Non invasive tests for diagnosis of parasitic infections of CNS

Central nervous system (CNS) infections are among the most devastating diseases with high mortality and morbidity. In the pre-human immunodeficiency virus (HIV) era, the occurrence of CNS infections was very infrequent. However, in the past four decades or so, with a global increase in the immunocompromised population, the incidence of opportunistic infections of the CNS has changed. This includes a global increase in the incidence of parasitic infections such as Toxoplasma gondii. Infections such as neurocysticercosis and cerebral malaria are quite prevalent in developing countries. Early diagnosis of these infections is crucial for instituting accurate therapy and preventing mortality and morbidity. Despite advances in neuroimaging techniques, laboratory diagnosis remains the mainstay for confirmation of diagnosis. We present an update on the noninvasive tests available for laboratory diagnosis of parasitic infections of the CNS.

Central nervous system infections caused by pathogenic free-living amoebae: An Indian perspective

@#Pathogenic free-living amoebae (FLA), namely Acanthamoeba sp., Naegleria fowleri and Balamuthia mandrillaris are distributed worldwide. These neurotropic amoebae can cause fatal central nervous system (CNS) infections in humans. This review deals with the demographic characteristics, symptoms, diagnosis, and treatment outcomes of patients with CNS infections caused by FLA documented in India. There have been 42, 25, and 4 case reports of Acanthamoeba granulomatous amoebic encephalitis (GAE), N. fowleri primary amoebic meningoencephalitis (PAM), and B. mandrillaris meningoencephalitis (BAE), respectively. Overall, 17% of Acanthamoeba GAE patients and one of the four BAE patients had some form of immunosuppression, and more than half of the N. fowleri PAM cases had history of exposure to freshwater. Acanthamoeba GAE, PAM, and BAE were most commonly seen in males. Fever, headache, vomiting, seizures, and altered sensorium appear to be common symptoms in these patients. Some patients showed multiple lesions with edema, exudates or hydrocephalus in their brain CT/MRI. The cerebrospinal fluid (CSF) of these patients showed elevated protein and WBC levels. Direct microscopy of CSF was positive for amoebic trophozoites in 69% of Acanthamoeba GAE and 96% of PAM patients. One-fourth of the Acanthamoeba GAE and all the BAE patients were diagnosed only by histopathology following autopsy/biopsy samples. Twenty-one Acanthamoeba GAE survivors were treated with cotrimoxazole, rifampicin, and ketoconazole/amphotericin B, and all eleven PAM survivors were treated with amphotericin B alongside other drugs. A thorough search for these organisms in CNS samples is necessary to develop optimum treatment strategies.

Imaging of CNS Infections with Clinico-pathological Correlation

Introduction: CNS infections are an emerging health problemwith poor prognosis if the treatment is not prompt andadequate. Thus, establishing a correct diagnosis is necessaryto quickly start the appropriate treatment. This study wasundertaken to study the etiology and the imaging spectrum ofCNSI in and around western Uttar Pradesh in a tertiary healthcare set up and to correlate the neuro-imaging findings withclinic-pathological data.Material and Methods: In this Prospective Observationalstudy 80 patients clinically suspected of CNS infection werestudied by CT/MRI and the neuro imaging findings werecorrelated with clinical and CSF findings.Results: Based on clinical features, CSF findings, thetreatment given and the response to treatment tuberculousinfection (TBM) was most common infection (41.2%)followed by pyogenic meningitis (36.2%) and viral infection(22.5%). In 29 patients of pyogenic CNS infection mostcommon imaging finding was leptomeningitis(62%)followed by pachymeningitis (31%), hydrocephalus (24.1%),abscess (6.8%), post vasculitic infarct(6.8%) and extra axialcollection(6.8%). In 33 patients of tubercular CNS infectionmost common imaging finding was basal leptomeningitis(78.7%) followed by tuberculoma (72.7%), pachymeningitis(33.3%), hydrocephalus (27.2%), abscess (12.1%), postvasculitis infarct (12.1%) and spinal cord involvement in1 (3%) patient. In the 18 viral CNS infection cases mostcommon imaging finding was parenchymal hyperintensity onMRI or hypodensity on CT with/without peripheral vasogenicedema (94.4%) followed by leptomeningeal/pachymeningealinvolvement (61.1%) and post vasculitis infarct (11.1%).Conclusion: The sensitivity of neuroimaging in pyogenicCNS infection was 81.2% and specificity was 93.7% whilesensitivity of neuroimaging in tubercular CNS infection was88.8% and specificity was 97.8% and in viral CNS infectionsensitivity was 84.2% and specificity was 96.7%. There wassignificant association (p value <0.05) of basal leptomeningitisand granulomas on imaging with tubercular infection andparenchymal signal changes with viral infections

Association between Cerebrospinal Fluid S100B Protein and Neuronal Damage in Patients with Central Nervous System Infections

