Transcript Central nervous system infections

Central nervous system:
 The brain and
 Spinal cord
They are protected from mechanical pressure or
deformation by enclosure in rigid containers:
 the skull and
 vertebral column, which also act as barriers to the
spread of infection.
Central nervous system infections
 Blood vessels and
 Nerves that traverse the walls of the skull and vertebral
column are the main routes of invasion.
Central nervous system infections
 Blood-borne invasion is the most common route of
infection:
 polioviruses
 Neisseria meningitidis.
Central nervous system infections
 Invasion via peripheral nerves is less common:
 herpes simplex,
 varicella-zoster and
 rabies viruses.
Central nervous system infections
 Local invasion :
-from infected ears or sinuses,
-local injury
-congenital defects such as spina bifida
-invasion from the olfactory tract :
amebic meningitis: rare.
INVASION OF THE CENTRAL NERVOUS
SYSTEM
 Natural barriers act to prevent blood-borne
invasion
Blood-borne invasion takes place across:
 the blood-brain barrier: encephalitis
 the blood-cerebrospinal fluid (CSF) barrier:
meningitis .
Structures of the blood-brain and blood-cerebrospinal fluid
(CSF) barriers.
CNS invasion
 rare
 most microorganisms fail to pass from blood to the
CNS across the natural barriers.
 CNS involvement by polio, mumps, rubella or
measles viruses is seen in only a very small
proportion of infected individuals.
 The factors that determine such CNS invasion are
unknown.
Herpes simplex virus (HSV)
Varicella-zoster virus (VZV)
 present in skin or mucosal lesions
 travel up axons
 to reach the dorsal root ganglia
Rabies virus
 introduced into muscle or subcutaneous tissues by
the bite of a rabid animal,
 infects muscle fibers and muscle spindles after the
virus binds to the nicotinic acetylcholine receptor.
 It then enters peripheral nerves and travels to the
CNS, to reach glial cells and neurones, where it
multiplies
The mechanism of central nervous system (CNS) invasion by
poliovirus.
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THE BODY'S RESPONSE TO INVASION
 CSF cell counts increase in response to infection
The response to invading viruses
 is reflected by an increase in
-lymphocytes,
mostly T cells, and
monocytes in the CSF
The response to invading viruses
-A slight increase in protein also occurs,
the CSF remaining clear.
This condition is termed 'aseptic' meningitis.
The response to invading bacteria
 more spectacular and more rapid increase in
polymorphonuclear leukocytes and proteins
 the CSF becomes visibly turbid.
 This condition is termed 'septic' meningitis.
 Certain slower growing or less pyogenic
microorganisms induce less dramatic changes, such
as in tuberculous or listerial meningitis.
Change in CSF in response to invading microorganism
The pathologic consequences of CNS
infection depend upon the microorganism
 Invading bacteria and protozoa generally
induce more dramatic inflammatory events,
which limit local spread so that infection is
soon localized to form abscesses.
Pathologic changes
 For viruses:
 several days
 occasionally, years ( subacute
sclerosing panencephalitis (SSPE)
 Bacteria
 Rapid
MENINGITIS
 Bacterial meningitis
 Acute bacterial meningitis is a life-threatening
infection, needing urgent specific treatment
 Bacterial meningitis is more severe, but less common,
than viral meningitis and may be caused by a variety
of agents
Bacterial MENINGITIS
 Haemophilus influenzae type b (Hib): Prior to the
1990s before the vaccine
 Neisseria meningitidis
 Streptococcus pneumoniae
 All have a polysaccharide capsule.
Meningococcal meningitis
 Neisseria meningitidis is carried by
about 20% of the population, but in
epidemics higher rates are seen
 Meningococcal septicemia showing a
mixed petechial and maculopapular
rash on the extremities and exterior
surfaces.
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Meningococcal meningitis
 Neisseria meningitidis
 Gram-negative diplococcus
 The bacteria are attached by their pili to the
epithelial cells in the nasopharynx.
 Invasion of the blood and meninges is a rare
and poorly understood event.
Meningococcal meningitis
 Neisseria meningitidis
 Person-to-person spread:by droplet infection
 Overcrowding such as prisons, military barracks
and college dormitories contribute to the
frequency of infection in populations
 During outbreaks of meningococcal meningitis,
which most frequently occur in late winter and
early spring, the carrier rate may reach 60-80%.
A diagnosis of acute Meningococcal meningitis is usually
suspected on clinical examination
 Laboratory identification of the bacterial cause of acute
meningitis is essential
 so that appropriate antibiotic therapy can be given and
prophylaxis of contacts initiated.
