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.

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 living conditions (e.g., college dormitories, military barracks, retirement homes (listeriosis), kindergartens)
• Close contact with an infected person

Common pathogens by patient group

Population	Pathogens
Newborns	Group B streptococcus (most common but incidence decreasing because of screening and prophylaxis during pregnancy) Escherichia coli Listeria monocytogenes Haemophilus influenzae Enterobacter cloacae
Infants	Streptococcus pneumoniae and Neisseria meningitidis (most common) Haemophilus influenzae Listeria monocytogenes Group B streptococcus
Children and teenagers	Neisseria meningitidis (most common) Streptococcus pneumoniae Listeria monocytogenes Haemophilus influenzae if not immunized Enteroviruses (especially coxsackievirus and echovirus) Herpes simplex virus (HSV-2) Mumps virus
Adults 20–60 years	Streptococcus pneumoniae (most common) Enteroviruses (especially coxsackievirus and echovirus) Herpes simplex virus (HSV-2)
Adults ≥ 60 years	Streptococcus pneumoniae (most common) Neisseria meningitidis Haemophilus influenzae if not immunized Group B streptococcus E. coli Listeria monocytogenes Enteroviruses (especially coxsackievirus and echovirus) Herpes simplex virus (HSV-2)
Immunocompromised individuals	Listeria monocytogenes Gram-negative bacilli Streptococcus pneumoniae Cryptococcus spp. (particularly in individuals with HIV) CMV, VZV, HSV, JC virus Mycobacterium tuberculosis (tuberculous meningitis) Toxoplasma gondii
Pregnant women	Listeria monocytogenes Streptococcus agalactiae
Hospitalized patients	Staphylococci (most frequently S. aureus) [1] Gram-negative bacteria (e.g., Pseudomonas aeruginosa)

Less common pathogens

• Bacterial meningitis
  • Borrelia spp. → Lyme meningitis
  • Treponema pallidum → syphilitic meningitis
• Viral meningitis: often associated with encephalitis (meningoencephalitis)
  • Herpesviruses: HSV1 (meningitis is more commonly caused by HSV2 than HSV1), CMV, EBV, VZV
  • Lymphocytic choriomeningitis virus (LCMV)
  • Mumps virus
  • Some arboviruses (e.g., West Nile virus, TBEV in Eurasia)
  • Influenza virus
  • HIV
• Fungal meningitis
  • Coccidioides
  • Candida spp.
  • Aspergillus spp.
• Parasitic meningitis: helminths such as Echinococcus spp.
• Noninfectious meningitis
  • Sarcoidosis
  • Tumor metastases (meningeal carcinomatosis and meningeal leukemia)
  • Medication (e.g., NSAIDs)

References:^{[2][3][4][5][6][7]}

Pathways of infection

• Most pathogens that cause meningitis colonize the nasopharynx or the upper airways before entering the CNS via:
  • Hematogenous dissemination . ^[8]
  • 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) ^[1]

Incubation periods

• Bacterial meningitis: usually 3–7 days ^[9]
• Viral meningitis: usually 2–14 day, depending on the type of virus

References:^[3][9][5]

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)

Often nonspecific 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) ^[10]
• Late symptoms
  • Fontanelle bulging
  • High-pitched crying
  • Seizures

Children and adults

• Classic triad of meningitis: fever, headache, and neck stiffness (this triad is often not present in neonates and infants)
• 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

Physical examination ^[3][11]

• 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) ^[12]
• Signs of underlying infections
  • Bulging and redness of tympanic membrane: acute otitis media
  • Skin manifestations ^[13]
    • Cutaneous petechiae in meningococcal meningitis: suggestive of meningococcemia
    • Maculopapular rash in some viral meningitis (e.g., West Nile virus, enterovirus)

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

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

References:^{[2][11][14][15]}

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 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). ^[16]

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 ^{[17][18][19][20][16]}

• Obtain samples immediately for blood cultures, routine laboratory tests, and screening for organ dysfunction.
• Confirm the diagnosis with LP and CSF analysis (if no 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 ^{[17][19][20][16]}

• 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 ^[17]
• 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 ^[17][18][1]

