Meningitis Disease
Wednesday, April 1, 2015
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Clinical Presentation:
Symptoms commonly associated with both microbe and viral meningitis consist of acute onset of fever, headache, neck stiffness (meningismus), photophobia, and confusion. Microbe meningitis brings about significant morbidity (neurologic sequelae, particularly sensorineural hearing loss) and mortality and thus requires immediate antibiotic treatment.
With rare exceptions, only supportive care with analgesics is essential for viral meningitis. Because the clinical presentations of microbe and viral meningitis might be indistinguishable, laboratory studies from the cerebrospinal fluid are critical in differentiating these entities. Cerebrospinal fluid leukocyte pleocytosis (white blood cells in the cerebrospinal fluid) may be the hallmark of meningitis.
Symptoms commonly associated with both microbe and viral meningitis consist of acute onset of fever, headache, neck stiffness (meningismus), photophobia, and confusion. Microbe meningitis brings about significant morbidity (neurologic sequelae, particularly sensorineural hearing loss) and mortality and thus requires immediate antibiotic treatment.
With rare exceptions, only supportive care with analgesics is essential for viral meningitis. Because the clinical presentations of microbe and viral meningitis might be indistinguishable, laboratory studies from the cerebrospinal fluid are critical in differentiating these entities. Cerebrospinal fluid leukocyte pleocytosis (white blood cells in the cerebrospinal fluid) may be the hallmark of meningitis.
Microbe meningitis is generally characterized by neutrophilic pleocytosis (predominance of polymorphonuclear neutrophils in the cerebrospinal fluid). Typical causes of lymphocytic pleocytosis include viral infections (eg, enterovirus, West Nile virus), fungal infections (eg, cryptococcus in HIV-infected persons), and spirochetal infections (eg, neurosyphilis or Lyme neuroborreliosis).
Noninfectious brings about this kind of as cancer, connective tissue diseases, and hypersensitivity reactions to drugs can also trigger lymphocytic pleocytosis. The cerebrospinal fluid in bacterial meningitis is usually characterized by marked elevations in protein concentration, an very reduced glucose level, and, in the absence of previous antibiotic treatment, a positive Gram stain for bacteria.
However, there is frequently substantial overlap between the cerebrospinal fluid findings in bacterial and nonbacterial meningitis, and differentiating these entities at presentation is really a significant clinical challenge.
Noninfectious brings about this kind of as cancer, connective tissue diseases, and hypersensitivity reactions to drugs can also trigger lymphocytic pleocytosis. The cerebrospinal fluid in bacterial meningitis is usually characterized by marked elevations in protein concentration, an very reduced glucose level, and, in the absence of previous antibiotic treatment, a positive Gram stain for bacteria.
However, there is frequently substantial overlap between the cerebrospinal fluid findings in bacterial and nonbacterial meningitis, and differentiating these entities at presentation is really a significant clinical challenge.
Etiology:
The microbiology of microbe meningitis within the United States has changed dramatically following the introduction from the Haemophilus influenzae conjugate vaccine. The routine use of this vaccine in the pediatric population has essentially eliminated H influenzae as a trigger of meningitis, resulting in a shift in median age among sufferers with microbe meningitis from 9 months to 25 years.
Microbe agents causing meningitis vary according to host age. In infants younger than 3 months, E coli, Listeria, and group B streptococci are the most common brings about of meningitis. For kids three months to 18 many years of age, S pneumoniae and N meningitidis are the most common brings about, with H influenzae a concern between nonimmunized kids.
For adults aged 18-50 many years, S pneumoniae and N meningitidis are the leading brings about of meningitis, whereas the elderly are at chance for those pathogens as well as for Listeria. Additional bacteria should be considered for postneurosurgery sufferers (S aureus, P aeruginosa), sufferers with ventricular shunts (S epidermidis, S aureus, gram-negative bacilli), pregnant patients (Listeria), or neutropenic sufferers (gram-negative bacilli, including P aeruginosa).
