The Meningitis

Clinical Presentation:mechanisms are inadequate to control the
Symptoms commonly associated with bothinfection.
microbe and viral meningitis consist of acute onsetUsually, complement elements are minimal or
of fever, headache, neck stiffness (meningismus),absent in the cerebrospinal fluid. Meningeal
photophobia, and confusion. Microbe meningitisinflammation leads to increased, but still reduced,
brings about significant morbidity (neurologicconcentrations of complement, inadequate for
sequelae, particularly sensorineural hearing loss)opsonization, phagocytosis, and removal of
and mortality and thus requires immediateencapsulated meningeal pathogens. Immunoglobulin
antibiotic treatment.concentrations are also reduced in the
With rare exceptions, only supportive care withcerebrospinal fluid, with an average blood to
analgesics is essential for viral meningitis. Becausecerebrospinal fluid IgG ratio of 800:1.
the clinical presentations of microbe and viralAlthough the absolute quantity of immunoglobulin
meningitis might be indistinguishable, laboratorywithin the cerebrospinal fluid increases with
studies from the cerebrospinal fluid are critical ininfection, the ratio of immunoglobulin within the
differentiating these entities. Cerebrospinal fluidcerebrospinal fluid relative to that in the serum
leukocyte pleocytosis (white blood cells in theremains low. The ability of meningeal pathogens to
cerebrospinal fluid) may be the hallmark ofinduce a marked subarachnoid space inflammatory
meningitis.response contributes to many from the
Microbe meningitis is generally characterized bypathophysiologic consequences of bacterial
neutrophilic pleocytosis (predominance ofmeningitis.
polymorphonuclear neutrophils in the cerebrospinalAlthough the microbe capsule is largely responsible
fluid). Typical causes of lymphocytic pleocytosisfor intravascular and cerebrospinal fluid survival
include viral infections (eg, enterovirus, West Nilefrom the pathogens, the subcapsular surface
virus), fungal infections (eg, cryptococcus inelements (ie, the cell wall and lipopolysaccharide)
HIV-infected persons), and spirochetal infectionsof bacteria are more essential determinants of
(eg, neurosyphilis or Lyme neuroborreliosis).meningeal inflammation. The major mediators of
Noninfectious brings about this kind of as cancer,the inflammatory process are thought to be IL-1,
connective tissue diseases, and hypersensitivityIL-6, matrix metalloproteinases, and tumor
reactions to drugs can also trigger lymphocyticnecrosis aspect (TNF).
pleocytosis. The cerebrospinal fluid in bacterialWithin 1-3 hours after intracisternal inoculation of
meningitis is usually characterized by markedpurified lipopolysaccharide in an animal model,
elevations in protein concentration, an verythere's a brisk release of TNF and IL-1 to the
reduced glucose level, and, in the absence ofcerebrospinal fluid, preceding the improvement of
previous antibiotic treatment, a positive Graminflammation. Indeed, direct inoculation of TNF and
stain for bacteria.IL-1 to the cerebrospinal fluid produces an
However, there is frequently substantial overlapinflammatory cascade identical to that seen with
between the cerebrospinal fluid findings in bacterialexperimental bacterial infection.
and nonbacterial meningitis, and differentiatingCytokine and proteolytic enzyme release leads to
these entities at presentation is really a significantloss of membrane integrity, with resultant cellular
clinical challenge.swelling. The improvement of cerebral edema
Etiology:contributes to an increase in intracranial pressure,
The microbiology of microbe meningitis within thepotentially resulting in life-threatening cerebral
United States has changed dramatically followingherniation. Vasogenic cerebral edema is principally
the introduction from the Haemophilus influenzaecaused by the increase in blood-brain barrier
conjugate vaccine. The routine use of this vaccinepermeability.
in the pediatric population has essentially eliminatedCytotoxic cerebral edema results from swelling
H influenzae as a trigger of meningitis, resulting infrom the cellular elements from the brain simply
a shift in median age among sufferers withbecause of toxic factors from bacteria or
microbe meningitis from 9 months to 25 years.neutrophils. Interstitial cerebral edema reflects
Microbe agents causing meningitis vary accordingobstruction of flow of cerebrospinal fluid, as in
to host age. In infants younger than 3 months, Ehydrocephalus. The literature suggests that
coli, Listeria, and group B streptococci are theoxygen free radicals and nitric oxide might also be
most common brings about of meningitis. For kidsimportant mediators in cerebral edema.
three months to 18 many years of age, SOther complications of meningitis consist of
pneumoniae and N meningitidis are the mostcerebral vasculitis with alterations in cerebral blood
common brings about, with H influenzae a concernflow. The vasculitis leads to narrowing or
between nonimmunized kids.thrombosis of cerebral blood vessels, resulting in
For adults aged 18-50 many years, S pneumoniaeischemia and feasible brain infarction. Understanding
and N meningitidis are the leading brings about ofthe pathophysiology of bacterial meningitis has
meningitis, whereas the elderly are at chance fortherapeutic implications.
those pathogens as well as for Listeria. AdditionalEven though bactericidal antibiotic treatment is
bacteria should be considered forcritical for adequate treatment, rapid bacterial
postneurosurgery sufferers (S aureus, Pkilling releases inflammatory bacterial fragments,
aeruginosa), sufferers with ventricular shunts (Spotentially exacerbating inflammation and
epidermidis, S aureus, gram-negative bacilli),abnormalities of the cerebral microvasculature. In
pregnant patients (Listeria), or neutropenicanimal models, antibiotic treatment has been
sufferers (gram-negative bacilli, including Pshown to cause rapid bacteriolysis and release of
aeruginosa).microbe endotoxin, resulting in increased
Subacute or chronic meningitides may be causedcerebrospinal fluid inflammation and cerebral
by M tuberculosis, fungi (eg, Coccidioides immitis,edema.
