Transcript infections of the central nervous system

INFECTIONS OF THE CENTRAL
NERVOUS SYSTEM
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Meningitis
Encephalitis
Brain abscess
MENINGITIS
A medical emergency!
Clinical features that suggest the
diagnosis of acute meningitis
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Headache
Irritable
Neck stiffness
Photophobia
Fever
Vomiting
Varying levels of consciousness
Rash
Groups in which clinical features
are not so specific
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Neonates (first few weeks of life)
Elderly
Immunosuppressed
Incidence:
Primary meningitis:
spread via the bloodstream
BACTERIAL
Secondary meningitis:
Ears, sinuses, trauma,
Surgery
Main pathogens:
Neisseria meningitidis
Strept. Pneumoniae
Haemophilus influenzae
N meningitidis (meningococcus)
and meningococcal meningitis
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The most common cause of acute bacterial
meningitis
Most cases in children and young adults
Gram negative diplococcus
3 main serological types A, B. C
Person to person transmission
Reservoir nasopharynx (2-25% carriage)
Respiratory droplet spread
Incubation period 1-3 days
Higher carriage rates in:
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Children
Overcrowding
Schools, universities, other
institutions
military
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Most cases are sporadic
Close family contacts of cases at risk
Outbreaks may occur in eg, schools
Group B serotype traditionally most
frequent cause
Group C serotype has become
increasingly common
Epidemics occur in eg, Africa, South
America
Nasopharyngeal carriage
Bloodstream infection
Meningitis
CLINICAL FEATURES
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May be sore throat
Progression from headache, drowsiness, signs
of meningitis
Haemorrhagic skin rash (non-blanching)
Sepsis complicated by intravascular coagulation,
shock, acute renal failure
Bleeding into organs may occur eg, adrenal
gland causing Waterhouse Friderichsen
syndrome
Gangrene of peripheral limbs
TREATMENT OF ACUTE BACTERIAL
MENINGITIS KEYPOINTS:
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Once the diagnosis is clinically suspected don’t
delay treatment
If the causative agent is not clear eg, no rash,
give ceftriaxone or cefotaxime
This provides cover of the 3 main causes until a
microbiological diagnosis is made
If meningococcal meningitis confirmed then a
change to high doses of benzylpenicillin can be
considered
Chloramphenicol can be an alternative if allergy
to beta lactams
MICROBIOLOGICAL DIAGNOSIS
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If possible collect Cerebrospinal fluid (may
not be, if raised intracranial pressure)
Blood culture, both before antibiotic
therapy
Sample from petechial skin lesion may
yield meningococcus
CSF subjected to cell count, gram stain of
deposit, and culture on chocolate agar in
CO2 atmosphere
CSF Abnormalities in Meningitis
Condition
Appearance Cells/cu mm
Gram
Protein
Glucose
Normal
Clear,
colourless
0-5
lymphocytes
Bacterial
Cloudy,
turbid
100-2000
polymorphs
Orgs
High
Low
‘Aseptic’
(viral)
Clear,
slightly
cloudy
10-500
lymphocytes
Normal
Normal
TB
Clear,
slightly
cloudy
10-500
lymphocytes
High
Low
Cryptococcal
Clear
10-200
lymphocytes
Normal,
slightly
elevated
Normal,
slightly
reduced
Additional lab investigations
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Latex agglutination test on CSF to detect
meningo polysaccharide antigen
PCR to amplify bacterial DNA in blood (EDTA
sample) or CSF which may be positive even
after start of antibiotics
Save serum sample for antibody tests with a
subsequent “convalescent” sample
Set up antibiotic sensitivities to penicillin,
cephalosporins, ampicillin, chloramphenicol and
others
Some features of meningococcal
isolate
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Gram: gram negative cocci some within
neutrophils (intracellular)
Grows within 24-48 hours best on
chocolate agar in CO2
Will agglutinate with group specific
antisera eg, B, C
Caution needed in lab as making
suspensions can be a hazard to the lab
worker (may acquire pathogen)
MENINGOCOCCAL MENINGITIS
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Notifiable to public health authorities
Close contacts in home, school/university,
nursery should be given antibiotic prophylaxis
Rifampicin X 2 days (ciprofloxacin is used but
not licensed)
Hospital contacts only need prophylaxis if
contact with secretions, eg, mouth to mouth
resuscitation
Vaccine against group C now widely in use and
for overseas travellers group A vaccine may be
indicated
Pneumococcal meningitis
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Strep pneumoniae is the cause, a
capsulate gram positive coccus
Highest incidence in those at extremes of
age, infants <3yrs and elderly
Alcoholism, debilitation, malnutrition,
hyposplenism
May spread from middle ear or sinus
infection
Or following trauma causing basal skull #
Pneumococcal meningitis: clinical
features
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Acute onset with rapid development of
loss of consciousness
Skin rash not a feature
May be a history of ear infection,
splenectomy
Bacteraemia a feature
Higher mortality than other causes
High incidence of complications in
survivors
Microbiological investigations
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CSF and blood cultures should be taken
Gram stain of CSF deposit shows gram
positive cocci in short chains
Culture on blood and choc agar in CO2
gives alpha haemolytic (green) colonies
with “draughtsmen”
Direct sensitivities for penicillin,
cefotaxime, ceftriaxone, ampicillin
Treatment
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High doses of penicillin eg, 1.2g (2mill
units) 2 hourly
Note some strains have reduced
susceptibility to penicillin, and some are
resistant!
