Initial Cerebrospinal Fluid Research Articles

Repeat lumbar puncture in adults with bacterial meningitis

In a prospective nationwide cohort study performed in the Netherlands from 2006 to 2014 we analysed clinical and laboratory characteristics of adults with community-acquired bacterial meningitis who underwent repeat lumbar puncture. Repeat lumbar puncture was performed in 124 of 1490 included episodes (8%), most commonly because of clinical deterioration (42%). Median cerebrospinal fluid (CSF) leucocyte count on admission was 1473 cells/mm3. Median CSF cell count showed a decrease of 19% when repeated within 2 days; of 84% within 3–7 days, of 93% within 8–14 days and of 98% within 15–21 days. Repeat lumbar puncture confirmed the diagnosis of meningitis in eight patients with normal initial CSF examination. Repeat CSF cultures yielded bacteria in nine patients, which led to identification of an underlying source of infection in two. We conclude that repeat lumbar puncture is performed in a small proportion of adults. Although it should not be seen as routine it can be useful in selected cases to confirm diagnosis, to exclude relapsing or persistent infection, or for therapeutic purpose in communicating hydrocephalus.

A Case of Aspergillus Endophthalmitis as a Preceding Symptom of Central Nervous System Lymphoma

Purpose: To report a rare case of Aspergillus endophthalmitis as a preceding symptom of central nervous system (CNS) lymphoma. Case summary: A 66-year-old female was admitted to our clinic with mental change for 3 days. Seven months earlier, she had been diagnosed with retinal vasculitis in an ophthalmology clinic because of blurred vision in both eyes and was administered steroid therapy. Three months earlier, because of progressive symptoms, vitreous fluid culture had been performed and showed Aspergillus endophthalmitis. She was treated with intravitreous voriconazole injection and oral voriconazole. Initial brain magnetic resonance imaging (MRI) and cerebrospinal fluid study was normal. Two months later, a second MRI showed multiple enhancing lesions, which were aggravated on the third MRI at admission to our clinic. Although brain biopsy was not performed due to the poor condition of the patient, CNS lymphoma was suspected based on the neuroimaging. After steroid pulse therapy and whole brain radiation, follow-up neurologic examination showed improved mental state, and follow-up MRI showed remarkable shrinkage of multiple lesions. Conclusions: As Aspergillus endophthalmitis is an opportunistic infection in those with an immune-compromised state and the orbit is near the central nervous system, the clinician should be alert to concomitant disorders in CNS. For a prompt and accurate diagnosis of CNS disorder, early evaluation of neurologic symptoms beyond symptoms of endophthalmitis and neuroimaging is essential. J Korean Ophthalmol Soc 2016;57(4):672-676

Enterovirus infections and meningitis in children

To compare clinical characteristics in children with enterovirus infections (EVI) and meningitis with detailed characteristics of the changes in the content of cerebrospinal fluid (CSF) confirmed in the laboratory. The results of examinations of 97 children, aged from 2.5 to 15 years, 3 adolescents and 1 adult female patient with EVI were analyzed. Enterovirus RNA isolation and detection in feces and CSF was performed using PCR. Enterovirus RNA in CSF was detected in 44 children, including 3 patients with cytosis (5-7-19 cells in 3 mm3). The frequency and severity of symptoms in 42 patients with EVI and meningitis, 14 children with EVI without meningitis and 8 patients with ICD-10 «Meningitis unspecified» are presented. The initial CSF pleocytosis in 1-3 day (4-5 day for two-wave course) in EVI and meningitis was <100 in 4, from 100 to 1000 in 33, >1000 (max 3036) cells in 3 mm3 in 5 patients, including 15 with the predominance of neutrophils (from 77 to 97% in cytosis 114-2300 cells in 3 mm(3)). In the peripheral blood, leukocytosis 10.9-13.8×10(9)/л was noted in 12 children and leukocytosis 14.4-18.7×10(9)/л with the «left shift» in 7. Most of the children (n=37) with EVI and meningitis were discharged from the hospital within 10-17 days. The authors suggest the importance of including the variety of clinical presentations of EVI in the additional item «B10 Enterovirus infections» in upcoming ICD-11.

