Meningitis

Meningitis is a serious infection of the meninges in the brain or spinal cord that is most commonly viral or bacterial in origin, although fungal, parasitic, and noninfectious causes are also possible. Enteroviruses and herpes simplex virus are the leading causes of viral meningitis, while Neisseria meningitidis and Streptococcus pneumoniae are the pathogens most commonly responsible for bacterial meningitis. Rarer forms of bacterial meningitis include tuberculous meningitis and Lyme-associated meningitis. The classic triad of meningitis is fever, headache, and neck stiffness. In infants and young children, the presentation is often nonspecific. Patients may also present with neurological deficits, altered mental status, and seizures, indicating increased intracranial pressure (ICP). The diagnosis is confirmed with lumbar puncture (LP) and CSF analysis. If increased ICP is suspected, a CT of the head should be performed first. Bacterial meningitis requires rapid initiation of empiric treatment. A life-threatening complication of bacterial meningitis (especially meningococcal meningitis) is Waterhouse-Friderichsen syndrome, which is characterized by disseminated intravascular coagulation and acute adrenal gland insufficiency. Viral meningitis typically resolves on its own and has a far less severe course than bacterial meningitis, which is generally fatal if left untreated. When N. meningitidis or S. pneumoniae are identified as the pathogen, the CDC should be notified and preventative measures taken to prevent dissemination of the infection.

• In the pediatric population, meningitis most often occurs in children < 1 year of age. ^[1]
• The median age for meningitis in the adult population is 43 years. ^[2]
• Sub-Saharan Africa has the worldwide highest incidence of meningitis caused by N. meningitidis. ^[3]

Epidemiological data refers to the US, unless otherwise specified.

Common causes

• Otitis media
• Sinusitis
• CSF leak after head trauma or neurosurgery
• Maternal group B streptococcal infection during birth
• Sepsis

Risk factors

• Immunocompromise (e.g., due to AIDS, asplenia, heavy alcohol use disorder, chronic illness, cancer, sickle cell anemia, old age, pregnancy)
• Crowded occupational or living conditions (e.g., college dormitories, military barracks, retirement homes, kindergartens)
• Close contact with an infected person

Most common causative agents of bacterial meningitis by age group and underlying condition ^[4][5]

Less common bacterial pathogens

• Borrelia spp. (Lyme meningitis)
• Treponema pallidum (syphilitic meningitis)
• Mycobacterium tuberculosis (tuberculous meningitis)
• Actinomyces israelii
• Leptospira (leptospirosis)

Other etiologies

• Viral meningitis: often associated with encephalitis (meningoencephalitis)
  • Enteroviruses (especially coxsackieviruses and echoviruses): the most common cause of all types of meningitis in all patient groups ^[12]
  • Herpesviruses: HSV (meningitis is more commonly caused by HSV2 than HSV1) , CMV, EBV, VZV
  • Lymphocytic choriomeningitis virus (LCMV)
  • Mumps virus
  • Measles virus
  • Some arboviruses (e.g., West Nile virus, TBEV in Eurasia)
  • Poliovirus (nonparalytic poliomyelitis: aseptic meningitic form)
  • St. Louis encephalitis virus
  • California encephalitis virus
  • Western equine encephalitis virus
  • Influenza virus
  • HIV
  • JC virus ^[13]
• Fungal meningitis
  • Coccidioides
  • Candida spp.
  • Aspergillus spp.
• Parasitic meningitis
  • Helminths (e.g., Echinococcus spp., Strongyloides stercoralis, Angiostrongylus cantonensis, Baylisascaris procyonis)
  • Protozoa (e.g., Naegleria fowleri; , Acanthamoeba)
• Noninfectious meningitis
  • Sarcoidosis
  • Tumor metastases (meningeal carcinomatosis and meningeal leukemia)
  • Medication (e.g., NSAIDs, sulfa drugs) ^[14]

