Viral Infections of CNS Flashcards
Classification of Infections
Acute (days)
- Direct - damage due to presence of viruses in cells; primary or reactivation; neurotropic viruses with viral genome detected in CNS
- Post-exposure - immune mediated pathology after infection or exposure to virus; culprit virus may not be neurotropic ; viral genome NOT detected in CNS
Chronic (mths - yrs)
- subacute sclerosing panencephalitis
- progressive multifocal leukoencephalopathy
- subacute spongiform encephalopathies
Pathology of viral disease in CNS: neuron and inflammatory response, interpretation of IgM in CSF (2)
Neuron
- lysis, demyelination, spongioform degeneration (swollen appearance)
Inflammatory response
- lymphocytic infiltration with perivascular cuffing, microglia activation
- specific IgM in CNS not crossing BBB (IgG can pass through) –> if there is IgM in CSF = severe BBB damage or production IgM within CSF in response to CNS infection
Acute infection route of entry and examples (3)
Haematogenous
- infected macrophages or lymphocytes (normally virus unable to cross BBB)
- e.g. arbovirus (Jap B encephalitis)
Reactivation
- from latency e.g. herpesvirus
Neural route
- via peripheral nerve e.g. rabies (replicate in muscle and invade into nerve ending)
Acute infection syndromes (6) and causative agents
Meningitis: Enterovirus, HSV-2, VZV
- inflammation of meninges +/- some degree of encephalitis
Encephalitis: HSV-1, Rabies, Arbovirus (Jap B encephalitis), HSV-2, HHV6A and 6B
- neuronal necrosis, inflammation
Myelitis (spinal cord): polioviruses, occasionally enteroviruses (EV71)
- meningitis, lysis of LMN
Meningoencephalitis: HSV-1, arboviruses
- neuronal necrosis
AIDS dementia complex: HIV
Tropical spastic paraparesis: HTLV-1 - uncommon in HK
Acute Viral Meningitis: causative agents (4), presentation (4), outcome, CSF picture (5)
Key agents:
- ENTEROVIRUSES (often in children)
- HSV-2, VZV
- Mumps (countries without vaccine)
Inflammation of meninges
Presentation:
- abrupt onset of headache, neck rigidity, fever, vomiting, photophobia
- self-limiting - resolves quickly with no long-term sequelae
CSF picture: ASEPTIC MENINGITIS
- non-bacterial inflammation of meninges
- clear fluid
- WBC normal (<100), lymphocyte predominant
- protein normal (or slight increase at later stage)
- glucose normal (>60% serum glucose vs bacterial <40%)
Acute Viral Encephalitis: causative agents (3), definition, presentation (5), outcome, specific types of encephalitis and their causes
Key agents:
- HSV-1
- Rabies, Jap B encephalitis
- other herpesviruses/arboviruses
Inflammation of brain parenchyma
Presentation:
- overlap with meningitis (fever, headache) – meningoencephalitis
- abnormal cerebral function – drowsiness, confusion, ataxia, convulsions, focal neurological signs
Outcome: morbidity and mortality is high
Classification of encephalitis:
- Focal encephalitis: Herpesviruses (**HSV-1, HSV-2, HHV-6)
- Pan-encephalitis: rabies, Jap B encephalitis
Herpes Simplex Encephalitis - prevalence, pathogenesis, clinical features
Most common cause of (sporadic) encephalitis
Agents:
- children and adults: HSV-1 reactivation (MC), localised
- neonates: disseminated primary infection by HSV-2 (acquired during vaginal delivery)
Clinical features:
- insidious onset of LOCALISING SIGNS (has preferential site of reactivation)
- low-grade fever, decreases consciousness, confusion, disorientation, seizures, dysphagia, change in personality etc.
