Normal Cerebrospinal Fluid Cell Count Research Articles

Clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis

We studied the clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis. Their symptoms included seizures, hallucinations, memory impairment, apathy, anxiety, agitation, faciobrachial dystonic seizure (FBDS), and ictal piloerection. All five patients showed hippocampal fluid attenuated inversion recovery (FLAIR) hyperintensity on brain MRI even though their cell counts of cerebrospinal fluid (CSF) were normal range. Four patients had syndrome of inappropriate secretion of antidiuretic hormone. One patient with FBDS also showed basal ganglia lesion on her brain MRI. Sodium channel blockers apparently lowered the frequency of FBDS. One patient had a thyroid cancer and underwent thyroidectomy. Substantial response to immunotherapy was seen in four out of five cases. At follow-up ≥2 years, all five patients had never relapsed. In cases of limbic encephalitis with normal CSF cell counts and hyponatremia, we should consider LGI1 antibody-positive encephalitis and conduct immunotherapy immediately.

What is autoimmune encephalitis-associated epilepsy? Proposal of a practical definition.

Seizures resulting from cerebral autoimmunity are either acutely symptomatic in the context of autoimmune encephalitis (AIE) with neural surface antibodies, or they are indicative of an enduring predisposition to seizures, that is, epilepsy. Here, we propose a practical definition for autoimmune encephalitis-associated epilepsy (AEAE): Seizures associated with antibodies against glutamic acid decarboxylase, paraneoplastic syndromes, or Rasmussen encephalitis are classified as AEAE. AEAE secondary to AIE with antibodies against the N-methyl-D-aspartate receptor, leucine-rich glioma inactivated protein 1, contactin-associated protein-2, or γ-aminobutyric acid-B receptor can be diagnosed if the following criteria are met: seizures persist for at least 2 years after immunotherapy initiation; no signs of encephalitis on magnetic resonance imaging and no fluorodeoxyglucose positron emission tomography hypermetabolism; normal cerebrospinal fluid cell count; and a substantial decrease in antibody titers. This classification corresponds to different disease mechanisms. While AIE results from the pathogenic effects of neural antibodies, AEAE is probably the consequence of encephalitis-related tissue damage and thereby mainly structurally mediated. The distinction between AIE and AEAE also has practical consequences: In AIE, immunotherapy is usually highly beneficial, whereas anti-seizure medication has little effect. In AEAE, immunotherapy is less promising and the usual anti-seizure interventions are preferable. In addition, the diagnosis of AEAE has social consequences in terms of driving and professional limitations.

Quantitative proteomic analysis of cerebrospinal fluid from patients with idiopathic facial nerve palsy.

Idiopathic facial palsy (IFP) accounts for over 60% of peripheral facial palsy (FP) cases. The cause of IFP remains to be determined. Possible etiologies are nerve swelling due to inflammation and/or viral infection. In this study, we applied an integrative mass spectrometry approach to identify possibly altered protein patterns in the cerebrospinal fluid (CSF) of IFP patients. We obtained CSF samples from 34 patients with FP. In four patients, varicella-zoster virus was the cause (VZV-FP). Among the 30 patients diagnosed with IFP, 17 had normal CSF parameters, five had slightly elevated CSF cell counts and normal or elevated CSF protein, and eight had normal CSF cell counts but elevated CSF protein. Five patients with primary headache served as controls. All samples were tested for viral pathogens by PCR and subjected to liquid chromatography tandem mass spectrometry and bioinformatics analysis and multiplex cytokine/chemokine arrays. All CSF samples, except those from VZV-FP patients, were negative for all tested pathogens. The protein composition of CSF samples from IFP patients with normal CSF was comparable to controls. IFP patients with elevated CSF protein showed dysregulated proteins involved in inflammatory pathways, findings which were similar to those in VZV-FP patients. Multiplex analysis revealed similarly elevated cytokine levels in the CSF of IFP patients with elevated CSF protein and VZV-FP. Our study revealed a subgroup of IFP patients with elevated CSF protein that showed upregulated inflammatory pathways, suggesting an inflammatory/infectious cause. However, no evidence for an inflammatory cause was found in IFP patients with normal CSF.

