessed in the serum. IgA concentrations were determined in the serum and CSF., Results: Clinical resolution of SRMA was achieved in all 20 dogs. Serum CRP concentration remained increased at remission in 16/20 dogs whereas CSF cytology was within normal limits in 20/20 dogs. Serum APPs decreased significantly on treatment (P<.05) except Hp, which remained unaltered. Serum and CSF IgA concentrations remained increased for the duration of treatment., Conclusions and Clinical Importance: The prednisolone regimen presented was successful in treating SRMA without the need for additional drugs. Serum APPs are of use in the diagnosis and management of SRMA, particularly in relation to identifying relapse. Serum and CSF IgA concentrations remain increased throughout disease, aiding in diagnosis but not contributing to the management of SRMA.

A 20-day-old female infant developed fever. Sepsis evaluation revealed cerebrospinal fluid (CSF) pleocytosis and a modestly decreased CSF glucose. After 48 hours of broad-spectrum antibiotics, the infant remained febrile. Repeat CSF analysis showed increased pleocytosis and a very low glucose value. Subsequently, a rectothecal fistula and sacral abnormalities were found, leading to the diagnosis of Currarino syndrome. Parameningeal foci should be considered in treatment-resistant meningitis.

Background: Marked eosinophilic meningitis or meningoencephalomyelitis (EME) is rarely reported in dogs and the cause is usually undetermined. Long-term prognosis for dogs with cerebrospinal fluid (CSF) eosinophilia is variable., Animals: Twenty-three client-owned dogs., Methods: Retrospective case series. Dogs with eosinophilic CSF, defined as total nucleated cell count (TNCC) >3 cells/microL with >20% eosinophils, were identified by a computerized search of all dogs having cisternal and/or lumbar CSF analyzed as part of the diagnostic workup between 1992 and 2007., Results: TNCC in CSF ranged from 4 to 4,740 cells/microL (median 84 cells/microL, reference range

Background: The most frequent central nervous system complication of systemic non-Hodgkin's lymphoma (NHL) is lymphomatous meningitis (LM)., Objective: A clinical series to test the feasibility of combining intra-CSF liposomal ara-C and rituximab for the treatment of recurrent LM., Design: Clinical series of 14 patients with CSF positive lymphomatous meningitis., Setting: Tertiary-care university medical center., Results: Fourteen patients with recurrent, cytologically positive lymphomatous meningitis were treated. All 14 received liposomal ara-C and rituximab utilizing an Ommaya reservoir. Six patients also received involved-field radiotherapy (brain only two patients; brain and spine two patients; spine only two patients). Best response to treatment included 10 partial responses and four with progressive disease. Estimated median duration of response was 4.0 months (range 1-6 months). Survival ranged from 1.5 to 7 months with an estimated median of 5 months, four patients remain alive and continue to be followed. Cause of death was progressive neurological disease in 7, systemic disease in 1, and combined systemic and neurological disease in 2 patients., Conclusions: The combination of intra-CSF liposomal ara-C and rituximab administered in this schedule appears to have no additive toxicity and has modest palliative activity in patients with recurrent LM.

Background: Analysis of cerebrospinal fluid (CSF) to discriminate between benign and malignant conditions is of fundamental importance for the physician and the patient because of the differential therapeutic options and resulting morbidity and mortality. Most human tumours demonstrate increased telomerase activity (TA). Recent technical advances in the detection of TA allow for sensitive and specific detection within 4 h. Thus, the detection of TA is suitable for routine clinical testing., Methods: This study examines TA in cellular proteins in CSF from 111 patients compared to cytomorphological and laboratory examination., Results: A positive result for TA in cellular proteins of CSF was correlated significantly with Meningeosis neoplastica, but not with non-malignant conditions. Telomerase was not detected in CSF supernatant, despite positive results in cellular proteins from identical patients. Furthermore, a 48-h time delay during the pre-analytic processing is not critical for detection of TA detection in native CSF when stored at room temperature., Conclusions: We conclude that TA is a promising marker for the detection of Meningeosis neoplastica and warrants further study.

