Razonable RR. Meningitis. Mayo Clinic College of Medicine.

Updated: Aug 26, 2009

available athttp://emedicine.medscape.com/article/232915

Meningitis is a clinical syndrome characterized by inflammation of the
meninges.
Signs and symptoms
The classic triad of bacterial meningitis consists of the following:
Fever
Headache
Neck stiffness
Other symptoms can include nausea, vomiting, photalgia (photophobia),
sleepiness, confusion, irritability, delirium, and coma. Patients with viral
meningitis may have a history of preceding systemic symptoms (eg, myalgias,
fatigue, or anorexia).
The history should also address the following:
Epidemiologic factors and predisposing risks
Exposure to a patients or animals with a similar illness
Previous medical treatment and existing conditions
Geographic location and travel history
Season and temperature
Acute bacterial meningitis in otherwise healthy patients who are not at the
extremes of age presents in a clinically obvious fashion; however, subacute
bacterial meningitis often poses a diagnostic challenge.
General physical findings in viral meningitis are common to all causative
agents. Enteroviral infection is suggested by the following:
Exanthemas
Symptoms of pericarditis, myocarditis, or conjunctivitis
Syndromes of pleurodynia, herpangina, and hand-foot-and-mouth disease
Infants may have the following:
Bulging fontanelle (if euvolemic)
Paradoxic irritability (ie, remaining quiet when stationary and crying when
held)
High-pitched cry
Hypotonia
The examination should evaluate the following:
Focal neurologic signs
Signs of meningeal irritation
Systemic and extracranial findings
Chronic meningitis
In chronic meningitis, it is essential to perform careful general, systemic, and
neurologic examinations, looking especially for the following:
Lymphadenopathy
Papilledema and tuberculomas during funduscopy
Meningismus
Cranial nerve palsies
Patients with aseptic meningitis syndrome usually appear clinically nontoxic,
with no vascular instability. They characteristically have an acute onset of
meningeal symptoms, fever, and CSF pleocytosis that is usually prominently
lymphocytic.
See Clinical Presentation for more detail.
Diagnosis
The diagnostic challenges in patients with clinical findings of meningitis are as
follows:
Early identification and treatment of patients with acute bacterial meningitis
Assessing whether a treatable CNS infection is present in those with
suspected subacute or chronic meningitis
Identifying the causative organism
Blood studies that may be useful include the following:
Complete blood count (CBC) with differential
Serum electrolytes
Serum glucose (which is compared with the CSF glucose)
Blood urea nitrogen (BUN) or creatinine and liver profile
In addition, the following tests may be ordered:
Blood, nasopharynx, respiratory secretion, urine or skin lesion cultures
Syphilis testing
Serum procalcitonin testing
Lumbar puncture and CSF analysis
Neuroimaging (CT of the head and MRI of the brain)
See Workup for more detail.
Management
Initial measures include the following:
Shock or hypotension Crystalloids
Altered mental status Seizure precautions and treatment (if necessary),
along with airway protection (if warranted)
Stable with normal vital signs Oxygen, IV access, and rapid transport to
the emergency department (ED)
Treatment of bacterial meningitis includes the following:
Prompt initiation of empiric antibacterial therapy as appropriate for patient
age and condition
After identification of the pathogen and determination of susceptibilities,
targeted antibiotic therapy as appropriate for patient age and condition
Steroid (typically, dexamethasone) therapy
In patients with nosocomial meningitis, intrathecal antibiotics
The following systemic complications of acute bacterial meningitis must be
treated:
Hypotension or shock
Hypoxemia
Hyponatremia
Cardiac arrhythmias and ischemia
Stroke
Exacerbation of chronic diseases
Most cases of viral meningitis are benign and self-limited, but in certain
instances, specific antiviral therapy may be indicated, if available.
Other types of meningitis are treated with specific therapy as appropriate for
the causative pathogen, as follows:
Fungal meningitis - Cryptococcal (amphotericin B, flucytosine, fluconazole,
itraconazole), Coccidioides immitis (fluconazole, intrathecal amphoytericin B,
itraconazole), Histoplasma capsulatum (liposomal amphotericin B,
itraconazole), or Candida (IM or aqueous penicillin G, probenecid)
Tuberculous meningitis (isoniazid, rifampin, pyrazinamide, ethambutol,
streptomycin)
Parasitic meningitis Amebic (amphotericin B, miconazole, rifampin) or
helminthic (largely supportive)
Lyme meningitis (ceftriaxone; alternatively, penicillin G, doxycycline,
chloramphenicol)
See Treatment and Medication for more detail.
Image library
Acute bacterial meningitis. This axial nonenhanced computed
tomography scan shows mild ventriculomegaly and sulcal effacement
Background
Infections of the central nervous system (CNS) can be divided into 2 broad
categories: those primarily involving the meninges (meningitis; see the image
below) and those primarily confined to the parenchyma (encephalitis).
Pneumococcal meningitis in a patient with alcoholism. Courtesy of the
CDC/Dr. Edwin P. Ewing, Jr.
Meningitis is a clinical syndrome characterized by inflammation of the
meninges, the 3 layers of membranes that enclose the brain and spinal cord.
These layers consist of the following:
Dura - A tough outer membrane
Arachnoid - A lacy, weblike middle membrane
Subarachnoid space - A delicate, fibrous inner layer that contains many of
the blood vessels that feed the brain and spinal cord
Risk factors for meningitis include the following:
Extremes of age (< 5 or >60 years)
Diabetes mellitus, renal or adrenal insufficiency, hypoparathyroidism, or
cystic fibrosis
Immunosuppression, which increases the risk of opportunistic infections and
acute bacterial meningitis
HIV infection, which predisposes to bacterial meningitis caused by
encapsulated organisms, primarily Streptococcus pneumoniae, and
opportunistic pathogens
Crowding (such as that experienced by military recruits and college dorm
residents), which increases the risk of outbreaks of meningococcal
meningitis
Splenectomy and sickle cell disease, which increase the risk of meningitis
secondary to encapsulated organisms
Alcoholism and cirrhosis
Recent exposure to others with meningitis, with or without prophylaxis
Contiguous infection (eg, sinusitis)
Dural defect (eg, traumatic, surgical, or congenital)
Thalassemia major
Intravenous (IV) drug abuse
Bacterial endocarditis
Ventriculoperitoneal shunt
Malignancy (increased risk of Listeria infection)
Some cranial congenital deformities
Clinically, meningitis manifests with meningeal symptoms (eg, headache,
nuchal rigidity, or photophobia), as well as pleocytosis (an increased number
of white blood cells [WBCs]) in the cerebrospinal fluid (CSF). Depending on
the duration of symptoms, meningitis may be classified as acute or chronic.
(See Etiology and Presentation.)
Anatomically, meningitis can be divided into inflammation of the dura
(sometimes referred to as pachymeningitis), which is less common, and
leptomeningitis, which is more common and is defined as inflammation of the
arachnoid tissue and subarachnoid space. (See Anatomy.)
Meningitis can also be divided into the following 3 general categories:
Bacterial (pyogenic)
Granulomatous
Aseptic
The most common cause of meningeal inflammation is irritation caused by
bacterial or viral infections. The organisms usually enter the meninges through
the bloodstream from other parts of the body. Most cases of bacterial
meningitis are localized over the dorsum of the brain; however, under certain
conditions, meningitis may be concentrated at the base of the brain, as with
fungal diseases and tuberculosis. (See Etiology.)
Bacterial meningitis consists of pyogenic inflammation of the meninges and
the underlying subarachnoid CSF. If not treated, it may lead to lifelong
disability or death.
[1, 2]
Before the antimicrobial era, bacterial meningitis was
uniformly fatal, but with the advent of antimicrobial therapy, the overall
mortality from this disease has decreased. Nonetheless, it remains alarmingly
high: approximately 25%. (See Epidemiology.)
The emergence of resistant bacterial strains has prompted changes in
antibiotic protocols in some countries, including the United States. Apart from
dexamethasone, neuronal cell protectants still hold only future promise as
adjunctive therapy. (See Treatment and Medication.)
The specific infectious agents that are involved in bacterial meningitis vary
among different patient age groups, and the inflammation may evolve into the
following conditions:
Ventriculitis
Empyema
Cerebritis
Abscess formation
Meningitis can also be also classified more specifically according to its
etiology. Numerous infectious and noninfectious causes of meningitis have
been identified. Examples of common noninfectious causes include
medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs] and
antibiotics) and carcinomatosis. (See Etiology.)
Bacterial meningitis
Acute bacterial meningitis denotes a bacterial cause of this syndrome. This is
usually characterized by an acute onset of meningeal symptoms and
neutrophilic pleocytosis. Depending on the specific bacterial cause, the
syndrome may be called, for example, any of the following:
Pneumococcal meningitis
Haemophilus influenzae meningitis
Staphylococcal meningitis
Meningococcal meningitis
Tuberculous meningitis
Pediatric bacterial meningitis
Chronic meningitis is a constellation of signs and symptoms of meningeal
irritation associated with CSF pleocytosis that persists for longer than 4
weeks.
Unlike subacute (developing over 1-7 days) or chronic (>7 days) meningitis,
which have myriad infectious and noninfectious etiologies, acute meningitis (<
1 day) is almost always a bacterial infection caused by 1 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 (and usually >12 hours) duration.
Patients with acute bacterial meningitis may decompensate very quickly.
Consequently, they require emergency care, including the administration of
appropriate antimicrobial therapy as soon as possible once bacterial
meningitis is suspected or proven.
Nonbacterial meningitis
Fungal and parasitic forms of meningitis are also named according to their
specific etiologic agent (eg, cryptococcal meningitis, Histoplasma meningitis,
and amebic meningoencephalitis).
In many cases, a cause of meningitis is not apparent after initial evaluation,
and the disease is therefore classified as aseptic meningitis. These patients
characteristically have an acute onset of meningeal symptoms, fever, and
CSF pleocytosis that is usually prominently lymphocytic.
When the cause of aseptic meningitis is discovered, the disease can be
reclassified according to its etiology. If appropriate diagnostic methods are
performed, a specific viral etiology is identified in 55-70% of cases of aseptic
meningitis. However, the condition can also be caused by bacterial, fungal,
mycobacterial, and parasitic agents.
If, after an extensive workup, aseptic meningitis is found to have a viral
etiology, it can be reclassified as a form of acute viral meningitis (eg,
enteroviral meningitis or herpes simplex virus [HSV] meningitis).
Pathophysiology
Most cases of meningitis are caused by an infectious agent that has colonized
or established a localized infection elsewhere in the host. Potential sites of
colonization or infection include the skin, the nasopharynx, the respiratory
tract, the gastrointestinal (GI) tract, and the genitourinary tract. The organism
invades the submucosa at these sites by circumventing host defenses (eg,
physical barriers, local immunity, and phagocytes or macrophages).
An infectious agent (ie, a bacterium, virus, fungus, or parasite) can gain
access to the CNS and cause meningeal disease via any of the 3 following
major pathways:
Invasion of the bloodstream (ie, bacteremia, viremia, fungemia, or
parasitemia) and subsequent hematogenous seeding of the CNS
A retrograde neuronal (eg, olfactory and peripheral nerves) pathway
(eg,Naegleria fowleri or Gnathostoma spinigerum)
Direct contiguous spread (eg, sinusitis, otitis media, congenital
malformations, trauma, or direct inoculation during intracranial manipulation)
Invasion of the bloodstream and subsequent seeding is the most common
mode of spread for most agents. This pathway is characteristic of
meningococcal, cryptococcal, syphilitic, and pneumococcal meningitis.
Rarely, meningitis arises from invasion via septic thrombi or osteomyelitic
erosion from infected contiguous structures. Meningeal seeding may also
occur with a direct bacterial inoculate during trauma, neurosurgery, or
instrumentation. Meningitis in the newborn may be transmitted vertically,
involving pathogens that have colonized the maternal intestinal or genital tract,
or horizontally, from nursery personnel or caregivers at home.
Local extension from contiguous extracerebral infection (eg, otitis media,
mastoiditis, or sinusitis) is a common cause. Possible pathways for the
migration of pathogens from the middle ear to the meninges include the
following:
The bloodstream
Preformed tissue planes (eg, posterior fossa)
Temporal bone fractures
The oval or round window membranes of the labyrinths
The brain is naturally protected from the bodys immune system by the barrier
that the meninges create between the bloodstream and the brain. Normally,
this protection is an advantage because the barrier prevents the immune
system from attacking the brain. However, in meningitis, the blood-brain
barrier can become disrupted; once bacteria or other organisms have found
their way to the brain, they are somewhat isolated from the immune system
and can spread.
When the body tries to fight the infection, the problem can worsen; blood
vessels become leaky and allow fluid, WBCs, and other infection-fighting
particles to enter the meninges and brain. This process, in turn, causes brain
swelling and can eventually result in decreasing blood flow to parts of the
brain, worsening the symptoms of infection.
[3]

