Diagnosis Of CNS Infections Research Articles

Detection of intrathecal IgG antibody for varicella and measles diagnosis by evaluation and comparison of a commercial IgG chemiluminescent immunoassay with two ELISAs.

Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test,respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For theVaricella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.

Use of multiplex PCR based molecular diagnostics in diagnosis of suspected CNS infections in tertiary care setting—A retrospective study

ObjectivesCNS infections like meningitis and encephalitis pose enormous healthcare challenges due to mortality, sequelae and socioeconomic burden. In tertiary setting, clinical, microbiological, cytological and radiological investigations are not distinctive enough for diagnosing microbial etiology. Molecular diagnostics is filling this gap. We evaluated the clinical impact of a commercially available multiplex molecular diagnostic system − SES for diagnosing suspected CNS infections. Patients and methodsThis study was conducted in our tertiary level Neurology ICU. 110 patients admitted during Nov-2010 to April-2014 were included. CSF samples of patients clinically suspected of having CNS infections were subjected to routine investigation in our laboratory and SES test at XCyton Diagnostics. We studied the impact of SES in diagnosis of CNS infections and its efficacy in helping therapeutic management. ResultsSES showed detection rate of 42.18% and clinical specificity of 100%. It had 10 times higher detection rate than conventional tests. Streptococcus pneumoniae and Mycobacterium tuberculosis were two top bacterial pathogens. VZV was most detected viral pathogen. SES results elicited changes in therapy in both positive and negative cases. We observed superior patient outcomes as measured by GCS scale. 75% and 82.14% of the patients positive and negative on SES respectively, recovered fully. ConclusionDetecting causative organism and ruling out infectious etiology remain the most critical aspect for management and prognosis of patients with suspected CNS infections. In this study, we observed higher detection rate of pathogens, target specific escalation and evidence based de-escalation of antimicrobials using SES. Institution of appropriate therapy helped reduce unnecessary use of antimicrobials.

Tuberculous Meningitis in The Differential Diagnosis of Cns Infection and the Urgency of Antituberculosis Treatment

Tuberculous Meningitis in The Differential Diagnosis of Cns Infection and the Urgency of Antituberculosis Treatment

Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system.

The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF) analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

Radiological diagnosis of CNS infections

MRI offers unprecedented interrogation of intracranial and spinal pathologies and has become the standard of care for CNS imaging with a role in detection, characterisation and monitoring of disease. There are multiple sequences that are employed for neuroimaging and each has its own strengths and limitations. These sequences are reviewed with an emphasis on each sequences utility. An ongoing major challenge is the differentiation of CNS infection from other CNS pathologies. Common mimics and differential diagnoses of CNS infection are presented with a focus on distinguishing features. Finally, characteristic features of a number of specific CNS infections are then highlighted.

Varicella Zoster Virus Meningitis in a Young Immunocompetent Adult without Rash: A Misleading Clinical Presentation

Meningitis caused by varicella zoster virus (VZV) is rare in healthy population. Predominantly immunocompromised patients are affected by reactivation of this virus with primary clinical features of rash and neurological symptoms. Here we report a young otherwise healthy man diagnosed with a VZV meningitis without rash. He complained of acute headache, nausea, and vomiting. The clinical examination did not show any neurological deficits or rash. Cerebrospinal fluid (CSF) analysis revealed a high leukocyte cell count of 1720 cells/µL and an elevated total protein of 1460 mg/L misleadingly indicating a bacterial infection. Further CSF analyses, including polymerase chain reaction (PCR) and detection of intrathecal synthesis of antibodies, showed a VZV infection. Clinical and CSF follow-up examinations proved the successful antiviral treatment. In conclusion, even young immunocompetent patients without rash might present with VZV meningitis. CSF examination is a key procedure in the diagnosis of CNS infections but in rare cases the standard values cell count and total protein might misleadingly indicate a bacterial infection. Thus, virological analyses should be considered even when a bacterial infection is suspected.

Diagnosing infection of the CNS with MRI

MRI is an important tool in the diagnosis of CNS infections. It allows for identifying various infectious patterns, differentiates them from vascular pathologies or neoplasms, may raise suspicion about a specific pathogen agent and plays an important role in monitoring response to treatment. Recent advances in MRI (e.g., diffusion-weighted imaging and diffusion-tensor imaging, MR spectroscopy, susceptibility-weighted imaging and perfusion-weighted imaging) may further improve the specificity of the MR findings.

