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12 CNS INFECTION 2 Lectures
12 CNS INFECTION 2 Lectures
SYSTEM
Meningitis and encephalitis are neurologic emergencies.
Infections of the central nervous system either a primary event or part of systemic infection
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The possibility of meningitis or encephalitis should be suspected in any
severely ill patient presenting with alteration in consciousness, with or without
focal neurologic signs.
With a patient who may have acquired an infection of the nervous system while
traveling: through which country or countries, did the patient travel? And what would
a doctor from the country or travel consider in the differential diagnosis?
Predisposing factors
1. Systemic (especially upper and lower respiratory tract) and parameningeal
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infection.
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2. Mechanical defect of the meninges to the subarachnoid space.
3. Suppressed immunity.
Epidemiology
The annual incidence bacterial meningitis is between 3-5/100000 overall population. The
highest attack rate of all bacterial species is in children under 1 year of age and falls
off rapidly with increasing age.
Aetiological agents:
The agents causing bacterial meningitis vary with the age of the patient, the route by which
infection is acquired, and the presence of associated or predisposing conditions.
1. Group B streptococci.
2. Escherichia coli.
3. Listeria monocytogenes.
1. Haemophilus influenzae.
2. Neisseria meningitides.(Meningococcus)
3. Streptococcus Pneumoniae.
1. Neisseria meningitides.(Meningococcus)
2. Streptococcus pneumoniae.
1. Streptococcus Pneumoniae.
2. Listeria monocytogenes.
subarachnoid space.
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1. staphylococci.
2. Escherichia coli.
3. Pseudomonas aeruginosa.
4. Streptococcus Pneumoniae.
1. Streptococcus Pneumoniae.
2. Listeria monocytogenes.
3. Pseudomonas aeruginosa.
4. Escherichia coli.
Once in the subarachnoid space; bacteria multiply in the cerebrospinal fluid. A critical
event in the pathogenesis of bacterial meningitis is the inflammatory reaction induced by
the invading bacteria. Many of the neurologic manifestations and complications of bacterial
meningitis result from the immune response to the invading pathogen rather than from
direct bacteria-induced tissue injury. The lysis of bacteria with the subsequent release of
cell-wall components into the subarachnoid space is the initial step in the induction of the
inflammatory response and the formation of a purulent exudate in the subarachnoid space.
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Clinical features
Meningitis can present as either an acute fulminant illness that progress rapidly in a few
hours that the patient becomes comatose within a few hours of the first symptoms or
progressively worsens over several days.
Neck stiffness is the pathognomonic sign of meningeal irritation and is present when the
neck resists passive flexion. Kernig's sign (with the hip joint flexed to a 90°angle, extension
at the knee causes spasm in the hamstring muscles and inability to allow full knee
extension) and Brudzinski's sign (passive flexion of the neck causes flexion of the thighs
and knees) are also classic signs of meningeal irritation. Meningism seen in about 80% of
the cases,but are often absent in the two extremes of life and in comatose patients.
In awake patients, a more sensitive test is to ask patients to put their chin on their chest
with the mouth closed.
Seizures occur as part of the initial presentation of bacterial meningitis or during the
course of the illness.
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coagulation. There is associated profound hypotension, shock with peripheral cyanosis,
gangrene of the extremities, and spontaneous systemic bleeding.
The petechial rash is evident in 60% of adults and up to 90% of children
Diagnosis
Early diagnosis and treatment reduces mortality and the incidence of complications.
The diagnosis depends on:
1. Suspicious clinical symptoms and signs.
2. CT of head to rule out abscess or other space-occupying lesion, if it can be done
quickly. CT scanning can reveal skull fractures, or parameningeal septic foci.
3. Lumbar puncture.
Examination of cerebrospinal fluid is crucial for the diagnosis of meningitis. The main risk
of lumbar puncture is fatal pressure coning; this is rare in spontaneous meningitis. If there
is any suggestion of raised intracranial pressure and/or focal neurological signs, newly
onset seizure, immunocompromized patient or disturbance level of consciousness, CT
scanning is indicated.
3. A bleeding diathesis.
very sensitive ). CSF bacterial antigen assay is positive in 50-95 %. CSF bacterial PCRs
are increasingly available.
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Other tests
1. Blood cultures should be taken. The causative organisms of bacterial meningitis can
often be detected in blood cultures.
2. Petechial skin lesions, if present, should be biopsied. The rash of meningococcemia
results from the dermal seeding of organisms with vascular endothelial damage, and
biopsy may reveal the organism on Gram's stain.
3. Blood count. May reveal polymorphnuclear leukocytosis related to systemic infection or
leucopenia reflecting immunosuppression.
4. Chest and skull (sinus) radiography to identify the primary source of infection.
5. Serum C-reactive protein and procalcitonin levels can aid in the differentiation of
bacterial from viral meningitis. These inflammatory markers are more elevated in
bacterial infection.