Subacute or chronic meningitides may be caused by M tuberculosis, fungi (eg, Coccidioides immitis, Cryptococcus neoformans), and spirochetes such as Treponema pallidum (the bacterium causing syphilis) or Borrelia burgdorferi (the bacterium causing Lyme disease). The diagnosis of meningitis triggered by these organisms may be delayed simply because many of these pathogens are difficult to culture and need special serologic or molecular diagnostic techniques.
The microbiology of microbe meningitis within the United States has changed dramatically following the introduction from the Haemophilus influenzae conjugate vaccine. The routine use of this vaccine in the pediatric population has essentially eliminated H influenzae as a trigger of meningitis, resulting in a shift in median age among sufferers with microbe meningitis from 9 months to 25 years.
Microbe agents causing meningitis vary according to host age. In infants younger than 3 months, E coli, Listeria, and group B streptococci are the most common brings about of meningitis. For kids three months to 18 many years of age, S pneumoniae and N meningitidis are the most common brings about, with H influenzae a concern between nonimmunized kids.
For adults aged 18-50 many years, S pneumoniae and N meningitidis are the leading brings about of meningitis, whereas the elderly are at chance for those pathogens as well as for Listeria. Additional bacteria should be considered for postneurosurgery sufferers (S aureus, P aeruginosa), sufferers with ventricular shunts (S epidermidis, S aureus, gram-negative bacilli), pregnant patients (Listeria), or neutropenic sufferers (gram-negative bacilli, including P aeruginosa).
Subacute or chronic meningitides may be caused by M tuberculosis, fungi (eg, Coccidioides immitis, Cryptococcus neoformans), and spirochetes such as Treponema pallidum (the bacterium causing syphilis) or Borrelia burgdorferi (the bacterium causing Lyme disease). The diagnosis of meningitis triggered by these organisms may be delayed simply because many of these pathogens are difficult to culture and need special serologic or molecular diagnostic techniques.
Pathogenesis:
The pathogenesis of bacterial meningitis involves a sequence of events in which virulent microorganisms overcome the host defense mechanisms. Most instances of bacterial meningitis begin with bacterial colonization of the nasopharynx. An exception is Listeria, which enters the bloodstream via ingestion of contaminated food.
Pathogenic bacteria such as S pneumoniae and N meningitidis secrete an IgA protease that inactivates host antibody and facilitates mucosal attachment. Many of the causal pathogens also possess surface characteristics that enhance mucosal colonization. N meningitidis binds to nonciliated epithelial cells by finger-like projections known as pili.
Once the mucosal barrier is breached, bacteria obtain access to the bloodstream, where they should overcome host defense mechanisms to survive and invade the CNS. The bacterial capsule, a feature typical to N meningitidis, H influenzae, and S pneumoniae, is probably the most important virulence factor in this regard.
Host defenses counteract the protective effects of the pneumococcal capsule by activating the alternative complement pathway, resulting in C3b activation, opsonization, phagocytosis, and intravascular clearance from the organism. This defense mechanism is impaired in patients who have undergone splenectomy, and this kind of patients are predisposed to the development of overwhelming bacteremia and meningitis with encapsulated bacteria.
Activation from the accentuate system membrane attack complex is an essential host defense mechanism against invasive disease by N meningitidis, and sufferers with deficiencies from the late accentuate components (C5-9) are at elevated chance for meningococcal meningitis.
The mechanisms by which bacterial pathogens obtain access to the CNS are largely unknown. Experimental studies suggest that receptors for microbe pathogens are present on cells within the choroid plexus, which might facilitate movement of these pathogens to the subarachnoid space.
Invasion from the spinal fluid by a meningeal pathogen results in elevated permeability of the blood-brain barrier, with leakage of albumin to the subarachnoid room, wherever local host defense mechanisms are inadequate to control the infection.