Causes of meningitis in immunocompromised individuals

• Bacterial
  • Certain immune deficiencies can predispose to certain types of meningitis. ^[15]
    • Defects in humoral immunity (including splenectomy): encapsulated bacteria (N. meningitidis, S. pneumoniae, H. influenzae, etc.)
    • Defects in cell-mediated immunity (e.g., in HIV, drug-induced immunosuppression): M. tuberculosis, L. monocytogenes
  • Immunocompromised individuals are at increased risk of recurrent bacterial meningitis compared to those with intact immunity. ^[10]
• Viral: Risk is higher in individuals with cell-mediated immune deficiencies (e.g., in HIV infection). ^[16]
  • Herpesviruses: CMV, EBV, VZV, and HSV6
  • HIV
  • Adenovirus
  • JC virus ^[13]
• Fungal: Risk is higher in individuals with cell-mediated immune deficiencies (e.g., HIV infection). ^[17]
  • Cryptococcus spp.
  • Candida spp.
  • Histoplasma capsulatum
  • Aspergillus spp.
• Protozoal: Toxoplasma gondii (rare) ^[18]

References:^{[19][20][21][22][23][24]}

Pathways of infection

• Most pathogens that cause meningitis colonize the nasopharynx or the upper airways before entering the CNS via:
  • Hematogenous dissemination . ^[25]
  • Contiguous spread of infections in nose, eyes, and ears
  • Retrograde transport along or within peripheral or cranial nerves
• Direct infection (e.g., due to trauma or head surgery) ^[26]

Incubation periods

• Bacterial meningitis: usually 3–7 days ^[27]
• Viral meningitis: usually 2–14 days, depending on the type of virus

References:^[20][22][27]

Clinical features of bacterial and viral meningitis are similar, although viral meningitis is less acute and usually self-limiting within 7–10 days.

Neonates (neonatal meningitis)

In neonates, meningitis often manifests with nonspecific symptoms and without the classic triad of meningitis.

• Early symptoms
  • Lethargy
  • Muscle hypotonia
  • Irritability
  • Poor appetite, vomiting
  • Hyperthermia or hypothermia
  • Dyspnea, abnormal breathing patterns (e.g., Biot respiration) ^[28]
• Late symptoms
  • Fontanelle bulging
  • High-pitched crying
  • Seizures

Children and adults (meningismus)

• Classic triad of meningitis: fever, headache, and neck stiffness (this triad is often not present in neonates and infants) ^[29][30]
• Altered mental status
• Photophobia
• Nausea, vomiting
• Malaise
• Seizures
• Possibly cranial nerve palsies
• In the case of N. meningitidis
  • Myalgia and, possibly, petechial or purpuric rash (especially in children)
  • Possibly Waterhouse-Friderichsen syndrome
• Common symptoms of viral meningitis
  • Prodrome with flu-like symptoms
    • Low-grade fever
    • Malaise, fatigue
    • Myalgia
    • Upper respiratory symptoms (e.g., sore throat)
  • Pharyngitis, herpangina, and/or rash

Subarachnoid hemorrhage can manifest with the classic triad of meningitis but has a more sudden onset and patients often lose consciousness.

The classical features of acute bacterial meningitis are fever, neck stiffness, and headache. However, this triad of symptoms only manifests in approx. 50% of cases.

Physical examination ^[20][31]

• Signs of meningeal irritation
  • Neck stiffness
  • Kernig sign
  • Brudzinski sign
• Systemic signs of inflammation
  • Fever
  • Hypotension
  • Tachycardia
• Signs of increased intracranial pressure: : e.g., papilledema (< 5% of cases) ^[32]
• Signs of underlying infections
  • Bulging and redness of tympanic membrane: acute otitis media
  • Skin manifestations ^[33]
    • Cutaneous petechiae in meningococcal meningitis: suggestive of meningococcemia
    • Maculopapular rash in some viral meningitis (e.g.,; West Nile virus, enterovirus)
    • Nonblanching rash: should raise suspicion for meningococcal meningitis or Rocky Mountain spotted fever (see “Subtypes and variants”)

Features suggestive of meningoencephalitis ^[34][35]

In addition to the features of meningitis, meningoencephalitis is characterized by signs of inflammation of the brain parenchyma (encephalitis).