We performed a study on levels of the total prion protein (PrP) in humans affected by different neurological diseases and assessed the influence of several factors such as age, gender, and disease severity on the cerebrospinal fluid PrP levels. PrP-ELISA technique was used to analyze cerebrospinal fluid (CSF) samples. 293 CSF samples of patients with Creutzfeldt-Jakob-disease (CJD), Alzheimer's disease, dementia with Lewy-bodies, Parkinson's disease, multiple sclerosis, cerebral ischemia, generalized epileptic seizures, and meningitis and encephalitis in comparison to controls were analyzed. We found a significant reduction of CSF PrP levels in patients suffering from all neurodegenerative disorders analyzed. This group exhibited mean PrP values of 164 ng/ml while non-neurodegenerative disorder patients and healthy controls showed PrP levels of 208 ng/ml and 226 ng/ml, respectively. CSF levels correlated with disease severity in CJD, Alzheimer's disease, and dementia with Lewy-bodies. The finding of decreased PrP levels in the CSF of patients not only with CJD but also in other neurodegenerative disorders is intriguing. Age-, gender-, and genetic-specific factors might be involved in the PrP c regulation.

A very rare clinical entity, so-called eosinophilic meningitis, classified by prevalence of eosinophils in cerebrospinal fluid (CSF), with the presence of pleiocytosis, has been recorded in our laboratory four times only in the last 24 years. A low glucose level, elevation of total protein and lactic acid in CSF were detected in all the clinical cases. The last two cases were made possible by using flow cytometry method; surprisingly, the presence was found in mature T-cells in CSF, predominantly helpers (CD3+, CD4+) and, practically, none is B-cells (CD19+), plasma cells (CD138+) and NK-cells.

Introduction: Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in septic shock, but its role in central nervous system infection (CNS) remains to be defined., Methods: We investigated cerebrospinal fluid (CSF) levels of MIF in 171 patients who were clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis of known aetiology, 20 purulent meningitis of unknown aetiology, 59 lymphocytic meningitis and 11 encephalitis, whereas 50 were suspected of having but had no evidence of CNS infection., Results: CSF MIF levels were significantly higher in patients with purulent meningitis of known aetiology (median [interquartile range]: 8,639 [3,344 to 20,600] ng/l) than in patients with purulent meningitis of unknown aetiology (2,209 [1,516 to 6,550] ng/l; Mann-Whitney test, P = 0.003), patients with lymphocytic meningitis (1,912 [1,302 to 4,105] ng/l; P < 0.001) and patients suspected of having but without evidence of CNS infection (1,472 [672 to 3,447] ng/l; P < 0.001). Also, patients with encephalitis (6,937 [3,961 to 8,353] ng/l) had higher CSF MIF than did patients without CNS infection (P < 0.01). Among patients with purulent meningitis, CSF MIF levels were significantly higher in patients infected with pneumococci than in those with meningococcal infection (11,569 [8,615 to 21,935] ng/l versus 5,006 [1,717 to 10,905] ng/l; P = 0.02), in patients who required versus those not requiring assisted ventilation (10,493 [5,961 to 22,725] ng/l versus 3,240 [1,563 to 9,302] ng/l; P = 0.003), and in patients with versus those without impaired consciousness (8,614 [3,344 to 20,935] ng/l versus 2,625 [1,561 to 7,530] ng/l; P = 0.02). CSF MIF levels correlated significantly with meningeal inflammation (P < 0.05) but not with systemic inflammatory response (P > 0.05) in patients with purulent meningitis of known aetiology, those with lymphocytic meningitis and those with encephalitis., Conclusions: MIF was significantly increased in the CSF of patients with purulent meningitis and encephalitis, and was to some degree associated with severity of the infection. Our findings indicate that MIF may play an important role in CNS infection.

