CNS Infections Flashcards
What are the 3 main different types of primary infections of the CNS?
- Meningitis
- Encephalitis
- Brain abscess
What is a brain abscess?
An abscess caused by inflammation and collection of infected material within the brain tissue
What are the leptomeninges?
The inner two meninges, the arachnoid and the pia mater, between which circulates the cerebrospinal fluid.
Meningitis vs meningoencephalitis?
- Meningitis refers to an inflammatory process of leptomeninges and CSF
- Meningoencephalitis refers to inflammation to meninges and brain parenchyma
What are the 3 classifications of meningitis?
- Acute pyogenic
- Aseptic
- Chronic
What is acute pyogenic meningitis typically caused by? (3 organisms)
Usually bacterial meningitis;
- Haemophilus influenzae
- Streptococcus pneumoniae
- Neisseria meningitidis
What is aseptic meningitis?
Aseptic meningitis is the inflammation of the meninges, a membrane covering the brain and spinal cord, in patients whose cerebral spinal fluid test result is negative with routine bacterial cultures.
Which organisms is aspeptic meningitis typically caused by?
Usually viral meningitis
What is lymphocytic pleocytosis?
Lymphocytic pleocytosis is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF).
Which organisms is chronic meningitis typically caused by?
Mycobacterium tuberculosis (TBM), spirochetes (neurosyphilis), Cryptococcus neoformans
When can meningitis be defined as chronic?
Has an onset measured in weeks to months (but is generally defined when symptoms, signs, and the CSF remain abnormal for at least 4 weeks)
4 ways that infectious agents can enter the CNS?
- a) Haematogenous spread
- most common
- usually via arterial route
- can be retrograde (veins)
- b) Direct implantation
- i) most often is traumatic
- ii) iatrogenic (rare)
- iii) congenital (meningomyelocele)
- c) Local extension
- Secondary to established infections: most often from mastoid, frontal sinuses, infected tooth, etc.
- d) Along peripheral nerves; usually viruses e.g. Herpes Zoster
Pathogenesis of meningitis?
Which virus can travel along peripheral nerves and enter the CNS?
Herpes Zoster
A local extension of established infections can lead to infection of the CNS. Where are these infections usually originating from?
Most often from mastoid, frontal sinuses, infected tooth, etc.
Which organisms most commonly cause acute bacterial meningitis in;
- <1 month olds
- 1-23 month olds
- 2-50 year olds
- >50 year olds
- a) Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes
- b) Streptococcus pneumoniae, Neisseria meningitidis Streptococcus agalactiae, Escherichia coli, Haemophilus influenzae
- c) Streptococcus pneumoniae, N.meningitidis
- d) Streptococcus pneumoniae, N. meningitidis, Listeria monocytogenes, aerobic Gram negative bacilli
Why is the management of meningitis caused by Listeria monocytogenes different?
Listeria is NOT susceptible to usual cephalosporins used!
How is Listeria monocytogenes typically spread?
Contaminated food e.g. unpasturised dairy
What is meningism?
Clinical syndrome of headache, neck stiffness and photophobia (often with nausea & vomiting)
Clinical features of meningitis?
- Meningism
- Headache
- Irritable
- Neck stiffness
- Photophobia
- Fever
- Vomiting
- Varying levels of consciousness
- Rash
Which groups can have non-specific symptoms of meningitis?
- Neonates
- Elderly
- Immunosuppressed
Laboratory diagnosis of meningitis?
- Blood cultures
- Lumbar puncture: CSF for microscopy, Gram stain, culture & Biochemistry
- EDTA blood for PCR
In normal CSF fluid, describe the;
a) appearance
b) cells
c) protein levels
d) glucose levels
a) clear, colourless
b) 0-5; lymphocytes
c) very little protein
d) the glucose level in CSF is proportional to the blood glucose level
In CSF fluid of bacterial meningitis describe the;
a) appearance
b) cells
c) protein levels
d) glucose levels
a) cloudy, turbid
b) 100-200 polymorphs
c) high protein
d) low glucose
In CSF fluid of ‘asepctic’ (viral) meningitis describe the;
a) appearance
b) cells
c) protein levels
d) glucose levels
a) clear, slightly cloudy
b) 100-500 lymphocytes (lymphocytic pleocytosis)
c) normal
d) normal
In CSF fluid of TB meningitis describe the;
a) appearance
b) cells
c) protein levels
d) glucose levels
a) clear, slightly cloudy
b) 100-500 lymphocytes (lymphocytic pleocytosis)
c) high
d) low
In CSF fluid of cryptococcal infection describe the;
a) appearance
b) cells
c) protein levels
d) glucose levels
a) clear
b) 100-200 lymphocytes (lymphocytic pleocytosis)
c) normal, slightly elevated
d) normal, slightly reduced
Which age group does viral meningitis typically affect?
Primarily affects children and young adults
How do signs and symptoms in viral meningitis differ from bacterial?
- Milder signs and symptoms but longer period of presentation
- Full recovery expected
Main viruses causing viral meningitis?
- May start as respiratory or intestinal infection then viraemia
- Enteroviruses: Echo, Coxsackie A, B
- Paramyxovirus: Mumps
- Herpes simplex, Varicella Zoster virus
- Adenoviruses
- Other: Arboviruses, Lymphocytic choriomeningitis, HIV
Where is TB meningitis typically seen in?
