1.CNS infections Meningitis, Encephalitis, Parameningeal abscesses (subdural empyema andepidural abscess), Brain abscesses, & CSF shunt infections.

2. Meningitis is an inflammatory response to bacterial infection of thepia-arachnoid and CSF of the subarachnoid space 3. Epidemiology Incidence is between 3-5 per 100,000 More than 2,000 deaths annually in the U.S. 4. Bacterial meningitis and other CNS infections areconsidered infectious disease emergencies that can cause significant patient morbidity and mortality. 5. Mortality/Morbidity Bacterial meningitis -uniformly fatal before the antimicrobialera. overall mortality rate has decreased, but remains alarmingly high - - Higher in developing countries Varies with the specific etiologic agent S pneumoniae 19-26% H influenzae - 3-6% N meningitidis 3-13%, L monocytogenes 15-29% 6. ` Survivors end up with complications Children suffers mostly with complications 7. Morbidity associated with complications in childrenIn adultssensorineural hearing loss / Cranial nerve palsiesbrain infarction,,epilepsyhydrocephalus,diffuse brain swelling hydrocephalus, cerebral vein thrombosis, cerebral palsy More with H.influenzae meningitis**** Severe morbidity is associated with H.influenzae meningitis and TB meningitis due to fibrinous exudates 8. Viral meningitis Viral meningitis (without encephalitis) is less than 1%. In patients with deficient humoral immunity (eg,agammaglobulinemia), enterovirus meningitis may have a fatal outcome. 9. MeningococcalMeningitis belt -Faso, Chad, Ethiopia and Niger; in 2002, the outbreaks occurring in Burkina Faso, Ethiopia and Niger accounted for about 65% of cases 10. Pathogenesis of MeningitisSurvival and Multiplication in the subarachnoid spaceNasopharyngeal colonization Neisseria meningitides (meningococcus) and nasopharyngeal colonization with S pneumoniae (pneumococcus).Crossing of the BBB and entry into the CSFNasopharyngeal epithelial cell invasionBacteremia with intravascular survivalBloodstream invasion 11. Pathogenesis of Meningitis eg, Naegleria fowleri,Free living amoeba in natural resovoiresMeningitisNasopharyngeal epithelial cell invasionRetrograde flow to meninges through the olfactory bulb 12. Pathogenesis of Post traumatic/Neurosutgery MeningitisColonizing bacteria in sinuses/auditory canal otitis media, congenital malformations, trauma, direct inoculation during intracranial manipulationSpread along the CSF fistulous tractMeningitis 13. Pathogenesis cont. With in the CNS, the infectious agents likely survive asimmunoglobulins, neutrophils, complement components absent or activity limited replication of infectious agents remain uncontrolled triggersthe cascade of meningeal inflammation Increased CSF concentrations of TNF-alpha, IL-1, IL-6, andIL-8 are characteristic findings in patients with bacterial meningitis 14. Treatment using rapidly bactericidal agents maytransiently worsen the patients condition due to rapid release of pyrogenic substances in to CSF Increase of proinflammatory mediators 15. Specific Pathogens 16. Age groupPredominant PathogenAge 0-4 weeksS agalactiae (group B streptococci) E coli K1 L monocytogenesAge 4-12 weeksS agalactiae E coli H influenzae S pneumoniae N meningitidisAge 3 months to 18 yearsN meningitidis (worldwide epidemic strains A,B,C W135) S .pneumoniae H influenzaeAge 18-50 yearsS pneumoniae N meningitidis H influenzaeAge older than 50 yearsS pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilliImmunocompromised stateS pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli 17. Intracranial manipulation, including neurosurgeryStaphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosaBasilar skull fractureS pneumoniae H influenzae Group A streptococciCSF shuntsCoagulase-negative staphylococci S aureus Aerobic gram-negative bacilli***Direct extension from the throat or nasal or ear colonization an give rise to post traumatic meningitis 18. Other causes Bacteraemic infectionof Salmonella, Brucella and Staphylococcus aureus can cuase meningitis Gram Negative meningitis in overwhelming infections due to Strogyloides / Hyper infection due to Strongyloides stercorhalis Leptospira and Treponema Protozoa Acanthomoeba and Naeglaria fowleri Fungi Histoplasma and Nematodes Angyostrogilus cantonensis 19. Clinical diagnosis unreliable- symptoms unreliable specially extremesof age The efficacy of treatment (CNS) infections -depends on the accuracy ofthe etiologic diagnosis. requires the best specimen at the appropriate time, transporting it to the laboratory under optimum conditions, processing the specimen efficiently and timely manner, and selecting the tests necessary to identify the spectrum of possibleetiologies 20. Clinical sign Kernig's signsensitivity, 5%; likelihood ratio for a positive test result [LR(+)], 0.97)Brudzinski's sign(sensitivity, 5%; LR(+), 0.97),Nuchal rigidity(sensitivity, 30%; LR(+), 0.94)Degree of meningeal inflamation 6 up to 100Clinical signs are unreliableInbetweenUnreliable(>/=1000 WBCs/mL of CSFNuchal rigidity shows diagnostic value- sensitivity 100% and negative