Background: Lyme disease is a multiorgan disease, caused by spirochetes of Borrelia species. Clinical picture is diverse, borreliosis can affect skin, nervous system, musculoskeletal system and heart. Neopterin is a marker of cytotoxic lymphocytes T activities, it is produced by monocytes/macrophages stimulated with IFNgamma., Aim: The aim of our study was to evaluate the level of neopterin in serum and cerebrospinal fluid in borreliosis and correlate it with the symptoms, markers of inflammation in cerebrospinal fluid (CSF), and serological tests against Borrelia burgdorferi., Methodology: We have enrolled in the study 39 patients treated for Lyme borreliosis. The level of neopterin in serum was assessed in all patients, among patient with suspicion of neuroborreliosis (n = 33) we assessed the level of neopterin, protein, glucose and chlorium in CSF., Results: The level of neopterin in CSF was lower among patients who were treated due to presence of erithema migrans in their past regarding patients who had never had erithema migrans (p = 0.008). The level of neopterin in CSF was higher (6.6 nmol/l) in patients with the presence of inflammation in CSF versus patients with no changes in CSF (3.8 mmol/l; p = 0.019). There was no correlation between neopterin in serum or CSF and Westernblot test., Conclusions: Patients with neuroborreliosis who had lymphocytic meningitis had higher level of neopterin in CSF. We suggest the role of neopterin in pathogenesis on neuroborreliosis. Neopterin as a marker of cytotoxic lymphocytes T activities can be useful in borreliosis diagnosis but more studies regarding this problem should be done.

A 5-year-old child presented with the second episode of meningitis when we started investigating her to find a cause for recurrent episode of meningitis. During this she suffered from a third attack after which she was diagnosed as having isolated C(3) deficiency. She was put on penicillin prophylaxis and vaccinated against encapsulated bacteria, after which she is now doing well.

Recent studies suggest inflammatory mechanisms involved in the pathogenesis of major psychiatric disorders (MPD). T cells play a major role during inflammation, but little is known about T cell subpopulations in the cerebrospinal fluid (CSF). We investigated the frequency of cells positive for the surface markers CD4, CD8, CD25, CD45, CD69, and CD127 in 45 paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples by multiparameter flow cytometry from patients with MPD of the schizophrenic and affective spectrum with normal CSF cell counts and compared them with those from patients with non-inflammatory (NIND), chronic inflammatory (CIND) neurological disorders, and meningitis (MEN). In MEN patients, CD4+ cell frequency in PB, but not in CSF, was significantly increased as compared to CIND and NIND. No difference between patient groups was observed for CD8+. CD4+CD45RO+ double positive cells in PB were significantly lower in CIND than in MEN or NIND. The frequency of CD4+CD25+ cells in PB was significantly higher in MEN than in MPD or CIND. For CSF, the percentage of CD4+CD127(dim) cells was significantly lower in MEN than in MPD. CD4+CD127(dim) in PB and CSF showed overlapping characteristic clusters between MPD and CIND and MEN patients. Overall, the hypothesis of low degree inflammation in a subgroup of MPD is supported. The analysis of lymphocyte subsets in PB and CSF constitutes a novel promising tool to understand underlying pathomechanisms in psychiatric and neurological disorders on an individual case level.

