CNS INFECTION

FM Brett MD., FRCPath

ORGANISMSORGANISMS

~ PATHOGENIC - cause disease in every individual

~ OPPORTUNISTIC – Affect people with lower resistance

CNS INFECTIONCNS INFECTION

Development and outcomeDevelopment and outcomedepends ondepends on

Organism Organism natureroute of entrydose

HostHost Anatomical defenses - skull, meninges

Physiological - immune defense mechanisms

BacteriaBacteria

Entry into the cranial cavityEntry into the cranial cavity

Haematogenous -Haematogenous - distant foci e.g lung

Local spread -Local spread - Skull - middle ear, nasal sinus, osteomyelitis

Abnormal routesAbnormal routes - Trauma -fractures Surgery - shunts

Congenital sinus

BACTERIAL INFECTIONSBACTERIAL 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 INFECTIONPYOGENIC 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 meningitisComplications of acute meningitis in the neonatein the neonate

• Obstructive hydrocephalus

• Cavitating lesions in the white matter

MeningococcusMeningococcus

NasopharynxNasopharynx

BloodBlood

BacteraemiaBacteraemia SepticaemiaSepticaemia

Chronic Meningitis Endotoxic shockimmune complexes acute meningitis DICarthritis, vasculitis

CSFBacterial Viral TB

low N low glucose

v. high Slightly increased

Raised protein

neutrophils

lymphocytes

lymphocytes

cells

Complications of bacterial meningitisComplications of bacterial meningitis

• Acute inflammation of adjacent structures

• Organisation of inflammatory structures

Organisation of inflammatory exudate

Impedes flow of Impedes flow of CSF into CSF into venous sinusesvenous sinuses

Obstructs CSF outflow fromObstructs CSF outflow fromIV ventricleIV 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 Slightly increased

Raised

cells neutrophils

lymphocytes

lymphocytes

SyphylisSyphylis

• Asymptomatic CNS involvement• Syphylitic meningitis – 1-2 yrs• meningovascular syphylis – 7yrs• parenchymatous neurosyphylis• gummatous neurosyphylis

1 syphylis1 syphylis – spirochaete dissemination – chancre

22ndnd – haematogenous dissemination - rash, adenopathy,

3 3 – CVS, CNS, gumma

Latent Latent – lasts mths – yrs. Pts may progress straight to the stage of latent syphylis without developing secondary syphylis

SyphylisSyphylis

I syphylisI syphylis – spirochaete dissemination – chancre22ndnd – haematogenous dissemination - rash,

adenopathy, 3 3 – CVS, CNS, gummaLatent 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 infectionsAcute viral infections

• Aseptic meningitisAseptic meningitis

• PoliomyelitisPoliomyelitis• Herpesvirus Herpesvirus - - HSV, VCZ, EBV,

cytomegalo, HHV6

• RubellaRubella

• RabiesRabies

Aseptic meningitis-common Aseptic meningitis-common causescauses

• Echovirus

• Coxsachie B virus

• Coxsachie A virus

• HSV-2

• Mumps

• Measles

• Adenovirus

CSF

bacterial Viral TB

glucose low N low

protein v. high Slightly increased

Raised

cells neutrophils

lymphocytes

lymphocytes

PoliomyelitisPoliomyelitis

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

EncephalitisFocal neurologic signsMortality 25-50%

HSE -HSE - oral labial vesicles - retrograde axonal spread – trigeminal ganglion- (latency)

ReactivationReactivation (spontaneously, trauma, UV light, systemic disease)

Entry of HSV-1 into CNS – olfactory nervesReactivation of latent virus in trigeminal nerveReactivation from temporal lobes

Chronic viral infectionsChronic viral infections progress over mths - yearsprogress over mths - years

SSPESSPE – follows exposure to measles virus Age of onset – 5-15 yrs prognosis poor

PMLPML- 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 – retrovirusHIV – retrovirus

~ Infects cells carrying CD4 antigen i.e CD4+ T helper cells and monocytes/macrophages

~ This leads to a) cell mediated immunodeficiency – AIDSb) 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

ToxoplasmosisCNS lymphomaTuberculomaPMLCMVLesion not related to HIV - glioma

Toxoplasma cyst

Toxoplasma ICC

Introduction of HAART (1995-96) dramatically improvedThe 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