Lecture 13- Infection of CNS

Question 1

What is meningitis

Answer 1

Infection/inflammation of meninges- bacterial (rarer/life- threatening) or viral
Meninges guarded by blood-CSF barrier, with porous fenestrated endothelium> most organisms causing infection cross this into meninges

Question 2

What is encephalitis

Answer 2

Inflammation of white matter of brain- blood-brain barrier: endothelia of brain BV not fenestrated so more difficult for organisms to infect parenchyma this way.
However infective encephalitis usually caused by neurotropic viruses (HSV, VSV and rabies)- peripheral nerves, ascend CNS using normal retrograde transport mechanisms

Question 3

What is meningoencephalitis

Answer 3

Combination of meningeal and brain white matter inflammation/ infection

Question 4

What is prion disease

Answer 4

Presence of a specific protein alters the configuration of other proteins to cause white matter loss

Question 5

What organisms cause common CNS infections?

Answer 5

Neisseria meningitidis- GN, pairs (diplococcus)
Haemophilus influenzae (encapsulated type B, GN coccosaccilus)
Streptococcus pneumoniae- GP, Pairs (NHS core group)
URTI commensal, meningeal infection with bloodstream spread
HSV, listeria monocytogenes (GP bad in elderly, NN and IS, FOODBORNE), mycobacterium TB, VZV

Question 6

CNS infection in neonates

Answer 6

NHS group may not be as problematic due to maternal antibodies by GBS/ streptococcus agalactiae, e.coli and listeria monocytogenes (vaginal conolisation) dangerous- sepsis
Phagocyte activity and parts of complement pathway/ humoral/CM immunity maturing over first months of life

Question 7

CNS infection in immunocompromised

Answer 7

Neisseria, haemophilus and strep pneumo prime pathogens
IC people also infected by opportunistic pathogens
Cryptococcus neoformans- yeast, HIV/AIDS and chemo patients
Toxoplasma gondii- protozoa, asymptomatic, mild with fever/lymphadenopathy (swollen lymph nodes)- IC w/ low CD4, brain infection
Listeria monocytogenes- gram positive rod, foodborne- lives in cold

Question 8

Viral encephalopathies

Answer 8

Infection of brain, can be caused by HSV, VZV (1- chickenpox, dormant in DRG then shingles)
Vaccine preventable viruses- polio, measles, mumps
Zoonotic/vector borne viruses- rabies, zika, japanese encephalitis
encephalitis- confusion, altered consciousness, abnormal behaviour, seizures, nausea/vomiting and fever

Question 9

Clinical features of bacterial meningitis

Answer 9

Headache, fever, neck stiffness, photophobia, non-blanching purpuric rash
Neurological deficits
Prodromal URTI symptoms
AKI, disseminated intravascular coagulation
Shock, peripheral ischaemia and necrosis (peripheries, amputations)

Question 10

Diagnostic approach

Answer 10

Antibacterials on suspicion (before cultures)
Imagining
Lumbar puncture CSF- if CSF at high pressure this can cause coning and death
White cells in CSF abnormal, suggestive of bacterial infection
Cell count, chemistry (GP) and microbiology
Blood for culture, throat swabs, blood and CSF for PCR (NM, S.pneumo, enterovirus, HSV)

Question 11

Correct management of bacterial meningitis

Answer 11

(all IV)
Ceftriaxone (ceftoxamine in neonates- albumin> bilirubin, jaundice, liver damage)
steroids to reduce inflammation
Amoxicillin to cover listeria
Ciprofloxacin to eradicate carriage in nasopharnyx
If penicillin allergy life threatening > chloramphenicol

Question 12

Review the clinical features of encephalitis

Answer 12

Brain tissues is involved- function disturbed
Altered behaviour, altered consciousness > coma
Neurological symptoms
Fever, without significant rise in inflamm. markers (peripheral white cells/ CRP)
Vesicular rash in VZV, HSV- reactivation in trigeminal ganglia, infection in temporal lobes
Non- vesicular- Enterovirus meningoencephalitis

Question 13

Diagnosing viral encephalopathies

Answer 13

Clincal
CT/ MRI
LP- coning (herniation of cerebellar tonsils, brainstem through foramen magnum)
PCR from throat, blood and CSF
EEG

Question 14

Management approaches

Answer 14

SUPPORTIVE- sedation, ventilation ( ICU access, can deteriorate quickly), hydration, seizure management (carbamazepine, gabapentin, phenytoin etc)
Osmotherapy for raised IC pressure
Steroids
Antivirals

Question 15

Mode of action for aciclovir and related antivirals

Answer 15

Nucleoside analogue- competes with deoxyguanosine for viral DNA incorporation, much more attractive to HSV DNA polymerase than human (selective toxicity)
Prodrug, phosphorylated in virally infected cells to aciclovir triphosphate
GI upset, photosensitive skin rash, neurological excitation, nephrotoxicity due to formation of crystals in urine side effects

Question 16

Spectrum of activity and clinical usage

Answer 16

Topically for HSV labialis/ eye infections think cold sores etc
Orally for HSV genital infections/ VZV infections severe/ in vulnerable patients
IV for life-threatening HSV/VZV Infections
Hydration important in high dose prolonged treatment

Question 17

Related drugs to aciclovir

Answer 17

valaciclovir- ester that is better orally tolerated (prophylaxis of CMV)
Ganiciclovir- immunosuppressed patients with severe CMV infection
Goal to reduce CMV load in patients
CMV usually self limiting but in immunosuppressed eg solid organ transplants