Cerebrospinal fluid analysis in emergency patients with suspected infection of the central nervous system.

Meningitis and encephalitis are potentially life-threatening diseases that require fast and accurate diagnostics and therapy. The value of polymerase chain reaction (PCR) multiplex testing in clinical practice is still a matter of debate. This study aims to evaluate its benefits and limitations in emergency patients. We assessed the value of a meningoencephalitis PCR array in the clinical routine of an emergency department. Of 1578 emergency patients who received a lumbar puncture, 43% received it for a clinically suspected central nervous system (CNS) infection. After initial workup for cerebrospinal fluid (CSF) cell count, protein and glucose, a CNS infection was still considered likely in 307 patients. In these patients, further microbiologic workup was performed. A total of 230 samples were examined by PCR and a pathogen was detected in 66 of these samples. In the case of a positive microbiologic result, a comparison between PCR array and standard method was available for 59 samples, which demonstrated an overcall agreement of 80% (n= 47/59). Of interest, exclusively array-positive results were observed for patients with meningitis found to be positive for Streptococcus pneumoniae; four out of five patients had been treated with antibiotics before the lumbar puncture. In samples with normal CSF cell count only two positive array results were obtained, both for human herpesvirus 6, and these were not clinically relevant. Our data suggest that the array substantially contributes to a detection of pathogens in patients with suspected CNS infection and seems of particular interest in patients with acute bacterial meningitis under empiric antibiotic treatment. In CSF samples with normal cell count, it might be dispensable.

Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report

BackgroundSevere acute respiratory syndrome virus 2 (SARS-CoV-2) is spreading globally and causes most frequently fever and respiratory symptoms, i.e. Coronavirus disease 2019 (COVID-19), however, distinct neurological syndromes associated with SARS-CoV-2 infection have been described. Among SARS-CoV-2-infections-associated neurological symptoms fatigue, headache, dizziness, impaired consciousness and anosmia/ageusia are most frequent, but less frequent neurological deficits such as seizures, Guillain-Barré syndrome or ataxia may also occur.Case presentationHerein we present a case of a 62-year-old man who developed a subacute cerebellar syndrome with limb-, truncal- and gait ataxia and scanning speech 1 day after clinical resolution of symptomatic SARS-CoV-2 infection of the upper airways. Apart from ataxia, there were no signs indicative of opsoclonus myoclonus ataxia syndrome or Miller Fisher syndrome. Cerebral magnetic resonance imaging showed mild cerebellar atrophy. SARS-CoV-2 infection of the cerebellum was excluded by normal cerebrospinal fluid cell counts and, most importantly, absence of SARS-CoV-2 RNA or intrathecal SARS-CoV-2-specific antibody production. Other causes of ataxia such as other viral infections, other autoimmune and/or paraneoplastic diseases or intoxication were ruled out. The neurological deficits improved rapidly after high-dose methylprednisolone therapy.ConclusionsThe laboratory and clinical findings as well as the marked improvement after high-dose methylprednisolone therapy suggest a post-infectious, immune-mediated cause of ataxia. This report should make clinicians aware to consider SARS-CoV-2 infection as a potential cause of post-infectious neurological deficits with an atypical clinical presentation and to consider high-dose corticosteroid treatment in case that a post-infectious immune-mediated mechanism is assumed.

