Infectious Diseases Of The Ne... Health Article
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Meningitis
Although the word meningitis suggests an inflammation of the meninges only, there is always some involvement of the most superficial parts of the brain that are contiguous to the meninges. Often there are also alterations in the flow of cerebrospinal fluid (CSF). An occlusive arteritis is common in the subpial cortex, so meningitis is properly considered as a meningoencephalitis in all cases. Causative organisms include bacteria, spirochetes, viruses, fungi, and protozoa; sometimes carcinomatous invasion of the meninges produces meningeal inflammation that is hard to clinically differentiate from infective meningitis.
The most common organisms responsible for bacterial meningitis in people over the age of 2 months are Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Listeria monocytogenes, but other organisms such as Escherichia coli and group B streptococci must be considered in neonates. Any of the above organisms and also staphylococci, anaerobes, and mixed infections can be identified in patients with CNS defects or local infections and in those taking immunosuppressants. Most cases of meningitis are associated with infection in the upper respiratory tract, but one should always consider whether the patient may have a lowered resistance to infections or an abnormal portal of entry for organisms to reach the nervous system.
When managing a patient with possible meningeal inflammation, the first step is to confirm the diagnosis and the second is to start appropriate therapy (even before the results of the Gram's stain are available) selected on the basis of an educated guess as to the most likely organism. One has also to consider why this patient developed this infection at this time.
Meningitis may present as an acute, subacute, chronic, or recurrent inflammation of the meninges. It is classed as bacterial (or septic or purulent) when organisms are isolated by routine culture methods. With bacterial infection, polymorphonuclear leukocytes predominate in the CSF. Viruses usually cause an aseptic meningitis in which mononuclear cells predominate and routine cultures do not grow the organism.
Certain pathologic conditions consistently predispose to CNS infections (meningitis, abscess, and encephalopathy) and they must be considered in all patients, if not in the acute stage at least immediately after it. Thus immunosuppressed patients (those with leukemia, lymphoma, or acquired immunodeficiency syndrome [AIDS]; those receiving immunosuppressive drugs including steroids; or after splenectomy) are at risk of infection by measles, herpes zoster, cytomegaloviruses (CMVs), fungi, streptococci, Listeria, or gram-negative bacilli. Skull defects and cranial trauma, including brain surgery, make pneumococcus, staphylococcus, and gram-negative infections more likely. Progressive multifocal leukoencephalopathy is always associated with impaired immune responsiveness, and toxoplasmosis is a common infecting agent in patients with AIDS.
In children, prematurity, perinatal complications, and neural tube defects are predisposing factors for meningitis, which in such cases is usually due to gram-negative organisms.
Acute meningitis is a neurologic emergency. It is most common in the earliest years of life, particularly in premature infants, of whom up to half may die as a result. The peak incidence is in the first 2 years and about three fourths of all cases occur before the age of 10. The death rate in older patients has decreased to about 20%, but continuous developments in therapy do not seem to have lowered it
Acute meningitis evolves over hours or, at most, days. Patients who have been quite healthy or have only had an upper respiratory infection now begin to complain of the symptoms of meningeal irritation and of raised intracranial pressure (ICP). Malaise; fever; headaches of traction type; nausea; vomiting; anorexia; stiff, painful neck; and photophobia are the usual initial symptoms. Depression in the level of consciousness, delirium, seizures, and various focal neurologic signs may follow. The association of fever and any form of mental deterioration must make one consider meningoencephalitis as a possible diagnosis. Inflammatory cells in the CSF and accompanying cerebral edema may cause a rapid rise in ICP and produce false localizing signs.
Examination usually shows meningism, with stiff neck and resistance to flexion of the spine or to straight leg raising. Such signs may be absent in overwhelmingly ill adults and in neonates, who may just show the features listed in , such as a bulging fontanelle, neck stiffness, and drowsiness. Children may also show head retraction, which can be so marked as to warrant the term opisthotonos.
General examination may show a rash (particularly if the meningococcus is involved or echovirus or coxsackievirus is involved); signs of infection in the ears, joints, bones, chest, or heart; and sometimes purpura and hypotension. Shock is common if a gram-negative organism is the cause of septicemia with secondary meningitis and in meningococcal septicemia causing adrenal infarction (WaterhouseFriderichsen syndrome). The combination of fever and purpura in this context can occur with N. meningitidis, echovirus, E. coli, Pseudomonas, Proteus, L. monocytogenes, streptococcus, gonococcus, or Staphylococcus aureus infections.