Human Immune Response Varies by the Degree of Relative Cryptococcal Antigen Shedding.

Background. Cerebrospinal fluid (CSF) cryptococcal glucuronoxylomannan antigen (CrAg) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. Some patients have higher CrAg titers with lower fungal burdens and vice versa. We hypothesized that the relative discordancy between CrAg titer and quantitative culture burden reflects the relative degree of CrAg shedding by Cryptococcus neoformans and is associated with human immune responses. Methods. One hundred ninety human immunodeficiency virus-infected individuals with cryptococcal meningitis were enrolled in Uganda and South Africa. We compared initial CSF CrAg titers relative to their CSF quantitative cultures to determine low (n = 58), intermediate (n = 68), or high (n = 64) CrAg shedders. We compared cytokines measured by Luminex multiplex assay on cryopreserved CSF and 10-week mortality across shedding groups using linear and logistic regression and distribution of genotypes by multilocus sequence typing. Results. The relative degree of CrAg shedding was positively associated with increasing CSF levels of the following: interleukin (IL)-6, IL-7, IL-8, and tumor necrosis factor-α (each P < 0.01), which are all secreted by antigen-presenting cells and negatively associated with vascular endothelial growth factor (P = .01). In addition, IL-5, IL-13, granulocyte colony-stimulating factor, and macrophage chemotactic protein were decreased in low-CrAg shedders compared with intermediate shedders (each P ≤ .01). Type 1 T-helper cells (Th1) cytokine responses and 10-week mortality did not differ between the shedding groups. Cryptococcal genotypes were equally distributed across shedding groups. Conclusions. Discordancy between CrAg shedding and expected shedding based on quantitative fungal burden is associated with detectable immunologic differences in CSF, primarily among secreted cytokines and chemokines produced by antigen-presenting cells and Th2.

Zeta-Chain-Associated Protein Kinase-70 (Zap-70) Promotes Acute Lymphoblastic Leukemia (ALL) Infiltration into the Central Nervous System By Enhancing Chemokine Receptor 7 (CCR7) Expression