Background: Cerebrospinal fluid (CSF) findings are often used to diagnose meningitis in neonates given antibiotics before the lumbar puncture is performed. Traumatic lumbar punctures are common and complicate interpretation of CSF white blood cell counts. The purpose of this study is to evaluate the diagnostic utility of adjusting CSF white blood cell counts based on CSF and peripheral red blood cell counts., Methods: Cohort study of lumbar punctures performed between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. Traumatic lumbar punctures were defined as CSF specimens with > or =500 red blood cells/mm. CSF white blood cell counts were adjusted downward for traumatic lumbar punctures using several commonly used methods. We calculated sensitivity, specificity, likelihood ratios, and area under the receiver operating characteristic curve of unadjusted and adjusted CSF white blood cell counts for predicting meningitis in neonates with traumatic lumbar punctures., Results: Of 6374 lumbar punctures, 2519 (39.5%) were traumatic. 114/6374 (1.8%) were positive for meningitis; 50 neonates with traumatic lumbar punctures had meningitis. The areas under the receiver operating characteristic curve for white blood cell count unadjusted and adjusted by all methods were similar., Conclusions: Adjustment of CSF white blood cell counts to account for increased red cells does not improve diagnostic utility. Adjustment can result in loss of sensitivity with marginal gain in specificity. Adjustment of WBC counts in the setting of a traumatic lumbar puncture does not aid in the diagnosis of bacterial and fungal meningitis in neonates.

Steroid-responsive Meningitis-Arteritis (SRMA) is a systemic inflammatory disease of juvenile to young adult dogs with a relapsing course and most prominent manifestation in the cervical meninges. Immunophenotyping and flow cytometric measurement of lymphocytes in peripheral blood (PB) and CSF was performed in the acute phase of SRMA (n=12) and during glucocorticosteroid treatment (n=10). Values were compared to those from dogs with other neurologic diseases (n=63) and healthy individuals (n=7). Dogs with SRMA had high CD4:CD8alpha ratios in PB and low T:B cell ratios in PB and CSF suggesting that a T(H)2-mediated immune response occurs. The T:B cell ratio in CSF was markedly lower than that in PB indicating that either a selective recruitment of B cells or, alternatively, their strong intrathecal proliferation takes place. SRMA appears to be a valuable animal model for the investigation of compartmentalization of immune responses and for studies on differences in local central nervous system and systemic immune responses.

Objectives: To characterise dogs with meningomyelitis and to compare signalment, body temperature and vaccination status to a representative control group., Methods: Dogs with meningomyelitis were identified retrospectively. Signalment, history, vaccination status, body temperature, severity of neurological dysfunction (modified Frankel score), diagnostic procedures, aetiology, survival to discharge and long-term survival were analysed., Results: Affected dogs were younger (P<0.05) and more frequently hound or toy breeds (P<0.05) when compared with controls. Hound and toy breed dogs less than or equal to three years of age had a 13 times higher odds of meningomyelitis compared with other breeds (P<0.001). General proprioceptive ataxia, limb paresis and paraspinal hyperaesthesia were the most common clinical signs. Meningomyelitis of unknown aetiology and granulomatous meningomyelitis were the most common diagnoses. The median time to death or continued follow-up in dogs alive at discharge was 213 days. Meningomyelitis resulted in death or euthanasia in 14 of 28 dogs. Clinical signs improved or resolved in seven of 28 dogs., Clinical Significance: Meningomyelitis is a differential diagnosis for dogs with clinical signs of myelopathy. Young dogs and toy or hound breeds seem to be predisposed. Clinical signs of meningomyelitis improve or resolve in some dogs.

Objectives: Described here is the clinical presentation and etiology of community-acquired meningitis in adult patients in a Baltimore community hospital from 1997 to 2006., Method: A retrospective chart review was performed. Data were collected regarding demographics, presenting symptoms, cerebrospinal fluid findings, and outcome., Results: Of 80 patients identified, 17 were diagnosed with bacterial meningitis, 18 with viral meningitis, 39 with aseptic meningitis of unclear etiology, and 6 with other noninfectious causes. Streptococcus pneumoniae was the most common bacterial pathogen. Herpes simplex virus, enteroviruses and West Nile encephalitis virus were the most common viral pathogens. The classic triad of fever, neck stiffness and change of mental status was less common than previously reported, found in 5.0% of all the patients and 21.4% of the patients with bacterial meningitis., Conclusion: Meningitis should be suspected with any suggestion of central nervous system complaint, even in the absence of the classic triad of symptoms and signs.

