Introduction
Background
Meningitis is an inflammation of the leptomeninges and underlying subarachnoid cerebrospinal fluid (CSF). It can be useful to divide symptom onset into acute, subacute, and chronic categories. Unlike subacute (1-7 d) or chronic (>7 d) meningitis, which have myriad infectious and noninfectious etiologies, acute meningitis (<1 d) is almost always a bacterial infection caused by one of several organisms. Depending on age and general condition, these gravely ill patients present acutely with signs and symptoms of meningeal inflammation and systemic infection of less than 24 hours' duration, and usually less than 12 hours duration. Patients with acute bacterial meningitis may decompensate very quickly and so they require emergency care, including antimicrobial therapy, ideally within 30 minutes of emergency department (ED) presentation.
Most bacterial meningitis is not acute. Approximately 75% of patients with bacterial meningitis present subacutely with symptoms beginning several days prior. These ill patients still require urgent ED diagnosis and care to prevent further decompensation.
The emergence of resistant strains has prompted changes in antibiotic protocols in some countries, including the US. Apart from dexamethasone, neuronal cell protectants still hold only future promise as adjunctive therapy.
The challenges for emergency physicians when treating meningitis are to (1) identify and treat patients with acute bacterial meningitis, (2) assess whether a treatable central nervous system (CNS) infection is present in those with suspected subacute or chronic meningitis, and (3) identify the causative organism. Bacterial meningitis must be excluded. Emergency physicians should be aware that future therapies will be based on improved understanding of the pathogenesis of acute bacterial meningitis and may include caspase inhibitors, antioxidants, poly (ADP-ribose) polymerase inhibitors, inhibitors of lipid peroxidation, and metalloproteinase inhibitors, in addition to antibiotics and steroids.
Pathophysiology
A number of factors influence the development of acute and subacute bacterial meningitis, including virulence of the strain, host defenses, and bacteria-host interactions.
Bacterial seeding usually occurs by hematogenous spread. In those without an identifiable source of infection, local tissue and bloodstream invasion by bacteria colonized in the nasopharynx may be a common source. Rarely, infected contiguous structures invade via septic thrombi or osteomyelitic erosion; meningeal seeding also may occur with a direct bacterial inoculate during trauma, neurosurgery, or instrumentation. Meningitis in the newborn is transmitted vertically from colonized pathogens in the maternal intestinal or genital tract or horizontally from nursery personnel or caregivers at home.
Once in the CSF, the paucity of antibodies, complement components, and white blood cells (WBCs) allows the bacterial infection to flourish. Bacterial cell wall components initiate a cascade of complement- and cytokine-mediated events that result in increased permeability of the blood-brain barrier, cerebral edema, and presence of toxic mediators in the CSF. Replicating bacteria, increasing numbers of inflammatory cells, cytokine-induced disruptions in membrane transport, and increased vascular and membrane permeability perpetuate the infectious process and account for the characteristic changes in CSF cell count, pH, lactate, protein, and glucose. Exudates extend throughout the CSF, particularly to the basal cisterns, damaging cranial nerves (eg, cranial nerve VIII, with resultant hearing loss), obliterating CSF pathways (causing obstructive hydrocephalus), and inducing vasculitis and thrombophlebitis (causing local brain ischemia).
As intracranial pressure (ICP) continues to rise and brain edema progresses, CNS autoregulatory processes begin to fail. This pivotal event may occur when the transient increase in cerebral blood flow (CBF) reverses and begins to decrease. CBF reduction correlates with the patient's decreasing alertness and changes in mental status.
Without medical intervention, the cycle of decreasing CBF, worsening cerebral edema, and increasing ICP proceeds unchecked. Ongoing endothelial injury may result in vasospasm and thrombosis, further compromising CBF, and may lead to stenosis of large and small vessels. Systemic hypotension (septic shock) also may impair CBF, and the patient soon dies from systemic complications or from diffuse CNS ischemic injury.
The pathophysiologies of nonbacterial pathogens are less well understood. Fungal meningitis is thought to unfold in a manner similar to but less acute than bacterial meningitis.
Frequency
United States
The incidence of bacterial meningitis declined from 1.9 to 1.5 cases per 100,000 from 1998 to 2003, in part, due to the introduction of the conjugate Haemophilus influenzae type b and pneumococcal conjugate vaccines. There continues to be an increased incidence of bacterial meningitis among persons aged 60 years and older, independent of other factors.1
International
Meningococcal meningitis is endemic in parts of Africa, India, and other developing nations. Periodic epidemics occur in the so-called sub-Saharan "meningitis belt" as well as among religious pilgrims traveling to Saudi Arabia for the Hajj. A significant increase in the incidence of penicillin-resistant S pneumoniae meningitis has occurred worldwide.
Mortality/Morbidity
Morbidity and mortality depend on pathogen, patient's age and condition, and severity of acute illness.2
- Among bacterial pathogens, pneumococcal meningitis causes the highest rates of mortality (21%) and morbidity (15%).
- Mortality rate is 50-90% and morbidity even higher if severe neurologic impairment is evident at the time of presentation (or with extremely rapid onset of illness), even with immediate medical treatment.
Race
Statistically, blacks are at greater risk than other races, although race may not be an independent risk factor.
Sex
In neonates, male-to-female ratio is 3:1. No sex preference exists among adults.
Age
According to the Centers for Disease Control and Prevention (CDC),3 the median age is 39 years. In 1986, it was 15 months.
- Excluding meningococcal meningitis, patients younger than 5 years and older than 60 years are at increased risk.
- Newborns are at highest risk for acute bacterial meningitis. After the first month of life, the peak incidence is in infants aged 3-8 months.