Usually, complement elements are minimal or absent in the cerebrospinal fluid. Meningeal inflammation leads to increased, but still reduced, concentrations of complement, inadequate for opsonization, phagocytosis, and removal of encapsulated meningeal pathogens. Immunoglobulin concentrations are also reduced in the cerebrospinal fluid, with an average blood to cerebrospinal fluid IgG ratio of 800:1.
Although the absolute quantity of immunoglobulin within the cerebrospinal fluid increases with infection, the ratio of immunoglobulin within the cerebrospinal fluid relative to that in the serum remains low. The ability of meningeal pathogens to induce a marked subarachnoid space inflammatory response contributes to many from the pathophysiologic consequences of bacterial meningitis.
Although the microbe capsule is largely responsible for intravascular and cerebrospinal fluid survival from the pathogens, the subcapsular surface elements (ie, the cell wall and lipopolysaccharide) of bacteria are more essential determinants of meningeal inflammation. The major mediators of the inflammatory process are thought to be IL-1, IL-6, matrix metalloproteinases, and tumor necrosis aspect (TNF).
Within 1-3 hours after intracisternal inoculation of purified lipopolysaccharide in an animal model, there's a brisk release of TNF and IL-1 to the cerebrospinal fluid, preceding the improvement of inflammation. Indeed, direct inoculation of TNF and IL-1 to the cerebrospinal fluid produces an inflammatory cascade identical to that seen with experimental bacterial infection.
Cytokine and proteolytic enzyme release leads to loss of membrane integrity, with resultant cellular swelling. The improvement of cerebral edema contributes to an increase in intracranial pressure, potentially resulting in life-threatening cerebral herniation. Vasogenic cerebral edema is principally caused by the increase in blood-brain barrier permeability.
Cytotoxic cerebral edema results from swelling from the cellular elements from the brain simply because of toxic factors from bacteria or neutrophils. Interstitial cerebral edema reflects obstruction of flow of cerebrospinal fluid, as in hydrocephalus. The literature suggests that oxygen free radicals and nitric oxide might also be important mediators in cerebral edema.
Other complications of meningitis consist of cerebral vasculitis with alterations in cerebral blood flow. The vasculitis leads to narrowing or thrombosis of cerebral blood vessels, resulting in ischemia and feasible brain infarction. Understanding the pathophysiology of bacterial meningitis has therapeutic implications.
Even though bactericidal antibiotic treatment is critical for adequate treatment, rapid bacterial killing releases inflammatory bacterial fragments, potentially exacerbating inflammation and abnormalities of the cerebral microvasculature. In animal models, antibiotic treatment has been shown to cause rapid bacteriolysis and release of microbe endotoxin, resulting in increased cerebrospinal fluid inflammation and cerebral edema.
The importance of the immune response in triggering cerebral edema has led researchers to study the role of adjuvant anti-inflammatory medications for bacterial meningitis. The use of corticosteroids has been shown to decrease the chance of sensorineural hearing loss between kids with H influenzae meningitis and mortality among adults with pneumococcal meningitis, and these agents are routinely given at the time of initial antibiotic therapy.
The pathogenesis of bacterial meningitis involves a sequence of events in which virulent microorganisms overcome the host defense mechanisms. Most instances of bacterial meningitis begin with bacterial colonization of the nasopharynx. An exception is Listeria, which enters the bloodstream via ingestion of contaminated food.
Pathogenic bacteria such as S pneumoniae and N meningitidis secrete an IgA protease that inactivates host antibody and facilitates mucosal attachment. Many of the causal pathogens also possess surface characteristics that enhance mucosal colonization. N meningitidis binds to nonciliated epithelial cells by finger-like projections known as pili.
Once the mucosal barrier is breached, bacteria obtain access to the bloodstream, where they should overcome host defense mechanisms to survive and invade the CNS. The bacterial capsule, a feature typical to N meningitidis, H influenzae, and S pneumoniae, is probably the most important virulence factor in this regard.