Background: Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals., Objective: To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases., Animals: One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE)., Methods: Prospective, observational study: C-reactive protein (CRP), alpha(2)-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid., Results: Serum CRP was significantly higher in dogs with SRMA (x=142 microg/mL+/-75) and sepsis (x=114 microg/mL+/-67) in comparison with dogs with other neurologic diseases (x=2.3-21 microg/mL; P< .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower (P< .01) in dogs with SRMA (x=3.2 g/dL+/-0.41) than in other groups (x=3.6-3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels (r=0.515, P= .003)., Conclusions and Clinical Importance: CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs.

Background and Purpose: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis., Methods: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment. The association of HGF with non-infectious diseases and clinically or microbiologically proven bacterial, tuberculous, viral, fungal and parasitic meningitis was observed, along with its relation to other parameters of the cerebrospinal fluid., Results: Forty six of the 65 patients (71%) were diagnosed as having meningitis. Cerebospinal fluid HGF level was significantly elevated in patients with meningitis compared with patients with non-infectious diseases (1501 vs 578 pg/mL; Mann-Whitney U test, p=0.001). The highest HGF level was found in bacterial meningitis (2699 pg/mL), followed by tuberculous meningitis (1540 pg/mL), viral meningitis (1431 pg/mL), fungal meningitis (714 pg/mL) and parasitic meningitis (174 pg/mL). There was no association between HGF level and other parameters of the cerebrospinal fluid (Pearson's correlation test)., Conclusion: Cerebrospinal fluid HGF may offer additional information in the classification of meningitis. This may assist in patient management when no pathogen is cultured from the cerebrospinal fluid and when other parameters of the cerebrospinal fluid demonstrate equivocal results.

Diagnostic lumbar puncture (LP) is essential to the diagnosis of central nervous system infections and subarachnoid haemorrhage. Life or limb-threatening adverse events due to the procedure are rare, but less severe complications may be common. Clinical practice in diagnostic LP is often not evidenced based. The aim of the study was to use best available published evidence to address questions on minimizing complications associated with diagnostic LP. We searched PubMed for studies in the English language using key words relevant to the complications of diagnostic LP. We emphasized randomized controlled trials and systematic reviews enrolling adult patients undergoing diagnostic LP. Uncontrolled studies and studies involving children or spinal anaesthesia were considered when no other evidence was available. There were nine prospective studies and three systematic reviews on reducing complications from LP. Recommendations on interventions to minimize complications of LP are graded based on the quality and strength of evidence.

Neonatal meningitis is one of the important causes of infant mortality and morbidity. Periventricular white matter of neonatal brain is known to be vulnerable to oxidative and hypoxic/ischemic injury secondary to neuro-infections. The aim of this study was to assess periventricular white matter damage in neonatal bacterial meningitis using diffusion tensor imaging (DTI). DTI was performed in 7 age/sex matched controls and 14 neonates with proven bacterial meningitis at the time of diagnosis and after 3 weeks of antibiotic treatment. Region of interest were placed on periventricular white matter to quantify fractional anisotropy (FA) and mean diffusivity (MD). Based on the clinical prognosis and conventional MRI, patients were grouped into those with normal and with abnormal outcome. Compared to controls significantly decreased FA values were observed in entire periventricular white matter except for left parietal white matter in patients with abnormal outcome. Even in those with normal outcome significant decrease in FA values were observed in right parietal and bilateral occipital white matter compared to controls. Decreased FA values in the periventricular white matter regions in neonatal meningitis confirm microstructural white matter injury.

Neoplastic meningitis (NM) occurs in approximately 5% of all patients with cancer. NM is a disease affecting the entire neuraxis, so staging and treatment need to encompass all cerebrospinal fluid (CSF) compartments. Central nervous system staging of NM includes contrast-enhanced brain and spine imaging and radionuclide CSF flow study. Treatment of NM incorporates involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytosine arabinoside, and thiotepa) administered on a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative, with an expected median patient survival of 3 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.