Clinical
History
Distinguishing acute, subacute, and chronic meningitis helps identify the pathogen. Approximately 25% of patients with bacterial meningitis present acutely, well within 24 hours of onset of symptoms. Other patients with subacute bacterial meningitis and most patients with viral meningitis present with neurologic symptoms developing over 1-7 days. Chronic symptoms lasting longer than 1 week suggest meningitis caused by some viruses as well as tuberculosis, syphilis, fungi (especially cryptococci), and carcinomatous meningitis.
- Classic symptoms (not evident in infants or seen often in the elderly) include the following:
- Headache
- Nuchal rigidity (generally not present in children <1 y or in patients with altered mental status)
- Fever and chills
- Photophobia
- Vomiting
- Prodromal upper respiratory infection (URI) symptoms (viral and bacterial)
- Seizures (30-40% in children, 20-30% in adults)
- Focal neurologic symptoms (including focal seizures)
- Altered sensorium (confusion may be sole presenting complaint, especially in elderly)
- Symptoms in infants
- Fever
- Lethargy and/or change in level of alertness
- Poor feeding and/or vomiting
- Respiratory distress, apnea, cyanosis
- Partially treated meningitis: As many as 40% of patients with acute or subacute bacterial meningitis were treated previously with oral antibiotics. Seizures may be the sole presenting symptom; fever and changes in level of alertness or mental status occur less commonly than in untreated meningitis.
- Low-grade ventriculitis associated with ventriculoperitoneal shunt: Patients may have a less dramatic presentation than those with acute bacterial meningitis, with headache, nausea, minimal fever, and malaise.
- Fungal meningitis: Headache, low-grade fever, and lethargy are the primary symptoms; the course may be mild with fluctuating symptoms, especially in immunocompromised patients.
- Tuberculous meningitis: Fever, weight loss, night sweats, and malaise, with or without headache and meningismus are common symptoms; this infection may follow a protracted course with vague, nonspecific presentation.
Physical
Otherwise healthy patients within age extremes present with clinically obvious acute bacterial meningitis. In contrast, most patients with subacute bacterial meningitis present a diagnostic challenge. Systemic examination occasionally reveals a pulmonary or otitis media co-infection.
- Signs of meningeal irritation
- Nuchal rigidity or discomfort on neck flexion
- Kernig sign: Passive knee extension in supine patient elicits neck pain and hamstring resistance.
- Brudzinski sign: Passive neck or single hip flexion is accompanied by involuntary flexion of both hips.
- Papilledema is present in only one third of meningitis patients with increased ICP; it takes at least several hours to develop.
- Focal neurologic signs
- Isolated cranial nerve abnormalities (principally III, IV, VI, VII) in 10-20% of patients
- Associated with a dramatic increase in complications from lumbar puncture (LP) and portends a worse outcome
- Systemic findings
- Extracranial infection (eg, sinusitis, otitis media, mastoiditis, pneumonia, urinary tract infection) may be noted.
- Arthritis is seen with N meningitidis, less commonly with other bacteria.
- Nonblanching petechiae and cutaneous hemorrhages are seen classically with N meningitidis; however, these also can occur with other bacterial and viral infections.
- Endotoxic shock with vascular collapse is characteristic of severe N meningitidis infection.
- Altered mental status, from irritability to somnolence, delirium, and coma
- Infants
- Bulging fontanelle (if euvolemic)
- Paradoxic irritability (ie, quiet when stationary, cries when held)
- High-pitched cry
- Hypotonia
- Examine skin over entire spine for dimples, sinuses, nevi, or tufts of hair, which may indicate a congenital anomaly communicating with the subarachnoid space.
Causes
Meningitis is caused by the following pathogens in each age group:
- Neonates - Group B or D streptococci, nongroup B streptococci, Escherichia coli, and L monocytogenes
- Infants and children -H influenzae (48%), S pneumoniae (13%), and N meningitidis
- Adults -S pneumoniae, (30-50%), H influenzae (1-3%), N meningitidis (10-35%), gram-negative bacilli (1-10%), staphylococci (5-15%), streptococci (5%), and Listeria species (5%)
- Risk factors
- Aged 60 years or older
- Aged 5 years or younger, especially children with diabetes mellitus, renal or adrenal insufficiency, hypoparathyroidism, or cystic fibrosis
- Immunosuppressed patients are at increased risk of opportunistic infections and acute bacterial meningitis. Immunosuppressed patients may not show dramatic signs of fever or meningeal inflammation.
- Crowding (eg, military recruits and college dorm residents) increases risk of outbreaks of meningococcal meningitis.
- Splenectomy and sickle cell disease increase the risk of meningitis secondary to encapsulated organisms.
- Alcoholism and cirrhosis: Multiple etiologies of fever and seizures in these patients make meningitis challenging to diagnose.
- Diabetes
- Recent exposure to others with meningitis, with or without prophylaxis
- Contiguous infection (eg, sinusitis)
- Dural defect (eg, traumatic, surgical, congenital)
- Thalassemia major
- Intravenous (IV) drug abuse
- Bacterial endocarditis
- Ventriculoperitoneal shunt
- Malignancy (increased risk of Listeria species infection)
- Some cranial congenital deformities
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Further Reading
Keywords
inflammation of the leptomeninges, inflammation of the underlying subarachnoid cerebrospinal fluid, bacterial meningitis, meningococcal meningitis, pneumococcal meningitis, Neisseria meningitidis, N meningitidis, Streptococcus pneumoniae, S pneumoniae, Listeria monocytogenes, L monocytogenes, group B streptococci, Haemophilus influenzae, H influenzae , Haemophilus influenzae type b, H influenzae type b, brain edema, nuchal rigidity, fungalmeningitis, tuberculous meningitis, Kernig sign, Brudzinski sign, papilledema, increased intracranial pressure, increased ICP