Differential diagnosis
3. Aseptic meningitis.
Complications
1. Hydrocephalus.
2. Subdural empyema. This is a collection of pus in the subdural space.
3. Cerebral infarction.
6. Septic shock.
Management
Unlike most other diseases, the management of patients with suspected meningitis or
encephalitis begins with empiric therapy. The etiologic organism cannot always be
identified. The goal is to identify those that are treatable, provide supportive care for those
that are not, and, when possible, prevent the neurologic complications of these infections.
Antibiotic treatment must be started immediately the diagnosis is suspected clinically; this
is especially important in meningococcal meningitis/septicaemia. Antimicrobial treatment
should then be started, based on clinical assessment, before the results of the
examination of cerebrospinal fluid are known. Empirical treatment is dictated by the clinical
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In Immunocompromised patients (over age 50, or those with suspected impaired cell-
mediated immunity because of chronic illness, organ transplantation, pregnancy,
malignancies, or immunosuppressive therapy), ampicillin should be added to vancomycin
and ceftazidime combination.
Once the aetiological agent has been isolated and its susceptibilities determined, the
empirical treatment should be changed, if necessary, to an agent or agents specific for the
isolate.
Septicaemic patients require careful monitoring and treatment of shock. Multiple organ
failures may require intensive medical support, including ventilation and dialysis.
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Raised intracranial pressure: raising the head of the bed to 30°, administration of mannitol
or dexamethasone, and mechanical hyperventilation may lower intracranial pressure.
Prevention
Household and other closed contacts of patients with Meningococcal infection, prophylaxis
should be given. Two days of oral Rifampicin 600mg/12hours or single dose of
Ciprofloxacin 500mg.
Prognosis
Acute bacterial meningitis carries an untreated mortality of 70 to 100 per cent.
Mortality is 3 to 7% for meningitis caused by H. influenzae, N. meningitidis, or group B
streptococci; 15% for that due to L. monocytogenes; and 20% for S. pneumoniae.
Pneumococcal disease is also more likely to result in long term sequelae. In
meningococcus infection, mortality is doubled if the patient presents with features of
septicaemia rather than meningitis. Recurrent pyogenic meningitis implies an underlying
anatomical or immunological defect.
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Tuberculous central nervous system infection usually results from reactivation of
latent infection with mycobacterium tuberculosis which is an acid-fast bacillus. It is passed
between persons through respiratory droplets. Mycobacteria multiply in alveolar spaces,
and within 2 to 4 weeks hematogenous spread from the primary lesion to extrapulmonary
sites occurs. But it can be as a result of seeding through the bloodstream from a site of
chronic infection. Tuberculous central nervous system infection develops most commonly
shortly after a primary infection in children and adolescents or as part of miliary
tuberculosis. Rather, small, caseous microtubercles develop in the brain, meninges, skull
or vertebrae close to the meninges in the course of primary infection. Here the organism
remains in a dormant state in tubercles. Tuberculous meningitis results from rupture of a
subependymal microtubercle, discharging tuberculoprotein and mycobacteria into the
subarachnoid space. Deeper tubercles enlarge and become tuberculomas.
Mycobacterial infection may involve the spinal cord either as a spinal arachnoiditis,
producing radiculopathy or myelopathy. Or by extradural compression from a tuberculoma
or vertebral bone infection. Tuberculous spondylitis may result in an epidural abscess.
Usually the thoracic cord is affected. Infarction in the territory of the anterior spinal artery
can be caused by the endarteritis.
Fluid, electrolyte, and acid-base disturbances are common, the result of vomiting,
inadequate fluid intake, and the syndrome of inappropriate secretion of antidiuretic
hormone.
Mycobacterial infection develops when a caseating focus discharges its contents into the
subarachnoid space. Microglial cells are the principal targets of Mycobacterium
tuberculosis. Tumor necrosis factor released from these cells plays a critical role in
containing the infection.
Cerebral vessels may be affected by adjacent meningeal inflammation, producing
vasospasm, constriction, and eventually thrombosis with cerebral infarction. Infarcts are
most often located within the internal capsule, basal ganglia, and thalamus.
The hallmark pathologic feature of tuberculous central nervous system infection is the
presence of a thick exudate most prominent in the basilar meninges. This exudate can
block the flow of CSF and result in hydrocephalus. The entrapment of intracranial vessels
within exudates often produces cerebral infarction. If the basal inflammatory process
affects the brain parenchyma, it can result in encephalopathy.
Clinical features
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Mycobacterium tuberculous central nervous system infections take a variety of forms
including:
1. Subacute meningitis
About 10 per cent of patients develop symptoms and signs of spinal arachnoiditis
(radiculopathy: radicular pain, segmental weakness and urinary retention), or (myelopathy:
weakness with sensory loss below the level of the lesion).Tuberculous spondylitis may
result in epidural abscess
3. Tuberculoma (a large caseous tubercle): The patient may present with constitutional
symptoms and manifestations of space occupying lesion.