• Focal neurological signs (e.g., paresis, extrapyramidal symptoms, aphasia)
• Seizures (focal-onset or generalized)
• Behavioral changes, psychosis
• Altered consciousness

References:^{[19][31][36][37]}

General approach

• Bacterial meningitis is a medical emergency and requires immediate treatment.
• Diagnostic and treatment steps should be initiated simultaneously and empiric treatment should not be delayed for diagnostic steps.
  • If the patient is stable and has no LP contraindications: Perform LP as soon as possible before starting empiric antibiotics.
  • If the patient is unstable, requires neuroimaging (see criteria for imaging prior to LP in suspected meningitis), or has relative contraindications to LP (e.g., coagulopathy): Defer LP and start empiric antibiotic treatment (see empiric antibiotic therapy for bacterial meningitis). ^[5]

Do not delay empiric antibiotic therapy in patients suspected of having bacterial meningitis.

Challenges

• Diagnosis
  • There is a significant overlap in presentation between bacterial and other etiologies.
  • LP and CSF analysis can be time-consuming and risky.
  • Patients may present with relative contraindications to LP (e.g., signs of elevated ICP).
• Treatment
  • Bacterial meningitis can be rapidly progressive and life-threatening.
  • Patients may present as critically ill and with complications (e.g., sepsis, multiorgan failure) requiring early aggressive supportive care.
  • Empiric antibiotic treatment must be initiated as soon as possible (i.e., often prior to diagnosis).

Approach ^{[5][29][30][38][39]}

• Obtain samples immediately for blood cultures, routine laboratory tests, and screening for organ dysfunction.
• Confirm the diagnosis with LP and CSF analysis (if no LP contraindications are present).

Start empiric antibiotics immediately after obtaining blood cultures and CSF samples. If LP is delayed for any reason (e.g., the need for a CT or hemodynamic stabilization), obtain blood cultures and administer antibiotics until it can be performed.

Laboratory studies ^{[5][29][30][38]}

• Routine tests
  • Blood cultures (two sets): obtain before starting antibiotic therapy
  • CBC
    • Normal/↑ WBC count
    • In severe infections, ↓ WBC count and thrombocytopenia
  • BMP: Blood glucose is needed to analyze CSF glucose.
    • Common finding: mild electrolyte disturbances (e.g., hyponatremia from SIADH)
    • In critically ill patients: possible signs of acute kidney injury
  • CRP: elevated ^[38]
• Additional tests
  • Assess for organ damage and complications.
    • Coagulation panel: especially if there is suspicion for disseminated intravascular coagulation (e.g., petechiae, purpura)
    • Blood gas: metabolic acidosis may be present in critically ill patients
  • Consider testing for atypical infections

Neuroimaging ^[26][38][39]

Imaging is not necessary to establish the diagnosis of meningitis in most patients and should only be considered in patients with significant risk factors for complications.

• Indications
  • To assess the risk of brain herniation precipitated by LP ^[38]
  • Identify abscesses or other localized lesions (e.g., in postsurgical patients in whom infection is suspected) ^[26]
  • Suspected healthcare-associated ventriculitis/meningitis ^[26]
  • Patients with devices (e.g., CSF shunts) ^[26]
• Recommended criteria for imaging prior to LP in suspected meningitis ^[38][39][40]
  • Focal neurological deficits
  • Altered mental status ^[39]
  • Immunocompromised status (e.g., HIV, post-transplant, taking immunosuppressants)
  • Papilledema
  • History of CNS disease (e.g., mass, stroke, abscess)
  • Seizures (new-onset) ^[38]
• Modalities
  • CT head (with or without IV contrast): before LP if increased ICP is suspected ^[41]
  • MRI brain with IV contrast and diffusion: especially useful in patients with devices or after surgery ^[26]
• Supportive findings
  • Usually normal or showing mild meningeal enhancement
  • May identify predisposing factors for the infection (e.g., fractures, mastoiditis) or complications (e.g., abscess)
  • See “Subtypes and variants” for characteristic findings of specific pathogens.