Need to review to find a potential
underlying risk factor
Polyvalent vaccine for risk groups eg,
before splenectomy
Haemophilus influenzae meningitis
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Gram negative coccobacillus, capsulated strains
(type b used predominate)
Peak incidence 2 years old, range 3 months to 5
years
Incidence has declined greatly since the
successful introduction of Hib vaccine
More insidious onset, no rash, lower mortality
Diagnostic approach as for other causes
Treament with cefotaxime or ceftriaxone
Other bacterial causes of
meningitis in adults and children
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Post trauma or surgery
Staph aureus, streps, anaerobes, coliforms,
Pseudomonas
Immunocompromised
Listeria monocytogenes
Others
M tuberculosis, Leptospira, Borrelia burgdorferi
Tuberculous meningitis
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Higher incidence in immigrant populations who come
from countries with a higher incidence of TB
Insidious onset
High frequency of complications, cranial nerve palsies
Delayed diagnosis makes complications more likely
CSF shows predominantly lymphocytic response but
polymorphs also present
High protein, low/absent sugar
Treat: probably with 3 agents eg, isoniazid, rifampicin,
pyrazinamide
Note occasional reports of MDR TB
CSF Abnormalities in Meningitis
Condition
Appearance Cells/cu mm
Gram
Protein
Glucose
Normal
Clear,
colourless
0-5
lymphocytes
Bacterial
Cloudy,
turbid
100-2000
polymorphs
Orgs
High
Low
‘Aseptic’
(viral)
Clear,
slightly
cloudy
10-500
lymphocytes
Normal
Normal
TB
Clear,
slightly
cloudy
10-500
lymphocytes
High
Low
Cryptococcal
Clear
10-200
lymphocytes
Normal,
slightly
elevated
Normal,
slightly
reduced
NEONATAL MENINGITIS
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Group B streptococcus (S agalactiae) and Esch coli are
the principal causes
Travel via the bloodstream but direct infection may occur
Premature rupture of membranes, pre-term delivery
(“VLBW”) are risk factors
May complicate maternal infection
High morbidity and mortality
Clinical features can be non-specific
Early onset Group B infection more common than late
onset disease
Other causes: Listeria, Staph, Salmonella, other GNB
Treat: Cephalosporin, or penicillin + aminoglycoside
BACTERIAL
VIRAL
FUNGAL,
OTHER
VIRAL MENINGITIS
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Primarily affects children and young adults
Milder signs and symptoms
May start as respiratory or intestinal
infection then viraemia
CSF shows raised lymphocyte count (50200/cu mm); protein and sugar usually
normal
Full recovery expected
Causes of viral meningitis
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Enteroviruses: Echo, coxsackie A ,B, polio
Paramyxovirus: mumps
Herpes simplex, VZV
Adenoviruses
Other: arboviruses, lymphocytic
choriomeningitis, HIV
Diagnosis: viral meningitis
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Examination of CSF
Storage at -700C of CSF for subsequent
virus isolation
Additionally throat swab, stool, paired sera
CSF Abnormalities in Meningitis
Condition
Appearance Cells/cu mm
Gram
Protein
Glucose
Normal
Clear,
colourless
0-5
lymphocytes
Bacterial
Cloudy,
turbid
100-2000
polymorphs
Orgs
High
Low
‘Aseptic’
(viral)
Clear,
slightly
cloudy
10-500
lymphocytes
Normal
Normal
TB
Clear,
slightly
cloudy
10-500
lymphocytes
High
Low
Cryptococcal
Clear
10-200
lymphocytes
Normal,
slightly
elevated
Normal,
slightly
reduced
Fungal meningitis
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Cryptococcus neoformans is main cause
HIV and immunosuppressed pts at risk
Insidious onset of headache, fever, neck
stiffness
Diagnosis made on CSF examination
Shows raised lymphocyte count, protein,
low sugar, capsulate yeasts, antigen
Treat with amphotericin B +flucytosine
CSF Abnormalities in Meningitis
Condition
Appearance Cells/cu mm
Gram
Protein
Glucose
Normal
Clear,