Depending on the severity of bacterial meningitis, the inflammatory process
may remain confined to the subarachnoid space. In less severe forms, the pial
barrier is not penetrated, and the underlying parenchyma remains intact.
However, in more severe forms of bacterial meningitis, the pial barrier is
breached, and the underlying parenchyma is invaded by the inflammatory
process. Thus, bacterial meningitis may lead to widespread cortical
destruction, particularly when left untreated.
Replicating bacteria, increasing numbers of inflammatory cells, cytokine-
induced disruptions in membrane transport, and increased vascular and
membrane permeability perpetuate the infectious process in bacterial
meningitis. These processes account for the characteristic changes in CSF
cell count, pH, lactate, protein, and glucose in patients with this disease.
Exudates extend throughout the CSF, particularly to the basal cisterns,
resulting in the following:
Damage to cranial nerves (eg, cranial nerve VIII, with resultant hearing loss)
Obliteration of CSF pathways (causing obstructive hydrocephalus)
Induction of vasculitis and thrombophlebitis (causing local brain ischemia)
Intracranial pressure and cerebral fluid
One complication of meningitis is the development of increased intracranial
pressure (ICP). The pathophysiology of this complication is complex and may
involve many proinflammatory molecules as well as mechanical elements.
Interstitial edema (secondary to obstruction of CSF flow, as in hydrocephalus),
cytotoxic edema (swelling of cellular elements of the brain through the release
of toxic factors from the bacteria and neutrophils), and vasogenic edema
(increased blood brain barrier permeability) are all thought to play a role.
Without medical intervention, the cycle of decreasing CSF, worsening cerebral
edema, and increasing ICP proceeds unchecked. Ongoing endothelial injury
may result in vasospasm and thrombosis, further compromising CSF, and
may lead to stenosis of large and small vessels. Systemic hypotension (septic
shock) also may impair CSF, and the patient soon dies as a consequence of
systemic complications or diffuse CNS ischemic injury.
Cerebral edema
The increased CSF viscosity resulting from the influx of plasma components
into the subarachnoid space and diminished venous outflow lead to interstitial
edema. The accumulation of the products of bacterial degradation,
neutrophils, and other cellular activation leads to cytotoxic edema.
The ensuing cerebral edema (ie, vasogenic, cytotoxic, and interstitial)
significantly contributes to intracranial hypertension and a consequent
decrease in cerebral blood flow. Anaerobic metabolism ensues, which
contributes to increased lactate concentration and hypoglycorrhachia. In
addition, hypoglycorrhachia results from decreased glucose transport into the
spinal fluid compartment. Eventually, if this uncontrolled process is not
modulated by effective treatment, transient neuronal dysfunction or permanent
neuronal injury results.
Cytokines and secondary mediators in bacterial meningitis
Key advances in understanding the pathophysiology of meningitis include
insight into the pivotal roles of cytokines (eg, tumor necrosis factor alpha
[TNF-] and interleukin [IL]-1), chemokines (IL-8), and other proinflammatory
molecules in the pathogenesis of pleocytosis and neuronal damage during
occurrences of bacterial meningitis.
Increased CSF concentrations of TNF-, IL-1, IL-6, and IL-8 are characteristic
findings in patients with bacterial meningitis. Cytokine levels, including those
of IL-6, TNF-, and interferon gamma, have been found to be elevated in
patients with aseptic meningitis.
The proposed events involving these inflammation mediators in bacterial
meningitis begin with the exposure of cells (eg, endothelial cells, leukocytes,
microglia, astrocytes, and meningeal macrophages) to bacterial products
released during replication and death; this exposure incites the synthesis of
cytokines and proinflammatory mediators. This process is likely initiated by the
ligation of the bacterial components (eg, peptidoglycan and
lipopolysaccharide) to pattern-recognition receptors, such as the Toll-like
receptors (TLRs).
TNF- and IL-1 are most prominent among the cytokines that mediate this
inflammatory cascade. TNF- is a glycoprotein derived from activated
monocyte-macrophages, lymphocytes, astrocytes, and microglial cells.
IL-1, previously known as endogenous pyrogen, is also produced primarily by
activated mononuclear phagocytes and is responsible for the induction of
fever during bacterial infections. Both IL-1 and TNF- have been detected in
the CSF of individuals with bacterial meningitis. In experimental models of
meningitis, they appear early during the course of disease and have been
detected within 30-45 minutes of intracisternal endotoxin inoculation.
Many secondary mediators, such as IL-6, IL-8, nitric oxide, prostaglandins (eg,
prostaglandin E2 [PGE2]), and platelet activation factor (PAF), are presumed
to amplify this inflammatory event, either synergistically or independently. IL-6
induces acute-phase reactants in response to bacterial infection. The
chemokine IL-8 mediates neutrophil chemoattractant responses induced by
TNF- and IL-1.
Nitric oxide is a free radical molecule that can induce cytotoxicity when
produced in high amounts. PGE2, a product of cyclooxygenase (COX),
appears to participate in the induction of increased blood-brain barrier
permeability. PAF, with its myriad biologic activities, is believed to mediate the
formation of thrombi and the activation of clotting factors within the
vasculature. However, the precise roles of all these secondary mediators in
meningeal inflammation remain unclear.
The net result of the above processes is vascular endothelial injury and
increased blood-brain barrier permeability, leading to the entry of many blood
components into the subarachnoid space. In many cases, this contributes to
vasogenic edema and elevated CSF protein levels. In response to the
cytokines and chemotactic molecules, neutrophils migrate from the
bloodstream and penetrate the damaged blood-brain barrier, producing the
profound neutrophilic pleocytosis characteristic of bacterial meningitis.
Genetic predisposition to inflammatory response
The inflammatory response and the release of proinflammatory mediators are
critical to the recruitment of excess neutrophils to the subarachnoid space.
These activated neutrophils release cytotoxic agents, including oxidants and
metalloproteins that cause collateral damage to brain tissue.
Pattern recognition receptors, of which TLR A4 (TLRA4) is the best studied,
lead to increase in the myeloid differentiation 88 (MyD88)-dependent pathway
and excess production of proinflammatory mediators. At present,
dexamethasone is used to decrease the effects of cellular toxicity by
neutrophils after they are present. Researchers are actively seeking ways of
inhibiting TLRA4 and other proinflammatory recognition receptors through
genetically engineered suppressors.
[4]

