4. CNS infections Flashcards
Routes of infection
- Direct implantation
- Trauma
- Meningomyelocele - Local extension
- Sinusitis
- Otitis media
- Dental caries - Hematogenous spread
- Septicaemia
- Infective emboli (e.g. from infective endocarditis)
- Facial infections (retrograde venous spread through anastomoses with veins of face) - Transport along peripheral nervous system
- Rabies virus
- Herpes simplex virus
Pattern of involvement of microbes
Coverings:
- Extra-/subdural abscess: Bacteria
- Meningits: Bacteria, Fungi, Viruses
Brain parenchyma:
- Cerebral abscess: Bacterial, Fungi
- Encephalitis: Viruses, Prions
Both:
Meningo-encephalitis: Viruses
Types of clinical presentations from CNS infections
- Subdural empyema & Extradural abscess
- Meningitis
- Cerebral abscess
- Encephalitis
- Specific pathogen-related CNS infections
Subdural empyema
Direct implantation or local extension (usually bacteria)
Clinical features of subdural empyema
- Spinal tap: similar to that of cerebral abscess
2. Local symptoms, meningitis symptoms
Complications of subdural empyema
Thrombophlebitis of bridging veins leading to cerebral infarction
Treatment of subdural empyema
surgical drainage
Extradural abscess
Direct implantation or local extension (usually bacteria)
Complications of extradural abscess
In the case of a spinal cord epidural infection, it may cause spinal compression, constituting a neurosurgical emergency
Definition of meningitis
Inflammation of the meninges & CSF within the subarachnoid space
Causes of meningitis
- Acute bacterial meningitis
- Aseptic meningitis
- Tuberculous meningitis
Causes of acute bacterial meningitis
- Neonate:
- Escherichia coli
- Listeria monocytogenes
- Group B Streptococci
→ empiric treatment: ampicillin + gentamicin - Child < 5 years old
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitidis
→ empiric treatment: ceftriaxone - Adolescent
- Neisseria meningitidis
→ empiric treatment: ceftriaxone - Adult
- Neisseria meningitidis
- Streptococcus pneumoniae
→ empiric treatment: ceftriaxone - Elderly & Immunocompromised
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria menigitidis
- Listeria monocytogenes
→ empiric treatment: ceftriaxone + ampicillin
Aseptic Meningitis
- Usually viral (enteroviruses such as echovirus & coxsackievirus)
- Commonly causes concomitant encephalitis (viral
meningoencephalitis) - Often self-limiting
Tuberculous Meningitis
- Mycobacterium tuberculosis
- Causes a chronic meningitis often affecting the base
of the brain
Morphology of tuberculous meningitis
Gross appearance:
i) Gelatinous exudate in subarachnoid space often at base of brain
ii) White granules (tubercles) scattered all over meninges
Complications of tuberculous meningitis
- obliterative endarteritis of arteries in subarachnoid space (leading to cerebral ischemia & infarct)
- fibrous adhesive arachnoiditis (leading to cranial nerve palsies & hydrocephalus)
- tuberculoma (producing space-occupying symptoms)
- May cause concomitant encephalitis (tuberculous meningoencephalitis)
Clinical presentation of meningitis
- Headache, fever, malaise
- Photophobia
- Neck stiffness
- Kernig’s sign (leg bent at the knee & hip at 90
degrees, with subsequent extension being painful)
Pathological effects & complications of meningitis
- Cerebral infarction (due to thrombophlebitis)
- Meningeal fibrosis
- May lead to hydrocephalus - Cranial nerve palsies
- Especially TB as it affects base of brain - Raised intracranial pressure
- Mental retardation (in children)
- Waterhouse-Friderichsen Syndrome
- Hemorrhagic adrenalitis resulting from meningitis-related septicaemia
- Most often occurring with meningococcal or pneumococcal meningitis
Causes of cerebral abscess
- Routes of spread
- Single abscess (direct implantation, local extension)
- Multiple abscesses (hematogenous spread; predisposing factors include infective endocarditis, congenital right-to-left cardiac shunts, chronic pulmonary sepsis – bronchiectasis, immunosuppression) - Causative organisms (usually bacteria)
- Streptococci
- Staphylococcus aureus
- Bacteroides spp.