colourless
0-5
lymphocytes
Bacterial
Cloudy,
turbid
100-2000
polymorphs
Orgs
High
Low
‘Aseptic’
(viral)
Clear,
slightly
cloudy
10-500
lymphocytes
Normal
Normal
TB
Clear,
slightly
cloudy
10-500
lymphocytes
High
Low
Cryptococcal
Clear
10-200
lymphocytes
Normal,
slightly
elevated
Normal,
slightly
reduced
ENCEPHALITIS
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Affects children and adults mostly
A variety of symptoms and signs
Drowsiness, confusion, coma, fits, nerve
palsies, paresis
May have sequelae eg, memory loss,
motor impairment, death
EEG, brain scan, CSF exam, brain biopsy
may establish diagnosis
Causes of encephalitis
• Sporadic:
 Herpes simplex, mumps, VZV, EBV rabies
• Epidemic:
 Togaviruses: equine, louping ill, Japanese B,
enteroviruses
• Post-infectious:
 Measles, rubella, post-vaccination
• Degenerative:
 Measles (SSPE), vCJD, JC virus (PML)
Herpes simplex encephalitis
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Most common cause of sporadic
encephalitis in previously healthy
May be evidence of herpes infecion of
skin, mucosae
Causes severe haemorrhagic encephalitis
affecting temporal lobe,
Focal signs and epilepsy features
High mortality so treatment urgently
needed with aciclovir
Other causes
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VZV
Mumps
Rabies
Mycoplasma pneumoniae
Rickettsiae
Toxoplasma
Subacute sclerosing
panencephalitis (SSPE)
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A rare complication of measles infection
Usually affects children
Intellectual impairment, involuntary
movements
High titres of measles antibody
Brain biopsy shows measles virus
Fatal outcome
Prion diseases
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Degenerative disorders
Long incubation periods
Slow progressive spongiform
encephalopathy
Fatal outcome
• Kuru: occurred in New Guinea, diue to
cannibalism, eating human brain
• Sporadic Creutzfeldt-Jacob disease (CJD): rare
degenerative disease in over 50’s
• Recipients of growth hormone at increased risk,
use of surgical instruments contamined with
prion protein
• Prions are (Prp) proteins in abnormal
configuration resistant to destruction
• Mutations of genes encoding these proteins can
be inherited
New variant CJD
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In 1980’s emergence of bovine spongiform
encephalopathy (BSE)
Could be experimentally transmitted from brains
of sheep with scrapie
Similarities between BSE and nvCJD
Occurs in young people rapidly fatal
Possibly acquired from eating infected beef/ beef
products
Diagnosis on brain biopsy (? Tonsillar tissue)
No treatment
Brain abscess
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Can arise from direct inoculation of infection
following trauma, surgery; from spread of
infection of ear or sinuses; or haematogenous
spread from eg, lungs, heart (endocarditis)
May be non-specific signs, neurological
symptoms
Needs urgent investigation by CT/MRI scan
Surgical treatment +antibiotics
Causes of brain abscess
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Ear: mixed anaerobes, coliforms
Sinus: pneumococci, streptococci
Trauma/surgery: Staph aureus
Chest: strep, staph, pneumococci
Diagnosis and treatment
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Examination of pus aspirated from
abscess
CSF
Blood cultures
Surgical drainage a priority
Antibiotics chosen with good penetration
of CNS
Guillain-Barre syndrome
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Infectious polyneuritis
Paraesthesiae, progressive weakness of
limbs, respiratory failure
High CSF protein
Post infectious
Various infections implicated including
Campylobacter, EBV, Mycoplasma
Recovery likely to occur with supportive
care
Congenital CNS infections
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Intrauterine infections: toxoplasma,
rubella, cytomegalovirus, syphilis
During birth: herpes simplex, hepatitis B
HIV