Meningitis

Mohd Saif Khan

EPIDEMIOLOGY, DIAGNOSIS AND MANAGEMENT

Headings

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

• Meningitis is a clinical syndrome characterized by inflammation of the meninges.

CNS infections

Meningitis Encephalitis

Leptomeningitis

Pachymeningitis

Anatomy

Emissary veins

PATHOPHYSIOLOGY

WBC

Mechanical effects Inflammatory effects

Impairment of CSF flowOcclusion of cortical blood vessels

CytokinesOxidantsProteolytic enzymes

HydrocephalusDisruption of BBB

Disruption of BBBEnhanced bacterial entryEnhanced WBC recruitmentOverwhelming damage to neural structures

Breach in piamater

Infection of brain parenchyma (encephalitis)Brain abscess

PATHOPHYSIOLOGY

Cranial nerve palsies (VIII CN)Thrombophlebitis of cortical veinsIschemia and infarcts

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

Presentation

Fever

Neck stiffnessHeadache

Only about 44% of adults with bacterial meningitis

Altered mentationNausea and vomitingPhotophobiaDouble visionsConfusionIrritabilityDelirium Seizures Coma

Symptom onsetAcute (<24 hours)

Subacute (1-7 days)

Chronic (>7 days)

Bacterial

Viral

Tuberculosis, Syphilis, Fungi (especially cryptococci), Carcinomatosis

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.

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

D/Ds

• Central nervous system (CNS) vasculitis• Stroke• Encephalitis• All causes of altered mental status and coma• Leptospirosis• Subdural empyema

Management

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.

Diagnosis

• 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.).

Typical CSF Parameters in Patients with Meningitis

Etiology WBC Count(cells/mm3)

Predominantcell type

Protein(mg/dL)

Glucose(mg/dL)

Opening Pressure(cm H2O)

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.

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. Comatose2. 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 CNSmass lesion)4. Immunosuppressed (HIV, transplant, neoplasm, steroids)

No Yes

LPCSF findings s/o Bacterial meningitis

Continue therapy

Yes

negative

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.

Antimicrobial therapyPredisposing conditions Antibiotics

Age <1 month 1 month – 2 years 2-50 years >50 years

Ampicillin+cefotaxime/aminoglycosideVanco+ 3rd Gen CephaloVanco+ 3rd Gen CephaloVanco+Ampi+3rd Gen Cephalo

Head trauma Basilar fracture Penetrating

Vanco+ 3rd Gen CephaloVanco+ 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

Duration of antimicrobial therapy

Supportive treatment

• Analgesics• Antipyretics• Anticonvulsants• ICP lowering measures• Intubation and mechanical ventilation

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 cathetersFor MDR GNBIntraventricular antibiotic administrationNot FDA approved, indications are not well defined.Vancomycin and gentamicin are most commonly given via this route

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/mm3)

Predominantcell type

Protein(mg/dL)

Glucose(mg/dL)

Opening Pressure(cm H2O)

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

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

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.

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.

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

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.

Neuroimaging in TBM

• CECT or MRI scan• The most common

findings in descending order are meningeal enhancement, hydrocephalus, basal exudates, infarcts, and tuberculomas

Treatment

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

• 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.

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.

• 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.

Thank you