Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective

bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=358273

Bacterial surface components, complement, and inflammatory cytokines (eg, tumor necrosis factor, IL-1) draw neutrophils into the CSF space. The neutrophils release metabolites that damage cell membranes including those of the vascular endothelium. The result is vasculitis and thrombophlebitis, causing focal ischemia or infarction, and brain edema. Vasculitis also disrupts the blood-brain barrier, further increasing brain edema. The purulent exudate in the CSF blocks CSF reabsorption by the arachnoid villi, causing hydrocephalus. Brain edema and hydrocephalus increase intracranial pressure.

Systemic complications include hyponatremia due to the syndrome of inappropriate antidiuretic hormone (SIADH), disseminated intravascular coagulation (DIC), and septic shock. Occasionally, bilateral adrenal hemorrhagic infarction (Waterhouse-Friderichsen syndrome) results.

http://www.merck.com/mmpe/sec16/ch218/ch218b.html

Three major pathways exist by which an infectious agent (ie, bacteria, virus, fungus, parasite) gains access to the central nervous system (CNS) and causes disease. Initially, the infectious agent colonizes or establishes a localized infection in the host. This may be in the form of colonization or infection of the skin, nasopharynx, respiratory tract, gastrointestinal tract, or genitourinary tract. Most meningeal pathogens are transmitted through the respiratory route, as exemplified by the nasopharyngeal carriage of Neisseria meningitides (meningococcus) and nasopharyngeal colonization with S pneumoniae(pneumococcus). From this site, the organism invades the submucosa by circumventing host defenses (eg, physical barriers, local immunity, phagocytes/macrophages) and gains access to the CNS by (1) invasion of the bloodstream (ie, bacteremia, viremia, fungemia, parasitemia) and subsequent hematogenous seeding of the CNS, which is the most common mode of spread for most agents (eg, meningococcal, cryptococcal, syphilitic, and pneumococcal meningitis); (2) a retrograde neuronal (ie, olfactory and peripheral nerves) pathway (eg, Naegleria fowleri, Gnathostoma spinigerum); or (3) direct contiguous spread (ie, sinusitis, otitis media, congenital malformations, trauma, direct inoculation during intracranial manipulation). Certain respiratory viruses are thought to enhance the entry of bacterial agents into the intravascular compartment, presumably by damaging mucosal defenses. Once inside the bloodstream, the infectious agent must escape immune surveillance (eg, antibodies, complement-mediated bacterial killing, neutrophil phagocytosis). Subsequently, hematogenous seeding into distant sites occurs, including the CNS. The specific pathophysiologic mechanisms by which the infectious agents gain access into the subarachnoid space remain unclear. Once inside the CNS, the infectious agents likely survive because host defenses (eg, immunoglobulins, neutrophils, complement components) appear to be limited in this body compartment. The presence and replication of infectious agents remain uncontrolled and incite a cascade of meningeal inflammation. This process of meningeal inflammation has been an area of extensive investigation in recent years that has led to a better understanding of meningitis pathophysiology. Key advances in the pathophysiology of meningitis include the pivotal role of cytokines (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]1), chemokines (IL-8), and other proinflammatory molecules in the pathogenesis of pleocytosis and neuronal damage during bacterial meningitis.

Increased CSF concentrations of TNF-alpha, IL-1, IL-6, and IL-8 are characteristic findings in patients with bacterial meningitis. The proposed interplay among these mediators of inflammation is as follows:
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The exposure of cells (eg, endothelium, leukocytes, microglia, astrocytes, meningeal macrophages) to bacterial products released during replication and death incites the synthesis of cytokines and proinflammatory mediators. Recent data indicate that this process is likely initiated by the ligation of the bacterial components (eg, peptidoglycan, lipopolysaccharide) to pattern-recognition receptors such as the Toll-like receptors. TNF-alpha and IL-1 are the most prominent among the cytokines that mediate this inflammatory cascade. TNF-alpha is a glycoprotein derived from activated monocytemacrophages, 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 molecules 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 (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-alpha and IL-1. Nitric oxide is a free radical molecule that can induce cytotoxicity when produced in high amounts. PGE2, a product of cyclooxygenase, appears to participate in the induction of increased blood-brain barrier (BBB) permeability. PAF, with its myriad of 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 and should be investigated further. Overall, the net result is vascular endothelial injury and increased BBB permeability leading to the entry of many blood components into the subarachnoid space. In many patients, 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 BBB, producing the profound neutrophilic pleocytosis characteristic of bacterial meningitis. The increased CSF viscosity resulting from the influx of plasma components into the subarachnoid space and diminished venous outflow lead to interstitial edema, and the products of bacterial degradation, neutrophils, and other cellular activation lead to cytotoxic edema. The ensuing cerebral edema (ie, vasogenic, cytotoxic, 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.