Host defenses counteract the protective effects of the pneumococcal capsule by activating the alternative complement pathway, resulting in C3b activation, opsonization, phagocytosis, and intravascular clearance from the organism. This defense mechanism is impaired in patients who have undergone splenectomy, and this kind of patients are predisposed to the development of overwhelming bacteremia and meningitis with encapsulated bacteria.
Activation from the accentuate system membrane attack complex is an essential host defense mechanism against invasive disease by N meningitidis, and sufferers with deficiencies from the late accentuate components (C5-9) are at elevated chance for meningococcal meningitis.
The mechanisms by which bacterial pathogens obtain access to the CNS are largely unknown. Experimental studies suggest that receptors for microbe pathogens are present on cells within the choroid plexus, which might facilitate movement of these pathogens to the subarachnoid space.
Invasion from the spinal fluid by a meningeal pathogen results in elevated permeability of the blood-brain barrier, with leakage of albumin to the subarachnoid room, wherever local host defense mechanisms are inadequate to control the infection.
Usually, complement elements are minimal or absent in the cerebrospinal fluid. Meningeal inflammation leads to increased, but still reduced, concentrations of complement, inadequate for opsonization, phagocytosis, and removal of encapsulated meningeal pathogens. Immunoglobulin concentrations are also reduced in the cerebrospinal fluid, with an average blood to cerebrospinal fluid IgG ratio of 800:1.
Although the absolute quantity of immunoglobulin within the cerebrospinal fluid increases with infection, the ratio of immunoglobulin within the cerebrospinal fluid relative to that in the serum remains low. The ability of meningeal pathogens to induce a marked subarachnoid space inflammatory response contributes to many from the pathophysiologic consequences of bacterial meningitis.
Although the microbe capsule is largely responsible for intravascular and cerebrospinal fluid survival from the pathogens, the subcapsular surface elements (ie, the cell wall and lipopolysaccharide) of bacteria are more essential determinants of meningeal inflammation. The major mediators of the inflammatory process are thought to be IL-1, IL-6, matrix metalloproteinases, and tumor necrosis aspect (TNF).
Within 1-3 hours after intracisternal inoculation of purified lipopolysaccharide in an animal model, there's a brisk release of TNF and IL-1 to the cerebrospinal fluid, preceding the improvement of inflammation. Indeed, direct inoculation of TNF and IL-1 to the cerebrospinal fluid produces an inflammatory cascade identical to that seen with experimental bacterial infection.
Cytokine and proteolytic enzyme release leads to loss of membrane integrity, with resultant cellular swelling. The improvement of cerebral edema contributes to an increase in intracranial pressure, potentially resulting in life-threatening cerebral herniation. Vasogenic cerebral edema is principally caused by the increase in blood-brain barrier permeability.
Cytotoxic cerebral edema results from swelling from the cellular elements from the brain simply because of toxic factors from bacteria or neutrophils. Interstitial cerebral edema reflects obstruction of flow of cerebrospinal fluid, as in hydrocephalus. The literature suggests that oxygen free radicals and nitric oxide might also be important mediators in cerebral edema.
Other complications of meningitis consist of cerebral vasculitis with alterations in cerebral blood flow. The vasculitis leads to narrowing or thrombosis of cerebral blood vessels, resulting in ischemia and feasible brain infarction. Understanding the pathophysiology of bacterial meningitis has therapeutic implications.
Even though bactericidal antibiotic treatment is critical for adequate treatment, rapid bacterial killing releases inflammatory bacterial fragments, potentially exacerbating inflammation and abnormalities of the cerebral microvasculature. In animal models, antibiotic treatment has been shown to cause rapid bacteriolysis and release of microbe endotoxin, resulting in increased cerebrospinal fluid inflammation and cerebral edema.