Bacterial seeding
Bacterial seeding of the meninges usually occurs through hematogenous
spread. In patients without an identifiable source of infection, local tissue and
bloodstream invasion by bacteria that have colonized the nasopharynx may
be a common source. Many meningitis-causing bacteria are carried in the
nose and throat, often asymptomatically. Most meningeal pathogens are
transmitted through the respiratory route, including Neisseria
meningitidis (meningococcus) and S pneumoniae (pneumococcus).
Certain respiratory viruses are thought to enhance the entry of bacterial
agents into the intravascular compartment, presumably by damaging mucosal
defenses. Once in the bloodstream, the infectious agent must escape immune
surveillance (eg, antibodies, complement-mediated bacterial killing, and
neutrophil phagocytosis).
Subsequently, hematogenous seeding into distant sites, including the CNS,
occurs. The specific pathophysiologic mechanisms by which the infectious
agents gain access to the subarachnoid space remain unclear. Once inside
the CNS, the infectious agents likely survive because host defenses (eg,
immunoglobulins, neutrophils, and complement components) appear to be
limited in this body compartment. The presence and replication of infectious
agents remain uncontrolled and incite the cascade of meningeal inflammation
described above.
Etiology
Causes of meningitis include bacteria, viruses, fungi, parasites, and drugs (eg,
NSAIDs, metronidazole, and IV immunoglobulin [IVIg]). Certain risk factors are
associated with particular pathogens.
HIV infection increases susceptibility to meningitis from a variety of
pathogens, including cryptococci, Mycobacterium tuberculosis, syphilis,
and Listeria species. In addition, HIV itself may cause aseptic meningitis
(see Meningitis in HIV).
Other viral causes of meningitis include the following:
Enteroviruses
West Nile virus
Human herpesvirus (HHV)-2
Lymphocytic choriomeningitis virus (LCM)
In patients who have had trauma or neurosurgery, the most common
microorganisms are S pneumoniae (if CSF leak is present), Staphylococcus
aureus, enterobacteria, and Pseudomonas aeruginosa. In patients with an
infected ventriculoperitoneal (atrial) shunt, the most common microorganisms
areStaphylococcus epidermidis, S aureus, enterobacteria, Propionibacterium
acnes,and diphtheroids (rare). Consultation with a neurosurgeon is indicated;
early shunt removal is usually necessary for cure.
Pachymeningitis
As indicated by the presence of abundant pus, pachymeningitis most often
results from a bacterial infection (usually staphylococcal or streptococcal) that
is localized to the dura. The organisms most often gain access to the
meninges via a skull defect (eg, a skull fracture) or spread from an infection of
the paranasal sinuses or cranial osteomyelitis.
Haemophilus influenzae meningitis
H influenzae is a small, pleomorphic, gram-negative coccobacillus that is
frequently found as part of the normal flora in the upper respiratory tract. The
organism can spread from one individual to another in airborne droplets or by
direct contact with secretions. Meningitis is the most serious acute
manifestation of systemic infection with H influenzae. (See Haemophilus
Meningitis.)
In the past, H influenzae was a major cause of meningitis, and the
encapsulated type b strain of the organism (Hib) accounted for the majority of
cases. Since the introduction of Hib vaccine in the United States in 1990, the
overall incidence of H influenzae meningitis has decreased by 35%, with Hib
accounting for fewer than 9.4% of H influenzae cases.
[5]