Hypoglycorrhachia in herpes zoster associated encephalitis of an immunocompetent young male

Sirs: A thirty-one year old male was admitted to the Department of Medicine in Yan Chai Hospital with fever and headache. He had history of fever and sore throat for one week. His family doctor made a diagnosis of acute pharyngitis and gave him a course of amoxicillin. Few days later, he developed bilateral hearing loss and increasing early morning headache, exacerbated by cough. His temperature was 38 °C. There was no sign of meningeal irritation. Scattered blisters were noted over the left side of his neck along the distribution of cervical nerve C3 and C4. Bilateral hearing loss was present. Audiometry test revealed neurosensory hearing loss in both ears. His complete blood count, renal and liver functions, chest radiograph, electrocardiogram and CT of the brain were normal. Lumbar puncture revealed clear CSF with an opening pressure of 200 mm H2O, white cell count 240 WBC per mm3 (polymorphs 10 %, lymphocyte 90 %), protein 1.8 g/L, glucose 1.9 mmol/L. Simultaneous serum glucose was 6.9 mmol/L. CSF bacterial antigen test, cryptococcal antigen, fungal culture, PCR for TB and herpes simplex virus (HSV) DNA were negative. Brain MRI showed nonenhancing signal change in the lower pons and medulla, which was hypodense on T1-weighted images, hyperintense on T2-weighted and FLAIR images. The features were compatible with rhomboencephalitis (Fig. 1). IV acyclovir 10 mg/kg q8h was administered for 14 days. His fever came down on day 3 after the treatment began. His blisters and headache resolved gradually. Follow-up lumbar puncture showed normalization of CSF sugar with improvement in CSF protein and white cell counts. CSF viral titer revealed a 4-fold rise for IgG against varicella (pre-treatment titer 1: < 4, follow-up titer 1:16). PCR varicella-zoster DNA in his CSF before treatment was positive. He had mild residual neurosensory hearing loss and reported occasional tinnitus six months after the encephalitis. This case is a reminder that despite being a rare entity, a strikingly low CSF glucose can occur in herpes zoster-associated encephalitis. It can be potentially confusing to the attending clinician by mimicking other common infectious disease such as tuberculosis. Among 2 case reports in the past [1, 2], anti-tuberculous therapy was given to one patient before serological confirmation of varicella zoster meningoencephalitis. With the help of PCR assays, an early diagnosis can be achieved through detection of VZV DNA in CSF as soon as 24 hours after the onset of symptoms [3]. Compared with antibody indices [4], the intrathecal production of antibody is rarely detected before day 5 after onset of neurological symptoms, limiting the use of antibody index for early diagnosis of CNS infection. Currently available VZV DNA PCR assay methods have high specificity and do not cross-react with herpes simplex infection. The diagnostic sensitivity, however, ranges from 29 % to 100 % [5]. Therefore, we suggest that simultaneous analysis of CSF for both varicella-zoster virus DNA and antibody level should be studied in all suspected cases of herpes-zoster associated encephalitis. The presence of either or both in CSF in the typical clinical setting helps the clinician to establish the diagnosis of herpes-zoster associated encephalitis. This approach is particularly useful in Asian regions such as Hong Kong where the prevalence of mycobacterium tuberculous infection is high. Our case illustrated that, though rare, hypoglycorrhachia can occur in herpes zoster associated encephalitis, which has a mortality rate of 4 % to 30 % [6, 7] and residLETTER TO THE EDITORS

Nosocomial infections in critically ill infectious disease patients: Results of a 7-year focal surveillance