Most children with B-cell precursor ALL (BCP-ALL) have an excellent prognosis but some patients are susceptible to CNS relapse, the mechanisms of which are largely unknown. Zap-70 is a tyrosine kinase mainly expressed in normal T- and NK-cells, but it is also expressed at low levels in normal B-cells. Zap-70 is however overexpressed in B-cell chronic lymphocytic leukemia (B-CLL) and is associated with an aggressive course of the disease. In B-CLL, Zap-70 was shown to up-regulate the expression of CCR7 (Calpe et al., 2011), which in turn allows T-lymphoblasts to enter the CNS (Buonamici et al., 2009). We hypothesized that Zap-70 mediated upregulation of CCR7 may enhance the homing and the survival of CNS-prone BCP-ALL cells in the CNS niche.We first transduced the 697 BCP-ALL cell line with a lentiviral vector carrying a non-targeting GFP (shGFP) or a Zap-70 (shZap-70) specific shRNA. Down-regulation of Zap-70 resulted in a significantly reduced CCR7 mRNA and surface protein expression. 697shGFP and 697shZap-70 cells were then injected intravenously into NSG mice, which were sacrificed when leukemic symptoms developed. There were no statistically significant differences in leukemic bone marrow infiltration and survival between the groups. However, immunohistochemical scoring of CNS infiltration (Krause et al., 2015) revealed that 9/10 animals (90%) in the 697shGFP group were CNS+ and only 2/7 animals (29%) in the 697shZap-70 group showed a CNS+ status (p = 0.0345). This suggests that Zap-70 mediated reduction in CCR7 impairs the CNS-positive phenotype of 697 cells in vivo.We next investigated if the Zap-70/CCR7 axis influences the ability of primary samples from patients to infiltrate the CNS of xenografts. Zap-70 mRNA was measured in pediatric BCP-ALL patients and patients with Zap-70 expression levels higher than the median were considered Zap-70high, and the remaining patients Zap-70low. 1 x 106 cells of 5 Zap-70high and 5 Zap-70low samples were injected intrafemorally into duplicate NSG mice. Interestingly, 7/10 (70%) of the mice injected with Zap-70high cells showed a CNS+ phenotype, whereas only 1/10 (10%) of the mice bearing Zap-70low samples were CNS+ (p = 0.0198). Importantly, leukemic cells of one Zap-70high patient purified from the xenograft CNS showed a marked upregulation of CCR7 expression as compared to cells isolated from bone marrow or spleen. These data suggest that the Zap-70/CCR7 axis is beneficial for patient BCP-ALL cells in the CNS of NSG mice.To test whether Zap-70/CCR7 is associated with CNS involvement in patients, we analyzed Zap-70 and CCR7 mRNA expression in diagnostic primary material of 76 BCP-ALL patients. The cohort contained 21 CNS-positive and 55 CNS-negative patients and was previously published by Cario et al. (2007). Patients were grouped into either Zap-70high/Zap-70low or CCR7high/CCR7low groups according to expression levels higher or lower than the median of the respective gene. Zap-70 expression was highly correlated with CCR7 expression (p = 0.0003; Spearman r = 0.401). There were no statistically significant differences in outcome surrogates such as prednisone response or MRD and there was no correlation between Zap-70/CCR7 expression and outcome (relapse or death). However, a trend towards high CCR7 levels and the occurrence of death could be observed (p = 0.055). Interestingly, high expression of Zap-70 or CCR7 correlated with the presence of blasts in the cytospin of the initial cerebrospinal fluid sample (p = 0.014 and p = 0.045, respectively). Furthermore, there was a significant correlation between high Zap-70 and a higher CNS status and a trend between high CCR7 and a higher CNS status according to AIEOP-BFM 2009 criteria (p = 0.024 and p = 0.098, respectively). We finally performed comparative correlations in 48/76 patients (63.2%) that were Zap-70high/CCR7high (n=24) or Zap-70low/CCR7low (n=24). Most importantly, a significant correlation between Zap-70high/CCR7high expression and a higher CNS status could be observed (p = 0.009). These data suggest that a high expression of Zap-70 or CCR7 is associated with CNS infiltration in BCP-ALL patients and that measurements of Zap-70 and CCR7 expression should be combined.Altogether, we show that Zap-70/CCR7 is important for BCP-ALL cells to enter the CNS and to survive in that niche. We propose Zap-70/CCR7 as a mechanism of CNS leukemia and a diagnostic marker with potential therapeutic implications. DisclosuresNo relevant conflicts of interest to declare.

Relapses in dogs with steroid-responsive meningitis-arteritis.

To describe relapse rates in steroid-responsive meningitis-arteritis and to describe clinical and laboratory parameters in dogs with and without relapses. Seventy-four dogs with steroid-responsive meningitis-arteritis were retrospectively identified and assigned to one of three groups: (1) without relapse; (2) at least one relapse and (3) unknown relapse status. The following parameters are reported for the first two groups: sex, age, breed, body weight, nucleated cell count, total protein concentration and percentage of neutrophils on initial cerebrospinal fluid analysis, immunoglobulin A in serum and initial cerebrospinal fluid analysis, nucleated cell count on cerebrospinal fluid analysis at 3-month re-evaluation, C-reactive protein in serum and initial cerebrospinal fluid analysis and at 3-month re-evaluation. Relapses occurred in 32 · 4% of dogs (one relapse: 62 · 5%; two relapses: 25 · 0%; three relapses: 8 · 3%; four relapses: 4 · 2%), 55 · 4% were relapse-free and in 12 · 2% the relapse status was unknown. C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 80% and 75% of dogs with relapses, respectively. In dogs without relapse, C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 100% and 90% of dogs, respectively. Relapses are frequent but no reliable predictive indicator has emerged in this study. Nevertheless, elevated C-reactive protein in serum warrants continuing therapy; normal C-reactive protein in serum does not exclude future relapse.