- Escherichia coli
Clinical features of cerebral abscess
- Swinging fever
- Signs of raised ICP
- Focal deficits
Complications of cerebral abscess
- Cerebral herniation
2. Abscess rupture leading to venous sinus thrombosis & meningitis
Types of encephalitis
- Acute encephalitis
- Delayed/subacute encephalitis
- Prion disease
Causes of acute encephalitis
- Often involves meninges concomitantly: acute meningoencephalitis
- Causative viruses: HSV, measles, CMV, HIV
- Fetal nervous system: CMV, rubella
Causes of delayed/subacute encephalitis
- Subacute sclerosing panencephalitis: measles
- Progressive multifocal leukoencephalopathy: JC virus
- Reactivation disease: VZV
Causes of prion disease
Single abscess (direct implantation, local extension)
CNS targets of specific viruses (Neurons & glia)
- HSV 1 (predilection for temporal lobe; characteristic Cowdry type A intranuclear inclusions)
- Rabies virus (characteristic negri body – intracellular eosinophilic bodies found in pyramidal neurons of hippocampus or Purkinje cells of cerebellum)
- Measles virus
- CMV (also infects endothelial cells)
CNS targets of specific viruses (motor neurons)
- Poliovirus (spinal cord motor neurons, leading to flaccid paralysis & hyporeflexia)
- Enteroviruses
CNS targets of specific viruses (Dorsal root ganglia)
VZV
CNS targets of specific viruses (oligodendrocytes)
JC virus
CNS targets of specific viruses (microglia)
HIV
Types of Specific Viral Infections
- Subacute Sclerosis Panencephalitis (SSPE)
- Progressive Multifocal Leukoencephalopathy (PML)
- HIV Infection
Subacute Sclerosis Panencephalitis (SSPE)
- Caused by altered measles virus
- Persistent but non-productive infection
- Occurs in children or young adults months to years after acute measles infection
- Presents with cognitive decline, spasticity & seizures
- Histologically: widespread gliosis, myelin degeneration, intranuclear viral inclusions within oligodendrocytes & neurons
Progressive Multifocal Leukoencephalopathy (PML)
- Caused by JC virus (papovirus) infection of oligodendrocytes resulting in demyelination
- Occurs mainly in immunocompromised patients
- Presents with progressive neurologic deficits
- Histologically: areas of pallor in white matter
(cerebrum, cerebellum, brainstem), atypical oligodendrocytes with viral inclusions, bizarre astrocytes
HIV Infection
- Direct effects of HIV on CNS: aseptic meningoencephalitis (histologically: multinucleated giant cells, microglial nodules, perivascular lymphocyte cuffing)
- Effects on spinal cord: vacuolar myelopathy of posterior columns & corticospinal tracts (‘holes’ in myelin sheath & macrophage infiltration)
- Associated pathological conditions: opportunistic CNS infections (toxoplasmosis, CMV, aspergillosis,
cryptococcosis, PML), lymphomas
Specific Pathogen-related CNS Infections
- Neurosyphilis
- Fungal infections
- Parasitic infections
- Prion disease
Neurosyphilis
- Meningovascular syphilis
- Granulomatous meningitis involving base of brain & more variably the cerebral convexities & spinal meninges
- Subintimal vessel thickening - General paresis of the insane
- Diffuse cortical microglial infiltrate, gliosis & iron deposits
- Insidious progressive mental deficits associated with mood alterations that eventually terminate in dementia - Tabes dorsalis
- Demyelination of the posterior columns
- Loss of joint position sense: ataxia
- Loss of pain perception: Charcot joints, skin damage
- Other sensory disturbances: lightning pains, absence
of deep tendon reflexes
Fungal infections
Usually occurs in immunocompromised patients
Causative organisms in fungal infections
- Candida albicans
- Cryptococcus neoformans
- Aspergillus fumigates
- Mucor
- Histoplasma capsulatum
Pathological effects & complications of fungal infections
- Vasculitis & thrombosis (leading to hemorrhage & cerebral infarction)
- Meningitis (especially Cryptococcus neoformans)
- Parenchymal invasion → abscesses & granulomas (Candida albicans, Cryptococcus neoformans)
Parasitic infections
Protozoal:
- Malaria
- Toxoplasma
- Typically produces abscesses in cerebral cortex (grey-white junction or deep grey nuclei)
- Can find tachyzoites & bradyzoites at periphery of necrotic foci
- Ring enhancing lesions in MRI - Naegleria fowleri (Primary amoebic meningoencephalitis)
- Trypanosoma
Helminthic
- Echinococcus
- Taenia solium (neurocysticercosis)
Pathogenesis of prion disease
- Mode of transmission: genetic (familial, sporadic contaminated transplant tissue, food ingestion)
- Prion protein (PrP) undergoes conformational change from alpha helix to beta pleated sheet which enables it to resist digestion
- PrP also induces protein misfiling in normal cells
Morphology of prion disease
- Grossly: almost normal
- Histologically:
- Spongiform transformation of cerebral cortex & deep grey matter
- Neuronal loss
- Reactive gliosis
- Amyloid deposits & plaques
Different spectrum of prion disease
- Creutzfeldt-Jakob disease
- Variant CJD (mad cow disease)
- Gerstmann-Straussler-Scheinker syndrome
- Fatal familial insomnia