An incidence study on nosocomial infections in critically ill infectious disease patients was carried out in the intensive care unit (ICU) of a university hospital for infectious diseases over a 7-year period (1 January 1990 to 31 December 1996). A total of 660 patients who stayed in the ICU for over 48 h were prospectively observed. The patients were divided into two groups: one with central nervous system infections (442 patients) and the other with other severe infections (218 patients). The risk of nosocomial sepsis and pneumonia was significantly higher in patients suffering from severe central nervous system infections. The incidence of sepsis was 24.2% vs 11.4% (relative risk 1.95; 95% confidence interval 1.32-2.89); the incidence of pneumonia was 30.5% vs 14.7% (relative risk 2.09; 95% confidence interval 1.47-2.96). The incidence of urinary tract infection was 14.3% vs 13.3% (relative risk 1.07; 95% confidence interval 0.71-1.61). Density rates of nosocomial septic episodes were 21.1 +/- 37.1 vs 11.7 +/- 32.4 episodes/100 central venous-line days (P < 0.006). Nosocomial pneumonia occurred only in mechanically ventilated patients (36.9 +/- 61.2 vs 28.5 +/- 65.8 episodes per 1000 ventilatory days, P = 0.012). Nosocomial urinary tract infection occurred only in patients with urinary catheters (11.6 +/- 60.7 episodes/1000 urinary catheter days vs 18.7 +/- 90.1, P = 0.886). Multivariate regression analysis identified age, diagnosis of CNS infection, duration of urinary tract catheterization, the use of central venous lines and mechanical ventilation as independent risk factors of nosocomial sepsis. Duration of mechanical ventilation, use of steroids and diagnosis of CNS infection were independent risk factors of nosocomial pneumonia. A subanalysis identified tetanus patients to be at particular risk of nosocomial infections.

Diagnostic Accuracy of Csf β2M Compared To Total Proteins in Neonates

The diagnosis of CNS infections may be difficult in neonates. CSF shunt infections may be particularly difficult to assess .Objectives: (1) to compare the diagnostic accuracy ofβ2-microglobulin (β2m) vs total proteins in the CSF, in neonates with suspected CNS infections; (2) to determine the value of CSFβ2m in the diagnosis of CSF shunt infections .Methods: Neonates were included prospectively if a lumbar puncture was performed as part of a sepsis or meningo-encephalitis work-up. β2m was measured by enzyme immunoassay; total proteins by nephelometry. Results: 105 neonates without CSF shunts were studied: 30 had CNS infection (13 bacterial meningitis, 11 viral, 6 congenital meningo-encephalitis), and 75 did not. Areas under the ROC curve were: β2m 0.95±0.02 (cut-off value 2.5 mg/L), and total proteins 0.84±0.05 (cut-off value 100 mg/dL). β2m showed higher sensitivity and positive predictive value than proteins (97 vs 78, and 92 vs 54, respectively, p<0.001). In addition, 10 infants with CSF shunt were studied; 4 had infection. β2m was higher in infants with infection around the time of clinical suspicion (6.1±1.75 vs 3.1±1.04 mg/L, p<0.01), and β2m levels tended to increase 2 to 5 days after (10.2±0.97 vs 6.1±1.75,p=0.06). Conclusion: β2m showed a high diagnostic accuracy, with higher specificity and positive predictive value than total proteins. Total proteins had a lower area under the ROC curve, although the difference was not statistically significant.β2m in the CSF might be a useful ancillary tool in the diagnosis of neonatal CNS infection, including infants with CSF shunts.

Cerebrospinal fluid 309-1309-1309-1in neonates with central nervous system infections

Beta2-microglobulin (β2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. β2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T=toxoplasmosis, O=others, R=rubella, C=cytomegalovirus and H=herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF β2m levels compared to neonates with sterile culture (6.24±2.66 vs 1.74±0.5 mg/l;P<0.0001). CSF β2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF β2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98±2.5 vs 3.2±0.25 mg/l;P<0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF β2m was accurate in distinguishing between neonates with and without CNS infection.

Cerebrospinal fluid ?2-microglobulin in neonates with central nervous system infections

Beta 2-microglobulin (beta 2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. Beta 2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T = toxoplasmosis, O = others, R = rubella, C = cytomegalovirus and H = herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF beta 2m levels compared to neonates with sterile culture (6.24 +/- 2.66 vs 1.74 +/- 0.5 mg/l; P < 0.0001). CSF beta 2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF beta 2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98 +/- 2.5 vs 3.2 +/- 0.25 mg/l; P < 0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF beta 2m was accurate in distinguishing between neonates with and without CNS infection. Conclusion. CSF beta 2m may be a useful ancillary tool in neonates when CNS infection is suspected.

Radiologic Techniques in the Diagnosis of CNS Infections

The radiologic diagnosis of CNS infections remains a challenge. CT scan findings, though admittedly nonspecific to a large extent, assume great diagnostic significance when considered in conjunction with clinical and laboratory findings. MRI is expected to show abnormalities in the earlier stages of these infections.

Diagnosis of CNS infections: source of CSF.

Diagnosis of CNS infections: source of CSF.