A 15-year retrospective analysis of prognostic factors in childhood bacterial meningitis.

This retrospective chart review aimed to identify factors in childhood bacterial meningitis that predicted disease severity and long-term outcome. The study included 112 episodes of microbiologically confirmed bacterial meningitis in children aged three days to 15 years who were admitted to a Singapore hospital from 1998 to 2013. The mortality rate was 6%, and 44% required intensive care unit (ICU) admission. Predictive factors associated with ICU admission included pneumococcal meningitis, with an odds ratio (OR) of 5.2 and 95% confidence interval (CI) of 1.5-18.2, leukopenia (OR 5.6, 95% CI 1.7-17.9) and a cerebrospinal fluid (CSF):serum glucose ratio <0.25 (OR 4.5, 95% CI 1.4-14.4). An initial CSF white blood cell count >1000/mm(3) (OR 0.26, 95% CI 0.086-0.76) was negatively associated with ICU admission. Five years after meningitis, 32% had residual sequelae, and the associated prognostic factors were Haemophilus influenzae type b (Hib) meningitis (OR 29.5, 95% CI 2-429), seizures during their inpatient stay (OR 10.6, 95% CI 1.9-60.2) and septic shock (OR 8.4, 95% CI 1.1-62.1). As mortality was low in this bacterial meningitis study, ICU admission was used as a marker of disease severity. These findings underscore the importance of the pneumococcal and Hib meningitis vaccines.

EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors.

Moderate diagnostic accuracy of MRI and initial cerebrospinal fluid (CSF) cytology analysis results in at least 10%-15% false negative diagnoses of leptomeningeal metastases (LM) of solid tumors, thus postponing start of therapy. The aim of this prospective clinical study was to determine the diagnostic value of epithelial cell adhesion molecule (EpCAM)-based flow cytometry versus cytology in CSF for the diagnosis of LM in patients with epithelial tumors. Patients with a clinical suspicion of LM but a negative or inconclusive MRI in whom a diagnostic lumbar puncture has to be performed were included. At least 5 mL of CSF for cytology, 5 mL for flow cytometry, 2 mL for cell count and biochemistry, and 8 mL whole blood samples for circulating tumor cells measurements and biochemistry were drawn. Tumor cells in CSF and whole blood were detected by multiparameter flow cytometry using EpCAM antibody. In total 29 eligible patients were enrolled in the study. Thirteen patients were ultimately diagnosed with LM. The flow cytometry assay showed 100% sensitivity and 100% specificity for diagnosing LM, while sensitivity of CSF cytology was only 61.5%. Cell count or biochemical parameters in CSF were abnormal in 100% of patients with LM. Our results suggest that the EpCAM-based flow cytometry assay is superior to CSF cytology for the diagnosis of LM in patients with an epithelial tumor, a clinical suspicion of LM, and a nonconclusive MRI. Confirmation of these data is needed in a larger dataset to recommend dual CSF diagnostics for LM. NCT01713699.

The utility of repeated cytologic evaluation of cerebrospinal fluid in individuals with metastatic breast cancer

Metastasis of breast cancer to the central nervous system, either in the brain parenchyma or leptomeninges (LMC), is a late feature of the disease . Detection of malignant cells in the cerebrospinal fluid (CSF) is the diagnostic standard for LMC. Repeated CSF examinations are often performed following an initial diagnosis positive for malignancy. This study evaluates the significance of repeated CSF evaluation in women with metastatic breast cancer to the central nervous system. Cases of adenocarcinoma of breast diagnosed by CSF cytology from 1990 through 2012 documenting: age, radiologic findings, treatment modality, and the number of repeated CSF cytology specimens and their respective interpretations. Fifty-one patients were identified; 28 patients (54.9%) had a single initial positive CSF performed and 23 (45.1%) had multiple CSF cytology samples (range = 2-25, mean = 5.5). Despite interval "negative" and "atypical cells" results on CSF cytology specimens, all 23 patients with multiple samples had at least one follow-up positive CSF cytology sample. The prognosis of the patients with an initial CSF diagnosis of adenocarcinoma was poor, regardless of the respective interpretations on the repeated CSF specimens, even in the presence of interval negative CSF.