The isolation of H influenzae in adults suggests the presence of an underlying
medical disorder, such as the following:
Paranasal sinusitis
Otitis media
Alcoholism
CSF leak after head trauma
Functional or anatomic asplenia
Hypogammaglobulinemia
Pneumococcal meningitis
S pneumoniae, a gram-positive coccus, is the most common bacterial cause
of meningitis. In addition, it is the most common bacterial agent in meningitis
associated with basilar skull fracture and CSF leak. It may be associated with
other focal infections, such as pneumonia, sinusitis, or endocarditis (as, for
example, in Austrian syndrome, which is the triad of pneumococcal meningitis,
endocarditis, and pneumonia).
S pneumoniae is a common colonizer of the human nasopharynx; it is present
in 5-10% of healthy adults and 20-40% of healthy children. It causes
meningitis by escaping local host defenses and phagocytic mechanisms,
either through choroid plexus seeding from bacteremia or through direct
extension from sinusitis or otitis media.
Patients with the following conditions are at increased risk for S
pneumoniaemeningitis:
Hyposplenism
Hypogammaglobulinemia
Multiple myeloma
Glucocorticoid treatment
Defective complement (C1-C4)
Diabetes mellitus
Renal insufficiency
Alcoholism
Malnutrition
Chronic liver disease
Streptococcus agalactiae meningitis
Streptococcus agalactiae (group B streptococcus [GBS]) is a gram-positive
coccus that inhabits the lower GI tract. It also colonizes the female genital
tract at a rate of 5-40%, which explains why it is the most common agent of
neonatal meningitis (associated with 70% of cases).
Predisposing risks in adults include the following:
Diabetes mellitus
Pregnancy
Alcoholism
Hepatic failure
Renal failure
Corticosteroid treatment
In 43% of adult cases, however, no underlying disease is present.
Meningococcal meningitis
N meningitidis is a gram-negative diplococcus that is carried in the
nasopharynx of otherwise healthy individuals. It initiates invasion by
penetrating the airway epithelial surface. The precise mechanism by which
this occurs is unclear, but recent viral or mycoplasmal infection has been
reported to disrupt the epithelial surface and facilitate invasion by
meningococcus.
Most sporadic cases of meningococcal meningitis (95-97%) are caused by
serogroups B, C, and Y, whereas the A and C strains are observed in
epidemics (< 3% of cases). Currently, N meningitidis is the leading cause of
bacterial meningitis in children and young adults, accounting for 59% of cases.
Risk factors for meningococcal meningitis include the following:
Deficiencies in terminal complement components (eg, membrane attack
complex, C5-C9), which increases attack rates but is associated with
surprisingly lower mortality rates
Properdin defects that increase the risk of invasive disease
Antecedent viral infection, chronic medical illness, corticosteroid use, and
active or passive smoking
Crowded living conditions, as is observed in college dormitories (college
freshmen living in dormitories are at highest risk) and military facilities, which
has been reported in clustering of cases
Listeria monocytogenes meningitis
Listeria monocytogenes is a small gram-positive bacillus that causes 3% of
bacterial meningitis cases and is associated with one of the highest mortalities
(20%).
[5]
The organism is widespread in nature and has been isolated in the
stool of 5% of healthy adults. Most human cases appear to be food-borne.
L monocytogenes is a common food contaminant, with a recovery rate of up to
70% from raw meat, vegetables, and meats. Outbreaks have been associated
with consumption of contaminated coleslaw, milk, cheese, and alfalfa tablets.
Groups at risk include the following:
Pregnant women
Infants and children
Elderly individuals (>60 years)
Patients with alcoholism
Adults who are immunosuppressed (eg, steroid users, transplant recipients,
or persons with AIDS)
Individuals with chronic liver and renal disease
Individuals with diabetes
Persons with iron-overload conditions (eg, hemochromatosis or transfusion-
induced iron overload)
Meningitis caused by gram-negative bacilli
Aerobic gram-negative bacilli include the following:
Escherichia coli
Klebsiella pneumoniae
Serratia marcescens
P aeruginosa
Salmonella species
Gram-negative bacilli can cause meningitis in certain groups of patients. E
coli is a common agent of meningitis among neonates. Other predisposing risk
factors for meningitis associated with gram-negative bacilli include the
following:
Neurosurgical procedures or intracranial manipulation
Old age
Immunosuppression
High-grade gram-negative bacillary bacteremia
Disseminated strongyloidiasis
Disseminated strongyloidiasis has been reported as a classic cause of gram-
negative bacillary bacteremia, as a result of the translocation of gut microflora
with the Strongyloides stercoralis larvae during hyperinfection syndrome.
Staphylococcal meningitis
Staphylococci are gram-positive cocci that are part of the normal skin flora.
Meningitis caused by staphylococci is associated with the following risk
factors:
Neurosurgery
Head trauma
Presence of CSF shunts
Infective endocarditis and paraspinal infection
S epidermidis is the most common cause of meningitis in patients with CNS
(ie, ventriculoperitoneal) shunts. (See Staphylococcal Meningitis.)
Aseptic meningitis
Aseptic meningitis is one of the most common infections of the meninges. If
appropriate diagnostic methods are employed, a specific viral etiology is
identified in 50-60% of cases of aseptic meningitis. However, aseptic
meningitis can also be caused by bacteria, fungi, and parasites (see Table 1
below). It is noteworthy that partially treated bacterial meningitis accounts for a
large number of meningitis cases with a negative microbiologic workup.
Table 1. Infectious Agents Causing Aseptic Meningitis (Open Table in a new
window)
Category Agent
Bacteria Partially treated bacterial meningitis



Listeria monocytogenes



Brucella spp



Rickettsia rickettsii



Ehrlichia spp



Mycoplasma pneumoniae



Borrelia burgdorferi



Treponema pallidum



Leptospira spp



Mycobacterium tuberculosis



Nocardia spp


Parasites Naegleria fowleri



Acanthamoeba spp



Balamuthia spp



Angiostrongylus cantonensis



Gnathostoma spinigerum



Baylisascaris procyonis



Strongyloides stercoralis



Taenia solium (cysticercosis)