predictive value 100% 21. Diagnosis Should not be delayed Inform laboratory Initial report based on Cell count and Direct smear Cytospin method gives more positive yield thantraditional overlaying Gram stain can be considered as the gold standard 22. Diagnosis Is established by investigation of CSF obtained from lumbar puncture, Cysternal puncture or ventricular puncture or fontanelle taps possible not done routinely Exclude raised intracranial pressure before performing the procedure due to possibility of herniation Place of CT/ MRI to exclude SOL When, contraindication +, diagnosis established using other means Blood culture, WBC/DC, CRP together with symptoms 23. Additional factors for success Communication between the clinician and laboratory-about clinical notes, Patient condition, antibiotic therapy, Patient delay and Doctor delay Seasonal prevalence of infectious diseases, for enteroviruses and arboviruses, the epidemiology of emerging diseases such as West Nile virus, and the immune status of the patient can beis helpful. 24. Specimen collection and transportation timing All specimens should be collected prior to theinitiation of antimicrobials If therapy initiated action to nullify it-Innoculating itto broth media 1:5 ratio< specially for cerebral abcess 25. Specimens for diagnosis of CNS infections DiseaseSpecimenMeningitisCerebrospi Mininmum of 1 mL nal fluid /culture (CSF) 1 to 2 mL [PCR]), 1 mL antibody test BloodEncephalit is or brain abscessQuantity5 to 10ml as for blood cultureNote For M. tuberculosis, and dimorphic and filamentous fungi require repeat CSF or large volumes (10 to 20 mL) of ventricular CSF.0.5 to 1.0 mL per culture request preferred1 to 10 mL can be added to blood culture medium antimicrobial effect- dilution of 1 :5 or 1:10TissueSubdural empyema or epiduralAbscess material or irrigation fluid0.5 cc preferredminced /gently ground. Mince only if filamentous fungi expected.Abscess material / irrigation0.51.0 mL per culture request preferredSmall volumes of pus diluted (ratio of 1:2) with sterile saline to allow washing of material from 26. Collection and transportation SpecimenContainerTransport/Storage ConditionsCerebrospinal fluid (CSF)Sterile tube.Room temperature. Ice/Refrigeration are detrimental to some bacteria and anaerobes. For PCR 4 Cfor 100,000 red blood cells per mm3OrangeBlood breakdown products High carotenoid ingestionPinkBlood breakdown productsGreenHyperbilirubinemia Purulent CSFBrownMeningeal melanomatosis 32. Normal CSF values Cell componentAge CategoryNormal ValueLeukocytesNeonates0 30 cells X 10 / L1 to 4 yr old0 20 X 10 / L5 to puberty0 10 X 10 / LNewborn0 675 X 10 / LAdults0 10 X 10 / LNeonates0.7 g/lAdults0.2 0.4 g/lErythrocytesProteinGlucose> 60% of RBS value is considered normalBacterial or viral counts should be considered where leukocyte counts are near the upper normal value 5 WBCs per mm3 (normal value) 33. differential diagnosis of various forms of meningitis DiagnosisPressureCells (10 / l)PMNGlucose ratioProtein (g/ l)Lactate (mmol/l)normal< 20 cm1-2 .5< 0.45 (15 45mg/dl)20 cm>1000> 50%< .4 (>.2)> 1(100 mg) > 4Chronicvariable> 1000Vary< .4> 0.45>2Aseptic (Viral)< 20 cm< 1000 .4Vary 12 hrs post ICH may have WBC counts up to 500 X 10 /l - due to inflammation 37. Direct smear Gram stain 38. a Gram stain of the cytospin CSF has a sensitivity of90% if the LP is carried out before the administration of antibiotics. 39. Effects of antibiotics in CSF culture and Direct smears In a retrospective review of 128 children with bacterialmeningitis, Kanegaye et al. (2001) compared 39 patients who received empiric antimicrobial therapy before LP with 55 who underwent LP before receiving antimicrobial therapy Treatment Group - Bacterial sterilizationTreatment groupMeningococcus sterilization occurred within 2 hrsUp to 24 to 48 hrs CSF cellular and biocheical parameters remained unchainedPneumococcus sterilization occurred within 4 hours 40. ConditionDiagnostic testBacterial meningitisCytospin Gram stain 6090100Culture90100Antigen detection assays *50100100Acid-fast stain10221003888100278595100Tuberculous meningitisCulture PCRSensitivity (%)Specificity (%)Effect of antibiotic treatment on 41. Blood cultures 50 to 80% patients with meningitis has accompaniedbacteremias - blood cultures would be useful to isolation of organisms more than CSF growth Specially where LP is contraindicated Blood cultures Volume 20ml or as recommended by the manufacturesCollected before antibiotic therapy > 2 cultures taken from different sites or three cultures with in 24 hrs Innoculate into broth medium at a ratio of >1:5 When suspecting Dimorphic fungi or cryptococcus blod should be colected to tube containing lysis solution for lysis centrifugation 42. Utility of Gram stain for diagnosis of Pyogenic meningitis EtiologySensitivityAll common etiologiesno previous antibiotics75% to 90%All common etiologiesantimicrobial therapy prior to lumbar puncture40% to 60%Streptococcus pneumoniae without antibiotics90%Neisseria meningitidis -75%Haemophilus influenzae86%Listeria monocytogenes