To cause bacterial meningitis, the infecting organism must be able to overcome host defence mechanisms that protect the neuraxis, and their neurotropic qualities derive from their ability to thwart these mechanisms. The upper respiratory tract is the favoured, but not the only, site for colonisation by these organisms which must cross the mucosal epithelium, which secretes IgA. The bacteria render IgA non-functional by secreting IgA proteases and attach to the epithelium by mechanisms that vary between species and await full characterisation. Transient bacteraemia ensues. To enter and survive in the bloodstream, the bacterium must avoid phagocytosis by neutrophils and attack by complement. In this they are often reliant on their polysaccharide capsule. All bacteria commonly causing meningitis have a capsule, the molecular basis of which varies between organisms. Once bacteria are established in the circulation, the blood-brain barrier must be penetrated to enter CSF; this is the least understood element of pathogenesis. The possession of pili to aid binding to surface molecules appears to influence virulence. Once inside the CSF, there is virtually no immunoglobulin, including anticapsular antibodies, or complement activity, so opsonic attack on invading bacteria cannot be mounted.
Host reaction to this bacterial invasion determines the resulting clinical features of meningitis. One of the major features of meningitis is a CSF neutrophil response. The release of bacterial cell wall components into the CSF stimulates the release of inflammatory cytokines, including interleukins 1 and 6, tumour necrosis factor, and prostaglandins, into the CSF and there is strong evidence that their presence induces inflammation and disruption of the blood-brain barrier. The inflammatory response recruits granulocytes to the CSF. By a complex series of interactions, as yet not fully understood, cerebral blood flow increases, inducing vasogenic cerebral oedema and raised intracranial pressure. With the progression of inflammation, cytotoxic oedema develops, cerebral blood flow falls, vasculitis progresses, and intracranial pressure rises further. Interstitial oedema results from obstruction of CSF flow from subarachnoid space to blood. Cerebrovascular autoregulation is disrupted and the brain becomes at risk from either hyper-or hypo-perfusion. Evidence is accumulating that many of these changes occur early in the course of meningitis and treatment regimens that reduce intracranial pressure while maintaining cerebral perfusion and blood flow may be useful.78,79 The clinical features of a typical case of meningitis are fever, malaise, headache, neck stiffness, irritability, and confusion.80 Usually these features appear over the space of a day or two, but in some fulminant cases the signs may develop within hours. In as many as 20% of cases, these typical features may be lacking: this is particularly so with the very young, the very old, the very ill, and those with compromised immune systems. The possibility of meningitis should be entertained in every child or adult in the above groups who has lethargy, altered mental status, drowsiness, or pyrexia, especially if neck stiffness is present. It is important to recognise that neck stiffness may not be present in the early stages of bacterial meningitis81,82 and the physician must include meningitis in the differential diagnosis of a very wide range of diseases.
Convulsions occur with meningitis in any age group, are particularly common in young children, affecting up to 40% of cases, and may be the presenting feature. Convulsions associated with pyrexia - "febrile convulsions" - commonly occur in the very young. Each such patient may have meningitis, which poses the question, does each require a lumbar puncture? Evidence suggests that the answer is "no".83,84 Many febrile convulsions are caused by infection with human herpesvirus type 6.85 If the convulsion is brief and not associated with continuing neurological deficit or focal feature, if the child rapidly regains consciousness and there are no other signs of meningitis, it is reasonable to observe the child closely for some hours rather than perform a lumbar puncture straight away.
Specific features may suggest the aetiology of meningitis. A diffuse maculopapular eruption, which progresses to include petechiae or frank purpura, accompanies 50-60% of cases of meningococcal meningitis. Other bacteria - L. monocytogenes, staphylococci, pneumococci, and H. influenzae - and viruses, particularly echovirus 9, may also cause rashes. Rarely, a rash may be due to a reaction to an antibiotic or other drug but this seldom occurs early in the course of the disease. Focal neurological signs, seizures, and cranial nerve palsies resulting from rhomboencephalitis are seen in some patients with listerial infection.86 Pneumococcal meningitis is associated with otitis media, a history of skull fracture, alcoholism, or sickle cell disease, and up to 50% will have pneumonia. Staphylococci or gram negative bacilli often cause meningitis complicating the implantation of neurosurgical devices such as shunts. In those with immune suppression, including AIDS, simultaneous infection with more than one organism may occur. If there is a history of meningitis, there is probably a dural fistula from previous head injury or, much more rarely, the patient suffers from an inherited complement-deficiency state.
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