Fungi Cryptococcus neoformans



Coccidioides immitis



Blastomyces dermatitidis



Histoplasma capsulatum



Candida spp



Aspergillus spp


Viruses Enterovirus Poliovirus



Echovirus



Coxsackievirus A



Coxsackievirus B



Enterovirus 68-71


Herpesvirus (HSV) HSV-1 and HSV-2



Varicella-zoster virus



Epstein-Barr virus



Cytomegalovirus



HHV-6 and HHV-7


Paramyxovirus Mumps virus



Measles virus


Togavirus Rubella virus
Flavivirus West Nile virus



Japanese encephalitis virus



St Louis encephalitis virus


Bunyavirus California encephalitis virus



La Crosse encephalitis virus


Alphavirus Eastern equine encephalitis virus



Western equine encephalitis virus



Venezuelan encephalitis virus


Reovirus Colorado tick fever virus
Arenavirus LCM virus
Rhabdovirus Rabies virus
Retrovirus HIV
HHV = human herpesvirus; HSV = herpes simplex virus; LCM = lymphocytic choriomeningitis.
Enteroviruses account for of the majority of cases of aseptic meningitis in
children, but West Nile virus and HSV-2 account for a substantial proportion of
cases in adults. The enteroviruses belong to the family Picornaviridae and are
further classified as follows:
Poliovirus (3 serotypes)
Coxsackievirus A (23 serotypes)
Coxsackievirus B (6 serotypes)
Echovirus (31 serotypes)
Newly recognized enterovirus serotypes 68-71
Enteroviruses are usually spread by fecal-oral or respiratory routes. Infection
occurs during summer and fall in temperate climates and year-round in
tropical regions.
The nonpolio enteroviruses (NPEVs) account for approximately 90% of cases
of viral meningitis in which a specific pathogen can be identified.
Echovirus 30 was reported as the cause of an epidemic in Japan in 1991. It
was also reported as the cause of 20% of cases of aseptic meningitis reported
to the Centers for Disease Control and Prevention (CDC) in 1991.
The Herpesviridae family consists of large, DNA-containing enveloped
viruses. Eight members are known to cause human infections, and all have
been implicated in meningitis syndromes, with the exception of HHV-8 or
Kaposi sarcomaassociated virus.
HSV accounts for 0.5-3% of cases of aseptic meningitis; it is most commonly
associated with primary genital infection and is less likely during recurrences.
HSV-1 is a cause of encephalitis, while HSV-2 more commonly causes
meningitis. Although Mollaret syndrome (a recurrent, but benign, aseptic
meningitis syndrome) is more frequently associated with HSV-2, HSV-1 has
also been implicated as a cause.
Epstein-Barr virus (EBV, or HHV-4) and cytomegalovirus (CMV, or HHV-5)
infection may manifest as meningitis in patients with the mononucleosis
syndrome. Varicella-zoster virus (VZV, or HHV-3) and CMV cause meningitis
in immunocompromised hosts, especially patients with AIDS and transplant
recipients. HHV-6 and HHV-7 have been reported to cause meningitis in
transplant recipients.
The most common arthropod-borne viruses are West Nile virus, St Louis
encephalitis virus (a flavivirus), Colorado tick fever virus, and California
encephalitis virus (bunyavirus group, including La Crosse encephalitis virus).
St Louis encephalitis virus is a mosquito-borne flavivirus that may cause a
febrile syndrome, aseptic meningitis syndrome, and encephalitis. Other
members of the flavivirus group that may cause aseptic meningitis include
tick-borne encephalitis virus and Japanese encephalitis virus.
California encephalitis is a common childhood disease of the CNS that is
caused by a virus in the genus Bunyavirus. Most of the cases of California
encephalitis are probably caused by mosquito-borne La Crosse encephalitis
virus.
LCM virus is a member of the arenaviruses, a family of single-stranded, RNA-
containing viruses in which rodents are the animal reservoir. The modes of
transmission include aerosols and direct contact with rodents. Outbreaks have
also been traced to infected laboratory mice and hamsters.
The mumps virus is the most common cause of aseptic meningitis in
unimmunized populations, occurring in 30% of all patients with mumps. Upon
exposure, an incubation period of approximately 5-10 days ensues, followed
by a nonspecific febrile illness and an acute onset of aseptic meningitis. This
may be associated with orchitis, arthritis, myocarditis, and alopecia.
Patients with acute HIV infection may present with aseptic meningitis
syndrome, usually as part of the mononucleosislike acute seroconversion
phenomenon. HIV should always be suspected as a cause of aseptic
meningitis in a patient with risk factors such as IV drug use or high-risk sexual
behaviors. These patients will have negative results on HIV serologic tests
(eg, enzyme-linked immunosorbent assay [ELISA] and Western blot); the
diagnosis is made by the detection of serum HIV RNA on polymerase chain
reaction (PCR) testing or of HIV p24 antigen.
Adenovirus (serotypes 1, 6, 7, and 12) has been associated with cases of
meningoencephalitis. Chronic meningoencephalitis has been reported with
serotypes 7, 12, and 32. The infection is usually acquired through a
respiratory route.
Toscana virus meningitis or encephalitis should be considered in travelers
returning from the a Mediterranean country (eg, Italy, Spain, or Greece) during
the summer. Toscana viruses are transmitted by the bite of a sandfly.
Toscana virus infection can be diagnosed by performing paired serologies and
CSF PCR, which in the United States is available only through the CDC.
[6]

Chronic meningitis
Chronic meningitis can be caused by a wide range of infectious and
noninfectious etiologies (see Table 2 below).
Table 2. Causes of Chronic Meningitis (Open Table in a new window)
Category Agent
Bacteria Mycobacterium tuberculosis