Whenever there is evidence of meningeal inflammation, a lumbar puncture (LP) must be done eventually, even though some patients with meningitis show early papilledema. Intracerebral abscess or expanding mass lesions, particularly in the posterior fossa, must be ruled out by physical examination, although in the presence of any focal signs an emergency computed tomography (CT) scan is necessary. In this situation an expert opinion should be requested if available. LP should be performed when any such masses are excluded because identification of the organism and determination of its sensitivities are essential; however, if a bacterial process is suspected, antibiotics should be started as soon as blood cultures are drawn and before an LP is done. A patient may be transferred to specialist care from remote areas, with the CSF sample kept warm beside him or her and after the first dose of antibiotic. In infants, LP is indicated in the investigation of pyrexia of unknown origin and may be indicated in any ill child with fever or septicemia, with or without neurologic signs and in the investigation of failure to thrive or seizures.
If the result of the first LP is not conclusive (i.e., no organisms are seen and the cells present are not polymorphonuclear neutrophil leukocytes [PMNs]) the patient can be carefully observed for a period without antibiotics and the test repeated in 12 to 18 hours with a greater chance of finding organisms or diagnostic cell patterns.
The CSF pressure need not be taken if the initial fluid is cloudy or bloodstained because knowledge of the pressure does not contribute to diagnosis in these circumstances. The fluid may be turbid or clear; microscopy may show any number of mononuclear or polymorphonuclear cells. PMNs almost always predominate in acute bacterial meningitis. Mononuclear cells usually predominate in the other forms of meningitis (due to Mycobacterium tuberculosis, viruses, or fungi).
CSF protein levels are raised in all forms of meningitis, particularly those of longer duration or with very high cell counts. Apart from Gram's and Ziehl-Neelsen stains, auramine stains for M. tuberculosis, India ink preparations for fungi, special stains for other organisms, and specific antigen or antibody studies may be needed. The sample should be examined immediately. Many of the above tests are being replaced by DNA amplification techniques. Current polymerase chain reaction (PCR) technology (using the LightCycler) can identify the causative organism within 30 minutes. In many instances a physician will have to rely on the conventional Gram's stain, and occasionally may have to do this personally and
A simultaneous estimation of the CSF blood sugar is mandatory when the LP is done. With most viral meningitides and parameningeal foci of infection, CSF sugar values are often normal. Values will be low (i.e., less than 50% of the blood level) in bacterial meningitis. High PMN counts are to
If there is clinical uncertainty as to whether the patient has bacterial or aseptic meningitis and the patient is not seriously ill, the physician may properly maintain careful observation, withhold antibiotics, and repeat the LP in 12 to 18 hours. With aseptic meningitis, the second CSF sample will almost always show a shift toward mononuclear cell predominance, whereas later examinations will show the eventual disappearance of all PMNs. In bacterial meningitis, PMNs increase quickly, CSF sugar falls, and the protein level rises (
Specific organisms that cause meningitis may be suspected from certain clinical features. Thus (apart from the clinical features of meningitis in general) meningococcal meningitis has a peak appearance between the ages of 2 and 25, tends to occur in epidemics , and may lead to disseminated intravascular coagulation, a purpuric skin rash, and shock from adrenal hemorrhage. Pneumococcal meningitis is mainly a disease of adult life, with a peak incidence in old age. It is particularly common in subjects with an obvious focus of infection elsewhere (e.g., ears, chest, recent skull fracture with CSF leak, or ear, nose, and throat [ENT] operation), in patients with immunologic deficiency, and in alcoholics. H. influenzae infection is common in children up to the age of 2 years in countries in which the vaccine is not used, but it is far less common after the age of 6 years. Patients have often had recent otitis or upper respiratory infection. Adults infected with H. influenzae are likely to have otitis or another parameningeal infection, a CSF leak, or immunologic deficiency.
Staphylococcal and gram-negative meningitis are usually complications of endocarditis or prior head trauma. In such cases the CSF may not show many leukocytes and may be sterile; a blood culture is mandatory in all cases of meningitis, however, so the correct diagnosis should not be missed. L. monocytogenes infections occur in neonates, the elderly, and patients with compromised host defenses. The abrupt onset of signs suggesting meningitis, encephalitis, or abscess in such patients should make one consider this organism. In the first 3 months of life, other commonly responsible organisms include streptococcus (group B), S. aureus, E. coli, and other Enterobacteriaceae.