PURPOSE: S100B protein is widely used as a measure of glial activity or damage in several brain conditions. Central nervous system (CNS) infections can cause neurological sequelae because of parenchyma invasion. It is difficult to predict further neuronal damage in the CNS infection. The present study is aimed to evaluate the role of the cerebrospinal fluid (CSF) S100B protein as an indicator of neuronal damage in CNS infection. MATERIALS AND METHODS: We measured the concentration of CSF S100B protein in 62 patients with a CNS infection using an Enzyme-Linked Immunosorbent Assay. The patients with CNS infections were classified as having no neuronal damage (CNS-N) or as having neuronal damage (CNS+N) according to the presence of neurological change or structural lesions on brain MRI. RESULTS: The CSF S100B protein level of the CNS+N group (n=22, 0.235 microg/L, 0.10-2.18) was significantly higher than that of the CNS-N group (n=40, 0.087 microg/L, 0.06-0.12) and control group (n=40, 0.109 microg/L, 0.07-0.14, p<0.01). Using an arbitrary cut off value, S100B-positive CSF was detected in 2.5% of the CNS-N group and in 50% of the CNS+N group (p<0.05). CONCLUSION: These findings suggest that increased S100B protein levels in the CSF may be associated with the neuronal damage following CNS infections.

Prospective study of level of serum zinc in patients of febrile seizures, idiopathic epilepsy and CNS infections.

The present study was carried out to study serum zinc levels for it’s prognostic significance as well as for it’s role in pathophysiology of febrile seizures, idiopathic epilepsy and acute CNS infections. In the present study, 100 cases who were admitted in our hospital during March 2009 to August 2010, aged between 1 month to 18 yrs were selected on the basis of clinical history, physical and CSF examination. They were grouped as groupA (pyogenic meningitis), group B (febrile seizures), group C (idiopathic epilepsy), group D (other acute CNS infections), group E (cerebral malaria) and group F (control). Cases of cerebral palsy, neuroanatomical malformations, neurobehavioural disorders, neurodegenerative disorders and drug induced neurological manifestations were not included in the present study. Mean serum zinc level was significantly lower in groups A, B & E, while no significant difference was observed in group C & D as compared to the control. No significant difference in serum zinc level was detected in relation to outcome and degree of consciousness in any of the study groups.

Comparison of a conventional polymerase chain reaction with real-time polymerase chain reaction for the detection of neurotropic viruses in cerebrospinal fluid samples.

Purpose : To compare a conventional polymerase chain reaction (PCR) and real-time PCR for the detection of neurotropic DNA viruses. Materials and Methods : A total of 147 cerebrospinal fluid (CSF) samples was collected from patients attending a tertiary care hospital in South India for a period from 2005 to 2008. All these samples were tested using a conventional multiplex/uniplex PCR and a real-time multiplex/uniplex PCR. This technique was used to detect a large number of herpes viruses responsible for central nervous system infections, including HSV-1, HSV-2, VZV, CMV and EBV and the polyoma virus JCV. Results : Overall, in the entire set of samples, the real-time PCR yielded 88 (59.9%) positives and conventional PCR had six (4.1%) positives. Conclusion : Our results suggest that the real-time PCR assay was more sensitive compared with the conventional PCR. The advantage of real-time PCR is that it can be performed much faster than conventional PCR. Real-time PCR is less time-consuming, less labour-intensive and also reduces the chance of contamination as there is no post-amplification procedure. In the entire study population, the major viruses detected using real-time PCR were EBV (34%), HSV-2 (10.8%) and VZV (6.8%).

Central Nervous System Infections: Practical Application of the Antimicrobial Agents

Infections of the central nervous system (CNS) can be rapidly progressive, RESULTing in death or permanent neurological damage in a short period of time, because of focal immunocompromised milieu with few complements and immunoglobulins in the cerebrospinal fluid. In order to provide effective antimicrobial therapy in a timely manner, all clinicians need to have a basic understanding of the antimicrobial agents and epidemiological data of the disease. It takes time to reveal the causative organisms of the infection. One should start antimicrobial treatment empirically as soon as possible after collecting the specimens from the patient. Many factors influence the choice of antimicrobial agents in the treatment of the infection which include microorganisms, environmental factors, and host factors such as age, sex, site of infection, and the underlying disease of the patient. Especially, in CNS infections, the efficacy of an antimicrobial agent depends upon its ability to penetrate the blood-brain barrier. The antimicrobial agent should also be active in purulent cerebrospinal fluid and demonstrate rapid bactericidal activity against the offending pathogen. The recent emergence of resistant pathogens, (also seen in Korea), has posed a challenge to the antimicrobial therapy. Therefore, the guidelines of antimicrobial therapy should be suitable for these considerations. This article reviews the basic therapeutic principles for the treatment of infections of the CNS and gives recommendations for the treatment of specific infections.