To remember the indications for imaging before LP, think of LP FAILS: Focal neurological deficits, Altered mental status, Immunocompromised or ↑ ICP, Lesions (space-occupying lesions in the brain), Seizures.

Cerebrospinal fluid analysis

Lumbar puncture is indicated in all patients with suspected meningitis (see “Lumbar puncture” for details on indications, LP contraindications, procedural steps, and complications).

Approach to interpretation

• Confirmatory findings: pathogen identification on CSF OR positive blood cultures in a patient with highly suggestive CSF findings
• Highly suggestive findings: pleocytosis (granulocytic or lymphocytic), low glucose, high protein
• Nonspecific findings: high opening pressure

Routine testing ^[38][39][40]

Atypical pathogen testing

Atypical pathogen testing is not necessary for all patients and should be performed as directed by clinical suspicion.

Additional microbiological testing

• Special microbiological stains
  • Acid-fast staining: if there is suspicion for tuberculous meningitis
  • India ink preparation: if there is suspicion for cryptococcus
  • Wright or Giemsa stain: if there is suspicion for toxoplasmosis
• Special cultures ^[40]
  • Viral culture
    • Not typically recommended
    • May confirm enterovirus, herpes simplex virus infection
  • M. tuberculosis cultures: Results can take up to 6 weeks. ^[40]
  • Fungal cultures: for the identification of Candida spp., Cryptococcus spp. ^[40]
  • For patients with CSF shunts or drains: Extend CSF cultures for at least 10 days.
• PCR for viral meningitis and specific bacterial subtypes ^[38][39]
  • Indications
    • Confirmation of viral meningitis/encephalitis (e.g., HSV)
    • Detection of intracellular bacteria (e.g., TB, rickettsial infections)
  • Disadvantages
    • No antibiotic sensitivity data for bacterial infections
    • Not readily available for unusual pathogens (especially bacteria)
• Latex agglutination test ^[38]
  • Bacterial antigen detection
    • Not routinely used because of variable accuracy ^[38]
    • Consider in patients in whom there is strong suspicion for bacterial meningitis despite negative Gram stain or culture after 48 hours
  • Fungal latex agglutinations: especially relevant for cryptococcal antigen testing (see cryptococcal meningitis)

Approach

• Apply appropriate isolation precautions.
• Stabilize the patient as needed.
• Administer empiric antibiotics as soon as possible, preferably within 1 hour (see empiric antibiotic therapy for bacterial meningitis).
  • If LP can be performed rapidly, administer antibiotics and adjuvant therapy (e.g., dexamethasone) after obtaining CSF.
  • If LP is delayed (e.g., because neuroimaging is required), administer antibiotics and adjuvant therapy (e.g., dexamethasone) immediately.
  • Add other antimicrobial therapy (e.g., antivirals, antifungals) as needed (see “Subtypes and variants” for details).
• Consult the infectious disease team.
• Tailor antimicrobial therapy once the pathogen is identified.
• Provide postexposure prophylaxis for close contacts if indicated (see postexposure chemoprophylaxis for bacterial meningitis).

Do not delay administering antibiotics if neuroimaging is indicated prior to LP. Obtain blood cultures, start antibiotics (and steroids, if needed) immediately, then proceed with the CT and LP.

Patient stabilization

• Airway management: Secure the airway (e.g., intubate) if GCS < 8, the patient has intractable seizures, or there are signs of cerebral herniation (see intubation of patients with high ICP).
• Provide hemodynamic support with fluids and/or vasopressors (see “Fluid resuscitation” and “Sepsis”).
• Identify and reverse any coagulopathy (see “Anticoagulant reversal”).
• Identify and treat elevated ICP (see “ICP management”).