The level of cytokines, including IL-6, TNF-alpha, and interferon-gamma, has been found to be elevated in patients with aseptic meningitis.

Another important component or 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 BBB permeability) are all thought to play a role in the development of increased ICP.

http://emedicine.medscape.com/article/232915-overview

BACTERIAL MENINGITIS Bacterial meningitis is the infection of the arachnoid membrane, subarachnoid space, and cerebrospinal fluid by bacteria. The subarachnoid space is bounded externally by the arachnoid membrane and internally by the pia, and dips into the brain along blood vessels in the perivascular ( Virchow-Robin) spaces. It extends from the optic chiasm to the cauda equina and surrounds the brain and spinal cord completely. Meningitis may have a focal origin (sinusitis, mastoiditis, brain abscess, penetrating injury, congenital defect), but more commonly results from hematogenous dissemination. The most common organisms of bacterial meningitis in children and adults are Streptococcus pneumoniae and Neisseria meningitidis. Streptococcus pneumoniae is declining after the introduction of conjugated vaccines. Hemophilus influenzae, once very common in children, is now rare thanks to vaccination. In newborns, the most common organisms areEschericia coli and beta hemolytic Streptococcus group B. Babies are frequently infected during passage through the birth canal. PATHOGENESIS. The organisms that cause bacterial meningitis colonize the nasopharynx. From there, they get into the blood stream and enter the subarachnoid space through complex interactions with endothelial cells. The porous structure of choroid plexus capillaries facilitates their spillage into the CSF. The CSF is an ideal medium for the spread of bacteria because it

provides enough nutrients for their multiplication and has few phagocytic cells, and low levels of antibodies and complement. Initially, bacteria multiply uninhibited and can be identified in smears, cultures, or by ELISA detection of their antigens before there is any inflammation. When bacteria die, lipids and oligosaccharides, including endotoxin, are released from their walls. Some of these components cause vascular injury and shock. Symptoms of sepsis may develop and even death from gram-negative shock may occur before any inflammation appears. Bacterial cell wall components also induce meningeal macrophages, astrocytes, and microglial cells to produce interleukin-1 (IL-1), tumor necrosis factor(TNF- ), and other inflammatory mediators. These cytokines attract circulating granulocytes and monocytes into the CSF. As they lyse, granulocytes and monocytes release powerful lysosomal enzymes and free radicals, which destroy neural tissue and damage blood vessels. Polyunsaturated fatty acids released from the membranes of dying neutrophils also cause increased vascular permeability. The results of vascular injury are increased permeability (cerebral edema) and vasculitis (ischemia). The results of inflammation are tissue and vascular injury (vasculitis) and increased intracranial pressure. Brain tissue, cranial nerve, and vascular injury is caused by lysosomal enzymes and free radicals released by granulocytes and monocytes. Increased intracranial pressure is caused by increased vascular permeability and leakage of proteins in the interstitial space (cerebral edema) and CSF. Vasculitis causes infarcts and increased intracranial pressure causes or aggravates hypoxic-ischemic encephalopathy (HIE). CLINICAL FINDINGS. The initial symptoms of meningitis are fever, severe headache, and stiff neck. The inflamed spinal structures are sensitive to stretch, and pain can be elicited by maneuvers that stretch the spine, such as bending the leg with an outstretched knee or bending the neck. As the disease progresses, confusion, coma, and seizures develop. These complications are due to HIE, increased intracranial pressure, and a toxic metabolic encephalopathy. HIE is due to shock. The toxic metabolic encephalopathy is probably caused by unknown diffusible substances (perhaps cytokines) that have a neurotoxic action. DIAGNOSIS AND PATHOLOGY. The cornerstone in the diagnosis of bacterial meningitis is CSF examination. The CSF in meningitis shows hundreds, even thousands of neutrophils and is teeming with organisms. CSF protein is elevated and glucose is low(because it is consumed by inflammatory cells).