 Preliminary microscopy results involving white cell counts
and Gram-staining for bacteria should be available within
an hour of receipt of the CSF sample in the laboratory.
 Results of culture of CSF and blood should follow after 24 h
 Antigen detection
 NAT
A diagnosis of acute Meningococcal meningitis is
usually suspected on clinical examination
 Close contacts in the family referred to as
'kissing contacts' should be given rifampin
chemoprophylaxis for 2 days.
 vaccine
Haemophilus meningitis
 Type b H. influenzae causes meningitis in infants and young
children
 H. influenzae is a Gram-negative coccobacillus.
 Maternal antibody protects the infant up to 3-4 months of age, but as it
wanes, there is a 'window of susceptibility' until the child produces
his/her own antibody.
Acute H. influenzae meningitis is
commonly complicated by severe
neurologic sequelae
 It is important to note that the organisms may be
difficult to see in Gram-stained smears of CSF,
particularly if they are present in small numbers.
 H. influenzae type b (Hib) vaccine is
effective for children from 2 months of age
 An effective Hib vaccine, suitable for children 2
months of age and upwards, is available.
Pneumococcal meningitis
 Streptococcus pneumoniae is a common cause of
bacterial meningitis, particularly in children and the
elderly
Pneumococcal meningitis
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Strep. pneumoniae
a capsulate Gram-positive diplococcus
carried in the throats of many healthy individuals
Invasion of the blood and meninges is a rare event, but
is more common:
 in the very young (<2 years of age),
 in the elderly, in those with sickle cell disease, in debilitated
or splenectomized patients and following head trauma.
 The protection is type-specific and there are more
than 85 different capsular types of Strep. pneumoniae.
Pneumococcal meningitis
 Since penicillin-resistant pneumococci have been
observed worldwide, attention must be paid to the
antibiotic susceptibility of the infecting strain, and
empiric chemotherapy usually involves a
combination of vancomycin and either cefotaxime
or ceftriaxone.
Laboratory diagnosis
 Microscopy is highly sensitive, as is culture, unless the
patient has been treated with antibiotics
 Antigen test for pneumococcal C polysaccharide is
sensitive with CSF (meningitis) but not with urine
(meningitis, pneumonia, other infections)
 Nucleic-acid-based tests are not commonly used for
diagnosis
 Culture requires use of enriched-nutrient media (e.g.,
sheep blood agar); organism highly susceptible to many
antibiotics, so culture can be negative in partially treated
patients
Pneumococcal meningitis
 Immunization with 7-valent conjugated vaccine is
recommended for all children younger than 2 years
of age; a 23-valent polysaccharide vaccine is
recommended for adults at risk for disease (e.g.
sickle cell disease, HIV infection, chronic illness or
weakened immune systems) for serious
pneumococcal infection.
Listeria monocytogenes meningitis
 Listeria monocytogenes causes meningitis in
immunocompromised adults
 Gram-positive coccobacillus
Neonatal meningitis
 especially those with low birth weight
Although mortality rates due to neonatal meningitis in resourcerich countries are declining, the problem is still serious
 the most frequent agents:
 group B hemolytic streptococci (GBS)
 E. coli
 nosocomial infection
 from the mother
Tuberculous meningitis
 always have a focus of infection elsewhere
 approximately 25% may have no clinical or historic
evidence of such an infection
 In >50% of cases, meningitis is associated with acute
miliary tuberculosis
 In areas with a high prevalence of tuberculosis:
 Most common: in children from 0-4 years of age
 In areas where tuberculosis is less frequent
 Most common: adults
Tuberculous meningitis usually presents with a
gradual onset over a few week
 Spinal tuberculosis is uncommon now except in
resource-poor countries; bacteria in the vertebrae
destroy the intervertebral disks to form epidural
abscesses. These compress the spinal cord and lead to
paraplegia.
Fungal meningitis
 Cryptococcus neoformans : major cause
 Coccidioides immitis
Cryptococcus neoformans meningitis
 Common in patients with depressed cell-mediated immunity
 capsulate yeasts: India-ink-stained preparations of CSF and can be
cultured .
 Antigen
 a useful diagnostic tool
 a measure of successful therapy.
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Protozoal meningitis
 Naegleria
 the free-living ameba
 If inhaled they can reach the meninges via the
olfactory tract and cribriform plate.
 rapid onset
 mortality rate is high.
 Under the microscope, Naegleria appear as
slowly motile amebae on careful
examination of a fresh wet sample of CSF.