Urgent management of bacterial meningitis is vital because severe cortical damage or death can result from delay. Blood cultures should be obtained and any skin lesions swabbed before the antibiotic is started. Having obtained the CSF, the physician should hold it up to the light to see if it is cloudy (over 500 cells/ml) or clear, and then take it to the laboratory, where a Gram's stain, culture, cell count, and differential should be performed and the protein and sugar levels estimated. Virus cultures and cytology might be indicated if septic meningitis is excluded by these tests.
Antibiotics should be started at once if the CSF is cloudy and bacterial infection is suspected. In many instances the physician won't know the exact organism until the cultures return, but treatment cannot be delayed that long. Unless clinical clues suggest one particular organism, the patient should begin an empirical regimen likely to be effective against the most common organisms . The smear will indicate the type of organism responsible and thus the correct therapy. If meningococcal meningitis is suspected, intravenous benzylpenicillin should be given even before the patient is transferred to the hospital; the organism may still be grown from the CSF, and this is no time for diagnostic niceties.
Seventy-five percent of adult cases of meningitis will be due to meningococcus or pneumococcus organisms. Penicillin-resistant D. pneumonia is now common in many countries, including the United States and Canada. This has changed our approach to the
Chloramphenicol and the sulfonamides always cross the blood-brain barrier, whereas penicillin and cephalosporins cross well only when there is inflammation of the meninges. Even with inflammation, however, penetration into the CSF is poor with tetracyclines, streptomycin, kanamycin, gentamicin, polymyxin, and colistin. Thus the choice of agents is crucial. The dose should be arrived at by consideration of the severity of the infection and the age of the patient.
Gram-negative meningitis in adults usually complicates trauma, surgery, spinal anesthesia, or chronic debilitating diseases, but is uncommon. Pseudomonas is the organism most often cultured. Ciprofloxacin, 400 mg every 6 hours intravenously, is probably the best agent, but all such cases should be referred to a specialist in infectious diseases.
The duration of antibiotic therapy varies with the organism, the age of the patient, and the clinical course but is usually at least 10 days (2 weeks with pneumococcal
Steroids are recommended as adjunctive therapy in patients with meningitis who are in a coma or who have markedly raised ICP, and in children with H. influenzae meningitis, in whom there is evidence that deafness can be prevented.
Prophylaxis should be used for all household contacts and others closely associated with patients suffering from meningococcal disease (e.g., children in the same nursery school). Rifampin, 600 mg bid for 2 days, is a recommended treatment for adult contacts, whereas in children the dose is 10 mg/kg bid, and in infants 3 months to 1 year of age, 5 mg/kg bid. Prophylaxis is also recommended in contacts of cases of H. influenzae meningitis; rifampin is recommended at a dosage of 20 mg/kg/day (not to exceed 600 mg/day) for adults and children in households or day care centers containing children 4 years of age and younger. The index case should also receive rifampin at the end of the definitive course of treatment. Vaccination against meningococcal disease is also available and is an important public health measure. At diagnosis, the public health service should be informed of all cases of meningitis.
Acute aseptic meningitis is characterized by fever, headache, and meningeal signs. Change in consciousness and localizing neurologic signs are rare. Patients with this disease look and feel wretched but are not severely ill. CSF examination will usually show an increase in mononuclear cells to fewer than 500/mm 3 (although PMNs may be increased in the early stages); the protein is normal or only slightly elevated, and the CSF sugar is usually normal, except with mumps infection.
70% of the known causes of aseptic meningitis are common viral infections (coxsackievirus, echovirus, Epstein-Barr virus, mumps, and lymphocytic choriomeningitis [LCM]). In about 25% of the cases the virus is not defined. The remaining long list of viruses identified includes measles, chickenpox, and influenza. Rarely, the clinical picture of aseptic meningitis may be seen in the preicteric stage of infectious hepatitis or in uremia and in patients with inadequately treated bacterial meningitis.
Management of acute septic meningitis requires only analgesics and reduction in fever; the prognosis here is much better than in bacterial meningitis—the patient is seldom as ill and usually recovers readily. One may attempt to identify the virus by culture of the CSF or by PCR. A chest radiograph, tuberculosis skin test, syphilis serology, blood cultures, and a collagen-vascular screen are commonly ordered. A CT scan may be required to rule out a parameningeal focus. Acute and convalescent antibody titers may implicate enteroviruses or other viruses, but usually no agent is incriminated.