Bacteria in the CSF

Inflammatory cells in the subarachnoid space

This purulent exudate covers the cerebral hemispheres and settles along the base of the brain, around cranial nerves and the openings of the fourth ventricle. TheMRI shows enhancement and high FLAIR signal intensity in the meninges, corresponding to the pathology. Meningitis-purulent exudate Meningitis-purulent exudate A child presenting with fever, headache, and CSF pleocytosis is a diagnostic dilemma. Less than 5% of such cases are due to bacterial meningitis and the rest are due to viral (aseptic) meningitis (see viral infections). Yet, to play it safe, physicians admit such patients to hospital and treat them with antibiotics. Unnecessary hospitalizations can be avoided if a standard set of criteria are taken into account. These are: CSF positive Gram stain, CSF absolute neutrophil count (ANC) >100 cells/L, CSF protein >80 mg/dL, peripheral blood ANC >10,000, and a history of preceding seizure. The presence of these findings strongly favors bacterial meningitis. Alternatively, viral PCR of CSF, which has a turnaround time of a few hours, can confirm aseptic meningitis. The late complications of meningitis include cranial nerve deficits and ischemic infarction. The thick fibrinopurulent exudate in the subarachnoid space organizes into fibrous tissue that blocks the exits of the fourth ventricle and impairs CSF circulation around the cerebral convexities. This causeshydrocephalus. These complications take time to develop and may appear after the inflammation has

Postmeningitic hydrocephalus
subsided.

Vascular narrowing after meningitis

They may be prevented by prompt treatment. The effects of HIE and cerebral infarction are especially devastating in newborn babies in whom the brain can literally melt away. The glia limitans, a thick tight mesh of astrocytic processes, joined by dense junctions and covered by basement membrane, resists penetration by bacteria and neutrophils. Undamaged, it provides an effective barrier that prevents the infection from spreading into brain tissue. Thus, brain abscess as a complication of meningitis is rare.

Severe brain atrophy post neonatal meningitis

Brain damage in meningitis is caused not only by bacteria but probably more by host responses. These responses have a protective purpose (to eliminate bacteria) but are excessive and indiscriminate and set in motion destructive cascades that damage everything in their way, mostly host tissues. Modulating these reactions, in addition to killing bacteria, can reduce the morbidity and mortality of meningitis. BRAIN ABSCESS Brain abscess is a newly formed cavity in brain tissue, filled with pus. The bacteria that cause brain abscess spread from adjacent air sinuses or the middle ear, or via the blood stream from

the lungs (bronchiectasis, lung abscess), or from the heart (bacterial endocarditis). The location of the abscess corresponds to its source. Frontal sinusitis causes frontal lobe abscess, and mastoiditis temporal lobe abscess. Hematogenous abscesses are often multiple.

Abscess, early phase

Temporal lobe abscess

Multiple absceses post meningitis

The bacterial flora of brain abscess depends on the source of the infection. In the case of sinusitis and otitis, it is usually mixed, including anaerobes. Bacteremia alone does not cause brain abscess. Some tissue damage, probably a small ischemic lesion, is required to start the process. Bacteria in the blood seed this necrotic nidus and spread around it causing brain necrosis and acute inflammation (cerebritis). The necrotic center cavitates while, at the periphery, a vascular zone of brain tissue with macrophages, mononuclear cells, and reactive astrocytes contains the infection. In 4-5 weeks, collagen (derived from vascular cells) is laid down in this reactive zone forming a thick capsule that walls off the infection. Increased vascular permeability in the inflamed tissue causescerebral edema. Hypervascularity and vascular leakage account for the "ring enhancing" pattern after contrast injection, which gives abscess its characteristic radiological image (necrotic tumors may have a similar appearance). Systemic antibiotics are effective in the phase of cerebritis. Once a capsule develops, it is a barrier to antibiotics. Thus, the treatment of chronic abscess requires drainage or surgical excision in addition to systemic antibiotics. Brain abscess Brain abscess causes loss of neurological function due to destruction of brain tissue. More important, it causes increased intracranial pressure. Its mass effect is due to the collection of pus and to cerebral edema around the abscess. Since the infection is contained within brain tissue, the CSF usually shows only a few mononuclear cells with normal protein and glucose.

http://www.neuropathologyweb.org/chapter5/chapter5aSuppurative.html

Bacterial Meningitis

Bacterial meningitis is a serious infection of the fluid in the spinal cord and the fluid that surrounds the brain.

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Bacterial meningitis is most commonly caused by one of three types of bacteria: Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae bacteria. The bacteria are spread by direct close contact with the discharges from the nose or throat of an infected person. Bacterial meningitis can be treated with antibiotics. Prevention depends on use of vaccines, rapid diagnosis, and prompt treatment of close personal contacts.

What is bacterial meningitis? Meningitis is an infection of the fluid in the spinal cord and the fluid that surrounds the brain. Meningitis is usually caused by an infection with a virus or a bacterium. Knowing whether meningitis is caused by a virus or a bacterium is important because of differences in the seriousness of the illness and the treatment needed. VIRAL MENINGITIS is usually relatively mild. It clears up within a week or two without specific treatment. Viral meningitis is also called aseptic meningitis. BACTERIAL MENINGITIS is much more serious. It can cause severe disease that can result in brain damage and even death.

