Week 7 . Central Nervous System Infections Flashcards
What is Meningitis?
Inflammation of the meninges
What is encephalitis?
Inflammation of the brain tissue
What is meningo-encephalitis?
It is inflammation of the meninges and brain tissue
What defines Aseptic meningitis?
White cell count >5x106/L (5/mm3) in cerebrospinal fluid (CSF) –> higher CSF count for children
Negative bacterial culture of the CSF
What is the main cause of aseptic meningitis?
Viruses are the most common cause
What are less common cause of aseptic meningitis?
Partially treated bacterial meningitis Listeria TB Syphilis Malignancy Autoimmune conditions Drugs
General virus structure?
Nucleic acid
Capsid
protein coat
made up of capsomeres (subunits)
Some have lipid envelope (derived from host cell membrane)
Some contain other proteins/enzymes
What is the mode of action of viral enzymes?
for replicating genetic material, influencing transcription, protein modification
What types of nucelic acid can you have in a virus?
DNA or RNA
Single stranded, double stranded
Linear or circular (e.g. Hepatitis B - DNA)
What is the action of viral proteins?
Form capsid/membrane projections
Who most commonly gets viral meningitis?
In children –> aged around 5
Neonates
What is the common causes of viral meningitis?
Enteroviruses –> leading cause
Herpes viruses
Mumps Virus
HIV
Give examples of enteroviruses that can cause viral meningitis? (5)
Echoviruses Coxsackie viruses Parecho viruses Enteroviruses 70 and 71 Poliovirus
What are the different types of herpes viruses that can cause viral meningits?
Herpes Simplex Virus 2 (HSV 2)»_space; HSV 1
Varicella Zoster Virus (VZV)
Cytomegalovirus (CMV), Epstein Barr Virus (EBV)
HHV6, HHV7
Is HSV 2 or HSV 1 common cause of viral meningitis?
HSV 2
What viruses can cause viral meningitis and the mosiquito is the vector?
Arboviruses–>
Japanese Encephalitis virus, yellow fever
What are 7 less common causes of viral meningitis?
Adenovirus
Measles
Influenza
Parainfluenza type 3
Lymphocytic choriomeningitis virus (LCMV)
What should be taken during a history of a person with suspected meningitis?
It’s very important to take a travel history, sexual history and check if the patient is immunocompromised
What is pathogenesis of viral meningitis?
Colonisation of mucosal surfaces
Invasion of epithelial surface
Replication in cells
Dissemination and CNS invasion
How is CNS invasion occur in viral meningitis?
Via cerebral microvascular endothelial cells –> haematogenous spread e.g enteroviruses
Via choroid plexus epithelium
Spread along the olfactory nerve –> neurotropic e.g. HSV and VZV
What is the symptoms of viral meningitis due to?
Symptoms mainly due to inflammatory response in the CNS
It is usually not the virus causing the inflammation but the bodies response to the body
What are the general clinical presentations of viral meningitis?
Fever
‘Meningism’
Headache
Neck stiffness
Photophobia
Sometimes ‘viral’ prodrome (e.g. lethargy, myalgias, arthralgias, sore throat, D&V, rash)
Is it easy to distinguish between viral and bacterial meningitis?
No it is difficult
What is the initial treatment of viral meningitis?
You treat with antibiotics until LP is done. Preventing process to it being a bacterial cause
What are the clinical presenation of viral meningitis in children?
Are lot more suttle
Look for nuchal rigidity (neck stiffness) and bulging anterior fontanelle
What are the different examinations that can be done to assess viral meningitis?
Kernig’s sign: With hip and knee flexed to 90o, the knee cannot be extended due to pain/stiffness in the hamstrings
B) Brudzinski’s sign
Flexing the neck causes the hips and knees to flex
Nuchal rigidity =
Resistance to flexion of the neck –> in very severe cases of meningitis
What are the different investigations that can be done for viral meningitis?
Blood test
Ct scan
Lumbar puncture
What are you testing for in a blood test for diagnosing viral meningitis?