Higher incidence in immigrant populations who come from countries with a higher incidence of TB
Onset of TB meningitis?
Insidious onset (slow growing organism)
What is recurrent meningitis defined as?
- >2 episodes meningitis
- Symptom-free intervals
- Normal CSF between episodes
- Must be differentiated from chronic meningitis
What is encephalitis?
An acute inflammatory process affecting the brain parenchyma
Which organism is the common cause of encephalitis?
- Viral infection is the most common and important cause, with over 100 viruses implicated worldwide
- Over 90% of causes in UK is HSV!!
Symptoms of encephalitis?
- Symptoms
- Fever
- Headache
- Behavioural changes
- Altered level of consciousness
- Focal neurologic deficits
- Seizures
Most common causes of encephalitis:
- Herpes viruses – HSV-1, HSV-2, Varicella Zoster virus, Cytomegalovirus, Epstein-Barr virus, Human Herpes virus 6
- Adenoviruses
- Influenza A
- Enteroviruses, Poliovirus
- Measles, Mumps, and Rubella viruses
- Rabies
- Arboviruses: Japanese encephalitis; St. Louis encephalitis virus; West Nile encephalitis virus
Which organism is the most common cause of sporadic encephalitis in previously healthy?
Herpes virus (HSV-1 normally)
How will herpes encephalitis typically present?
- May be evidence of herpes infection of skin, mucosae
- Causes severe haemorrhagic encephalitis affecting temporal lobe
- Focal signs and epilepsy features
- Acute infection or more commonly reactivation of latent infection (trigeminal nerve ganglion)
WHICH DRUG IS USED IN THE TREATMENT OF HERPES ENCEPHALITIS?
Aciclovir
What is rabies?
- Acute, progressive viral encephalitis
- Highest case fatality of any infectious disease
- One of the most ancient diseases described
- Model zoonosis
Pathogenesis of rabies?
- Virus enters through bite, grows at trauma site for a week and multiplies, then enters nerve endings and advances toward the ganglia, spinal cord and brain
- Infection cycle completed when virus replicates in the salivary glands
Where is the infection cycle of rabies completed?
In the salivary glands
What are the 4 clinical phases of rabies?
- Prodromal phase – fever, nausea, vomiting, headache, fatigue; some experience pain, burning, tingling sensations at site of wound
- Furious phase – agitation, disorientation, seizures, twitching, hydrophobia
- Dumb phase – paralyzed, disoriented, stuporous
- Progress to coma phase, resulting in death
What is neurosyphilis?
Infection of the CNS in a patient with syphilis;
- Central nervous system invasion occurs early in infection in 30-40% of patients
- Asymptomatic neurosyphilis can occur at any stage of syphilis
Early symptomatic forms of neurosyphilis (months to a few years)?
- Acute meningitis
- Meningovascular; presents with stuttering stroke involving middle cerebral artery
Late symptomatic forms of neurosyphilis (>2 years)?
- General paresis (of the insane); paralytic dementia
- Tabes dorsalis; nerves in dorsal column degenerate
Diagnosis of neurosyphilis?
Diagnosis by blood & CSF serology
Pathophysiology of a brain abscess?
- Direct spread from “contiguous” suppurative focus (e.g. from ear 40%, sinuses, teeth)
- Haematogenous spread from a distant focus e.g. endocarditis, bronchiectasis (often multiple abscesses)
- Trauma (e.g., open cranial fracture, post-neurosurgery)
- Cryptogenic (no focus is recognised ~15-20 per cent of cases).
Most common organisms causing brain abscesses?
- The bacteria responsible depend on the pathogenic mechanism involved
- Brain abscesses are often mixed (polymicrobial)
- Streptococci (60-70 %) e.g. Streptococcus “milleri”
- Staphylococcus aureus (10-15 percent) most common pathogen in abscesses after trauma/surgery
- Anaerobes e.g. Bacteroides spp.
- Gram negative enteric bacteria (E. coli, Pseudomonas spp.)
- Others e.g. fungi, Mycobacterium tuberculosis, Toxoplasma gondii
Clinical presentation of a brain abscess?
- Headache (most)
- Focal neurological deficit (30-50%)
- Fever (<50%)
- Nausea, vomiting
- Seizures
- Neck stiffness
- (Papilloedema)
Management of brain abscess?
-
Drainage is treatment of choice (N.B small abscesses can be treated with antibiotics alone) to:
- to urgently reduce intracranial pressure
- to confirm diagnosis
- to obtain pus for microbiological investigation
- to enhance efficacy of antibiotics
- to avoid spread of infection into the ventricles
Why should choice of antibiotic be carefully considered in brain abscesses?
- Physiological properties of blood-brain barrier and blood CSF-barrier are distinct SO only certain drugs penetrate BBB
- Penetration of drugs into CSF and brain tissue differ
Which antibiotics are most appropriate in a brain abscess?
Ampicillin, Penicillin, Cefotaxime, Ceftazidime, and Metronidazole achieve therapeutic concentrations in intracranial pus
Steroids (dexamethasone) is shown to decrease morbidity and mortality in meningitis caused by which bacteria?
- 10mg IV 15 minutes prior to antibiotics
- Shown to decrease morbidity & mortality in S. pneumoniae but NOT N. meningitidis
