Download cns-infection

CNS INFECTION
FM Brett MD., FRCPath
ORGANISMS
~ PATHOGENIC - cause disease in every individual
~ OPPORTUNISTIC – Affect people with lower resistance
CNS INFECTION
Development and outcome
depends on
Organism
Host
nature
route of entry
dose
Anatomical defenses - skull, meninges
Physiological - immune defense mechanisms
Bacteria
Entry into the cranial cavity
Haematogenous - distant foci e.g lung
Local spread - Skull - middle ear, nasal sinus,
osteomyelitis
Abnormal routes - Trauma -fractures
Surgery - shunts
Congenital sinus
BACTERIAL INFECTIONS
Depending on their virulence/pathogenicity bacteria can
induce:
1. Purulent lesions
2. Cellular inflammatory reactions with giant cells
3. Inflammatory oedema caused by toxins and other inflammatory
substances released by bacterial secretions or lysis, in the absence
of bacterial replication
PYOGENIC INFECTION
1. BONE – EPIDURAL – usually spinal sec to osteomyelitis
2. DURA MATER - SUB DURAL - sec to sinusitis, otitis etc.
3. ARACHNOID – SUBARACHNOID – sec to haematogenous
spread of bacteria
4. PIA - INTRAPARENCHYMAL - abscess
SUBDURAL
Three organisms responsible for acute
meningitis in childhood or adult life
• Meningococcus
• Haemophilus influenza
• Pneumococcus
Bacterial meningitis
Bacterial meningitis
Complications of acute meningitis
in the neonate
• Obstructive hydrocephalus
• Cavitating lesions in the white matter
Meningococcus
Nasopharynx
Blood
Bacteraemia
Septicaemia
Chronic
Meningitis
immune complexes acute meningitis
arthritis, vasculitis
Endotoxic shock
DIC
CSF
Bacterial Viral
TB
low
low
v. high
N
glucose
Slightly
Raised
protein
increased
neutrophil lymphocyt lymphocyt cells
s
es
es
Complications of bacterial meningitis
• Acute inflammation of adjacent structures
• Organisation of inflammatory structures
Organisation of inflammatory
exudate
Impedes flow of
CSF into
venous sinuses
Obstructs CSF outflow from
IV ventricle
A twelve year review of central nervous system bacterial
abscesses: presentation and aetiology.
Roche M, Humphreys H, Smyth E, Phillips J et al
Clin Mic & Inf 2003;9:803-14
1988-2000
163 patients
Cerebral abscess
~ Mean age – 35.2
~ P/C – headaches, pyrexia, altered mental state
(depends on site, number, and +/- secondary
cerebral lesion)
~ Site – frontal lobe commonest
~ Majority – associated with sinusitis, mastoiditis
20% no source
~ Bacteria isolated from 73%. Polymicrobial – 17.7%
~ Anaerobes – 13.6%
~ 9.8% died
~ 11% developed epilepsy
Cerebral abscess
Predisposing conditions
Local – otitis media, sinusitis, trauma
Systemic ~ chronic lung disease
~ cyanotic congenital heart
disease
~ transplants
~ immunosupression
Parenchymal abscess formation
~ Early cerebritis (days 1-3)
~ Late cerebritis (days 4-9)
~ Early capsule formation (days 10-13)
~ Late capsule formation (days 14 onward)
AIMS OF TREATMENT
~ Eliminate infectious process
~ Reduce mass effect within cranial cavity
– thus reduce secondary injury
~ Treat infections
Tuberculous meningitis
Usually M Tuberculosis
More commonly associated with
documented history of tuberculosis
exposure in children than adults
CSF
Bacterial
Viral
TB
glucose
low
N
low
protein
v. high
cells
Slightly
Raised
increased
neutrophil lymphocyt lymphocy
s
es
tes
Syphylis
• Asymptomatic CNS involvement
•
•
•
•