FBC, U&E, CRP, clotting
Blood culture
Why is a Ct scan done of a person with possible viral meningitis?
To look for any raised ICP.
To see if there is any alternative diagnosis, such as mass lesion, subarachnoid haemorrhage.
What are you testing for once you have done a lumbar puncture in a person with potential viral meningitis?
Microscopy, Culture, Sensitivity (MC&S)
Protein
Glucose (must check blood glucose at same time)
Viral PCR: enteroviruses, HSV, VZV
Why do you check glucose blood levels against CSF glucose levels?
It is not the absolute glucose levels in the CSF that is important but the ratio with blood glucose levels
What are the CSF findings in viral meningitis?
White cell count (Pleocytosis = white cells in CSF)
Lymphocytic, usually
What is the gold standard test for viral meningitis?
Viral PCR
When should you do a CT scan before lumbar puncture?
If there are:
Focal neurological signs, Presence of papilloedema, Continuous or uncontrolled Seizures or GCS ≤12
Clotting
What samples are needed to do a enterovirus PCR?
Throat swab/ stool sample
What are you testing for if you do a serology test?
Mumps
Epstein Barr Virus /Cytomegalovirus
HIV
Other viruses as indicated, e.g. travel-related
What is the general treatment of viral meningitis?
Start appropiate Iv antibiotics ( cefotaxime) if any risk of bacterial meningitis.
No specific treatment in viral meningitis, might treat HSV and VZV with aciclovir
Mainly supportive therapy –> analgesia and antipyretics
What is the outcome of viral mengitis?
Generally good prognosis but some evidence that long term patients can have headaches and cognitive dysfunction.
It is notifiable
What are the symtpoms and treatment of enteroviral mkenigitis?
Fever, vomiting, anorexia, rash, upper respiratory tract symptoms are common
No specific treatment
Full recovery normal
When is enteroviral meningitis usually present?
Most common cause
Classically late summer/autumn epidemics
What does HSV1 and 2 cause?
HSV1 – causes cold sores and viral encephalitis
HSV2 – causes genital herpes and meningitis –> 2nd most common cause
When does HSV2 cause viral meningitis?
Can follow primary infection (3-12/7 after genital lesions) or occur during/between relapses
Does aciclovir have a profound effect in preventing viral meninigitis?
No evidence that aciclovir is effective
What is Mollaret’s meningitis?
Repeated aseptic meningitis and commonest cause is HSV2
What does varcieela zoster virus usually cause?
Primary = chickenpox (varicella)
Secondary = shingles (zoster)
When does VZV cause viral meningitis?
Meningitis unusual but can occur during chickenpox, shingles (so look for a rash), on its own, or after vaccination
What cases of mumps causes viral meningitis?
10-30% of cases
What is the onset of mumps causing viral meningitis?
CNS symptoms 5 days after onset of parotitis
Other features:
Abdominal pain
Orchitis
What are the assoicated features of a HIV patient with viral meningitis?
Fever
Lymphadenopathy
Pharyngitis
Rash
What is the main cause of viral Encephalitis?
Herpes Simplex Virus (1 & 2)
90% are HSV 1
What are other causes of encephalitis?
VZV, EBV, CMV
Measles
Mumps
Enteroviruses (including polio)
Bacteria (e.g. Strep pneumoniae, Neisseria meningitidis, TB)
Acute disseminated encephalomyopathy (ADEM
What are the clinical features of encephalitis?
Altered mental state (confusion/bizarre behaviour -> coma)
Fever
Headache
Meningism (may be absent)
+/- Focal neurology:
Seizures - Cranial nerve palsy
Weakness - Ataxia
Dysphasia/aphasia
What investigations are done for encephalitis?
Blood tests:
CT – likely to be necessary before LP
MRI – may see changes typical of HSV encephalitis
Lumbar puncture: Same test as meningitis
EEG:
In HSV encephalitis 75% will show abnormal temporal lobe activity
What part of the brain does HSV1 attack?
