Meningitis: Epidemiology, diagnosis and management

Meningitis in ICU in adults is common neurological emergency where timely treatment saves and improves life quality free of disability.

1. Meningitis Mohd Saif Khan EPIDEMIOLOGY, DIAGNOSIS AND MANAGEMENT

2. Headings Background and Definition Anatomy Pathophysiology Etiology Clinical presentation Diagnosis Treatment Subacute meningitis-diagnosis and management Nosocomial meningitis

3. Meningitis is a clinical syndrome characterized by inflammation of the meninges . CNS infections Meningitis Encephalitis Leptomeningitis Pachymeningitis

4. Anatomy Emissary veins

5. PATHOPHYSIOLOGY WBC Mechanical effects Inflammatory effects Impairment of CSF flow Occlusion of cortical blood vessels Cytokines Oxidants Proteolytic enzymes Hydrocephalus Disruption of BBB

6. Disruption of BBB Enhanced bacterial entry Enhanced WBC recruitment Overwhelming damage to neural structures Breach in piamater Infection of brain parenchyma (encephalitis) Brain abscess PATHOPHYSIOLOGY Cranial nerve palsies (VIII CN) Thrombophlebitis of cortical veins Ischemia and infarcts

7. Etiology Predisposing risk MC organisms Trauma or neurosurgery Staphylococcus aureus species, gram negative bacilli, Infected VP shunt Staph. epidermidis , S aureus Elderly individuals (>60 years) And pregnant women Listeria monocytogenes Neonates Streptococcus agalactiae Immunocompromized Cryptococci, Mycobacterium tuberculosis, Infectious Non-Infectious Bacteria, viruses, fungi, parasites Drugs NSAIDs, metronidazole , and IVIG Tumor Leukemia, lymphoma

8. Presentation Fever Neck stiffness Headache Only about 44% of adults with bacterial meningitis Altered mentation Nausea and vomiting Photophobia Double visions Confusion Irritability Delirium Seizures Coma Symptom onset Acute (<24 hours) Subacute (1-7 days) Chronic (>7 days) Bacterial Viral Tuberculosis, Syphilis, Fungi (especially cryptococci ), Carcinomatosis

9. Physical examination focal neurologic deficits.. Signs of cranial nerve palsies Meningeal signs Signs of Extracranial infection ( eg , sinusitis, otitis media, mastoiditis , pneumonia, or urinary tract infection [UTI ]) Exanthemas Symptoms of pericarditis, myocarditis, or conjunctivitis Nonblanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N meningitidis (50%), H influenzae , S pneumoniae , or S aureus .

10. Complications Immediate complications : Septic shock with DIC Coma Seizures, which occur in 30-40% of children and 20-30% of adults Cerebral edema Septic arthritis Pericardial effusion Hemolytic anemia ( H influenzae ) Late complications : Decreased hearing or deafness Multiple seizures Focal paralysis Subdural effusions Hydrocephalus Intellectual deficits Ataxia Blindness Waterhouse- Friderichsen syndrome Peripheral gangrene

11. D/Ds Central nervous system (CNS) vasculitis Stroke Encephalitis All causes of altered mental status and coma Leptospirosis Subdural empyema

12. Management

13. The initial treatment approach to the patient with suspected acute meningitis depends on: early recognition of the meningitis syndrome, rapid diagnostic evaluation , and emergent antimicrobial and adjunctive therapy.

14. Diagnosis

15. Lumbar puncture (LP) should be performed emergently in all patients suspected of having bacterial meningitis unless contraindicated, although it is commonly unnecessarily delayed while neuroimaging is performed to exclude mass lesions. Life-threatening brain herniation has been reported to range from less than 1% to 6% (Neurology. 1959;9(4):290–297, Ann Neurol. 1980;7(6):524–528.).

16. Typical CSF Parameters in Patients with Meningitis Etiology WBC Count (cells/mm 3 ) Predominant cell type Protein (mg/ dL ) Glucose (mg/ dL ) Opening Pressure (cm H 2 O) Normal 0-5 Lymphocyte 15-40 50-75 8-20 Viral 10-500 Lymphocyte Normal normal 9-20 Bacterial 100-5000 Neutrophil >100 <40 20-30 Tubercular 50-300 Lymphocyte <100 <40 18-30 Cryptococcal 20-500 Lymphocyte 50-200 <40 18-30 Characteristic CSF findings for bacterial meningitis consist of polymorphonuclear pleocytosis , hypoglycorrhachia , and raised CSF protein levels.

17. CT scan Antibiotics+Dexa Antibiotics+Dexa Stat LP Management of Adults with Acute Meningitis Syndrome ( Fulminant course (<48 h) with fever, headache, usually with impaired sensorium and stiff neck.) Blood Cultures 1. Comatose 2. Inadequate History (patient unable to provide history and no family available) 3. Risk of Mass Lesion ( papilledema , focal neurologic defects, recent head trauma, malignant neoplasm, or history of CNS mass lesion) 4. Immunosuppressed (HIV, transplant, neoplasm , steroids) No Yes LP CSF findings s/o Bacterial meningitis Continue therapy Yes negative

18. Other laboratory test Gram staining of bacteria in CSF India Ink preparation CSF lactate: to distinguish bacterial from aseptic meningitis PCR Latex agglutination-based rapid tests Procalcitonin C-reactive protein Limulus lysate assay : useful test for patients with suspected gram-negative meningitis , detect ∼10 3 gram-negative bacteria/mL of CSF and as little as 0.1 ng /mL of endotoxin .