Cryptococcus neoformans), and spirochetes suchThe importance of the immune response in
as Treponema pallidum (the bacterium causingtriggering cerebral edema has led researchers to
syphilis) or Borrelia burgdorferi (the bacteriumstudy the role of adjuvant anti-inflammatory
causing Lyme disease). The diagnosis of meningitismedications for bacterial meningitis. The use of
triggered by these organisms may be delayedcorticosteroids has been shown to decrease the
simply because many of these pathogens arechance of sensorineural hearing loss between kids
difficult to culture and need special serologic orwith H influenzae meningitis and mortality among
molecular diagnostic techniques.adults with pneumococcal meningitis, and these
Pathogenesis:agents are routinely given at the time of initial
The pathogenesis of bacterial meningitis involves aantibiotic therapy.
sequence of events in which virulentClinical Manifestations:
microorganisms overcome the host defenseBetween sufferers who produce
mechanisms. Most instances of bacterial meningitiscommunity-acquired bacterial meningitis, an
begin with bacterial colonization of theantecedent upper respiratory tract infection is
nasopharynx. An exception is Listeria, whichtypical. Sufferers having a history of head injury
enters the bloodstream via ingestion ofor neurosurgery, especially those having a
contaminated food.persistent cerebrospinal fluid leak, are at
Pathogenic bacteria such as S pneumoniae and Nparticularly high risk for meningitis.
meningitidis secrete an IgA protease thatManifestations of meningitis in infants may be hard
inactivates host antibody and facilitates mucosalto recognize and interpret; consequently, the
attachment. Many of the causal pathogens alsophysician should be alert towards the possibility of
possess surface characteristics that enhancemeningitis in the evaluation of any febrile neonate.
mucosal colonization. N meningitidis binds toMost sufferers with meningitis have a rapid onset
nonciliated epithelial cells by finger-like projectionsof fever, headache, lethargy, and confusion.
known as pili.Fewer than half complain of neck stiffness, but
Once the mucosal barrier is breached, bacterianuchal rigidity is noted on physical examination in
obtain access to the bloodstream, where they30-70%. Other clues seen in a variable proportion
should overcome host defense mechanisms toof instances include altered mental status, nausea
survive and invade the CNS. The bacterial capsule,or vomiting, photophobia, Kernig's sign (resistance
a feature typical to N meningitidis, H influenzae,to passive extension from the flexed leg with the
and S pneumoniae, is probably the mostpatient lying supine), and Brudzinski's sign
important virulence factor in this regard.(involuntary flexion of the hip and knee when the
Host defenses counteract the protective effectsexaminer passively flexes the patient's neck).
of the pneumococcal capsule by activating theMore than half of patients with meningococcemia
alternative complement pathway, resulting in C3bproduce a characteristic petechial or purpuric rash,
activation, opsonization, phagocytosis, andpredominantly on the extremities. Although a
intravascular clearance from the organism. Thischange in mental status (lethargy, confusion) is
defense mechanism is impaired in patients whotypical in bacterial meningitis, up to one third of
have undergone splenectomy, and this kind ofpatients present with normal mentation. From
patients are predisposed to the development of10% to 30% of sufferers have cranial nerve
overwhelming bacteremia and meningitis withdysfunction, focal neurologic signs, or seizures.
encapsulated bacteria.Coma, papilledema, and Cushing's triad
Activation from the accentuate system(bradycardia, respiratory depression, and
membrane attack complex is an essential hosthypertension) are ominous signs of impending
defense mechanism against invasive disease by Nherniation (brain displacement through the
meningitidis, and sufferers with deficiencies fromforamen magnum with brain stem compression),
the late accentuate components (C5-9) are atheralding imminent death.
elevated chance for meningococcal meningitis.Any patient suspected of having meningitis
The mechanisms by which bacterial pathogensdemands emergent lumbar puncture for Gram
obtain access to the CNS are largely unknown.stain and culture from the cerebrospinal fluid,
Experimental studies suggest that receptors forfollowed immediately by the administration of
microbe pathogens are present on cells within theantibiotics and corticosteroids. Alternatively, if a
choroid plexus, which might facilitate movementfocal neurologic process (eg, brain abscess) is
of these pathogens to the subarachnoid space.suspected, antibiotics should be initiated
Invasion from the spinal fluid by a meningealimmediately, followed by brain imaging (computed
pathogen results in elevated permeability of thetomography or magnetic resonance imaging) and
blood-brain barrier, with leakage of albumin to thelumbar puncture performed only if there is no
subarachnoid room, wherever local host defenseradiologic contraindication.