Recent studies have suggested a diagnostic role of the B-lymphocyte attracting chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of 59 consecutive patients referred to hospital for suspected LNB. Thirty-seven patients were classified as definite LNB and used as the reference standard. Seven were classified as probable, and seven as possible LNB. Eight patients did not fulfil case definitions and were used as controls. At presentation, CSF CXCL13 was elevated in all patients with definite LNB, as compared to a positive CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment sensitivity of elevated CSF [corrected] Bb Al [corrected] was 100 % (95 % CI = 91-100) and 89 % [corrected] (95 % CI = 75-96) respectively (p = 0.053). Among the eight control patients, CSF CXCL13 was normal in five and only slightly elevated in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was similar 63 % (95 % CI = 31-86) (p = 1.0).CSF CXCL13 was elevated in 6/7 patients with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all these 14 patients. An additional control group consisted of 31 patients with multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g) and non-Lyme meningitis (23 ng/g) (p < 0.001). Four months post-treatment CSF CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a negative Bb AI in 10 % (p < 0.001).CSF CXCL13 may be a useful supplement in early diagnosis of acute LNB.

The levels of interleukin 5 (IL5), IL10, and IL13 in the cerebrospinal fluid (CSF) were markedly higher in 30 patients with eosinophilic meningitis associated with angiostrongyliasis (EOMA) than in the controls (P<0.001). IL2, IL4, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were not significantly different (P>0.05). IL5, IL10, and TNFalpha levels correlated with eosinophil levels (P=0.023, P=0.018, and P=0.005, respectively) while IL2, IL4, IL13, and IFNgamma did not (P>0.05). Our data suggest that local T-helper-2 (TH2) cytokine responses are predominant in the CSF of patients with EOMA. Data on T lymphocyte-parasite interactions are important for the design of effective vaccines and immunotherapies. The measurement of T-helper-1 (TH1)/TH2 cytokines in the CSF may also have some potential for the diagnosis of parasite associated meningitis.

Biochemical analysis of cerebrospinal fluid may provide answers to important clinical questions. This review summarizes these questions and outlines the value and limitations of cerebrospinal fluid analysis.

Whereas regulatory T (Treg) cells play an important role in the prevention of autoimmunity, increasing evidence suggests that their down-regulatory properties negatively affect immune responses directed against tumors. Treg cells selectively express chemokine receptors CCR4 and CCR8, and specific migration occurs following the release of various chemokines. Neoplastic meningitis (NM) resulting from leptomeningeal spread of systemic non-Hodgkin lymphoma (NHL) or carcinoma has a poor prognosis. We hypothesized that Treg-cell accumulation within the subarachnoid space as a result of interfering with tumor immunity may be relevant for survival of neoplastic cells. We collected cerebrospinal fluid (CSF) from 101 patients diagnosed with lymphomatous/carcinomatous NM and various inflammatory diseases (IDs) and noninflammatory neurologic disorders (NIDs). CSF Treg- cell counts were determined by flow cytometry, Treg cell-specific chemokines by enzyme-linked immunosorbent assay (ELISA), and Treg-cell trafficking by chemotaxis assay. Both frequencies of Treg-cell and Treg cell-specific chemotactic activities were significantly elevated in CSF samples of patients with NM. Local Treg-cell accumulation occurred without concomitant rise of conventional T (Tconv) cells, coincided with elevated concentrations of Treg cell-attracting chemokines CCL17 and CCL22 and correlated with numbers of atypical CSF cells. We conclude that Treg cells are specifically recruited into the CSF of patients with NM, suggesting that the presence of Treg cells within the subarachnoid space generates a microenvironment that may favor survival and growth of malignant cells.