Epidemiology and Outcome in Neonatal and Pediatric Herpes Simplex Encephalitis: A 13-Year Experience in a Singapore Tertiary Children's Hospital

Herpes simplex encephalitis (HSE) remains one of the most devastating infections of the central nervous system in children despite available antiviral therapy. Our aim was to determine the clinical epidemiology and long-term neuro-developmental outcome of neonates and children admitted to our hospital with proven HSE. Patients with HSE during November 1998 to December 2011 were identified from discharge and laboratory records and data collection was done by retrospective review of their case notes. HSE was proven by culture or polymerase chain reaction (PCR) or by a positive Herpes simplex virus (HSV)–specific intrathecal antibody. We identified 13 patients during the study period: nine neonates and four older children, all of whom were treated with intravenous acyclovir. In the neonatal cohort, three (33%) presented with seizures and only four (44%) had vesicles. The initial cerebrospinal fluid (CSF) HSV PCR was positive in seven (78%) and HSV type 2 was the most common. Repeat CSF study showed HSV positivity of 100%. Two (22%) neonates died and three (43%) had long-term neurodevelopmental sequelae. Developmental delay, focal neurological deficit, and cognitive deficit were among the most frequent neurological sequelae noted. In the pediatric cohort, three children (75%) had positive CSF HSV PCR and seizures. One (25%) died and two of the three survivors (67%) had neurodevelopmental sequelae. Early CSF studies may be negative in HSE, so a repeat CSF analysis should be considered, particularly in neonates. Early administration of acyclovir could prevent adverse outcomes in HSE.

Investigation into the Molecular Mechanisms Underlying Idiopathic Intracranial Hypertension (P2.099)

Objective: To investigate cerebrospinal fluid (CSF) secretion/drainage rates as putative underlying causes of idiopathic intracranial hypertension (IIH). Background: Various causative factors have been postulated as to the increasing incidence of IIH, however, none with any convincing evidence. Identifying biomarkers, already found to be elevated in patients with IIH, including pro-inflammatory cytokines; chemokine (C-C motif) ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as adipocyte derived hormone leptin and the glucocorticoid hydrocortisone has been used to present an insight into the pathogenesis of IIH. Design/Methods: To assess the effects of the elevated mediators on CSF volume/secretion rates, an in vivo ventriculo-cisternal perfusion was performed. In addition, an in vivo variable rate infusion technique assessed mediator effects on CSF drainage. Results: Hydrocortisone (2.65 μl/min) and TNF-α (2.58 μl/min) significantly increased CSF secretion rate, when compared to controls (1.90μl/min). IL-6 (0.91 μl/min) caused a significant decrease in CSF secretion rate. The volumes of the initial CSF within the cranium following intraperitoneal mediator injection, prior to perfusion of the animal with artificial CSF containing the mediator, were significantly higher for CCL2 (323.6 μl) and IL-17 (327.0 μl) when compared with controls (226.7 μl). CCL2 (55.6 mmH2O.min/μl) and IL-17 (52.7 mmH2O.min/μl) significantly increased pressure and resistance to CSF drainage when compared with controls (28.76mmH2O.min/μl). Conclusions: An impairment within the CSF drainage mechanisms could be postulated due to the significant increase in initial CSF volume; decrease in overall CSF secretion and increased resistance to CSF drainage associated with CCL2 and IL-17. The opposing results of CSF secretion/drainage suggest an altered compensatory mechanism associated with hydrocortisone, TNF-α and IL-6. Study supported by: Prof. Basil Sharrack, Dr. Ignacio A. Romero, Dr. A. Jane Loughlin, Dr. Jane E. Preston. Disclosure: Dr. Alimajstorovic has nothing to disclose.

Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis

Objectives: Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. Methods: In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. Results: Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). Conclusion: The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus neoformans in an Immunocompetent Host.