What bacteria cause bacterial meningitis? Bacterial meningitis is most commonly caused by one of three types of bacteria: Haemophilus influenzae type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Before the 1990s, Hib was the leading cause of bacterial meningitis, but new vaccines being given to children as part of their routine immunizations have reduced the occurrence of serious Hib disease. Today, Neisseria meningitidis and Streptococcus pneumoniae are the leading causes of bacterial meningitis. Meningitis caused by Neisseria meningitidis is also called MENINGOCOCCAL MENINGITIS. Meningitis caused by Streptococcus pneumoniae is called PNEUMOCOCCAL MENINGITIS. It is important to know which type of bacteria is causing the bacterial meningitis because antibiotics can prevent some types from spreading and infecting other people.

Where is bacterial meningitis found? Bacterial meningitis is found worldwide. The bacteria often live harmlessly in a person's mouth and throat. In rare instances, however, they can break through the body's immune defenses and travel to the fluid surrounding the brain and spinal cord. There they begin to multiply quickly. Soon, the thin membrane that covers the brain and spinal cord (meninges) becomes swollen and inflamed, leading to the classic symptoms of meningitis.

How do people get bacterial meningitis? The bacteria are spread by direct close contact with the discharges from the nose or throat of an infected person. Fortunately, none of the bacteria that cause meningitis are very contagious, and they are not spread by casual contact or by simply breathing the air where a person with meningitis has been.

What are the signs and symptoms of bacterial meningitis? In persons over age 2, common symptoms are high fever, headache, and stiff neck. These symptoms can develop over several hours, or they may take 1 to 2 days. Other symptoms can include nausea, vomiting, sensitivity to light, confusion, and sleepiness. In advanced disease, bruises develop under the skin and spread quickly. In newborns and infants, the typical symptoms of fever, headache, and neck stiffness may be hard to detect. Other signs in babies might be inactivity, irritability, vomiting, and poor feeding. As the disease progresses, patients of any age can have seizures.

Who is at risk for bacterial meningitis? Anyone can get bacterial meningitis, but it is most common in infants and children. People who have had close or prolonged contact with a patient with meningitis caused by Neisseria meningitidis or Hib can also be at increased risk. This includes people in the same household or day-care center, or anyone with direct contact with discharges from a meningitis patient's mouth or nose.

How is bacterial meningitis diagnosed? The diagnosis is usually made by growing bacteria from a sample of spinal fluid. The spinal fluid is obtained by a spinal tap. A doctor inserts a needle into the lower back and removes some fluid from the spinal canal. Identification of the type of bacteria responsible for the meningitis is important for the selection of correct antibiotic treatment. What complications can result from bacterial meningitis? Advanced bacterial meningitis can lead to brain damage, coma, and death. Survivors can suffer long-term complications, including hearing loss, mental retardation, paralysis, and seizures.

What is the treatment for bacterial meningitis? Early diagnosis and treatment are very important. If symptoms occur, the patient should see a doctor right away. Bacterial meningitis can be treated with a number of effective antibiotics. It is important, however, that treatment be started early.

How common is bacterial meningitis? In the United States, bacterial meningitis is relatively rare and usually occurs in isolated cases. Clusters of more than a few cases are uncommon. In parts of Africa, widespread epidemics of meningococcal meningitis occur regularly. In 1996, the biggest wave of meningococcal meningitis outbreaks ever recorded hit West Africa. An estimated 250,000 cases and 25,000 deaths in Niger, Nigeria, Burkina Faso, Chad, Mali, and other countries paralyzed medical care systems and exhausted vaccine supplies.

Is bacterial meningitis an emerging infectious disease? With the decline in Hib disease, cases of bacterial meningitis have decreased since 1986. Meningococcal meningitis is a continuing threat in day-care centers and schools. Healthy children and young adults are susceptible, and death can occur within a few hours of onset.

How can bacterial meningitis be prevented?