Millions of patients see physicians each year for headache, most of which are primary headaches. However, serious secondary headaches, such as meningitis, represent about 5% of children and 1% to 2% of adults seen in the emergency department for headache. A primary care or emergency department physician may initially miss individuals with bacterial meningitis. Considering meningitis as a headache cause is important because delay in the diagnosis may have adverse consequences. A careful history and physical examination are central in identifying individuals at high risk for meningitis. This article lists information that can be obtained from the patient that may be indicative of meningitis. Performing a lumbar puncture with appropriate examination of the cerebrospinal fluid (CSF) is the key to establishing the diagnosis of meningitis. This article also includes the types of meningitis that should be considered when the CSF demonstrates a pleocytosis.

During November 2004-January 2005, 5 cases of eosinophilic meningitis (EM) attributable to Angiostrongylus cantonensis infection were reported in Hawaii. To determine if this temporal clustering reflected an increased incidence, we ascertained EM and A. cantonensis cases by systematic review of statewide laboratory and medical records for January 2001-February 2005 and generalized the data to population estimates. We identified 83 EM cases; 24 (29%) were attributed to A. cantonensis infection, which was included in the discharge diagnoses for only 2 cases. Comparison of A. cantonensis infection incidence rates (per 100,000 person-years) for the baseline (January 2001-October 2004) and cluster (November 2004-February 2005) periods showed statistically significant increases for the state as a whole (0.3 vs. 2.1), the Big Island of Hawaii (1.1 vs. 7.4), and Maui County (0.4 vs. 4.3). These findings underscore the need to consider the diagnosis of A. cantonensis infection, especially in the state of Hawaii.

Aim: To look for the clinical implications of increased cortical fractional anisotropy (FA) in meningitis patients associated with brain abscess., Material and Methods: Diffusion tensor imaging was performed in 10 patients of meningitis associated with brain abscess and 10 controls. The region of interest analysis was performed to calculate FA and mean diffusivity values from the abscess cavity and cortical regions of patients (enhancing and nonenhancing meninges on postcontrast T1-weighted images) and controls., Results: Significantly increased FA values with no change in mean diffusivity values were found in enhancing (FA = 0.113 +/- 0.023, P = 0.000) as well as nonenhancing (FA = 0.085 +/- 0.009, P = 0.000) cortical region of patients compared with controls (FA = 0.067 +/- 0.010)., Conclusions: Increased FA values in the enhancing as well as nonenhancing cortical regions suggest diffuse inflammatory activity in the pia-arachnoid in meningitis patients. It also suggests that FA may be a better indicator of active and diffuse meningeal inflammation than postcontrast T1-weighted images.

Background: Lymphomatous meningitis (LM) represents a severe complication of malignant lymphomas. While clinical suspicion is raised by symptoms ranging from mild disturbances of sensation to severe pain or impaired consciousness, the definite diagnosis of LM is often difficult to obtain. Since B-cell lymphomas are clonally restricted to express either kappa or lambda immunoglobulin light chain, we hypothesised that analysis of free light chain (FLC) ratios might facilitate the diagnosis of LM., Methods: Kappa and lambda FLC were measured using a novel nephelometric assay in cerebrospinal fluid (CSF) and serum from 17 patients. 5/17 suffered from LM as demonstrated by cytology, immunocytology, and/or imaging procedures., Results: Measurement of FLC concentrations in CSF was achieved for all 17 patients. FLC levels in CSF were lower than serum FLC levels in samples for the same patient obtained at the same time (p < 0.01). CSF and serum FLC concentrations correlated weakly in all patients irrespective of LM status. Significantly more patients with cytopathologically and immunohistochemically proven LM displayed abnormal kappa/lambda FLC ratios in CSF compared to individuals with no LM (p < 0.01)., Conclusion: This is the first report demonstrating that a significant proportion of LM patients display an abnormal kappa/lambda FLC ratio in the CSF.