Cryptococcus spp is a common fungal infection and frequent cause of meningitis in immunocompromised patients; however, immunocompetent patients are also at risk of infection. Visual loss often occurs via elevated intracranial hypertension but can rarely occur through direct optic nerve, chiasm, or tract invasion. We report a case of a 38-year-old woman who presented with decreased acuity in both eyes. She had generalized visual field constriction in the right eye and temporal hemianopsia in the left eye. Magnetic resonance imaging of the brain and orbits showed multiple areas of ill-defined enhancement in the optic chiasm and tracts as well as in the diaphragmatic sella, prepontine and interpeduncular cisterns, and along cranial nerves VI, VII, and VIII bilaterally. Initial cerebrospinal fluid (CSF) showed 34 white blood cells, hypoglycorrhachia, and negative cryptococcal antigen and bacterial and fungal cultures. A transphenoidal biopsy of the dura and pituitary gland was unremarkable. Empiric steroids resulted in marked improvement in visual acuity in both eyes, but while tapering steroids, she developed rapid visual loss bilaterally. Repeat CSF performed 6 weeks later demonstrated a cryptococcal antigen titer of 1:512. Retroactive staining of the pituitary biopsy was positive for mucicarmine, a component of the polysaccharide capsule of Cryptococcus spp. After induction therapy with amphotericin B and flucytosine and 1 year of fluconazole, her visual acuity was 20/20 in both eyes. In summary, Cryptococcus can affect immunocompetent patients and often presents with insidious, chronic meningitis. Visual loss is common in cryptococcal meningitis but usually results from fulminant papilledema related to elevated intracranial pressure. In rare cases, direct nerve or chiasm infiltration by the fungus results in vision loss.

A nine-week-old girl with fever and seizures.

CASE PRESENTATION A nine-week-old girl presented to the emergency department with a 12 h history of fever and a 1 min generalized tonic-clonic seizure. Review of systems was otherwise negative. Her two-year-old sister experienced a fever and oropharyngeal ulcers two weeks before. On physical examination, she was febrile to 39.2°C rectal, but with otherwise normal vital signs. She was well-appearing and her examination was normal, including the neurological examination. Blood, urine and cerebrospinal fluid (CSF) specimens were obtained, and intravenous ceftriaxone, vancomycin and acyclovir were started. Laboratory investigations showed a normal complete blood cell count and transaminase levels. CSF examination revealed 55 white blood cells/μL (51% monocytes, 37% lymphocytes, 12% neutrophils), 7 red blood cells/μL, normal protein (0.35 g/L) and normal glucose (2.9 mmol/L). An electroencephalogram revealed active epileptiform activity over the right centroparietal regions. She was admitted to the pediatric ward and underwent magnetic resonance imaging of her head, which revealed multifocal nonenhancing lesions in the subcortical white matter of the right precentral gyrus, right cingular gyrus, right corticospinal tract, as well as the right internal capsule and thalamus (Figure 1). Bacterial cultures were without growth and antibiotics were discontinued after 48 h. CSF herpes simplex virus (HSV) 1 and HSV 2 polymerase chain reaction (PCR) (LightCycler 2.0 HSV 1/2 qualitative kit [Roche Diagnostics, Canada]) and enterovirus PCR were also negative. Repeat lumbar puncture and blood testing were performed on hospital day 3. DIAGNOSIS Both the CSF and blood samples obtained on hospital day 3 returned positive results for HSV-1 using PCR, confirming a diagnosis of HSV encephalitis. Extracted DNA from the initial CSF was re-tested using a different laboratory-developed HSV 1 and HSV 2 quantitative realtime PCR assay at another reference laboratory. In retrospect, the initial CSF specimen was positive for HSV 1 (2,675 copies/mL) using this assay, as were the second CSF specimen (21,905 copies/mL) and the blood sample (12,089 copies/mL).

Long-term neuropsychological sequelae in HIV-seronegative cryptococcal meningoencephalitis patients with and without ventriculoperitoneal shunts: a cine MRI study.