- FOCAL, UNILATERAL
- temporal/ frontal lobe
Herpes Simplex Encephalitis Diagnosis (specimen, best method, limitations of other methods)
- *CSF –> HSV PCR is first line method
- virus present in brain and CSF in reactivation
- Intrathecal HSV Ab takes >10 days to develop
- Ag detection and virus culture insensitive to low viral load in reactivation
MRI/CT/EEG normal until day 3-4 as it takes the for changes accumulate a large enough lesion to be detected –> too late
CSF profile non-specific
HSE Treatment protocol and rationale, cautions, possible side effects
Empirical Acyclovir IV (10-15 mg/kg Q8h) until PCR results available
- -> at least 3 weeks treatment if confirmed
- -> important to start empirically because delay in treatment greatly affects outcome and acyclovir is generally safe to use as long as within normal dosage
Caution: adequate hydration
Side effects of overdose (especially in elderly with renal impairment):
- encephalopathy
- nephropathy
Rabies encephalitis: source, clinical course (5), outcome, prevention (3)
Rabies virus: neurotropic
Source - dogs, raccoon, foxes, bats etc. –> virus replicates at muscle near bite –> move up peripheral nerves into CNS –> reaches brain and causes encephalitis
Worldwide (except UK, Australia)
Clinical course: 5 stages
- incubation period: 2 wks - 3 mths, up to years
- prodromal stage: fever, malaise, paraesthesia at wound site, 2-10 days
- acute neurological syndromes
- —> encephalitic: hydrophobia (fear due to throat ms spasm during swallowing), photophobia, delirium, hyperactivity, aggression, anxiety
- —> paralytic: flaccid paralysis
- convulsion and coma
- death (respiratory arrest)
Recovery is rare
Prevention:
- pre-exposure prophylaxis for at risk groups e.g. vets, labs –> inactivated vaccine
- post-exposure prophylaxis –> vaccine + rabies hyperimmune globulin (HRIG)
- veterinary measures: leash law, licensing of dogs, vaccines for dogs/cats
Myelitis: causative agents, age of infection, mechanism of disease, symptoms, prevention
Key agents:
- Poliovirus 1-3
- (enterovirus 71)
- Usually infected during childhood
- Direct infection of anterior horn cells of spinal cord –> fever and FLACCID PARALYSIS of group of muscles
(anterior horn cells are responsible for motor function hence infection affects muscle development and leads to atrophy)
Poliovirus eliminated by vaccination in most countries
- inactivated vaccine
- oral live vaccine (c.f. contraindicated in Rotavirus vaccination)
Post-infectious encephalomyelitis: pathology, cause, pathogenesis, outcome
Widespread demyelinating lesions in brain and spinal cord with lymphocytic infiltration and perivascular cuffing
- Rare complication during convalescent phase of certain viral infections or vaccination e.g. measles, mumps, rubella, VZV, influenza
- viral infections not necessarily neurotropic
- virus can’t be isolated from brain tissue or CSF
Autoimmune phenomenon - foreign antigens closely related to host proteins normally expressed in brain/ spinal cord
Outcome: PERMANENT NEUROLOGICAL DEFICITS common
Guillain-Barre Syndrome: pathology, cause, pathogenesis, symptoms, outcome
Demyelinating Polyradiculoneuropathy (damage both sensory and motor neurons)
Days-wks after acute phase of viral infection (also bacterial/ post-vaccine)
- Immunological phenomenon
Presentation: ASCENDING PARALYSIS associated with PARAESTHESIA
Outcome: recover spontaneously after a few wks/ mths, no specific treatment
Rare complication of vaccination (1/mil after flu vaccine)
Reye’s syndrome: cause, association, pathology (2), outcome
Post-infectious encephalopathy
- following infection e.g. influenza type B, chickenpox
Cerebral edema, fatty infiltration of liver (recall pathology - micro vesicular steatosis)
Associated with ASPIRIN
Outcome: 25% case fatality
Subacute sclerosing panencephalitis (SSPE): cause, pathogenesis
Due to persistent MEASLES infection in CNS
- latent but slowly active over time and causing progressive degeneration of the brain
- 6-8 years following primary uncomplicated measles infection
- no treatment