Syphylitic meningitis – 1-2 yrs
meningovascular syphylis – 7yrs
parenchymatous neurosyphylis
gummatous neurosyphylis
1 syphylis – spirochaete
dissemination – chancre
2nd – haematogenous
dissemination - rash,
adenopathy,
3 – CVS, CNS, gumma
Latent – lasts mths – yrs. Pts
may progress straight to the
stage of latent syphylis
without developing secondary
syphylis
Syphylis
I syphylis – spirochaete dissemination – chancre
2nd – haematogenous dissemination - rash,
adenopathy,
3 – CVS, CNS, gumma
Latent – lasts mths – yrs. Pts may progress straight
to the stage of latent syphylis without
developing secondary syphylis
Neurosarcoidosis
~ Chronic granulomatous disease of unknown
aetiology
~ CNS involved in 5%. CNS disease often
accompanied by PNS disease
~ Usually base of the brain
~ Facial nerve palsy common. May develop
deafness, vertigo, ataxia, DI, hypopituitrism
Acute viral infections
• Aseptic meningitis
• Poliomyelitis
• Herpesvirus - HSV, VCZ, EBV,
cytomegalo, HHV6
• Rubella
• Rabies
Aseptic meningitis-common
causes
•
•
•
•
•
•
•
Echovirus
Coxsachie B virus
Coxsachie A virus
HSV-2
Mumps
Measles
Adenovirus
CSF
bacterial
Viral
TB
glucose
low
N
low
protein
v. high
cells
Slightly
Raised
increased
neutrophil lymphocyt lymphocyt
s
es
es
Poliomyelitis
Precentral gyrus
Reticular formation
Motor nuclei of pons and medulla
Ant horn cells of spinal cord
HERPESVIRUS INFECTIONS
DNA VIRUSES - include HSV1, HSV2,
EBV, CMV and HHV6
HSE
Encephalitis
Focal neurologic signs
Mortality 25-50%
HSE - oral labial vesicles - retrograde axonal
spread – trigeminal ganglion- (latency)
Reactivation (spontaneously, trauma, UV light,
systemic disease)
Entry of HSV-1 into CNS – olfactory nerves
Reactivation of latent virus in trigeminal nerve
Reactivation from temporal lobes
Chronic viral infections
progress over mths - years
SSPE – follows exposure to measles virus
Age of onset – 5-15 yrs
prognosis poor
PML- JC virus
affects immunosupressed individuals
demyelination
HIV
~ First recognised in USA in 1981
~ Widely distributed worldwide
~ 30 million currently infected
~ 9000 infections daily - > 50% sub-saharan Africa
~ USA and western Europe – homosexual, and IVDA
~ Elsewhere heterosexual
~ Small proportion perinatal or breast feeding
~ Organ donors, blood etc
HIV – retrovirus
~ Infects cells carrying CD4 antigen i.e CD4+ T helper cells
and monocytes/macrophages
~ This leads to a) cell mediated immunodeficiency – AIDS
b) invasion of CNS by macrophage/monocytes
~ CNS disease
– infection by virus
- opportunistic infections
- Lymphomas
- HIV asssociated systemic disease affecting CNS
e.g metabolic, cvs etc.
- complications of treatment
Commonest processes identified
prior to HAART
~ Cryptococcus
~ Toxoplasmosis
~ PML
~ HIVE
~ HIVL
~ Cytomegalovirus infection
~ Vacuolar myelopathy
~ CNS Lymphoma
By and large did not have bacterial infections
Commonest causes of a cerebral mass
in a patient with HIV
Toxoplasmosis
CNS lymphoma
Tuberculoma
PML
CMV
Lesion not related to HIV - glioma
Toxoplasma cyst
Toxoplasma ICC
Introduction of HAART (1995-96) dramatically improved
The course and prognosis of HIV infection
Restored functional immune system – so less opportunistic
infection
Dramatic reduction in cerebral toxoplasmosis, CMV
encephalitis and HIV encephalitis
Unchanged incidence of PML and NHL