Temporal lobe
What are the findings of encephalitis?
Same as viral meningitis
What is the treatment of encephalitis?
High dose IV aciclovir
10mg/kg tds
14-21 days
Start on clinical suspicion (do not wait for CSF results – it is a medical emergency)
Oral switch not recommended
Insufficient evidence to recommend steroids
Herpes Simplex Encephalitis has a high incidence in what group of people?
Under 20’s and over 50’s.
Equal distribution beteen Males and Females
What is the primary cause of Herpes Simplex Encephalitis ?
Direct transmission of the virus along the neural/olfactory pathway
What is the reactivation cause of Herpes Simplex Encephalitis?
So reactivation at the trigeminal ganglia
What is the pathogenisis of Herpes Simplex Encephalitis ?
Acute focal necrotising encephalitis
Inflammation / swelling of brain tissue
What is the outcome of Herpes simplex Encephalitis?
Mortality if untreated: 70%
Mortality if treated remains high:
28% at 18 months
If GCS
What are the possible complications with HSE?
Paralysis
Speech loss
Personality change
What is Acute disseminated encephalomyelopathy (ADEM)?
Immune-mediated CNS demyelination
Cause of Acute disseminated encephalomyelopathy (ADEM)?
Can follow viral illness or vaccination (e.g. influenza)
What are the clinical features of ute disseminated encephalomyelopathy (ADEM)?
Clinical features same as encephalitis
CSF findings = viral meningitis.
MRI helpful.
What is the treatment and outcome of ADEM?
Treatment is immunosupressants and steroids.
Recovery is variable
What is the symptoms of brain abscess?
Insidious onset of fever, headache, +/- neck stiffness
+/- Altered conscious level, seizures, focal neurological signs
Usually bacterial, may be parasitic
What is the action of the skulll and verterbral column in terms of protection?
They protect the brain and spinal cord from mechanical pressure and spread of infection
Invasion by microrganism can occur via 2 ways , what are they?
Blood-borne invasion
Blood-brain barrier
Blood CSF barrier
Ascend up via the Peripheral nerves
What is the normal cell count in a healthy person?
less than 5
What is the normal glucose and protein levels in a normal healthy person?
Glucose 2.5-4 mmol/L
Protein 0.15-0.4g/L
What is the cell count and cell type of a person with bacterial meningitis?
greater than 200 and polymorphs cell type
What is the glucose and protein level of a bacterial meningitis comapred to normal?
Glucose
What is the cell count and cell type of viral meningitis?
20-200 and Lymphocytes
What is the glucose and protein level of viral meningitis compared to normal?
Glucose –> normal or reduced
Protein–> Normal or increased
What is the cell count and cell type of TB and Cryptococcus meningitis?
20-200 cell count
Cell type: lymphocytes
What is the glucose and protein levels of TB meningitis compared to normal?
Reduced glucose levels
Increased Protein levels
What is the glucose and protein levels of Crypotococcus meningitis compared to normal?
Normal or reduced Glucose levels
Increased Protein levels
How many capsular types of Neisseria meningitides is there? What are the 5 most common types?
13 capsular types: A, B, C, W135, Y most common
Where is the natural habitat of the Neisseria meningitidis?
Natural habitat in nasopharynx
5-20% carriers (increased in smokers)
Half carried strains non-capsulate
What type of bacteria is Neisseria meningitidis?
Gram negative diplococci
Require blood for growth
How many capsular types of Neisseria meningitidis is there?What are the 5 most common types?
13 capsular types: A, B, C, W135, Y most common
How can Neisseria meningitis be detected?
Can also be detected by nucleic acid amplification (PCR)
How does Neisseria meningitis survive in the blood stream?
Presence of a capsule - protects against complement-mediated bacteriolysis and phagocytosis
Ability to modify host cell inflammatory processes ie. host cell cytokine production
What is the mode of action of Neisseria meningitis?