Borrelia burgdorferi



Treponema pallidum



Brucella spp



Francisella tularensis



Nocardia spp



Actinomyces spp


Fungi Cryptococcus neoformans



Coccidioides immitis



Blastomyces dermatitidis



Histoplasma capsulatum



Candida albicans



Aspergillus spp



Sporothrix schenckii


Parasites Acanthamoeba spp



Naegleria fowleri



Angiostrongylus cantonensis



Gnathostoma spinigerum



Baylisascarisprocyonis



Schistosoma spp



Strongyloides stercoralis



Echinococcus granulosus


Brucellae are small gram-negative coccobacilli that cause zoonoses as a
result of infection with Brucella abortus, Brucella melitensis, Brucella
suis, or Brucella canis. Transmission to humans occurs after direct or indirect
exposure to infected animals (eg, sheep, goats, or cattle). Direct infection of
the CNS occurs in fewer than 5% of cases, with most patients presenting with
acute or chronic meningitis.
Persons at risk for brucellosis include individuals who had contact with
infected animals or their products (eg, through intake of unpasteurized milk
products). Veterinarians, abattoir workers, and laboratory workers dealing with
these animals are also at risk.
M tuberculosis is an acid-fast bacillus that causes a broad range of clinical
illnesses that can affect virtually any organ of the body. It is spread through
airborne droplet nuclei, and it infects one third of the worlds population.
Involvement of the CNS with tuberculous meningitis is usually caused by
rupture of a tubercle into the subarachnoid space.
Tuberculous meningitis should always be considered in the differential
diagnosis of patients with aseptic meningitis or chronic meningitis syndromes,
especially those with basilar meningitis, symptoms of more than 5 days
duration, or cranial nerve palsies. If tuberculous meningitis is suspected,
antituberculosis therapy, with or without steroids, should be empirically
started.
Treponema pallidum is a slender, tightly coiled spirochete that is usually
acquired by sexual contact. Other modes of transmission include direct
contact with an active lesion, passage through the placenta, and blood
transfusion (rare).
Borrelia burgdorferi, a tick-borne spirochete, is the agent of Lyme disease, the
most common vector-borne disease in the United States. Meningitis may be
part of a triad of neurologic manifestations of Lyme disease that also includes
cranial neuritis and radiculoneuritis. Lyme disease meningitis is typically
associated with a facial palsy that can sometimes be bilateral.
Cryptococcus neoformans is an encapsulated, yeastlike fungus that is
ubiquitous. It has been found in high concentrations in aged pigeon droppings
and pigeon nesting places. The 4 serotypes are designated A through D, with
the A serotype causing most human infections. Onset of cryptococcal
meningitis may be acute, especially among patients with AIDS.
Numerous cases occur in healthy hosts (eg, persons with no known T-cell
defect); however, approximately 50-80% of cases occur in
immunocompromised hosts. At particular risk are individuals with defects of T-
cellmediated immunity, such as persons with AIDS, organ transplant
recipients, and other patients who use steroids, cyclosporine, and other
immunosuppressants. Cryptococcal meningitis has also been reported in
patients with idiopathic CD-4 lymphopenia, Hodgkin disease, sarcoidosis, and
cirrhosis.
Coccidioides immitis is a soil-based, dimorphic fungus that exists in mycelial
and yeast (spherule) forms. Persons at risk for coccidioidal meningitis include
individuals exposed to the endemic regions (eg, tourists and local populations)
and those with immune deficiency (eg, persons with AIDS and organ
transplant recipients).
Blastomyces dermatitidis is a dimorphic fungus that has been reported to be
endemic in North America (eg, in the Mississippi and Ohio River basins). It
has also been isolated from parts of Central America, South America, the
Middle East, and India. Its natural habitat is not well defined. Soil that is rich in
decaying matter and environments around riverbanks and waterways have
been demonstrated to harbor B dermatitidis during outbreaks and are thought
to be risk factors for acquiring the infection.
Inhalation of the conidia establishes a pulmonary infection. Dissemination may
occur in certain individuals, including those with underlying immune deficiency
(eg, from HIV or pharmaceutical agents) and extremes of age, and may
involve the skin, bones and joints, genitourinary tract, and CNS. Involvement
of the CNS occurs in fewer than 5% of cases.
Histoplasma capsulatum is one of the dimorphic fungi that exist in mycelial
and yeast forms. It is usually found in soil and can occasionally cause a
chronic meningitis. The preferred means of making the diagnosis is CSF
histoplasma antigen detection.
Candida species are ubiquitous in nature. They are normal commensals in
humans and are found in the skin, the GI tract, and the female genital tract.
The most common species is Candida albicans, but the incidence of non-
albicanscandidal infections (eg, Candida tropicalis) is increasing, including
species with antifungal resistance (eg, Candida krusei and Candida glabrata).
Involvement of the CNS usually follows hematogenous dissemination. The
most important predisposing risks for acquiring disseminated candidal
infection appear to be iatrogenic (eg, the administration of broad-spectrum
antibiotics and the use of indwelling devices such as urinary and vascular
catheters). Prematurity in neonates is considered a predisposing risk factor as
well. Infection may also follow neurosurgical procedures, such as placement
of ventricular shunts.
Sporothrix schenckii is an endemic dimorphic fungus that is often isolated
from soil, plants, and plant products. Human infections are characteristically
lymphocutaneous. Extracutaneous manifestations of sporotrichosis may
occur, though meningeal sporotrichosis, which is the most severe form, is a
rare complication. AIDS is a reported underlying risk factor in many described
cases and is associated with a poor outcome.
Infection with free-living amebas is an infrequent but often life-threatening
human illness, even in immunocompetent individuals. N fowleri is the only
species ofNaegleria recognized to be pathogenic in humans, and it is the
agent of primary amebic meningoencephalitis (PAM). The parasite has been
isolated in lakes, pools, ponds, rivers, tap water, and soil.
Infection occurs when a person is swimming or playing in contaminated water
sources (eg, inadequately chlorinated water and sources associated with poor
decontamination techniques). The N fowleri amebas invade the CNS through
the nasal mucosa and cribriform plate.
PAM occurs in 2 forms. The first is characterized by an acute onset of high
fever, photophobia, headache, and altered mental status, similar to bacterial
meningitis, occurring within 1 week after exposure. Because it is acquired via
the nasal area, olfactory nerve involvement may manifest as abnormal smell
sensation. Death occurs in 3 days in patients who are not treated. The second
form, the subacute or chronic form, consists of an insidious onset of low-grade
fever, headache, and focal neurologic signs. Duration of illness is weeks to
few months.
Acanthamoeba and Balamuthia cause granulomatous amebic encephalitis,
which is a subacute opportunistic infection that spreads hematogenously from
the primary site of infection (skin or lungs) to the CNS and causes an
encephalitis syndrome. These cases can be difficult to distinguish from
culture-negative meningitis.
Angiostrongylus cantonensis, the rat lungworm, can cause eosinophilic
meningitis (pleocytosis with more than 10% eosinophils) in humans. The adult
parasite resides in the lungs of rats. Its eggs hatch, and the larval stages are
expelled in the feces. The larvae develop in the intermediate host, usually land
snails, freshwater prawns, and crabs. Humans acquire the infection by
ingesting raw mollusks.
Gnathostoma spinigerum, a GI parasite of wild and domestic dogs and cats,
may cause eosinophilic meningoencephalitis. Humans acquire the infection
after ingesting undercooked infected fish and poultry.
Baylisascaris procyonis is an ascarid parasite that is prevalent in the raccoon
populations in the United States and rarely causes human eosinophilic
meningoencephalitis. Human infections occur after accidental ingestion of
food products contaminated with raccoon feces.
Additional causes of meningitis
Congenital malformation of the stapedial footplate has been implicated in the
development of meningitis. Head and neck surgery, penetrating head injury,
comminuted skull fracture, and osteomyelitic erosion may infrequently result in
direct implantation of bacteria into the meninges. Skull fractures can tear the
dura and cause a CSF fistula, especially in the region of the frontal ethmoid
sinuses. Patients with any of these conditions are at risk for bacterial
meningitis.
Epidemiology
The incidence of meningitis varies according to the specific etiologic agent, as
well as in conjunction with a nations medical resources. The incidence is
presumed to be higher in developing countries because of less access to
preventive services, such as vaccination. In these countries, the incidence has
been reported to be 10 times higher than that in developed countries.
Meningitis affects people of all races. In the United States, black people have
a higher reported rate of meningitis than white people and Hispanic people.
Epidemiology of bacterial meningitis
With almost 4100 cases and 500 deaths occurring annually in the United
States, bacterial meningitis continues to be a significant source of morbidity
and mortality. The annual incidence in the United States is 1.33 cases per
100,000 population.
[5]