Protozoal meningitis
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Acanthamoeba spp.
In immunocompromised
enter via the skin or the respiratory tract.
Acanthamoeba causes a chronic condition (granulomatous
amebic encephalitis).
 can be visualized in brain biopsies.
Viral meningitis
 Viral meningitis is the most common type of meningitis
 milder disease than bacterial meningitis
 The CSF is clear in the absence of bacteria,
 the cells are mainly lymphocytes, although polymorphonuclear leukocytes may
be present in the early stages
 NAT
Viral meningitis
 Viral meningitis is the most common type of meningitis
 There are five groups of human enteroviruses which include the
echoviruses, coxsackie Group A and B viruses, and the three
polioviruses.
 Enteroviruses are common causes of seasonal aseptic meningitis.
 In contrast to bacterial meningitis, viral meningitis usually has a benign
course, and complete recovery is the rule.
Diagnosis
 NAT techniques
 Spesific antibody index (Serum and CSF antibody
and albumin or Immunoglobulin values)in (SSPE)
ENCEPHALITIS
 Encephalitis is usually caused by viruses, but there
are many cases where the infectious etiology is not
identified
HSV ENCEPHALITIS
In neonates: after vaginal
delivery: HSV-2
In older children and adults:
HSV-1, of which most are due
to virus reactivation in the
trigeminal ganglia
HSV ENCEPHALITIS
 Herpetic skin or mucosal lesions may be present.
 HSV DNA in CSF sample using PCR.
 In untreated patients : 70% mortality
 early and prolonged treatment with intravenous
aciclovir
Enteroviral infections
 Poliovirus used to be a common cause of encephalitis
 There are successful vaccines. The disease is
completely preventable by vaccination and has been
disappearing in resource-rich countries since
vaccination programs were first carried out in the
1950s .
Enteroviral infections
 Enterovirus-71-associated hand, foot and mouth
epidemic resulted in a high rate of neurologic
complications
 Other enteroviruses such as coxsackieviruses and
echoviruses occasionally cause meningoencephalitis.
Treatment is supportive and there is no vaccine.
Paramyxoviral infections
 Mumps virus is a common cause of mild encephalitis
 Asymptomatic CNS invasion may be common because
there are increased numbers of cells in the CSF in about
50% of patients with parotitis; on the other hand,
meningitis and encephalitis are often seen without
parotitis.
Paramyxoviral infections
 Nipah virus encephalitis, an emerging
zoonotic paramyxovirus infection
 In 1998, an outbreak of encephalitis with a
high mortality rate was reported among pig
farm workers in Malaysia. In total, there were
105 deaths among 265 patients with Nipah
virus encephalitis.
Rabies encephalitis
 The causative agent of rabies is a rhabdovirus, a bullet-
shaped single-stranded RNA virus. The Lyssavirus genus
sits within the Rhabdoviridae family.
Rabies encephalitis
 The virus is excreted in the saliva of infected dogs,
foxes, jackals, wolves, skunks, raccoons and vampire
and other bats, and transmission to humans follows a
bite or salivary contamination of other types of skin
abrasions or wounds.
 The infection is eventually fatal, although the course
of the disease varies considerably between species.
 If an apparently healthy dog is still healthy 10 days
after biting a human, rabies is extremely unlikely.
However, the virus may be excreted in the dog's saliva
before the animal shows any clinical signs of disease.
Rabies encephalitis
 The incubation period in humans is generally 4-13
weeks, although it may occasionally be as long as 6
months, possibly due to a delay in virus entry into
peripheral nerves. The virus travels up peripheral
nerves and, in general, the further the bite is from the
CNS, the longer the incubation period. For instance, a
bite on the foot leads to a longer incubation period
than a bite on the face.
Rabies encephalitis
 While the virus is travelling up the axons of motor or
sensory neurones, there is no detectable antibody or cellmediated immune response, possibly because antigen
remains sequestered in infected muscle cells. Hence,
passively administered immunoglobulin may be given
during the incubation period.
 Once rabies has developed it is fatal, death occurring
following cardiac or respiratory arrest. Paralysis is often a
major feature of the disease. One or two patients treated in
intensive care units have recovered, but with serious
neurologic sequelae.
Rabies encephalitis
 Rabies can be diagnosed by detecting viral antigen or
RNA
Laboratory diagnosis can be made by the detection of viral
antigen by immunofluorescence or using PCR to detect
rabies viral RNA in skin biopsies, corneal impression
smears or brain biopsy. Characteristic intracytoplasmic
inclusions called Negri bodies are seen in neurones . There
is no treatment except supportive care.