19. Antimicrobial therapy Predisposing conditions Antibiotics Age <1 month 1 month – 2 years 2-50 years >50 years Ampicillin+cefotaxime /aminoglycoside Vanco + 3 rd Gen Cephalo Vanco + 3 rd Gen Cephalo Vanco+Ampi+3 rd Gen Cephalo Head trauma Basilar fracture Penetrating Vanco + 3 rd Gen Cephalo Vanco + Cefepime / Ceftazidime / Meropenem Postneurosurgery Vanco + Cefepime / Ceftazidime / Meropenem CSF Shunt Vanco + Cefepime / Ceftazidime / Meropenem Impaired cellular immunity Vancomycin plus ampicillin plus either cefepime or meropenem

20. Duration of antimicrobial therapy

21. Supportive treatment Analgesics Antipyretics Anticonvulsants ICP lowering measures Intubation and mechanical ventilation

22. Nosocomial meningitis Invasive Procedures ( e.g., craniotomy, placement of internal or external ventricular catheters, lumbar puncture, intrathecal infusions of medications, or spinal anesthesia ), VP shunt/EVD Complicated Head Trauma Removal of the internal ventricular catheters For MDR GNB Intraventricular antibiotic administration Not FDA approved, indications are not well defined. Vancomycin and gentamicin are most commonly given via this route

23. Viral meningitis CAUSED BY ENTEROVIRUSES, HERPES SIMPLEX VIRUS (HSV), HUMAN IMMUNODEFICIENCY VIRUS (HIV), WEST NILE VIRUS (WNV), VARICELLA-ZOSTER VIRUS (VZV), MUMPS, AND LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCM) Most common Coxsackie , echovirus , other non-poliovirus enteroviruses Seasonal variation Etiology WBC Count (cells/mm 3 ) Predominant cell type Protein (mg/ dL ) Glucose (mg/ dL ) Opening Pressure (cm H 2 O) Normal 0-5 Lymphocyte 15-40 50-75 8-20 Viral 10-500 Lymphocyte Normal normal 9-20 CSF PCR Mollaret's meningitis HSV-2

24. Treatment of viral meningitis Generally supportive treatment is given. Pleconaril has been evaluated for enteroviral meningitis with modest benefit. Acyclovir (10 mg/kg IV every 8 hours) for HSV meningitis (controversial). Intravenous immunoglobin has been used in agammaglobulinemic patients with chronic enteroviral meningitis. Arboviruses , mumps, or LCM: No specific therapy HIV-associated meningitis should be treated with combination antiretroviral therapy. CMV meningitis : Ganciclovir

25. Cryptococcal meningitis 14-day induction phase of amphotericin B, 0.7 to 1 mg/kg/day IV, with or without flucytosine , 100 mg/kg/day PO dosed every 6 hours. Consolidation therapy with fluconazole , 400 mg daily, should be continued for 8 weeks following induction. Maintenance (or suppressive) therapy with fluconazole, 200 mg per day. Risk factors: HIV patients, Organ transplant recepients Diagnosis : CSF analysis, India ink staining Detection of cryptococcal antigen ( CrAg ) by lateral flow immunoassay and latex agglutination assay.

26. Other fungal meningitis T/t of coccidioidal meningitis is oral fluconazole. Therapy for H. capsulatum meningitis consists of amphotericin B, 0.7 to 1 mg/kg/day to complete a total dose of 35 mg/kg.

27. Tuberculous meningitis Sole manifestation of TB or concurrent with pulmonary or other extrapulmonary sites of infection. Cranial nerve (CN) palsies, hemiparesis, paraparesis , and seizures are common and should raise the possibility of MTB as the etiology of meningitis. Chest X-ray is suggestive of active or previous pulmonary TB in approximately 50% of cases

28. Lab Diagnosis CSF : Pleocytosis with lymphocytic predominance, high protein levels, and low glucose levels. In all suspected case send CSF for Ziehl-Neelsen (ZN) staining for AFB, Gram staining for bacteria, India ink preparations for fungi, and antigen testing for Cryptococcus neoformans . MTB cultures can take several weeks. Xpert MTB/RIF detect MTB and rifampicin resistance simultaneously in less than 2 hours.

29. Neuroimaging in TBM CECT or MRI scan The most common findings in descending order are meningeal enhancement, hydrocephalus, basal exudates, infarcts, and tuberculomas

30. Treatment The WHO guidelines recommend a first-line regimen of 2 months of HRZE(children ) or HRZS (adults ) followed by 10 months of HR.

31. HIV infected patients receiving ART are at risk for clinical deterioration after initiation of antiretroviral therapy (ART) due to immune reconstitution inflammatory syndrome (TBM-IRIS ). Defer ART to 4–6 weeks after beginning ATT. Steroid are of great use.

32. Summary Clinical triad is the hallmark of meningitis but absent in nearly half of the patients. Neuroimaging studies should precede lumbar puncture in the presence of papilledema , focal findings on neurologic examination, immunocompromise (human immunodeficiency virus [HIV]infection, malignancy, or transplant), seizures in the week priorto presentation, or coma. Empirical antibiotic therapy should begin as soon as possibleafter appropriate cultures have been obtained; these can bemodified later based on results of erebrospinal fluid (CSF) Gramstain and culture.

33. Patients with negative cultures and limited clinical response after 48 hours of therapy should undergo repeat lumbar puncture and head computed tomography (CT) or magnetic resonance imaging (MRI) scans. Initial combination therapy with dexamethasone and antibiotics has been associated with improved outcomes in patients with pneumococcal meningitis.

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