Inadequately treated bacterial meningitis, fungal infections, and tuberculous meningitis (TBM) are the more common causes of subacute meningitis; viral causes are much less common. TBM is the prototype and will be discussed at greatest length.
Tuberculosis is most likely to occur in North America among the native and immigrant populations, among alcoholics, and in those patients with immunologic deficiency or generalized illness. A third of the cases occur before the age of 10. About half of the patients will be known cases of tuberculosis. The illness usually occurs in the active stage of primary infection but may present years later. Tuberculin skin tests are positive in 85% of cases. The organism may be recovered in the sputum as well as from CSF.
Moderate but increasing signs of meningeal inflammation develop over days or weeks. Children present with lethargy, failure to thrive, anorexia, irritability, nausea, and vomiting. In adults, similar symptoms lead to a mild and gradual reduction in consciousness, with confusion and headaches, occasionally seizures, but only moderate evidence of meningeal irritation. Symptoms may have been precipitated by an initial flulike illness or measles.
If untreated, there occurs the slow but relentless progression of extraocular palsies, deafness, cerebellar signs, convulsions, optic atrophy, pupillary abnormalities, delirium, and possibly dementia. In the latest stages decerebrate rigidity occurs. The CSF contains mononuclear cells mainly, up to 500/mm 3 ; the protein is high and the sugar is low.
Unusual presentations include a single seizure in infants and children, isolated focal neurologic signs, the picture of acute meningitis, transverse myelopathy, or a preponderance of psychiatric symptoms in adults. Complications include blindness, deafness, hydrocephalus, spinal block, hypothalamic
The lesion is essentially a basal meningitis with secondary vasculitis. An accumulation of purulent cellular infiltrate over the inferior surface of the brain and brainstem, blocking CSF flow through the fourth ventricle roof foramina, is responsible for the nerve palsies and raised ICP. In meningococcal and pneumococcal meningitis the purulent material is seen over all of the brain surface.
In subacute meningitis, laboratory studies of CSF find large numbers of lymphocytes and elevated protein levels. In TBM, PMNs may predominate in the early stages, and the glucose level is almost always depressed, even to zero. The chance of finding the organism varies with the time taken looking for it on the Ziehl-Neelsen smears. PCR has revolutionized the diagnosis of TBM.
TBM can be treated successfully in almost all cases if therapy is started before the patient becomes unconscious. The generally accepted antibacterial regimen consists of quadruple therapy, with isoniazid, rifampin, pyrazinamide, and ethambutol .
There is disagreement about the use of intrathecal therapy, particularly with antibacterial agents, but it is a good general rule not to inject anything into the intrathecal space if possible. Perhaps the use of steroids intrathecally in TBM is an exception, because this tends to reduce the fibrotic reaction that may block CSF pathways as healing takes place. However, as better antituberculous agents are developed, the need for intrathecal steroids is decreasing.
Cryptococcal meningitis also has an insidious onset, with evidence of a confusional state, focal signs, and raised ICP. Although a smoldering meningitis is the usual presentation, abscesses may form. This condition also occurs in those with immunologic deficiencies, AIDS, diabetes, or chronic alcoholism.
A clinical point of interest in cryptococcal meningitis is the prolonged and severe nature of the headache that precedes cranial nerve palsies, meningism, or increased ICP. The sequential loss of cranial nerve function may be both dramatic and devastating. Diagnosis may be made with India ink–stained CSF preparations, but cryptococcal antigen should be detected in the blood and CSF.
Treatment is with amphotericin B, 0.6 mg/kg/day intravenously to a total dose of 2.5 gm with oral 5-fluorocytosine, continued for 6 weeks. Patients with AIDS need long-term suppressive treatment with fluconazole.
Secondary syphilis, brucellosis, sarcoidosis, and infiltration of the meninges by carcinoma, lymphoma, larval cysts, or fungi are uncommon causes of a similar subacute syndrome.
The term meningismus refers to the condition of meningism without any actual infection of the meninges. Tonsillitis, cervical adenitis, pyelonephritis, and lobar pneumonia are common causes. Other sources of meningeal irritation include blood in the CSF from any cause: otitis, sinusitis, spinal osteomyelitis, and epidural abscess (all parameningeal foci).