Background. Hydrocephalus in cryptococcal meningoencephalitis is most commonly managed with a ventriculoperitoneal shunt. This study applied cine magnetic resonance imaging (MRI) to evaluate initial disease severity on long-term cerebrospinal fluid (CSF) flow dynamics and associated neuropsychological sequelae in cryptococcal meningoencephalitis patients with and without ventriculoperitoneal shunts. Methods. Eighteen human immunodeficiency virus-seronegative cryptococcal meningoencephalitis patients (10 with shunts versus 8 without shunts) were compared with 32 age- and sex-matched healthy volunteers. All subjects underwent complete neurologic examination and neuropsychological testing. Cine MRI was conducted to evaluate CSF flow parameters. Initial CSF laboratory analysis and imaging findings were correlated with present CSF flow parameters and neuropsychological scores. Results. Patients without shunts had higher average flow than controls, suggesting chronic hydrocephalus. Initial Evans ratios and CSF glucose levels were associated with CSF peak velocity and flow. Worsening CSF flow parameters correlated with decreased neuropsychological performance. Conclusions. CSF flow parameter differences between the cryptococcal meningoencephalitis patients both with and without ventriculoperitoneal shunts could be detected by cine MRI and correlated with acute stage disease severity and chronic stage neuropsychological results. Cine MRI is useful for assessing the chronic hydrocephalus that may lead to neuropsychological deficits in cryptococcal meningoencephalitis patients.

Clinical Analysis of Results of Shunt Operation for Hydrocephalus Following Traumatic Brain Injury.

ObjectiveVentricular enlargement following head injury is a frequent finding but cases requiring shunt operation are rare. The incidence and developing factors of post-traumatic hydrocephalus (PTH) have been variously reported, but studies for factors influencing outcomes of shunt operation for PTH are rare. The incidence of PTH requiring shunt operation, causing injuries, and factors influencing outcome of shunt operation need to be identified.MethodsIn total, 1,142 patients suffering from traumatic brain injury (TBI) between January 2007 and December 2012 were admitted to our department. Of them, 23 patients underwent shunt operation for diagnosed PTH. In this clinical study, we reviewed retrospectively our TBI database and in the 23 patients, we evaluated outcomes with Glasgow Outcome Score just before the operation, at 14 days, 3 months, and 6 months according to initial Glasgow Coma Scale (GCS) score, interval time between shunt operation and trauma, and lumbar cerebrospinal fluid (CSF) pressure.ResultsThe incidence of PTH treated with shunt operation was 2.01%. Subdural hematoma (SDH) was the most common preceding head injury. The outcomes of shunt operation were not related with lumbar CSF pressure or interval time from trauma, but initial GCS score correlated with the outcome.ConclusionIn present study, 2.01% of TBI patients underwent shunt operation. SDH was the most common preceding injury. Admission GCS score was related to the outcome of shunt operation. However, there were no correlation between the outcome of shunt operation and initial lumbar CSF pressure or interval time of shunt operation after the trauma.

Insights into pediatric herpes simplex encephalitis from a cohort of 21 children from the California Encephalitis Project, 1998-2011.

Twenty-one children with confirmed herpes simplex encephalitis were identified in the California Encephalitis Project.Noteworthy features included 6 (29%) patients with an initial negative herpes simplex virus cerebrospinal fluid polymerase chain reaction test and 13 (62%) patients with extratemporal lobe involvement identified by neuroimaging [corrected]. Eleven cases were <4 years of age, but all 4 fatal cases occurred in adolescents.

Fatal cryptococcal meningitis in a HIV‐seronegative patient with liver cirrhosis

Introduction: A 41‐year‐old man with a history of alcoholic cirrhosis presented to Patan Hospital in Kathmandu, Nepal, with a severe headache. Case presentation: Clinical examination found an isolated sixth nerve palsy of the left side with normal blood parameters and a normal brain scan. An initial cerebrospinal fluid analysis found lymphocytosis, with a significantly elevated protein level and reduced glucose. Tubercular meningitis was considered; however, the patient did not improve and a re‐examination of the cerebrospinal fluid confirmed cryptococcal meningitis. Conclusion: After diagnosis the patient was treated with amphotericin B. Despite all efforts the patient died 5 days later.