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 ^[17]
  • Identify abscesses or other localized lesions (e.g., in postsurgical patients in whom infection is suspected) ^[1]
  • Suspected healthcare-associated ventriculitis/meningitis ^[1]
  • Patients with devices (e.g., CSF shunts) ^[1]
• Recommended criteria for imaging prior to LP in suspected meningitis ^[17][18][21]
  • Focal neurological deficits
  • Altered mental status ^[18]
  • Immunocompromised status (e.g., HIV, post-transplant, taking immunosuppressants)
  • Papilledema
  • History of CNS disease (e.g., mass, stroke, abscess)
  • Seizures (new-onset) ^[17]
• Modalities
  • CT head (with or without IV contrast): before LP if increased ICP is suspected ^[22]
  • MRI brain with IV contrast and diffusion: especially useful in patients with devices or after surgery ^[1]
• 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, 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 ^[17][18][21]

Cerebrospinal fluid analysis in meningitis [17][21]
	Normal	Bacterial meningitis	Viral meningitis
Appearance	Clear fluid	Cloudy, purulent fluid	Clear fluid
Cell count and differential	Cell count < 5/mm3	Elevated cell count with significant pleocytosis (leukocyte count > 1000/mm3) ↑ Granulocytes (> 80%)	Variable cell count (leukocyte count 10–500/mm3) ↑ Lymphocytes
Opening pressure [23]	5–18 cm H2O	↑↑	Normal or ↑
Lactate [18]	1.2–2.1 mmol/L	↑↑	Variable
Protein	15–45 mg/dL	↑	Normal or ↑
Glucose	40–75 mg/dL	↓	Normal
Gram stain and culture [18][21]	No organisms present	Positive gram stain and culture [18][21] Meningococci: gram-negative diplococci Pneumococci: gram-positive diplococci Listeria: gram-positive rods [18][21] Haemophilus influenzae: gram-negative coccobacilli	No organisms present

Atypical pathogen testing

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

Cerebrospinal fluid analysis in meningitis due to atypical pathogens [21]
	Tuberculous meningitis [24]	Lyme meningitis [25]	Cryptococcal meningitis [26]
Appearance	Clear fluid with a spiderweb clot	Clear fluid	Cloudy fluid
Cell count and differential	Variable cell count (30–300/mm3) [24] Pleocytosis (predominantly lymphocytes but also granulocytes and mononuclear cells)	Variable cell count (10–1000/mm3) Pleocytosis (lymphocytes, mononuclear cells) [25]	Variable cell count (20–200/mm3) Pleocytosis (lymphocytes) [26]
Opening pressure	↑↑	↑↑	↑↑
Lactate [18]	↑	Variable	↑
Protein	↑	Normal or ↑ [25]	↑ [26]
Glucose	↓	Normal or ↓	↓ [26]

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 ^[21]
  • Viral culture
    • Not typically recommended
    • May confirm enterovirus, herpes simplex virus infection
  • M. tuberculosis cultures: Results can take up to 6 weeks. ^[21]
  • Fungal cultures: for the identification of Candida spp., Cryptococcus spp. ^[21]
  • For patients with CSF shunts or drains: Extend CSF cultures for at least 10 days.
• PCR for viral meningitis and specific bacterial subtypes ^[17][18]
  • 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 ^[17]
  • Bacterial antigen detection
    • Not routinely used because of variable accuracy ^[17]
    • 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.
• Hemodynamic support with fluids and/or vasopressors (see fluid resuscitation and sepsis).
• Identify and reverse any coagulopathy (see disseminated intravascular coagulation).
• Identify and treat elevated ICP.

Antimicrobial therapy

Empiric antibiotic therapy ^[17]