Chronic meningitis is uncommon, although it is produced by the same organisms that cause subacute meningitis. The characteristic symptoms include mild fever, headache, depression, lethargy and malaise, and subtle personality change progressing to confusion. Signs include meningism and, frequently, cranial nerve palsies and evidence of raised ICP.
The CSF may show a persistent lymphocytosis with high protein and low glucose levels. In such cases viruses, fungi, bacteria (including leptospira, treponema, and acid-fast bacilli), or malignant cells have variously been found. In sarcoidosis, a chronic basal meningitis may cause focal neurologic signs and, rarely, hydrocephalus, cranial nerve palsies, paraplegia, optic atrophy, or seizures. Meningeal carcinomatosis and leukemias cause headaches and cranial nerve palsies, but seldom long tract signs.
The appropriate treatment of chronic meningitis depends, naturally enough, on its cause and will not be detailed here.
Chronic spinal arachnoiditis is a variant of chronic meningitis. It usually follows intrathecal injection of contrast media, steroids, anesthetics, or antibiotics, but spinal injury or surgery, prolapsed intervertebral disks, and numerous infections (e.g., tuberculosis, syphilis, or viral) have also been held responsible. The thickened meninges, usually in the lumbar region, entrap the nerve roots, causing bilateral burning leg pain at many root levels and local backache. Signs of multiple root lesions are usually detectable, and there may be loss of bladder function. If symptoms begin acutely after spinal surgery, fever may also occur.
Myelography (even though suspected to be a cause) and magnetic resonance imaging (MRI) scanning will confirm the diagnosis. Treatment is surgical, but it is not very effective and the condition tends to recur.
Recurrent acute or subacute meningitis should lead one to search for the reason why repeated infections have involved the CNS. Although spontaneous repeated infection by different organisms is possible, some defect opening up a pathway allowing organisms to penetrate the nervous system is far more likely. In such cases a midline sinus running to the meninges from the upper respiratory tract or from the skin of the head, neck, or spine should be carefully sought, possibly using a magnifying glass. Chronic mastoiditis, sinusitis, agammaglobulinemia, and immunodeficiency syndromes are other possibilities. The condition may occur after splenectomy, in infancy, and also in association with skull fractures, particularly if there has been CSF leakage. Pneumococcus is the most common organism cultured.
Acute meningitis may be mimicked by subarachnoid hemorrhage, encephalopathy of bacterial endocarditis, malignant hypertension, lead poisoning, porphyria, migraine, or viral encephalitis. It may also be hard to differentiate bacterial meningitis from autoallergic acute postinfectious (disseminated) encephalomyelitis (described below). Cerebral abscesses usually have a less acute onset, but thrombophlebitis in association with chronic mastoid or sinus infection and the toxic encephalopathy associated with bacterial endocarditis may present similarly, except that focal signs and evidence of increased ICP are usual in all of these latter conditions.
Certain causes of endarteritis, such as collagen-vascular disease, may also present a similar but milder picture, as may slow virus infections, neoplasms seeding throughout the CSF, and local infections such as spinal osteitis or cranial osteomyelitis (parameningeal foci).
Subacute or chronic meningitis can be confused with cerebral tumor, subdural hematoma, a rapidly progressive dementing illness such as Creutzfeldt-Jakob disease (CJD), or the paraneoplastic encephalopathy of carcinoma.
In patients who recover from meningitis there may be evidence of significant focal residua caused by bacterial vasculitis, cortical infarction, or hydrocephalus. Seizures occur in 10% of those recovering. In infants, subdural effusions and deafness may be associated with H. influenzae and pneumococcal infections, whereas acute or chronic obstructive or normal pressure hydrocephalus may follow meningitis from any cause. Obstructive hydrocephalus is particularly common with TBM, as are deafness or other lower cranial nerve palsies, which occur in 15% of patients with meningitis. Hypothalamic damage and optic atrophy are much less common, except in chronic basal meningitis .
Small infants and children who recover from meningitis may show signs of cerebral palsy, and such upper motor neuron signs may occur temporarily in adults recovering from severe meningitis. Because of the dangers of serious neurologic impairment, early diagnosis and appropriate specific therapy are essential to prevent such tragedies.
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Textbook of Primary Care Medicine, 3rd ed
By: T. Jock Murray, William Pryse-Phillips © 2005 ELSEVIER Inc. All Rights Reserved |
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