Diagnostic and prognostic value of cerebrospinal fluid analysis in Vogt‐Koyanagi‐Harada syndrome

AbstractPurpose To evaluate the diagnostic and prognostic values of lumbar puncture in Vogt‐Koyanagi‐Harada (VKH) syndrome.Methods Medical records of patients seen in a single tertiary center between 1995 and 2013, with confirmed VKH syndrome according to the Revised Diagnostic Criterias, were retrospectively reviewed. Clinical stage of the disease, cerebrospinal fluid (CSF) analysis, therapeutic strategy, and prognosis were compared.Results 68 patients with a confirmed diagnosis of VKH disease were initially reviewed. Among them, 29 patients (42%) had undergone a lumbar puncture (LP). 21 LP (72.4%) were performed at the early stage of the disease, and 11 were performed at the chronic stage of the disease (37.6%). 16 patients (55%) had a pleiocytosis. LP was abnormal in 66,7% at the acute phase and 27% at the chronic phase. An average of 62.3 lymphocytes /mm3 was observed when LP was performed during the acute phase and an average of 9.5 lymphocytes / mm3 was observed during the chronic phase ( p = 0,03). For two cases, the patient met the diagnostic criteria because of the LP findings. Patients dependant on low doses of steroids (&lt;5mg/d) had more lymphocytes (93,8 lymphocytesmm3) into the initial CSF analysis compared to the patients dependant on high doses of steroids (&gt;5mg/d) ( 29,3 lymphocytesmm3) (p=0.03) when LP was performed at the acute phase of the disease.Conclusion The number of lymphocytes in the CSF at the diagnostic phase seems to be one of the prognostic factors for the outcome of VKH. Patients with a low pleiocytosis in the initial lumbar puncture should be closely monitored and may require a more aggressive treatment. Those conclusions must be confirmed with a prospective study.

POTENCY OF SECRETING HCG- IN GERMINOMAS. CLINICAL AND BIOLOGICAL ANALYSIS

BACKGROUND: It has long been discussed whether HCG secreting germinomas are more malignant than pure germinomas. The Japanese study group insists of no difference in survival between two kinds of germinomas, whereas the European and American study groups put HCG germinomas into the high risk group. In order to solve the question, we analyzed the treatment results, the titer of a small amount of HCG-β in the cerebrospinal fluid (CSF), and the expression of HCGβ mRNA in germinoma cells. METHODS: (1) We selected 80 germinoma patients with or without HCG secretion for PFS analysis who were treated by proper radiation volume for their tumors developing in/around the third ventricle in the Japanese prospective study. (2) The initial serum and CSF samples were measured for HCG-β with the ultrasensitive technique to detect picogram levels of HCG-β in 36 histologically confirmed germinomas. (3) The expression of HCGβ mRNA was analyzed by qPCR in 76 germ cell tumors. RESULTS: (1) There was no significant difference in 15 year PFS between pure germinomas (93.1%, n = 61) and HCG-germinomas (80.7%, n = 19) in the Japanese prospective study. (2) In 36 germinomas examined, the HCG-β was detectable in both serum and CSF. The serum levels were 3.1–5851 pg/mL (median 44.8), and the CSF levels were 13–13116.3 pg/mL (median 119.5). (3) Most of the germ cell tumors expressed HCG-β mRNA in higher degrees compared with the normal brain tissue (comparative ratio to brain: 0.46 - 7.6 × 107). The expression of HCG-β mRNA in germinomas was highly variable, ranging from 72.6 - 2.1 × 105 to below the brain (0.46 - 1.4 × 103), and the differences of the expression among cases were linear, and not bimodal, suggesting no clear cut-off titer. CONCLUSIONS: These results suggest that all germinomas can produce HCG-β and fall into the same category in terms of HCG-β productivity. Based on this theory, all germinoma patients should be treated with the same protocol. SECONDARY CATEGORY: Pediatrics.