Antimicrobial therapy

Empiric antibiotic therapy ^[38]

• The choice of initial empiric therapy depends primarily on the prevalence of organisms in certain age groups and individual patient risk factors for resistant organisms.
• Factors to consider:
  • Epidemiological factors (e.g., local flora, resistance patterns)
  • Bioavailability: Antimicrobial agents should cross the blood-brain barrier and higher doses may be needed.
  • Individual patient risk factors and comorbidities

Ampicillin is added if patients are at risk of Listeria spp. infection (e.g., newborns, pregnant women, adults > 50 years of age, or immunocompromised patients) because cephalosporins are ineffective against Listeria spp.

Ceftriaxone is contraindicated in patients aged < 1 month because of a higher risk of biliary sludging and kernicterus. Cefotaxime or ceftazidime can be used instead. ^[46]

Empiric therapy for viral meningitis ^[19][48]

Most cases of viral meningitis (e.g., caused by enteroviruses) can be treated supportively. Specific antiviral therapy is only warranted if viral encephalitis is also suspected (see HSV encephalitis for further details).

• Indications
  • Concern for HSV encephalitis, for example:
    • Risk factors (e.g., neonates with a mother who has active genital HSV lesions)
    • Suggestive clinical features (e.g., focal neurological deficits, altered mental status, seizures, behavioral changes, coma)
    • Imaging findings (e.g., temporal lobe enhancement)
    • CSF: ↑ RBCs despite a nontraumatic LP (suggestive of hemorrhagic encephalitis)
  • Concern for other herpesviruses, e.g., VZV, EBV
• Recommended empiric antiviral agent: acyclovir
  • Continue treatment if either HSV or VZV is detected, otherwise discontinue.

Treatment with acyclovir should be started in all patients who present with typical clinical signs of viral meningoencephalitis and only discontinued after PCR and antibody tests are negative for HSV and VZV, even if CSF is initially normal.

Pathogen-specific therapy

The decision to narrow therapy should be guided by final culture and sensitivity results, as well as local resistance patterns. We list a few examples of antimicrobial agents that may be used against specific pathogens.

Corticosteroids ^[39][49]

• Indication: suspected or proven meningitis due to S. pneumoniae or H. influenzae in adults and children
• Mechanism: reduces the local and systemic inflammation seen in bacterial meningitis and improves outcomes
• Recommended agent: dexamethasone for 2–4 days ^[39][49]
  • Should be administered before or concomitant to antibiotics for optimal results ^[39]
  • Discontinue if a pathogen other than S. pneumoniae or H. influenzae is identified.
• Disadvantages: side effects, e.g., hyperglycemia, GI bleeding ^[49]

Do not delay antibiotics to administer adjuvant therapy. If dexamethasone is not readily available, start antibiotics immediately.

Supportive therapy

• Electrolyte repletion
• Analgesics as needed (see pain management)
• Antipyretics as needed
• IV fluids as needed
• IV antiemetics as needed
  • Ondansetron
  • Metoclopramide
  • Prochlorperazine

Monitoring and disposition

• Most patients with meningitis require admission; select patients may be considered for outpatient therapy with close follow-up. ^[38]
• Serial neuro examinations
• Consultations:
  • Infectious disease
  • Consider also ICU , neurology, neurosurgery as needed.

• Stabilize the patient and obtain IV access
• Identify and treat sepsis, if present.
• Obtain blood cultures (two sets) and routine laboratory studies (e.g., CBC, coagulation studies, CRP).
• Consider indications for imaging prior to LP (i.e., presence of any criteria for imaging prior to LP in suspected meningitis)
• Perform LP and order CSF analysis if there are no LP contraindications
• Begin empiric antibiotics and steroids as soon as possible (see empiric antibiotic therapy for bacterial meningitis). ^[38]
• Consider empiric viral coverage.
• Provide supportive therapy as needed.
• Admit to medicine or neurology service.
• Ensure 24 hours of droplet isolation for all patients suspected of having bacterial meningitis.
• Consider indications for prophylactic treatment (see postexposure chemoprophylaxis for bacterial meningitis).
• Consult infectious diseases.
• Consult ICU, neurology, neurosurgery as needed.

