CNS INFECTION FM Brett MD., FRCPath

ORGANISMS ORGANISMS ~ PATHOGENIC - cause disease in every individual ~ OPPORTUNISTIC – Affect people with lower resistance

CNS INFECTION Development and outcome depends on Organism Organism nature route of entry dose Host Host Anatomical defenses - skull, meninges Physiological - immune defense mechanisms

Bacteria Entry into the cranial cavity Haematogenous - Haematogenous - distant foci e.g lung Local spread - Local spread - Skull - middle ear, nasal sinus, osteomyelitis Abnormal routes Abnormal routes - Trauma -fractures Surgery - shunts Congenital sinus

BACTERIAL INFECTIONS 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 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

Complications of acute meningitis in the neonate in the neonate Obstructive hydrocephalus Cavitating lesions in the white matter

MeningococcusNasopharynxBlood BacteraemiaSepticaemia ChronicMeningitisEndotoxic shock immune complexes acute meningitisDIC arthritis, vasculitis

CSF

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: 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

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

1 syphylis 1 syphylis – spirochaete dissemination – chancre 2 nd 2 nd – 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

Syphylis I syphylis I syphylis – spirochaete dissemination – chancre 2 nd 2 nd – 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

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 Poliomyelitis Herpesvirus - Herpesvirus - HSV, VCZ, EBV, cytomegalo, HHV6 Rubella Rubella Rabies Rabies

Aseptic meningitis-common causes Echovirus Coxsachie B virus Coxsachie A virus HSV-2 Mumps Measles Adenovirus

CSF

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 - HSE - oral labial vesicles - retrograde axonal spread – trigeminal ganglion- (latency) Reactivation 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 SSPE – follows exposure to measles virus Age of onset – 5-15 yrs prognosis poor PML 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 ( ) 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