Normocellular Community-Acquired Bacterial Meningitis in Adults: A Nationwide Population-Based Case Series

This study sought to describe the clinical presentation of normocellular community-acquired bacterial meningitis in adults. Using the prospective, nationwide, population-based database of the Danish Study Group of Infections of the Brain, the study identified all adults with normocellular community-acquired bacterial meningitis who were treated at departments of infectious diseases in Denmark from 2015 through 2018. Normocellular community-acquired bacterial meningitis was defined as a cerebrospinal fluid leukocyte count of up to 10×106/L combined with detection of bacteria in the cerebrospinal fluid. Outcome was categorized according to the Glasgow Outcome Scale at discharge. Normocellular cerebrospinal fluid was observed in 12 of 696 (2%) patients with community-acquired bacterial meningitis. The median age was 70 years (range 17 to 92 years), and 8 of 12 (67%) patients were male. All patients had symptoms suggestive of community-acquired bacterial meningitis and pathogens identified by culture (Streptococcus pneumoniae, n=10; Staphylococcus aureus, n=1) or polymerase chain reaction (Neisseria meningitidis; n=1) of the cerebrospinal fluid. Bacteremia was found in 9 of 12 (75%) patients, and 1 of 12 (8%) presented with septic shock. None of the patients had serious underlying immunocompromising conditions. The median times from admission to lumbar puncture and meningitis treatment were 2.5 hours (interquartile range 1.1 to 3.9 hours) and 2.6 hours (interquartile range 0.9 to 22.8 hours). In 3 of 11 (27%) patients, empiric treatment for community-acquired bacterial meningitis was interrupted by a normal cerebrospinal fluid cell count. The overall case-fatality rate was 3 of 12 (25%); meningitis treatment was interrupted in 1 of these patients, and 8 of 12 (67%) had a Glasgow Outcome Scale score of 1 to 4 at discharge. Normocellular community-acquired bacterial meningitis is not very common, but it is important to consider and may be associated with a pneumococcal cause.

Leptomeningeal Metastasis: The Role of Cerebrospinal Fluid Diagnostics.

Background: Metastatic spread into the cerebrospinal fluid (CSF) represents a severe complication of malignant disease with poor prognosis. Although early diagnosis is crucial, broad spectrums of clinical manifestations, and pitfalls of magnetic resonance imaging (MRI) and CSF diagnostics can be challenging. Data are limited how CSF parameters and MRI findings relate to each other in patients with leptomeningeal metastasis.Methods: Patients with malignant cells in CSF cytology examination diagnosed between 1998 and 2016 at the Department of Neurology in the Hannover Medical School were included in this study. Clinical records, MRI findings and CSF parameters were retrospectively analyzed.Results: One hundred thirteen patients with leptomeningeal metastasis were identified. Seventy-six patients (67%) suffered from a solid malignancy while a hematological malignancy was found in 37 patients (33%). Cerebral signs and symptoms were most frequently found (78% in solid vs. 49% in hematological malignancies) followed by cranial nerve impairment (26% in solid vs. 46% in hematological malignancies) and spinal symptoms (26% in solid vs. 27% in hematological malignancies). In patients with malignant cells in CSF MRI detected signs of leptomeningeal metastasis in 62% of patients with solid and in only 33% of patients with hematological malignancies. Investigations of standard CSF parameters revealed a normal CSF cell count in 21% of patients with solid malignancies and in 8% of patients with hematological malignancies. Blood-CSF-barrier dysfunction was found in most patients (80% in solid vs. 92% in hematological malignancies). Elevated CSF lactate levels occurred in 68% of patients in solid and in 48% of patients with hematological malignancies. A high number of patients (30% in solid vs. 26% in hematological malignancies) exhibited oligoclonal bands in CSF. Significant correlations between the presence of leptomeningeal enhancement demonstrated by MRI and CSF parameters (cell count, lactate levels, and CSF/Serum albumin quotient) were not found in both malignancy groups.Conclusion: CSF examination is helpful to detect leptomeningeal metastasis since the diagnosis can be challenging especially when MRI is negative. CSF cytological investigation is mandatory whenever leptomeningeal metastasis is suspected, even when CSF cell count is normal.