Diagnosis
Because of the variety of presenting forms and the difficulty in diagnosis, high index of
suspicion should be maintained.
Its opening pressure is raised in most patients, but may be low in those developing block
from spinal arachnoiditis.
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The cerebrospinal fluid appears clear or slightly turbid but may form a spider's web clot on
standing. Lymphocytic pleocytosis. The glucose concentration in cerebrospinal fluid is low.
Tubercle bacilli can be detected in cerebrospinal fluid in 10 to 20 per cent of cases and
more in clot. This figure decrease children.
Differential diagnosis
1. partially treated bacterial meningitis.
2. neoplastic infiltrations of the meninges (for example, carcinomas, leukaemias,
lymphomas).
A febrile patient with cranial nerve palsies, cerebrospinal fluid (CSF) lymphocytosis and
low CSF glucose is likely to have tuberculosis, whereas an afebrile patient with normal or
mildly reduced CSF glucose is more likely to have malignant meningitis.
3. Fungal infections.
Treatment
Full treatment must be started when the diagnosis is suspected on clinical grounds.
First-line antituberculous medications include rifampicin, isoniazid, pyrazinamide,
ethambutol , and streptomycin.
Isoniazid and pyrazinamide are freely distributed into the cerebrospinal fluid. During this
active phase of meningitis, most antituberculosis drugs achieve therapeutic concentrations
in the cerebrospinal fluid.
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For multidrug resistant tuberculosis the intensive (initiation) phase extended to 4 months
and employs five drugs. the continuation phase extended to 18 months with three drugs.
In adults, daily single doses of 300 mg isoniazid, 600 mg rifampicin, and 1500 mg
pyrazinamide provide adequate concentrations in the serum and cerebrospinal fluid of
patients with active tuberculous central nervous system infection .
Tuberculomas usually respond very slowly to antituberculosis drugs and it usually takes at
least 24 months or longer for the lesions to disappear.
Complications
There are permanent complications in 10 to 30 per cent of survivors
intellectual impairment
recurrent seizures
blindness
deafness
squints
residual motor deficit
Prognosis
The untreated mortality of tuberculous central nervous system infection is close to
100 per cent.
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Complete recovery is the rule if treatment is started before the appearance of focal signs
or stupor.
The overall prognosis remains poor, 10–20% case fatality. Treatment delay, Age <5 or >50
years, and coma at the time of presentation is the most significant predictor of a poor
prognosis.
VIRAL ENCEPHALITIS
Definition In distinction to meningitis, where the infectious process and associated
inflammatory response is limited largely to the meninges, in encephalitis the brain
parenchyma is also involved. Many patients with encephalitis also have evidence of
associated meningitis (meningoencephalitis) and, in some cases, involvement of the
spinal cord or nerve roots (encephalomyelitis, encephalomyeloradiculitis).
Etiology
Clues that may suggest a specific virus include
1. The time of year
2. Recent travel
3. Contact with insects or other animals
4. Sexual contacts
5. Immunosuppression
Encephalitis has been postulated to follow spread of virus from trigeminal ganglia through
sensory fibers to the meninges overlying temporal lobes and orbitofrontal cortex.
Alternatively, encephalitis could arise following reactivation of a latent virus within the
brain.
Clinical Manifestations
In addition to the acute febrile illness with evidence of meningeal involvement
characteristic of meningitis, the patient with encephalitis commonly has an altered level of
consciousness, seizures and evidence of either focal or diffuse neurologic signs or
symptoms.
The most commonly encountered focal findings are aphasia, ataxia, hemiparesis,
involuntary movements, and cranial nerve deficits.
Features of viraemia include lymphadenopathy and pharyngitis.
Laboratory Diagnosis:
CSF examination should be performed in all patients with suspected viral encephalitis
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TREATMENT
Basic management and supportive therapy should include:
1. Careful monitoring of intracranial pressure.
2. Fluid restriction and avoidance of hypotonic intravenous solutions.
3. Suppression of fever.
4. Seizures should be treated with standard anticonvulsant regimens
Pathology
The lesions take the form of an intense hemorrhagic necrosis of the inferior and medial
parts of the temporal lobes and the orbital parts of the frontal lobes.
The temporal lobe lesions are usually bilateral but need not be symmetrical. This
distribution of lesions is so characteristic.
In the acute stages of the disease, intranuclear eosinophilic inclusions which are minute
particles are found in neurons and glial cells, in addition to the usual microscopic
abnormalities of acute encephalitis.