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Vaccines -- There are vaccines against Hib, some strains of Neisseria meningitidis, and many types of Streptococcus pneumoniae. The vaccines against Hib are very safe and highly effective. By age 6 months of age, every infant should receive at least three doses of an Hib vaccine. A fourth dose (booster) should be given to children between 12 and 18 months of age. The vaccine against Neisseria meningitidis (meningococcal vaccine) is not routinely used in civilians in the United States and is relatively ineffective in children under age 2 years. The vaccine is sometimes used to control outbreaks of some types of meningococcal meningitis in the United States. New meningococcal vaccines are under development. The vaccine against Streptococcal pneumoniae (pneumococcal vaccine) is not effective in persons under age 2 years but is recommended for all persons over age 65 and younger persons with certain medical problems. New pneumococcal vaccines are under development.

http://www.dhpe.org/infect/Bacmeningitis.html

First of all and primarily, you need to know the general inflammatory response because it is what occurs whenever there is any invasion by bacteria, virus or some foreign body or substance. That is basic to ALL body invasions: http://allnurses.com/forums/f50/histamine-effect-244836.html. When you see "itis" at the end of a medical disease, immediately start thinking about the inflammatory response-period, end of story. The cardinal signs and symptoms of inflammation are redness, heat, swelling and pain and these are due to the pathophysiology of the inflammatory response. They are because (1) redness due to the dilation of the blood vessels, (2) heat also due to the vasodilation and increased blood flow, (3) edema due to intravascular fluids leaking into the surrounding tissues from the increased permeability of the blood vessels, and (4) pain due to the pain receptors being stimulated by the swollen tissue and pH changes from all these chemicals excreted during the inflammatory response. It is easy to see these symptoms when the inflammation is, let's say, in a boo boo on the surface of the skin--you see the reddened skin, can feel the heat if you touch it, notice the swollen bump and see the draining pus. When it is occurring inside the body in tissues like the meninges you can't "see" these things happening with your own eyes, but take my word for it--it is going on! We have to

look for other assessment data as evidence of it. Now, with meningitis, the infection is either introduced directly through a fracture of the sinuses or skin contamination if there is a myelomeningocele. The inflammation response kicks right in. However, meningitis is often a complication of some other bacterial infection in the body, often in the paranasal sinuses due to sinusitis, the mastoid due to otitis media or even the lungs (pneumonia). How? The blood stream. Let's go back to the pathophysiology of the inflammatory response. Keep in mind that with any infection inflammation ALWAYS occurs; it is the general response to any bacterial invasion AND it results in vascular permeability. Think of vascular permeability as a free ticket and open doors in the cell walls, an invitation, for any bacteria to hop aboard the River Blood running nearby and take a ride. If they step off at the meninges, hello bacterial meningitis. Now, you are saying that you are having a hard time relating the signs and symptoms with the pathophysiology of meningitis. This is the list of symptoms that I come up with for bacterial meningitis. If I'm missing one that you found, please post it. Every single one of them in some way traces its way back to one of the 4 cardinal signs of inflammation. Keep in mind that the brain is encased in the skull and the spinal cord in the spinal canal so that swelling causes serious problems for them because the tissues have no room to expand, so swollen brain and spinal cord cells get crushed, irritated, start to elicit funky manifestations and if the swelling isn't stopped, they will start permanently dying. y y y y y y y y y headache, often worsens with movement (cardinal sign of Inflammation: Pain) Fever (cardinal sign of Inflammation: Heat--invading bacteria cause the body to reset it's thermostat to a higher level) nausea/vomiting (the effect of the toxic substances spewed into the body by the invading bacteria) weakness (weakness of the muscles secondary to irritation of the nerve cells that control them) photophobia [sensitivity to light] (cardinal sign of Inflammation: Edema--the edema irritates the nerve cells of the optic nerve which produces the visual changes) confusion, delirium (cardinal sign of Inflammation: Edema) seizures (cardinal sign of Inflammation: Edema--the edema irritates the nerve cells of the brain which produces the seizure) meningismus [the general term for irritation of the brain and spinal cord] rigors [sudden chills followed by profuse heat and sweating] (cardinal sign of Inflammation: Heat--invading bacteria cause the body to reset it's thermostat to a higher level) profuse sweating (cardinal sign of Inflammation: Heat--invading bacteria cause the body to reset it's thermostat to a higher level) Kernig's sign [reflex contraction and pain in the hamstring muscles when the leg is flexed and then extended] (a symptom of meningeal tissue irritation due to edema) Brudzinski's sign [neck pain and resistance to flexing the head and neck forward toward the sternum of the chest] (a symptom of meningeal tissue irritation due to edema)

y y y

y y y

declining level of consciousness (cardinal sign of inflammation: Edema) cranial nerve palsies (cardinal sign of Inflammation: Edema--the edema irritates the nerve cells of the spinal cord which results in the palsies) symptoms of increased intracranial pressure (cardinal sign of Inflammation: Edema)

http://allnurses.com/nursing-student-assistance/relating-pathophysiology-signs-301632.html

http://en.wikipedia.org/wiki/Intracranial_pressure