Many countries have developed vaccination programs for
domestic dogs, e.g. France, and in Canada and elsewhere,
wild foxes have been vaccinated by dropping food baited
with live virus vaccine from the air.
Rabies encephalitis
 After exposure to a possibly infected animal, immediate
preventive action should be taken
 This action includes:
 Prompt cleaning of the wound (alcoholic iodine, debridement)
 Confirmation of whether or not the animal is rabid (clinical
observation of suspected dogs, histologic observation of the brain of
other suspected species)
 Administration of human rabies immunoglobulin(HRIG) to ensure
prompt passive immunization. Half of the dose is given into the wound
and half intramuscularly
 If the risk is definite, active immunization with killed diploid cellderived rabies virus(HDCV) . The chances of preventing the disease are
greater when vaccination is started as early as possible after infection.
(0,3,7,28,90)
Multiple cytoplasmic Negri bodies in pyramidal
neurones of the hippocampus in rabies.
Togavirus and
Flavivirus(Arboviruses) meningitis
and encephalitis
 Numerous arthropod-borne togaviruses can cause meningitis or
encephalitis
 sometimes cause outbreaks of infection
 In different parts of the world, different mammals, birds or even reptiles act as
reservoirs and there are a variety of arthropod (mosquito and tick) vectors.
 Usually, <1% of humans infected develop neurologic disease . There may be a
febrile illness, but asymptomatic infection is common.
 In California:
 Western equine encephalomyelitis (WEE) virus
 St Louis encephalitis (SLE) virus : transmitted by the mosquito Culex tarsalis; a WEE
vaccine is available, but only for horses.
 Japanese encephalitis virus infection: in India a vaccine for humans has been
developed.
 West Nile virus, another emerging viral cause of encephalitis
Retrovirus meningitis and
encephalitis
 HIV can cause subacute encephalitis, often with dementia
 HIV often invades the CNS
 İndistinguishable from the neurologic disease caused by
microorganisms such as T. gondii, C. neoformans, cytomegalovirus and
JC virus. JC virus, a polyomavirus, occasionally invades
oligodendrocytes in immunodeficient people, particularly in AIDS, and
eventually gives rise to progressive multifocal leukoencephalopathy
(PML).
Viral myelopathy
 inflammation of the spinal cord, a myelitis:
 by polio, coxsackie, enterovirus 71 and West Nile virus infection, a
number of herpes viruses including HSV, CMV, EBV and VZV
 Chronic myelopathy :HTLV-1 ,HIV-1 infection
Post-vaccinial and post-infectious
encephalitis

 Encephalitis following viral infection or vaccination possibly has an
autoimmune basis

 An analogous inflammatory demyelinating condition of the peripheral nervous
system called Guillain-Barré syndrome has been associated with a variety of
viral infections, as well as with immunization with non-infectious material. In
1976, most adults in the USA were given inactivated influenza virus vaccine,
which resulted in a small but highly significant number of cases of GuillainBarré syndrome.
NEUROLOGIC DISEASES OF POSSIBLE VIRAL ETIOLOGY ?
 neurologic diseases of unknown origin:
 multiple sclerosis
 amyotrophic lateral sclerosis
 Parkinson's disease
 Schizophrenia
 senile dementia
SPONGIFORM ENCEPHALOPATHIES CAUSED BY SCRAPIE-TYPE AGENTS

prion
 spongiform appearance of nervous tissues, caused by vacuolation and
plaque formation.
 Infections in animals seem to have originated from sheep and goats
with scrapie, which has been present in Europe for 200-300 years.
CNS DISEASE CAUSED BY PARASITES
 Toxoplasma gondii
 Plasmodium falciparum
 Toxocara cati
 Toxocara canis
 Echinococcus granulosus
 Taenia solium Cysticercosis
BRAIN ABSCESSES
 Brain abscesses are usually associated with predisposing factors
 Since the development of antibiotics, brain abscesses have become
rare and usually follow surgery or trauma, chronic osteomyelitis of
neighboring bone, septic embolism or chronic cerebral anoxia. They
are also seen in children with congenital cyanotic heart disease in
whom the lungs fail to filter off circulating bacteria.
 Acute abscesses are caused by various bacteria, generally of
oropharyngeal origin, including anaerobes. There is usually a mixed
bacterial flora.
 Chronic abscesses may be due to Mycobacterium tuberculosis or C.
neoformans. In immunosuppressed patients, opportunistic infection
may occur with fungi and protozoan etiologic agents.