Clinical Features
The symptoms, which evolve over several days, are in most cases like those of any other
acute encephalitis namely, fever, headache, seizures, confusion, stupor, and coma.
Other manifestations include olfactory or gustatory hallucinations, anosmia, temporal lobe
seizures, a brief period of personality change, bizarre or psychotic behavior, aphasia, and
hemiparesis.
The CSF is often under increased pressure and almost invariably shows a lymphocytic
pleocytosis. oftenly there are few red cells. The protein content is increased in most cases.
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Rarely, the CSF glucose levels may be reduced to slightly less than 40 mg/dL
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Differential diagnosis
1. Cerebral vasculitis
2. Brain abscess
Diagnosis The diagnosis may be difficult. Acute herpes simplex encephalitis must be
distinguished from other types of viral encephalitis.
The EEG changes, consisting of lateralized periodic slow-wave complexes in the temporal
regions are suggestive though not specific for the disease.
CT and MRI show the affected areas with surrounding oedema and sometimes with
scattered areas of haemorrhage occupying the inferior parts of the frontal and temporal
lobes.
The application of the polymerase chain reaction to amplify DNA from the CSF are proving
to be useful in diagnosis in the first few days of the illness, while the virus is replicating,
and enable one to avoid brain biopsy. The only other absolute way to establish the
diagnosis of acute HSV encephalitis is by fluorescent antibody study and by viral culture of
cerebral tissue obtained by brain biopsy.
Treatment Acyclovir is given intravenously in a dosage of 30-45 mg/kg per day and
continued for 14 to 21 days in order to prevent relapse. The main problems with acyclovir
are local irritation of the veins used for infusion, mild elevation of hepatic enzymes, or
transient impairment of renal function.
Clinical manifestation
Initial manifestations include poor school performance and mood and personality changes.
Typical signs of a CNS viral infection, including fever and headache, do not occur. As the
disease progresses, patients develop progressive intellectual deterioration, focal and/or
generalized seizures, myoclonus, cerebellar ataxia, and visual disturbances. In the late
stage of the illness, patients develop disturbance of level of consciousness, and spastic
quadripareses.
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Diagnostic studies
MRI is often normal early areas develop in the white matter of the brain and brainstem as
disease progresses.
The EEG may initially show only nonspecific slowing, but with disease progression,
patients develop a characteristic periodic pattern with bursts of high-voltage, sharp, slow
waves every 3–8 s, followed by periods of attenuated (“flat”) background.
The CSF is acellular with a normal or mildly elevated protein concentration and a markedly
elevated gamma globulin level (>20% of total CSF protein). CSF antimeasles antibody
levels are invariably elevated, and oligoclonal antimeasles antibodies are often present.
Measles virus can be cultured from brain tissue.
Viral antigen can be identified immunocytochemically, and viral genome can be detected
by in situ hybridization or PCR amplification.
TREATMENT
No definitive therapy for SSPE is available. Treatment with isoprinosine alone or in
combination with intrathecal or intraventricular alpha interferon, has been reported to
prolong survival and produce clinical improvement in some patients.
Fungal meningitis
Fungal meningitis is a rare infection in immunocompetent patients, but it remains a
significant cause of morbidity and mortality in immunocompromised, elderly, and with
cancer. Cryptococcal meningitis is the most common form of fungal meningitis, but there
are dozens of fungi that can cause meningitis. Certain geographic areas have a higher
incidence of certain forms of fungal meningitis based on the relatively higher
concentrations of the organism in those areas.
Epidemiology
Cryptococcal meningitis comprises 4–8% of all forms of meningitis in the elderly or
patients with cancers.
Clinical manifestation
Patients with fungal meningitis often present with subacute course of headache and
meningeal irritation signs with or without fevers. The most important factor in diagnosing
fungal meningitis is suspecting it.
Laboratory Studies
A lumbar puncture helps the clinician to narrow the differential diagnosis, but confirming
fungal meningitis requires specific organism specific testing.
The combination of a lymphocytic predominance on CSF cell counts and normal to mildly
low glucose suggests a nonbacterial and possibly fungal etiology . An India ink stain can
be helpful in identifying cryptococcal meningitis, but it has a low sensitivity. Serum and
CSF antigens and antibodies to specific organisms can confirm a diagnosis if positive, but
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Treatment
Fungi as a class of organisms generally respond well to a few broad-spectrum antifungal
medications. Treatment of fungal meningitis must balance the morbidity from the organism
against the toxicity of the medications.
Fungal infections respond well to amphotericin and/or fluconazole.
Prognosis
There are many factors that affect the prognosis in patients with fungal meningitis.
Because the majority of patients that get fungal meningitis are immunocompromised, the
patient’s underlying comorbidities dramatically affect the patient’s outcome. Certain
factors, such as hydrocephalus, altered mental status, and an elevated CSF pressure,
increase the risk of an unfavorable outcome.
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