Able to cross the BBB and multiple in the subarachnoid space
What are the 4 common infections caused by Neisseria meningitidis?
Fulminant (suddenly and quickly) septicaemia
Septicaemia with purpuric rash
Septicaemia with meningitis
Pyogenic (purulent) meningitis with no rash
What are less common infections caused by neisseria meningitidis?
Chronic meningococcal bacteraemia with arthralgia (pain in joint)
Focal sepsis
Conjunctivitis = is a common condition that causes redness and inflammation of the thin layer of tissue that covers the front of the eye
Endophthalmitis= is an inflammation of the internal coats of the eye
What is the treatment against neisseria meningitidis?
Ceftriaxone, cefotaxime–> first line
Penicillin = If the strain is sensitive to it will use penicillin
When do you give chemoprophylaxis to treat Neisseria meningitidis?
When there is contact of invasie disease so close or kissing contacts.
Give rifampicin and ciprofloxacin
What vaccinations are there aginst neisseria meningitis?
Active gainst group A, C and W135
Not active against group B
Is the prevelance of Neisseria meningitidis constant throughout the year?
No fluctuates over time, winter peaks, variable serogroup predominance
What are local outbreaks of Neisseria meningitidis dependent on?
Population of susceptible individuals
High transmission rate
Virulent, capsulate strain
What is the carriage of Haemophilis influenza?
Restricted to humans
Only 5-10% carry capsulate strains
Blood loving” : Unable to grow in the absence of blood or certain constituents of blood
How does Haemophilis influenza enter the blood stream?
Present in the throat carriage.
It invades the submucosa
Then invades the blood stream
What type of bacteria is Haemophilus influenza?
Small, pleopmorphic Gram negative cocco-bacilli or bacilli
What can Haemophlis influenza cause and in who?
Meningitis
Infants > 2months – 2 years
How many strains of Haemophlis influenzae is there and which caues the most invasive disease?
Six antigenic types a-f
Type b causes the most invasive disease
Some strains produce polysaccharide capsule
What is the structure of Type B capsule?
Fimbriae. IgA proteases, Outer membrane proteins/lipolysaccahride
Does Haemophilis influenza cause influenza?
NO
What is the treatment of Haemophils influenzae?
Ceftriaxone, cefotaxime
Ampicillin
β-lactamase producing strains common
What Chemoprohylaxis is given for invasive contact?
Rifampicin
What has been the effect of H.infleunza Type B conjugate vaccine?
Massive reduction in the incidence of invasive disease
What type of bacteria is Streptococcus pneumoniae?
Gram positive cocci, with cells in pairs
What does Strep. pneumoniae require to grow?
Requires blood or serum for growth. α-haemolytic activity on blood
What colour does agar look when Strept. pneumoniae has been cultured?
Green colour
How many types of polysaccahride capusle does Strept. penumoniae have?
95 cpsular types
Where is the normal habitiat of Strept. pneumoniae?
Human respiratory tract
How is Strept. pneumonia transmitted?
Transmission is via droplet spread
What is Optochin?
It is a chemical used in cell culture technizues for the presumptive identification of Steptococcus pneumoniae
What age is Pneumococcal meningitis seen in?
Seen in all ages
Who is at more risk of getting infected by pneumococcal meningitis?
More common and more severe in elderly.
Also more common in immunocompromised patients
What is the treatment for Pneumococcal meningitis?
Cefriaxone and cefotaxime
Do you give chemoprophlaxis of close contact in treatment for Pneumococcal meningitis?
No
When should steroids be given for adults with meninigitis?
Must be given shortly before or with first dose of antibiotics.
Be given if S.penumoniae is suspected but no benefit in meniningcoccal meningitis?
What antibiotic should be given and for how long for treating a adult with meningitis?
Dexamethasone 0.15 mg/kg IV every 6 hours x 2-4 days
What causes Pneumococcal meningitis?
Streptococcus pneumoniae
What infections causes neonatal meningitis?
