Diagnosis

Meningitis

Etiology

Cause [24b]

• Bacterial: Streptococcus pneumonia, Haemophilus influenzae, Staphylococcus aureus, Neisseria meningitidis, Listeria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, Tuberculosis, Syphilis

• Viral: Enteroviruses (coxsackievirus, echovirus, coxsackievirus), Arboviruses (West Nile virus), Mumps (Paramyxovirus), Herpes family viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6), Adenovirus, Measles (Morbillivirus) and HIV

• Fungal: Cryptococcus, Coccidioides immitis, Blastomyces dermatitidis, Histoplasma capsulatum, Candida species, S schenckii, Aspergillus, Candida, Mucormycosis

• Parasitic: Amebic (Naegleria fowleri, Acanthamoeba, Balamuthia)

• Lyme meningitis: Borrelia burgdorferi

• Aseptic meningitis: NSAIDs, metronidazole, IV immunoglobulin and carcinomatosis

Pathophysiology [24b]

1. An agent can invade the CNS and cause meningitis via the following pathways:

   1. Invasion of the bloodstream (hematogenous seeding of the CNS)

   2. A retrograde neuronal pathway (Naegleria fowleri or Gnathostoma spinigerum)

   3. Direct contiguous spread (sinusitis, otitis media, congenital malformations, trauma, surgery, osteomyelitic erosion)

2. The inflammatory response release free radical molecules that are cytotoxic

3. Neuronal damage: Ventriculitis, empyema, cerebritis, abscess, obliteration of CSF pathways causing hydrocephalus, vasculitis and thrombophlebitis

4. Elevated ICP:

   • Hydrocephalus: obliteration of CSF pathways

   • Cytotoxic edema: toxic factors from bacteria/neutrophils cause cellular swelling

   • Vasogenic edema: increased blood brain barrier permeability

Complications [24b]

• Hearing loss

• Blindness

• Paralysis

• Retardation

• Focal neurologic deficits: Cranial nerve dysfunction, Ataxia, Seizure,

• Hydrocephalus

• Cerebral atrophy

• Waterhouse-Friderichsen syndrome

Risk factors [24b]

• Chronic medical disorders (renal failure, diabetes, adrenal insufficiency, cystic fibrosis)

• Extremes of age: <5 years and >65 years

• Incomplete vaccination

• Immunodeficiency (transplant recipients, congenital immunodeficiency, AIDS)

• Crowded conditions (military barracks, college dorms)

• Exposures: Travel to endemic areas, vectors (mosquitoes, ticks)

• Alcohol use disorder

• Ventriculoperitoneal shunt

• Endocarditis

• Malignancy

• Dural defects

• IV drug use

• Sickle cell anemia/thalassemia

• Splenectomy

• Sinusitis

• Dural defect (trauma, surgery)

Epidemiology

Incidence per 100.000 [1vq][vm1][zss][ymb][i6z]

Approach

• Blood test

• Blood culture

• Blood gas

• Toxicology

• Nasopharynx

• Lumbar puncture: cell count, pH, lactate, protein, glucose, culture, PCR, microscopy, serology for antibodies

  • Viral: Multiplex and specific PCRs

  • Fungal: CSF fungal culture, India ink stain for Cryptococcus

  • Mycobacterial: CSF Acid-fast bacilli smear and culture

  • Syphilis: CSF VDRL

  • Lyme disease: CSF burgdorferi antibody

• CT caput

• MR caput

• Brain biopsy

Treatment

1. Airway protection in case of altered mental status [6zi][24b]

2. Breathing: oxygen mask

3. Circulation: IV) access for crystalloid infusion

4. Obtain blood cultures (lumbar puncture/CSF unless signs of increased ICP)

5. Bacterial meningitis:

   • Antibiotic: [24b]

     • 3rd generation cephalosporin: S pneumoniae and N meningitidis

     • Ampicillin: L monocytogenes

     • Vancomycin: penicillin-resistant S pneumoniae and S aureus

     • Age 0-4 wk: Ampicillin + Cefotaxime or Aminoglycoside + Acyclovir IV

     • Age 1 mo-50 y: Ampicillin/Vancomycin + Cefotaxime or Ceftriaxone

     • Age >50 y: Ampicillin + Vancomycin + Ceftriaxone or Cefotaxime

   • Intrathecal antibiotics: considered in meningitis after neurosurgery

   • Dexamethasone: 0.15 mg/kg every 6 hours for 2-4 days)

6. Viral menigitis:

   • CMV: Ganciclovir 5 mg/kg IV every 12 hours for 21 days

   • Enteroviruses: Immunoglobulin replacement in immunocompromised individuals

   • HSV: Acyclovir 10 mg/kg IV every 8 hours (controversial)

   • HIV: Antiretroviral therapy

7. Fungal menigitis:

   • Cryptococcal: Amphotericin B 0.7-1 mg/kg/day IV for at least 2 weeks + flucytosine (100 mg/kg orally) + Fluconazole 400 mg/day for 8 weeks

   • C immitis: oral fluconazole (400 mg/day)

   • Histoplasma capsulatum: Liposomal amphotericin B (5 mg/kg/day IV for a total of 175 mg/kg given over 4-6 weeks), followed by oral itraconazole (200-300 mg 2 or 3 times daily for at least 1 year

   • Candidal meningitis: Amphotericin B (0.7 mg/kg/day) + Flucytosine (25 mg/kg every 6 hours)

   • Sporothrix schenckii: Liposomal amphotericin B + itraconazole 200 mg x 2

8. Tuberculosis: Isoniazid 300 mg + Rifampin 600 mg/day + Pyrazinamide 15-30 mg/kg/day + Ethambutol 15-25 mg/kg/day + Streptomycin 7.5 mg/kg every 12 hours for 9 to 12 months

9. Syphilis: Penicillin G (2-4 million U/day IV every 4 hours for 10-14 days)

10. Parasitic meningitis: usually fatal, high-dose IV and intrathecal amphotericin B or miconazole and rifampin

11. Lyme meningitis: Ceftriaxone (2 g/day for 14-28 days)

12. Symptomatic treatment:

    • Fever

    • Pain

    • Increased ICP: elevate head, hyperventilation, furosemide 20 mg or mannitol 1 g/kg

    • Seizure

    • Hyponatremia (SIADH)

    • Cardiac arrhythmias and ischemia

    • Stroke

    • Exacerbation of chronic diseases

13. Prophylaxis: H influenzae vaccine, N meningitidis vaccines, Pneumococcal vaccine

Differential diagnoses

Brain abscess, Brain tumor, Delirium tremens, Encephalitis, Endocarditis, Epilepsy, Febrile seizure, Leptospirosis, Migraine, Stroke, Subarachnoid hemorrhage, Subdural empyema, Subdural hematoma, Syndrome of inappropriate antidiuretic hormone secretion, Systemic lupus erythematosus