Chronic Meningitis

Sub acute andChronic MeningitisDr. Padma S GunaratneMD(SL), FRCP(Glasg), FCCP

Case 1• 28 years, Transfer• Fever, Headache , confusion – 3 wks• Blurring of vision, double vision - 2 days• O/E Drowsy, neck stiffness. ↓vision, chronic papilloedema, Rt VI th palsy• Patient was treated with antibiotics• Inv;– WBC – Neutrophil leucocytosis + Lymphopenia– ↑ESR & CRP– CT Brain - Normal– CSF – sugar 109 mg /dl (RBS160mg/dl)• Proteing 15 mg .dl• Cells – nil• Fungal studies – Capsulated yeast (India ink staining positive)Culture – Cryptococcus Neoformans• Retroviral studies – Negative• Neutrophil functions and immunoglobulin levels – Normal• CD4 counts -normal• T lymphocyte functions & lymphocyte subclass analysis- Awaiting• Treatment –– IV Amphotericin B – 5 wks –India ink & Fungal culture remained positive– EVD• IV Fluconazole for 21 days – India ink staining remained positive• IV Voriconazole 56 days followed by oral voriconazole• Patient was saved

Gadolinium enhanced T 1 MRINormalPatient

CT brain

Significance• Presence of cryptoccocal meningitis• Value of early diagnosis• Difficulties in treating fungal meningitis• Knowing your limitations

Sub Acute or ChronicMeningitisPersistent signs and symptoms lasting atleast 4wks with continued CSFinflammation

• Vancomycin Saphyloccous aureusMRSAEmpirical Treatment; Acute MeningitisIntravenous• C. Penicillin Streptococcus pneumoniaNeisseria meningitidis• Cefotaxime, Ceftriaxone Streptococcus PneumoniaeNeisseria mningitidisHaemophilus influenzaeE. coli• Meropenem Streptococcus PneumoniaeNeisseria mningitidisPseudomonas aeruginosa• Ampicillin Listeria Monocytogenes

Diagnosis of ChronicMeningitisFungiCryptoccus neoformansAspergillus speciesCandidaCoccidioides immitisHistoplasma CapsulatumVirusesHIVNeoplasticLeptomenigeal metastasis;Breast, lung,melanoma, LeukemiaLymphomaParasitesNeuro cysticercosisAmoebicMeningoenchephalitisEosinophilic meningVasculitisGiant CellarteritisSLEChemicalMeningitisDermoid cystRickettsiaEhrlichia chaffeensisPartially Rxed BacterialTBTreponema PalLyme DiseaseSacoidosisUndiagnosed15%

VirologistPATIENTS

• Mrs. X, 27 Yrs, Transfer• Fever 2/12, Headache – 5/52, diagnosed case of meningitis• Treated with iv cefotaxime 12/365• Improved and deteriorated on 10 th day– Developed confusion, doublevision, incontinence• O/E LR palsy, early papilloedema• CT brain - Normal• CSF– Protein 65mg /dl– Glucose 52mg/ dl (RBS – 104mg /dl)– Polymorphs 30/Cml– Lymphocytes 80/Cml– CSF and blood bacterial culture - No growth– CSF AFB - Negative– TB PCR - Negative– Mantoux - Negative– Fungal PCR - Negative– HIV - Negative• Patient improved with anti TB treatmentCase 2

Diagnosis of TBM• CSF Full report– Lymphocytic pleocytosis– Increased protein– Decreased glucose• CSF AFB (5 – 25%)• AFB culture– Single LP 20 – 40%– 3 LP, high volume CSF – 50 – 80%• PCR– 50 – 75% (High sensitivity & specificity)• TB Gold

TB Gold(FDA approved)Test detects the release of interferon gamma,when blood sample is incubated with amixture of synthetic peptides ESAT 6 (Earlysecretary antigen target), and CEP 10(culture filtrate protein) that are found in TBbacillus.Test appears to be sensitive for acute TBSpecificity – not certain

Caseating Tuberculoma

History & Physical examination• Place of origin• Recent travel• Past history• Review ofsymptoms• Animal exposure• Immune status• Iritis & Uveitis• Retinitis• Lymph nodes -• Ear, nose, sinuses• Lips mouth• Heart murmur• Lungs• Skin

Clinical Features in severechronic meningitis• Cranial Nerve palsies– VI, VII, II, III, IV• Meningeal Vasculitis causing SAH orinfarctions• Hydrocephalus• Focal Neurological signs• Rapid deterioration• Worse CSF changes