Tuberculous meningitis

• Pathogen: : Mycobacterium tuberculosis
• Incubation period: approximately 2–8 weeks
• Risk factors: immunocompromise (e.g., HIV infection)
• Clinical course
  • Subacute course over several weeks or months
  • Gradual manifestation with intermittent fever
• Clinical features
  • Typical symptoms of meningitis, including fever, headache, neck stiffness, and altered mental status (see “Clinical features” section above for details)
  • Focal neurological deficits (e.g., hemiparesis) due to hematogenous dissemination of cranial arteritis
  • Cranial nerve deficits; are most commonly seen in basal meningitis and predominantly involve the abducens nerve ^[50]
• Diagnostics
  • CSF fluid
    • Presence of acid-fast bacilli on CSF Gram stain ^[40][43]
    • Culture is the gold standard for diagnosis, but results may take weeks. ^[40]
    • Analysis of adenosine deaminase (ADA) activity
      • ↑↑ Activity in CSF of individuals with tuberculous meningitis compared to CSF of individuals with other types of meningitis (e.g., cryptococcal or bacterial meningitis)
      • For the differentiation of tuberculous from other types of meningitis, combining serum and CSF ADA activity can increase sensitivity and specificity. ^[51]
      • However, reported sensitivity and specificity vary greatly in the literature; confounding factors include the CSF ADA cut-offs, assay types, and comorbidities (especially HIV). ^[52]
  • CT/MRI: possible hydrocephalus, basilar meningeal thickening, tuberculomas, edema, infarcts ^[43]
• Complications
  • Communicating (malabsorptive) hydrocephalus
  • Pituitary gland insufficiency
• Treatment
  • See “Treatment” in “Tuberculosis.”
  • Adjunctive glucocorticoid therapy with dexamethasone or prednisolone tapered over 6–8 weeks ^[53]

Cryptococcal meningitis

• Pathogen: Cryptococcus neoformans (a type of encapsulated yeast)
• Risk factors
  • AIDS
  • Exposure to pigeon droppings
• Clinical course: : subacute onset with (low) fever, fatigue, and headaches
• Clinical features
  • See section on “Clinical features” above
  • Meningeal symptoms are often absent
• Diagnostics ^[54]
  • Cryptococcal antigen testing of CSF and serum
    • Highly specific and sensitive ^[54]
    • Typically performed via latex agglutination or enzyme immunoassay
  • CSF culture (Sabouraud agar)
  • CSF gram staining: India Ink (clear halo), mucicarmine (red inner capsule)
  • MRI: gelatinous pseudocysts (soap bubble appearance)
• Treatment ^[55]
  • Induction: Intravenous amphotericin B; PLUS flucytosine for at least 2 weeks
  • Consolidation: fluconazole for at least 8 weeks
  • Maintenance: fluconazole for at least 1 year
  • Important consideration: Delay initiation of cART for 4–6 weeks after starting antifungal therapy to reduce the risk of immune reconstitution syndrome.

Tick-borne diseases

North America

• Lyme meningitis: See Lyme disease.
• See Rocky Mountain spotted fever (RMSF).
• See Ehrlichiosis.

Eurasia: Tick-borne meningoencephalitis

• Pathogen: tick-borne encephalitis virus (TBEV)
  • TBEVs are part of the Flaviviridae family and occur predominantly in parts of Europe, Russia, and Asia.
  • TBEV is very closely related to the Powassan virus in the US and Russia, which is a rare cause of encephalitis.
• Route of infection: tick-borne
  • Ixodid tick acts as a vector; therefore, transmission is predominantly in June/July and September/October.
  • Occasional transmission via unpasteurized dairy products from infected livestock
• Incubation period: usually 7–14 days
• Clinical features:
  • Nearly 90% of cases are asymptomatic.
  • Biphasic course: initial flu-like symptoms and fever, followed (after ∼ 8 days) by a fever-free interval and subsequent increase in temperature, which is associated with the onset of meningoencephalitis
• Treatment: symptomatic
• Prognosis:
  • Full recovery is common (particularly in children and adolescents).
  • In symptomatic disease, residual symptoms may occur.
• Prevention: A vaccine is not available in the US.
  • Active immunization with an inactivated TBEV (inactivated vaccination): Large-scale implementation of this vaccination is not generally recommended.
  • The CDC's Advisory Committee on Immunization Practices (ACIP) recommends the vaccination only for individuals living, traveling, or working in high-risk areas (laboratory staff exposed to TBEV, foresters, etc.).