Group B beta-haemolytic Streptococci
Escherichia coli
Listeria monocytogenes
What are the different onset times of neonatal meningitis?
Early ( 5 days). Usually meningitis
What is the treatment of Neonatal meningitis?
Cefotaxime
Ampicillin and gentamicin:
Ampicillin covers all streptococci
Gentamicin covers all E.coli
What is the complications with meningitis?
Death
Overwhelming sepsis
Raised intracranial pressure
Longer term problems
Deafness Delayed development Seizures Stroke Hydrocephalus
What are the causes of lymphocytic meningitis?
Viral meningitis –> most common
Spirochete bacteria ( e.g.treponemal and borelia)
Polio virus can cause meningitis that may lead to paralysis
TB
What is the diagnosis difficult of Tb meningitis?
Acid fast bacilli often not seen on microscopy
Delay in diagnosis leads to a worse prognosis
What is the treatment for Tb meningitis?
12 months standard TB treatment
Steroids beneficial
What staining do you do for direct detection of TB? Why don’t you do alcohol and acid fast?
Don’t do alcohol and acid fast as the stain does not wash off.
Use Ziehl Neelsen stain
Or
Flourescent antibody stain
What is the cause of brai abscess?
Usually bacterial
Spread of organisms from adjacent structures
e.g. middle ear, sinuses: Streptococci anaerobes
Blood stream spread e.g Staphylococcus aureus
What is the diagnosis and treatment of brain abcess?
Need brain imaging to confirm the diagnosis
Prolonged course of antibiotic therapy
How does a patient become in contact with Toxomplasma gondii encephalitis and how do you get toxoplasmosis?
Exposed to under cooked food or cat faeces
Sits in the brain asymptomatically and is activated when the immune system is weakend.
What is the cause of Crypotococcal meningitis?
Cryptococcus is a yeast
What stain can you see cryptococcal meningitis?
Indian ink stain
In what patients is cryptoccocal meningitis a common problem in? What is the onset rate?
Common problem in patients with late stage HIV
Insidious onset
How is crpytococcal meningitis treated?
Prolonged course of treatment with amphotericin, flucytosine or fluconazole.
At what age is encephalitis caused by Japanese encephalitis virus common?
Most commonly affects children
What is the prognosis of encephalitis caused by Japanese encephalitis virus?
One third die in the acute illness
One third left with severe long term neurological disability
One third recover
How is rabies encephalitis and Japanese encephalitis virus prevented?
By vaccine
What type of bacteria is Clostridum tetani?
Gram positive spore forming bacillus
Terminal round spore (drumstick)
Strict anaerobe
How does clostridium tetani spread?
Organism widespread in the soil
Implantation of contaminated soil into a wound
Wound may be major or minor
What organism caues tetanus?
Clostridium tetani
How does Clostridium tetani cause tetanus?
It is not invasive but produces tetanospasmin a neurotoxin
How does the tetanospasmin work and spread?
Toxin genes plasmid encoded
Toxin spreads via bloodstream and retrograde transport
Binds to ganglioside receptors and blocks release of inhibitory interneurones
Convulsive contraction of voluntary muscles
What is the most common entry site of clostridium tetani?
Through the foot
What is the symptoms of Tetanus?
Tonic muscle spasms
Trismus
Opisthotonus
Respiratory difficulties
Cardiovascular instability
(sympathetic nervous system)
What is the treatment and prevention for tetani?
Treatment:
Antitoxin (horse or human)
Penicillin or metronidazole
Drugs for spasms
Muscle relaxants
Respiratory support
Prevention–> Toxoid
What infections have 1st line treatment of Ceftriaxone, cefotaxime?
Haemophilus influenzae
Neisseria meningitidis
Streptococcus pneumoniae
What is brain abscess?
A brain abscess is a focal suppurative process within the brain parenchyma (pus in the substance of the brain)
Is the cause of brain abscess due to one or multiple organisms?
Usually polymicrobial (mixed).
What is the most common cause of brain abscess?