• 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

Empiric antibiotic therapy for bacterial meningitis [17]
Patient characteristics	Recommended regimen
Age < 1 month	Ampicillin [17] PLUS an aminoglycoside (e.g., gentamicin ) [17] AND/OR a third-generation cephalosporin Cefotaxime [17] If cefotaxime is unavailable: ceftazidime [17] Ceftriaxone is contraindicated in patients aged < 1 month because of a higher risk of biliary sludging and kernicterus. [27]
Age > 1 month to < 50 years	Vancomycin [17] PLUS one of the following third-generation cephalosporins: Cefotaxime [17] Ceftriaxone [17]
Age > 50 years	Vancomycin [17] PLUS ampicillin [17] PLUS one of the following third-generation cephalosporins: Cefotaxime [17] Ceftriaxone [17]
Immunocompromised (E.g., as a result of HIV, AIDS, use of immunosuppressants, or following transplantation) [28]	Vancomycin [17] PLUS ampicillin [17] PLUS one of the following: Cefepime [17] Meropenem [17]
Healthcare-associated infections [1]	Vancomycin [17] PLUS one of the following antipseudomonal β-lactams: Ceftazidime [17] Cefepime [17] Meropenem [1]
Suspected rickettsial (e.g., RMSF) or ehrlichial infection [29]	Add doxycycline to the empiric regimen.
Basilar skull fracture	Vancomycin [17] PLUS one of the following third-generation cephalosporins: Cefotaxime [17] Ceftriaxone [17]
Penetrating head trauma	Vancomycin [17] PLUS one of the following: Cefepime [17] Ceftazidime [17] Meropenem [17]

Ampicillin is added if patients are at risk of Listeria spp. infection (e.g., newborns, pregnant women, the elderly, 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. ^[27]

Empiric therapy for viral meningitis ^[29][2]

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.

Pathogen-specific therapy in meningitis [17]
Pathogen	Examples of antimicrobial agents
S. pneumoniae (penicillin-resistant strains)	Vancomycin [17]
MRSA
S. epidermidis
H. influenzae	Third-generation cephalosporin (e.g., cefotaxime [17] OR ceftriaxone [17])
N. meningitidis
L. monocytogenes	Ampicillin [17]
S. agalactiae
E. coli	Third-generation cephalosporin (e.g., cefotaxime [17]OR ceftriaxone [17])
Enterococcus spp.	Gentamicin [17][1] PLUS either ampicillin [17] OR vancomycin [17]
P. aeruginosa	Cefepime [17]
R. rickettsii	Doxycycline
Herpesviruses	Acyclovir
Less frequent pathogens, e.g., M. tuberculosis, C. neoformans, B. burgdorferi	See “Subtypes and variants”.

Corticosteroids ^[18][30]

• 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 ^[18][30]
  • Should be administered before or concomitant to antibiotics for optimal results ^[18]
  • Discontinue if a pathogen other than S. pneumoniae or H. influenzae is identified.
• Disadvantages: side effects, e.g., hyperglycemia, GI bleeding ^[30]

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. ^[17]
• Serial neuro examinations
• Consultations:
  • Infectious disease
  • Consider also ICU , neurology, neurosurgery as needed.

Tuberculous meningitis

• Pathogen: Mycobacterium tuberculosis
• Incubation period: approximately 2–8 weeks
• Clinical course
  • Subacute course over several weeks or months
  • Gradual manifestation with intermittent fever
• Clinical features
  • Focal neurological deficits (e.g., hemiparesis) due to hematogenous dissemination of cranial arteritis
  • Cranial nerve deficits
    • Most commonly seen in basal meningitis
    • Predominantly involves the facial nerve and oculomotor nerve
• Diagnostics
  • Presence of acid-fast bacilli on CSF gram stain ^[24][21]
  • CSF Culture is gold standard for diagnosis but may take weeks ^[21]
  • CT/MRI: possible hydrocephalus, basilar meningeal thickening, tuberculomas, edema, infarcts ^[24]
• Complications
  • Communicating (malabsorptive) hydrocephalus
  • Pituitary gland insufficiency
• Treatment: see “Treatment” in tuberculosis

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 ^[31]
  • Cryptococcal antigen testing of CSF and serum
    • Highly specific and sensitive ^[31]
    • 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
  • Intrathecal amphotericin B with or without flucytosine (induction therapy lasting 10–14 days)
  • Followed by fluconazole (consolidation therapy lasting 8–10 weeks and maintenance therapy lasting at least 12 months)
  • cART therapy should be delayed for at least 2 weeks after initiation of antifungal therapy.

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 → transmission 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 amoebic meningoencephalitis ^[32]

• Pathogen: Naegleria fowleri, an amoeba found in warm, still standing 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 (brain-eating amoeba)
• 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
• Prognosis: nearly always fatal

References:^{[3][33][34][35][36][37][38][39][40]}

Neurologic

• Most common: sensorineural hearing loss (transient or permanent)
• Focal neurological deficits ^[41]
• 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) ^[42]

References:^{[2][11][43][41][44][45][46][42]}

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