Assessment of Diagnostic Yield of Nonculture Infection Testing on Cerebrospinal Fluid in Immune-Competent Children

Nonculture infection tests of cerebrospinal fluid (CSF) samples using polymerase chain reaction and antigen or antibody assays are frequently ordered on lumbar puncture specimens concurrently with routine CSF cell counts, but the value of CSF infection testing in otherwise healthy children is unknown. To determine the value of nonculture CSF infection testing in immune-competent children with normal CSF cell counts. This cross-sectional study reviewed screening and diagnostic tests in the electronic medical record system of a large academic tertiary care children's hospital. Records of children aged 0.5 to 18.9 years (n = 4083) who underwent lumbar puncture (n = 4811 procedures) in an inpatient or outpatient facility of Children's Hospital of Philadelphia between July 1, 2007, and December 31, 2016, were reviewed. Those with indwelling CSF shunts or catheters; those with active or past oncologic, immunologic, or rheumatologic conditions; or those taking immune-suppressing medications were excluded from analysis. This study was conducted from July 20, 2017, to March 13, 2019. Outcome variables included frequency of nonculture CSF infection testing and frequency of positive results in the entire cohort, and among those with normal cell counts. Normal cell counts were defined as CSF white blood cell counts lower than 5 cells/μL and CSF red blood cell counts lower than 500 cells/μL. In total, 4811 lumbar puncture procedures were performed on 4083 unique children, with a median (range) age of 7.4 (0.5-18.9) years, 2537 boys (52.7%), and 3331 (69.2%) with normal CSF cell counts. At least 1 nonculture CSF infection test was performed on 1270 lumbar puncture specimens with normal cell counts (38.1%; 95% CI, 36%-40%), and more tests were performed in the summer months. Only 18 (1.4%; 95% CI, 0.9%-2.2%) of 1270 lumbar puncture specimens with normal cell counts had at least 1 nonculture infection test with a positive result; 2 of these 18 children required clinical intervention for their positive results, but each also had other clear clinical signs of infection. Nonculture CSF infection testing appeared to be common in immune-competent children with normal CSF cell counts, but positive results were uncommon and were not independently associated with clinical care; delaying the decision to send nonculture infection tests until CSF cell counts are available could reduce unnecessary diagnostic testing and medical costs, which may improve value-based care.

Developmental outcomes and prevalence of SLC2A1 variants in young infants with hypoglycorrhachia

IntroductionThe neurodevelopmental outcomes of young infants with hypoglycorrhachia that is comparable to glucose transporter 1 deficiency syndrome (GLUT1DS), i.e. cerebrospinal fluid (CSF) glucose ≤40 mg/dL and CSF lactate <2.2 mM without causes of secondary hypoglycorrhachia are unknown. This study investigated the developmental outcomes and possibility of GLUT1DS in infants with hypoglycorrhachia, or low CSF glucose concentration. Material and methods1655 neurologically asymptomatic infants aged <4 months had CSF examinations for fever workup from 2006 to 2016. Among the infants with normal CSF cell counts and without isolated pathogens, there were hypoglycorrhachia group who had CSF glucose levels that were comparable to GLUT1DS, and age- and gender-matched non-hypoglycorrhachia group. Both groups were at a mean age of 5.9 ± 2.4 years (ranged 1–10 years) at neurodevelopmental evaluation in 2017. Mutational analysis of solute-carrier-family 2, which facilitated the glucose transporter member 1 (SLC2A1) gene was performed. ResultsAmong the 722 infants with normal CSF cell counts and without isolated pathogens, 30 (4.2%) had hypoglycorrhachia that was comparable to GLUT1DS. In the 25 infants with hypoglycorrhachia available for follow-up, 4 (16%) had abnormal outcomes, of which 3 (12%) had the history of mixed-type developmental delay before age 6 and 1 (4%) had type 1 diabetes mellitus. In the non-hypoglycorrhachia control group (n = 50), 2 patients (4%) showed abnormal outcomes, both with the history of pure speech delay. The hypoglycorrhachia group had a higher rate of the history of mixed-type of developmental delay than the control group (12% vs. 0%, P = 0.034). No SLC2A1 pathogenic variants were observed in the hypoglycorrhachia group. ConclusionHypoglycorrhachia may be a potential biomarker for neurodevelopmental delay instead of for GLUT1DS in neurologically asymptomatic young infants.

Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis.

Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10) and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other central nervous system (CNS) infections.

Cerebrospinal fluid features in adults with enteroviral nervous system infection

ObjectivesThe aim of this study was to investigate the clinical and laboratory features of adults with nervous system infections caused by enteroviruses, with special emphasis on cerebrospinal fluid (CSF). MethodsThe data of 46 patients who were PCR-positive for enteroviruses in the CSF between 2002 and 2017 were evaluated. ResultsMeningitis was the most common clinical manifestation (89%), followed by encephalitis (7%) and isolated cranial nerve involvement (4%). Twenty percent of patients reported a sudden onset of severe headache that led to the initial suspected diagnosis of subarachnoid haemorrhage. General signs of infection, such as fever, elevated C-reactive protein, and an elevated white blood cell count, were found in only 61%. Most patients exhibited consistent inflammatory CSF changes, with elevated cell counts (85%) and blood–CSF barrier dysfunction (83%). Patients with normal CSF cell counts were significantly older, less frequently presented with meningitis, and exhibited lower peripheral white blood cell counts. Sequencing revealed species Enterovirus B in all patients, with most sequences related to echovirus 30. ConclusionsThe absence of CSF pleocytosis, isolated cranial nerve involvement, and only infrequent general signs of infection may impede the diagnosis of enteroviral nervous system infections. A thorough CSF analysis including PCR is essential for a reliable diagnosis.

Is there more to a normal cerebrospinal fluid cell count?

Is there more to a normal cerebrospinal fluid cell count?

MIP-3β/CCL19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory CNS diseases in dogs.

BackgroundChemokines such as MIP-3β/CCL19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. The hypothesis of this study is that CCL19, also known as MIP-3β, is involved in the pathogenesis of inflammatory and non-inflammatory CNS diseases of dogs. Experiments were performed on cerebrospinal fluid (CSF) and serum samples of dogs affected with steroid responsive meningitis-arteritis (SRMA) during the acute phase as well as during treatment. Dogs with SRMA were compared to dogs with presumed meningoencephalomyelitis of unknown origin (MUO), and both groups sub-categorized into dogs receiving no therapy and with patients receiving prednisolone therapy. Idiopathic epilepsy (IE), a group with normal CSF cell count, was used as a control. Additionally, dogs with intervertebral disc disease (IVDD) of varying severity were analyzed. Chemokine concentrations were determined by enzyme linked immunosorbent assay. Migration assays were performed on seven selected CSF samples using a disposable 96-well chemotaxis chamber.ResultsCCL19 was detectable in CSF samples of all dogs. Dogs with untreated SRMA and MUO displayed pronounced CCL19 elevations compared to the control group and patients receiving glucocorticosteroid treatment. CSF cell counts of untreated SRMA and MUO patients were significantly positively correlated with the CCL19 CSF concentration. IVDD patients also had elevated CCL19 concentration compared to controls, but values were considerably lower than in inflammatory CNS diseases. Selected CSF samples displayed chemotactic activity for mononuclear cells in the migration assay.ConclusionsCCL19 CSF concentrations were markedly elevated in patients affected with the neuroinflammatory diseases SRMA and MUO and showed a strong correlation with the CSF cell count. This chemokine may play an important role in the pathogenesis of SRMA and MUO. The elevation of CSF CCL19 in IVDD suggests that it may also be involved in the secondary wave of spinal cord injuries.