The importance of the immune response in triggering cerebral edema has led researchers to study the role of adjuvant anti-inflammatory medications for bacterial meningitis. The use of corticosteroids has been shown to decrease the chance of sensorineural hearing loss between kids with H influenzae meningitis and mortality among adults with pneumococcal meningitis, and these agents are routinely given at the time of initial antibiotic therapy.
Clinical Manifestations:
Between sufferers who produce community-acquired bacterial meningitis, an antecedent upper respiratory tract infection is typical. Sufferers having a history of head injury or neurosurgery, especially those having a persistent cerebrospinal fluid leak, are at particularly high risk for meningitis.
Manifestations of meningitis in infants may be hard to recognize and interpret; consequently, the physician should be alert towards the possibility of meningitis in the evaluation of any febrile neonate. Most sufferers with meningitis have a rapid onset of fever, headache, lethargy, and confusion.
Fewer than half complain of neck stiffness, but nuchal rigidity is noted on physical examination in 30-70%. Other clues seen in a variable proportion of instances include altered mental status, nausea or vomiting, photophobia, Kernig's sign (resistance to passive extension from the flexed leg with the patient lying supine), and Brudzinski's sign (involuntary flexion of the hip and knee when the examiner passively flexes the patient's neck).
More than half of patients with meningococcemia produce a characteristic petechial or purpuric rash, predominantly on the extremities. Although a change in mental status (lethargy, confusion) is typical in bacterial meningitis, up to one third of patients present with normal mentation. From 10% to 30% of sufferers have cranial nerve dysfunction, focal neurologic signs, or seizures.
Coma, papilledema, and Cushing's triad (bradycardia, respiratory depression, and hypertension) are ominous signs of impending herniation (brain displacement through the foramen magnum with brain stem compression), heralding imminent death.
Any patient suspected of having meningitis demands emergent lumbar puncture for Gram stain and culture from the cerebrospinal fluid, followed immediately by the administration of antibiotics and corticosteroids. Alternatively, if a focal neurologic process (eg, brain abscess) is suspected, antibiotics should be initiated immediately, followed by brain imaging (computed tomography or magnetic resonance imaging) and lumbar puncture performed only if there is no radiologic contraindication.
Between sufferers who produce community-acquired bacterial meningitis, an antecedent upper respiratory tract infection is typical. Sufferers having a history of head injury or neurosurgery, especially those having a persistent cerebrospinal fluid leak, are at particularly high risk for meningitis.
Manifestations of meningitis in infants may be hard to recognize and interpret; consequently, the physician should be alert towards the possibility of meningitis in the evaluation of any febrile neonate. Most sufferers with meningitis have a rapid onset of fever, headache, lethargy, and confusion.
Fewer than half complain of neck stiffness, but nuchal rigidity is noted on physical examination in 30-70%. Other clues seen in a variable proportion of instances include altered mental status, nausea or vomiting, photophobia, Kernig's sign (resistance to passive extension from the flexed leg with the patient lying supine), and Brudzinski's sign (involuntary flexion of the hip and knee when the examiner passively flexes the patient's neck).
More than half of patients with meningococcemia produce a characteristic petechial or purpuric rash, predominantly on the extremities. Although a change in mental status (lethargy, confusion) is typical in bacterial meningitis, up to one third of patients present with normal mentation. From 10% to 30% of sufferers have cranial nerve dysfunction, focal neurologic signs, or seizures.
Coma, papilledema, and Cushing's triad (bradycardia, respiratory depression, and hypertension) are ominous signs of impending herniation (brain displacement through the foramen magnum with brain stem compression), heralding imminent death.
Any patient suspected of having meningitis demands emergent lumbar puncture for Gram stain and culture from the cerebrospinal fluid, followed immediately by the administration of antibiotics and corticosteroids. Alternatively, if a focal neurologic process (eg, brain abscess) is suspected, antibiotics should be initiated immediately, followed by brain imaging (computed tomography or magnetic resonance imaging) and lumbar puncture performed only if there is no radiologic contraindication.
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