Chronic meningitis with atypicalNeutrophil predominanceCSFEosinophil Predominance(10%)• M. TB• Brucella• Fungi• Craniotomy• Chemical meningitis/Drugs• Angiostrongylous Cantonensis• Cysticercosis• Toxocariasis• Hodgkin’s lymphoma• Medulloblastoma withmeningeal spread• Glial tumors with meningealspread

Fungal Infections• Immuno compromised– Aspergillus– Mucomycosis– Candida• Primary infection – C. Neoformans, C. immitis• Diagnosis– Culture - Poorly sensitive– PCR - Not that sensitive

Aspergillus Meningitis in Sri Lanka—A Post-Tsunami Effect?The New England Journal of Medicine356;7 www.nejm.org february 15, 2007

Table I: Clinical featuresCase 1 Case 2 Case 3 Case 4 Case 5 Case 6Age 26 Yrs 21 Yrs 27 Yrs 29 Yrs 38 Yrs 25 YrsIncubationperiod14 days 12 days 16 days 11 days 8 days 2 daysPyrexia,severe headache, vomiting+ + + + Headache only +Neckstiffness - +++ ++ + + +Kernings - + + + + -Lateral rectuspalsy- - Bilateral Bilateral - -Papilloedema - - - + - -Stroke L Hemiplegia Rhemiplegia- - VentricularHaemorrhage-OthersPartialseizuresDiabetesinsipidusPartial seizuresDeep veinthrombosisPapilloedemaCoagulopathyPolyuria

Table II: Laboratory investigationCase 1 Case 2 Case 3 Case 4 Case 5 Case 6BloodWBC/cmm(Neutrophil%)10,900(76%)12,800(79%) 15.000(74%) 11800(84%) 15000(79%)ESR(MM) 31 108 55 22 90CSFProtein mg/dl 68 49 134 33 28 35Sugar mg/100ml 56 25 21 45 61 60RBS mg/100ml 115 90 133 109 74Neutrophil/cmm 300 400 20 572 Nil NilLymphocytes/cmm 2 175 700 858 225 35Gram stain Nil Nil + cocci Nil Nil NegCytology Nil Nil Hyphe seen Nil Nil NilBacterial culture Neg Neg Neg Neg BacillussporebearerPseudomonasaeruginosaFungal culture Nil Nil nil AspergillusfumigatusNilNilPostmotemFungal culture ofbrainAspergillusfumigatusAspergillusfumigatusAspergillus

Workup for undiagnosedmeningitis• Repeated CSF examinations– CSF FR– Cultures– Multiple serological tests– PCR– Cytology for malignant cells– Flow cytometry• Imaging brain• Biopsies & Cultures of other body sites• Auto antibodies and serological tests for vasculitis• Brain biopsy

Blood and CSF laboratory testsAntibody tests• Borrelia burgdoferi• Treponema pallidum• Coxiella burneti• Ehrlichia Chaffeensis• Rickettsia rickettsii• Histoplasma capsulatum• Aspergillus species• Echinococcus granulosis• Taenia soliumAntigen tests• Cryptococcus neoformance• Histoplasma capsulatum• Aspergillus species• Candida speciesPCR assays of CSF• Enterovirus, HIV, HSV, CMV• TB , Treponema pallidumVasculitis & CVD• Rheumatoid, SLE, Weg.GranulomatosisSarcoidosis – ACE levels

Workup for undiagnosedmeningitis• Repeated CSF examinations– CSF FR– Cultures– Multiple serological tests– PCR– Cytology for malignant cells– Flow cytometry• Imaging brain• Biopsies & Cultures of other body sites• Brain biopsy

Brain biopsy• Include meninges and cerebral tissue• Diagnoses ; Leptomeningeal metastasis,Neurosarcoidosis, Vasculitis, TB , Fungalinfections.• Part should be cultured• Part should be checked with PCRtechniques

Carcinomatous meningitisTumor markers in CSF

Neurosarcoidosis• 5 -15% of systemic sarcoidosis• Non-caseating granulomas in meninges andparenchyma• CSF– Mild lymphocytic pleocytosis, ↑ protein, ↓ sugar• Other Ix– CXR – (80%)hilar lymphnodes, interstitial infiltrates– MRI – Meningeal enhancement– CSF ACE levels• Diagnosis– Biopsy of extra neural sites