Isolation of bacterial cerebrospinal fluid culture contaminants at a major military medical center

In recent decades, bacterial meningitis rates have decreased secondary to the success of routine vaccinations. Ironically, the decreased incidence may contribute to the challenge of establishing accurate and timely diagnoses. Studies have suggested that in immunocompetent patients with normal cerebrospinal fluid (CSF) white blood cell counts (WBC), positive CSF cultures may be disregarded as presumed contaminants, making the initial CSF WBC increasingly relevant. This single-institution retrospective study sought to integrate clinical data with positive cultures in an era when CSF contaminants may be more commonly isolated in culture than true pathogens. A total of 7715 adult and pediatric CSF samples from 1995 to 2009 were obtained at a major military medical center. Clinical and laboratory data from 121 positive bacterial cultures were reviewed. Our bacterial CSF contamination rate (false positives) was 0.91% (70/7715). True-positive (TP) CSF cultures totaled 51 (0.66%). Among TPs, 16% (8/51) demonstrated normal CSF cell counts. The notably low 15-year CSF contamination rate of 0.91%, suggests that positive cultures are likely to represent true infection in our institution. We believe efforts to decrease the contamination rate are among the most cost-effective, while targeted clinical re-evaluation for all patients with positive CSF cultures remains vital. In light of this data, a targeted approach to re-evaluating positive cultures while incorporating the clinical context remains prudent.

Suspected Early Lyme Neuroborreliosis in Patients With Erythema Migrans

Our objective was to obtain data on patients with erythema migrans (EM) who have symptoms/signs suggesting nervous system involvement and to compare epidemiologic, clinical, and microbiologic findings in patients with and without cerebrospinal fluid (CSF) pleocytosis. Adult patients with EM and suspected early Lyme neuroborreliosis were included in this study. Of 161 patients, 31 (19%) had elevated and 130 (81%) had normal CSF cell counts. In contrast to patients with normal CSF cell counts, those with pleocytosis (1) more often reported radicular pain and more often presented with meningeal signs but less frequently complained of malaise; (2) had larger EM skin lesions despite similar duration; (3) more commonly had Borrelia garinii isolated from EM skin lesions (odds ratio for pleocytosis was 31 times higher in patients with established B. garinii skin infection compared to patients with other Borrelia species isolated from their EM skin lesion) and from CSF; and (4) more frequently fulfilled microbiologic criteria for established borrelial infection of the central nervous system. The positive predictive value of pleocytosis for microbiologically proven borrelial infection of the central nervous system (defined by isolation of Borrelia from CSF and/or demonstration of intrathecal synthesis of borrelial antibodies) was 67.9%, whereas normal CSF white cell counts ruled out Lyme neuroborreliosis with a predictive value of 91.9%. Comparison of European patients with EM who had symptoms/signs suggesting early Lyme neuroborreliosis revealed several differences in the clinical presentation and in microbiologic test results according to CSF findings.

Early relapses in patients with primary CNS lymphoma treated with methotrexate-based chemotherapy without consolidating whole brain irradiation

Methotrexate (MTX)-based chemotherapy is used as upfront treatment for most patients with primary CNS lymphoma. Whether consolidating whole brain irradiation (WBI) should be recommended for patients who achieve complete remission (CR) is still a matter of debate. Patients who are predicted to experience an early relapse (ER, ≤12 months from diagnosis) might especially benefit from consolidating treatment. We therefore evaluated the incidence and prognostic impact of ER in patients with CR following chemotherapy without WBI. We identified 40 patients between 2000 and 2010 who had achieved CR following MTX-based chemotherapy. Of 36 evaluable patients 11 (31 %) experienced an ER. These patients had significantly impaired overall survival (46.0 vs. 79.0 months, p = 0.001). Normal cerebrospinal fluid cell count (11.0 vs. 76.0 months, p = 0.001) and frequent reduction of MTX dose due to impaired creatinine clearance (10.0 vs. 48.0 months, p = 0.005) had a significantly negative impact on relapse-free survival. Patients with CR following MTX-based induction chemotherapy represent a heterogeneous population. In these patients, ER is an independent risk factor for impaired overall survival. Therefore, these patients might especially benefit from consolidating treatment. These results have to be validated by prospective trials.