Meningococcal meningitis is endemic in parts of Africa, India, and other
developing areas. Periodic epidemics occur in the so-called sub-Saharan
meningitis belt, as well as among religious pilgrims traveling to Saudi Arabia
for the Hajj. In parts of Africa, widespread epidemics of meningococcal
meningitis occur regularly. In 1996, the biggest wave of meningococcal
meningitis outbreaks ever recorded arose in West Africa. An estimated
250,000 cases and 25,000 deaths occurred in Niger, Nigeria, Burkina Faso,
Chad, and Mali.
The incidence of neonatal bacterial meningitis is 0.25-1 case per 1000 live
births. In addition, the incidence is 0.15 case per 1000 full-term births and 2.5
cases per 1000 premature births. Approximately 30% of newborns with clinical
sepsis have associated bacterial meningitis.
N meningitidis causes approximately 4 cases per 100,000 children aged 1-23
months. The risk of secondary meningitis is 1% for family contacts and 0.1%
for daycare contacts. The rate of meningitis caused by S pneumoniae is 6.5
cases per 100,000 children aged 1-23 months.
Previously, Hib, N meningitidis, and S pneumoniae accounted for more than
80% of cases of bacterial meningitis. Since the late 20th century, however, the
epidemiology of bacterial meningitis has been substantially changed by
multiple developments.
The overall incidence of bacterial meningitis in the US declined from 2.0 to
1.38 cases per 100,000 population between 1998 and 2007.
[5]
This was
partially because of the widespread use of the Hib vaccination, which
decreased the incidence of H influenzae meningitis by more than 90% (see
Table 3 below). Routine Hib vaccination has nearly eliminating this pathogen
as a cause of meningitis in many developed countries.
More recent prevention measures such as the pneumococcal conjugate
vaccine and universal screening of pregnant women for GBS have further
changed the epidemiology of bacterial meningitis.
Table 3. Changing Epidemiology of Acute Bacterial Meningitis in United
States*(Open Table in a new window)
Bacteria 1978-1981 1986 1995 1998-2007
Haemophilus influenzae 48% 45% 7% 6.7%
Listeria monocytogenes 2% 3% 8% 3.4%
Neisseria meningitidis 20% 14% 25% 13.9%
Streptococcus agalactiae (group B streptococcus) 3% 6% 12% 18.1%
Streptococcus pneumoniae 13% 18% 47% 58%
*Nosocomial meningitis is not included; these data include only the 5 major meningeal pathogens.
The number of cases of invasive H influenzae disease among children
younger than 5 years that were reported to the CDC declined from 20,000 in
1987 to 255 in 1998. This shift has reportedly been less dramatic in
developing countries, where the use of Hib vaccine is not as widespread.
Because the frequency of bacterial meningitis in children has declined, the
condition is becoming more of a disease of adults. Whereas the median age
for persons with bacterial meningitis was 25 years in 1998, it was 15 months
in 1986.
[7]

The introduction of vaccines against S pneumoniae has substantially reduced
the incidence of pneumococcal meningitis in children. Routine screening for
GBS in pregnant women may have also reduced the incidence of meningitis
from this pathogen . Routine vaccination against serogroup C meningococcus
may also reduce the incidence of N meningitidis infections. During a 1998-
2007 survey, the incidence of meningitis declined by 31%,
[5]
a decrease that
can be credited to vaccination programs.
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. In addition, the
incidence is increased in persons aged 60 years and older, independent of
other factors. The annual incidence ranges from 1.7 to 7.2 cases per 100,000
adults; the mean annual incidence has been reported as 3.8 cases per
100,000 adults. Of patients with bacterial meningitis, 61% had no previous or
present accompanying diseases that may have predisposed them to
meningitis.
Depending on their age, individuals are also predisposed to meningitis from
other etiologic agents (see Table 4 below). E coli K1 meningitis and S
agalactiaemeningitis are common among neonates, and L
monocytogenes meningitis is common among neonates and the elderly. (The
development of neonatal meningitis is related to labor and delivery; it results
from colonized pathogens in the maternal intestinal or genital tract, immaturity,
and environment.)
Table 4. Most Common Bacterial Pathogens on Basis of Age and
Predisposing Risks (Open Table in a new window)
Risk or Predisposing Factor Bacterial Pathogen
Age 0-4 weeks Streptococcus agalactiae (GBS)



Escherichia coli K1



Listeria monocytogenes


Age 4-12 weeks S agalactiae



E coli



Haemophilus influenzae



Streptococcus pneumoniae



Neisseria meningitidis


Age 3 months to 18 years N meningitidis



S pneumoniae



H influenzae


Age 18-50 years S pneumoniae



N meningitidis



H influenzae


Age >50 years S pneumoniae



N meningitidis



L monocytogenes



Aerobic gram-negative bacilli


Immunocompromised state S pneumoniae



N meningitidis



L monocytogenes



Aerobic gram-negative bacilli


Intracranial manipulation, including neurosurgery Staphylococcus aureus



Coagulase-negative staphylococci



Aerobic gram-negative bacilli, including Pseudomonas aeruginosa


Basilar skull fracture S pneumoniae



H influenzae



Group A streptococci


CSF shunts Coagulase-negative staphylococci



S aureus



Aerobic gram-negative bacilli



Propionibacterium acnes


CSF = cerebrospinal fluid; GBS = group B streptococcus.
The reported attack rate for bacterial meningitis is 3.3 male cases per 100,000
population, compared with 2.6 female cases per 100,000 population.
However, in meningitis caused by the mumps virus, males and females are
affected equally. In neonates, the male-to-female ratio is 3:1.
Epidemiology of specific bacterial pathogens of acute meningitis
H influenzae meningitis primarily affects infants younger than 2 years. S
agalactiae meningitis occurs principally during the first 12 weeks of life but has
also been reported in adults, primarily affecting individuals older than age 60
years. The overall case-fatality rate in adults is 34%. Among the bacterial
agents that cause meningitis, S pneumoniae is associated with one of the
highest mortalities (19-26%).
Epidemiology of aseptic meningitis
Aseptic meningitis has a reported incidence of 10.9 cases per 100,000
person-years. It occurs in individuals of all ages but is more common in
children, especially during summer. No racial differences are reported. Aseptic
meningitis tends to occur 3 times more frequently in males than in females.
Viruses are the major cause of aseptic meningitis. The enteroviruses are
distributed worldwide, and the infection rates vary according to the season of
the year and a populations age and socioeconomic status. Most enteroviral
infections occur in individuals who are younger than 15 years, with the highest
attack rates in children who are younger than 1 year.
Arboviruses are an important cause of aseptic meningitis and encephalitis in
the summer and fall months in the United States. West Nile virus was
introduced to the United States in 1999 and has now spread throughout the
continent. In 2012, the largest outbreak of West Nile virus infection to date
occurred in the United States, with 5387 cases reported (about half of which
were neuroinvasive disease, such as meningitis or encephalitis) and a 4.5%
mortality.
[8]
West Nile virus can also cause acute flaccid paralysis, retinitis and
nephropathy.
Other less common arboviruses include St Louis encephalitis virus,
Jamestown canyon virus, La Crosse encephalitis virus, Powassan
encephalitis virus, and Eastern equine encephalitis virus. In the United States,
the last epidemic of St Louis encephalitis was in Monroe, Louisiana, in 2001;
63 cases were reported, with 3 deaths (4.7% mortality). Infection with the La
Crosse encephalitis virus also usually occurs during the summer and early fall,
with symptoms again being typical of acute aseptic meningitis.
[9]