Streptococci (60-70%) e.g. Streptococcus “milleri” –> pus forming
How does S. Aureus cause Brain abscess?
10-15%) most common after trauma/surgery
What are the Gram negavtive enteric bacteria that cause brain abscess?
E.coli, Pseudomonas spp
What other organisms can cause brain abscess?
Fungi, Mycobacterium tuberculosis, Toxoplasma gondii, Nocardia, Actinomyces
What are the 4 clinical setting in which brain abscess can develop in?
Direct spread from “contiguous” suppurative focus (e.g. from ear, sinuses, teeth)
Haematogenous spread from a distant focus e.g. endocarditis, bronchiectasis (often multiple abscesses)
Trauma (e.g., open cranial fracture, post-neurosurgery) –> S.aureus
Cryptogenic –> common in immunocompromised people
What is the clinical presentation of brain abscess?
Headache –> most common
Focal neurological deficit
Confusion
Fever ( use funduscope and if seen then not good
What is the management of brain abscess?
Drainage is treatment of choice (N.B small abscesses can be treated with antibiotics alone)
What is the aim draining brain abscess?
To urgently reduce intracranial pressure
Due to trauma or severe : to confirm diagnosis
Could be something else: like a lesion
To obtain pus for microbiological investigation
To enhance efficacy of antibiotics –> some treatment cannot penetrate through pus
To avoid spread of infection
into the ventricle
What is the difficulty in giving antibiotic treatment for brain abscess?
The physiological properties of the blood-brain barrier and the blood-CSF barrier are distinct
Penetration of drugs into the CSF and brain tissue differ
Can make it hard to achieve therapeutic concentrations in intracranial pus
What antibiotics achieve therapeutic concentrations in intracranial pus?
Ampicillin, penicillin, cefuroxime, cefotaxime, ceftazidime, and metronidazole
What is the empirical treatment regime for Sinugenic/odontogenic abscess?
iv cefotaxime 2g 6-hourly +
iv metronidazole 500mg 8-hourly
What is the empirical treatment regime for Otogenic abscess
iv benzyl penicillin 2.4g 6-hourly +
iv ceftazidime 2g 8-hourly +
iv metronidazole 500mg 8-hourly
Drained abscess: treat for 4-6 weeks, “oral switch” can be an option
What are the complications of brain abcess?
Raised intracranial pressure, mass effect, coning
Rupture (usually into ventricles) causing ventriculitis
What is subdural empyema?
Infection between dura and arachnoid mata
What are the causes of subdural empyema?
Causes: (often polymicrobial) anaerobes,
Streptococci
Aerobic Gram negative bacilli,
Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus
How does infection spread to cause subdural empyema?
Spread of infection from sinuses (50-80%), middle ear and mastoid (10-20%) or distant site (5%, haematogenous) and following surgery or trauma
What is the clinical presentation of subdural empyema?
Headache, fever, focal neurological deficit, confusion, seizure, coma
What is the management of sudural empyema?
There should be urgent surgical drainage of pus, antimicrobial agents
Culture of pus should guide antibiotic therapy
When is Ventriculoperitoneal (VP) shunt and external ventricular drain (EVD) used?
Inserted into there ventricle to monitor intracranial pressure or drain CSF in patients with hydrocephalus
What is the problem with Ventriculoperitoneal (VP) shunt and external ventricular drain (EVD)?
It can cause infection on the VP shunt and EVD as it can become colonised with orgnaisms that can lead to vasculitis
How do you diagnose Ventriculoperitoneal (VP) shunt and external ventricular drain (EVD) infection?
By CSF microscopy and culture
What is the most common cause of Ventriculoperitoneal (VP) shunt and external ventricular drain (EVD) infection?
Coagulase-negative staphylococci.
It is normal skin flora that is introduce to the device at time of indroduction.
It can either block the device or the bugs spill into the ventricle and other structures
What is the treatment for entriculoperitoneal (VP) shunt and external ventricular drain (EVD) infection?
Treatment: device removal, intraventricular antibiotics