Neoplastic Meningitis: How MRI and CSF Cytology Are Influenced by CSF Cell Count and Tumor Type

Background. Although CSF cytology and MRI are standard methods to diagnose neoplastic meningitis (NM), this complication of neoplastic disease remains difficult to detect. We therefore reevaluated the sensitivity of gadolinium (GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology and the relevance of tumor type and CSF cell count. Methods. We retrospectively identified 111 cases of NM diagnosed in our CSF laboratory since 1990 with complete documentation of both MRI and CSF cytology. 37 had haematological and 74 solid neoplasms. CSF cell counts were increased in 74 and normal in 37 patients. Results. In hematological neoplasms, MRI was positive in 49% and CSF cytology in 97%. In solid tumors, the sensitivity of MRI was 80% and of cytology 78%. With normal CSF cell counts, MRI was positive in 59% (50% hematological, 72% solid malignancies) and CSF cytology in 76% (92% in hematological, 68% in solid neoplasms). In cases of elevated cell counts, the sensitivity of MRI was 72% (50% for hematological, 83% for solid malignancies) and of CSF cytology 91% (100% for haematological and 85% for solid neoplasms). 91% of cytologically positive cases were diagnosed at first and another 7% at second lumbar puncture. Routine protein analyses had a low sensitivity in detecting NM. Conclusions. The high overall sensitivity of MRI was only confirmed for NM from solid tumors and for elevated CSF cell counts. With normal cell counts and haematological neoplasms, CSF-cytology was superior to MRI. None of the analysed routine CSF proteins had an acceptable sensitivity and specificity in detecting leptomeningeal disease.

Cerebrospinal fluid lactate and pyruvate concentrations and their ratio

ObjectivesDeterminations of cerebrospinal fluid (CSF) lactate and pyruvate concentrations and CSF lactate:pyruvate (L/P) ratios are important in several clinical settings, yet published normative data have significant limitations. We sought to determine a large dataset of stringently-defined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios. Design and methodsWe evaluated data from 627 patients who had determinations of CSF lactate and/or CSF pyruvate from 2001 to 2011 at the Cleveland Clinic. Inclusion in the normal reference population required normal CSF cell counts, glucose and protein and routine serum chemistries and absence of progressive brain disorder, epilepsy, or seizure within 24h. Brain MRI, if done, showed no evidence of tumor, acute changes or basal ganglia abnormality. CSF cytology, CSF alanine and immunoglobulin levels, and oligoclonal band analysis were required to be normal, if done. Various inclusion/exclusion criteria were compared. Results92 patients fulfilled inclusion/exclusion criteria for a reference population. The 95% central intervals (2.5%–97.5%) for CSF lactate and pyruvate levels were 1.01–2.09mM and 0.03–0.15mM, respectively, and 9.05–26.37 for CSF L/P. There were no significant gender-related differences of CSF lactate or pyruvate concentrations or of CSF L/P. Weak positive correlations between the concentration of CSF lactate or pyruvate and age were noted. ConclusionsUsing stringent inclusion/exclusion criteria, we determined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios in a large, well-characterized reference population. Normalcy of routine CSF and blood analytes are the most important parameters in determining reference intervals for CSF lactate and pyruvate.

Pseudotumor Cerebri in a Turkish Boy With Fanconi Anemia

Pseudotumor cerebri (PC) is a clinical syndrome characterized by increased intracranial pressure with a normal cerebrospinal fluid cell count and protein level in the absence of a space-occupying lesion or apparent obstruction to the cerebrospinal fluid pathway. Although PC is described in patients with various hematological diseases including iron-deficiency anemia, megaloblastic anemia, acquired aplastic anemia, hemolytic anemia, sickle cell disease, and paroxysmal nocturnal hemoglobinuria, there is no case of PC with Fanconi anemia in the English literature. Here, we report a first case of PC in an 11-year-old boy with a diagnosis of Fanconi anemia.

Heparin-binding protein: A diagnostic marker of acute bacterial meningitis*

The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis. One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed. Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included. None. Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters. Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.