Primary amebic meningoencephalitis ^[56]

• Pathogen: Naegleria fowleri (colloquially referred to as “brain-eating amoeba”), found in warm freshwater (e.g., ponds, hot springs)
• Route of infection: via contaminated water entering the nose (e.g., while swimming) → invades the CNS directly via the cribriform plate
• Clinical features: causes fulminant meningoencephalitis with rapid onset
• Diagnosis
  • CSF analysis
    • Findings similar to those of bacterial meningitis (e.g., neutrophilic pleocytosis, hypoglycorrhachia, increased CSF protein)
    • CSF erythrocytosis (due to hemorrhagic necrosis)
    • Microscopy shows trophozoites
• Treatment: amphotericin B, miltefosine
• Prognosis: nearly always fatal ^[57]

References:^{[20][58][59][60][61][62][63][64][65]}

Neurologic

• Most common: sensorineural hearing loss (transient or permanent)
• Focal neurological deficits ^[66]
• Seizures
• Cognitive impairment
• Spasticity or paresis
• Cerebral edema and elevated ICP
• Communicating hydrocephalus
• Cerebrovascular disease
• Rare: brain abscess; , subdural empyema, arteritis (risk of cerebral infarction and cerebral venous sinus thrombosis), ventriculitis, cerebritis

Waterhouse-Friderichsen syndrome

• Epidemiology: : predominantly affects small children and asplenic individuals
• Description: acute primary insufficiency of the adrenal gland most commonly caused by adrenal hemorrhage
  • Dangerous complication of a number of diseases but most commonly associated with meningococcal meningitis
  • Rarer causes include DIC, endotoxic shock, and septicemia due to other pathogens (e.g., S. pneumoniae)
• Pathophysiology: coagulopathy; triggered by endotoxins, which often leads to hemorrhagic necrosis of the adrenal glands
• Clinical features
  • Fever
  • Myalgia
  • Nonblanching, petechial rash (mostly on trunk and legs); in severe cases, even purpura fulminans with extensive necrosis of the skin
  • Severe malaise
  • Hypotension ; or even shock
  • Findings of disseminated intravascular coagulation
  • Findings of acute adrenal gland failure
  • Respiratory failure
• Treatment
  • Treatment of the underlying cause (see empiric antibiotic therapy for bacterial meningitis and pathogen-specific therapy in meningitis)
  • Parenteral fluid therapy and management of disorders of sodium balance
  • Coagulopathy treatment
• Prognosis: fatal without treatment and often fatal even with treatment, particularly if associated with meningococcal infection (> 40% mortality rate) ^[67]

References:^{[19][31][66][67][68][69][70][71]}

We list the most important complications. The selection is not exhaustive.

• Bacterial meningitis
  • Fatal if left untreated
  • Prognosis in treated patients depends on age, overall condition, immune status and the pathogen(s) involved.
• Viral meningitis
  • Resolves spontaneously in the majority of cases
  • Residual symptoms such as sensorineural hearing loss, epilepsy, and cognitive deficits are rare.
• Fungal meningitis
  • Associated with neurological sequelae and a high mortality rate
  • Treatment adherence is very important to avoid relapse.

References:^[68]

• Pre-exposure prophylaxis
  • Meningococcal vaccination (a polysaccharide conjugate vaccine)
  • Hib vaccination
  • Droplet prophylaxis
  • See immunization schedule.
• Postexposure measures in bacterial meningitis
  • Postexposure vaccination: may be considered if the particular serogroup is known and available as a vaccine ^[72]
  • Postexposure chemoprophylaxis: For meningococcal infections, this should ideally be administered within 24 hours of the index patient's symptom onset.

For N. meningitidis, ceftriaxone is the chemoprophylaxis of choice during pregnancy.