Infections with the LCM virus occur worldwide. Most human cases occur
among young adults during autumn.
Of fungal causes, B dermatitidis is reportedly endemic in North America (eg,
Mississippi and Ohio River basins). It has also been isolated from parts of
Central America, South America, the Middle East, and India. H
capsulatum has been reported from many areas of the world, with the
Mississippi and Ohio River valleys being the most endemic regions in North
America.
Of parasitic causes, A cantonensis is common in Southeast Asia and the
Pacific Islands. It has also been found in rats outside this region, particularly in
regions of Africa, Puerto Rico, and Louisiana, presumably introduced by ship-
borne rats from endemic areas. G spinigerum is common in Southeast Asia,
China, and Japan but has been reported sporadically worldwide.
Epidemiology of chronic meningitis
Brucella -associated chronic meningitis has a worldwide distribution and is
common in the Middle East, India, Mexico, and Central and South America. In
the United States, after the control of bovine infections, the incidence
decreased to less than 0.5 cases per 100,000 population, and only 79 cases
were reported to the CDC in 1998.
M tuberculosis is worldwide in distribution, and humans are its only reservoir.
In 1997, the estimated case rates among endemic countries ranged from 62 to
411 cases per 100,000 population.
B burgdorferi is a tick-borne spirochete that is found in the temperate regions
of much of the northern hemisphere. Endemic regions include North America
(eg, the northeastern United States, Minnesota, Wisconsin, and parts of
California and Oregon), Europe, and Asia.
C neoformans has a worldwide distribution. Serotypes B and C have been
restricted mostly to tropical and subtropical regions, and serotype B has been
isolated from eucalyptus trees.
The distribution of C immitis is limited to the endemic regions of the Western
Hemisphere, within the north and south 40 latitudes (ie, parts of the
southwestern United States, Mexico, and Central and South America).
Persons who have migrated from or traveled to endemic areas may
experience onset of disease in other parts of the world.
S schenckii has been reported worldwide. However, most cases come from
the tropical regions of the Americas.
Prognosis
Patients with meningitis who present with an impaired level of consciousness
are at increased risk for neurologic sequelae or death. A seizure during an
episode of meningitis also is a risk factor for mortality or neurologic sequelae,
particularly if the seizure is prolonged or difficult to control.
In bacterial meningitis, several risk factors are associated with death and with
neurologic disability. A risk score has been derived and validated in adults
with bacterial meningitis. This score includes the following variables, which are
associated with an adverse clinical outcome
[10]
:
Older age
Increased heart rate
Lower Glasgow Coma Scale score
Cranial nerve palsies
CSF leukocyte count lower than 1000/L
Gram-positive cocci on CSF Gram stain
Advanced bacterial meningitis can lead to brain damage, coma, and death. In
50% of patients, several complications may develop in the days to weeks
following infection. Long-term sequelae are seen in as many as 30% of
survivors and vary with etiologic agent, patient age, presenting features, and
hospital course. Patients usually have subtle CNS changes.
Serious complications include the following:
Hearing loss
Cortical blindness
Other cranial nerve dysfunction
Paralysis
Muscular hypertonia
Ataxia
Multiple seizures
Mental motor retardation
Focal paralysis
Ataxia
Subdural effusions
Hydrocephalus
Cerebral atrophy
Risk factors for hearing loss after pneumococcal meningitis are female
gender, older age, severe meningitis, and infection with certain pneumococcal
serotypes (eg, 12F).
[11]
Delayed complications include the following:
Decreased hearing or deafness
Other cranial nerve dysfunctions
Multiple seizures
Focal paralysis
Subdural effusions
Hydrocephalus
Intellectual deficits
Ataxia
Blindness
Waterhouse-Friderichsen syndrome
Peripheral gangrene
Seizures are a common and important complication, occurring in
approximately one fifth of patients. The incidence is higher in patients younger
than 1 year, reaching 40%. Approximately one half of patients with this
complication have repeated seizures. Patients may die as a result of diffuse
CNS ischemic injury or systemic complications.
Even with effective antimicrobial therapy, significant neurologic complications
have been reported to occur in as many as 30% of survivors of bacterial
meningitis. Close monitoring for the development of these complications is
essential.
Mortality for bacterial meningitis is highest in the first year of life, decreases in
midlife, and increases again in old age. Bacterial meningitis is fatal in 1 in 10
cases, and 1 of every 7 survivors is left with a severe handicap, such as
deafness or brain injury.
The prognosis in patients with meningitis caused by opportunistic pathogens
depends on the underlying immune function of the host. Many patients who
survive the disease require lifelong suppressive therapy (eg, long-term
fluconazole for suppression in patients with HIV-associated cryptococcal
meningitis).
Among bacterial pathogens, S pneumoniae causes the highest mortality (20-
30% in adults, 10% in children) and morbidity (15%) in meningitis. If severe
neurologic impairment is evident at the time of presentation (or if the onset of
illness is extremely rapid), mortality is 50-90% and morbidity is even higher,
even with immediate medical treatment. Meningitis caused by L
monocytogenes or gram-negative bacilli also has a higher case-fatality rate
than meningitis caused by other bacterial agents.
Reported overall mortality for meningitis from specific bacterial organisms is
as follows:
S pneumoniae - 19-26%
H influenzae - 3-6%
N meningitidis - 3-13%
L monocytogenes - 15-29%
Patients with meningococcal meningitis have a better prognosis than do those
with pneumococcal meningitis, with a mortality of 4-5%; however, patients with
meningococcemia have a poor prognosis, with a mortality of 20-30%.
The mortality for viral meningitis without encephalitis is less than 1%. In
patients with deficient humoral immunity (eg, agammaglobulinemia),
enteroviral meningitis may have a fatal outcome. Patients with viral meningitis
usually have a good prognosis for recovery. The prognosis is worse for
patients at the extremes of age (ie, < 2 or >60 years) and those with
significant comorbidities and underlying immunodeficiency.
Patient Education
Patients and parents of young children should be educated about the benefits
of vaccination in preventing meningitis. Vaccination against N meningitidis is
recommended for all US college students.
Close contacts of patients with known or suspected N meningitidis or Hib
meningitis may require education regarding the need for prophylaxis. All
contacts should be instructed to come to the emergency department
immediately at the first sign of fever, sore throat, rash, or symptoms of
meningitis. Rifampin prophylaxis only eradicates the organism from the
nasopharynx; it is ineffective against invasive disease.
For patient education information, see the Brain and Nervous System
Center and the Childrens Health Center, as well as Meningitis in
Adults, Meningitis in Children, Brain Infection, and Spinal Tap.