3. CNS infections - Meningitis + Encephalitis Flashcards
Define meningitis.
Inflammation of the meninges (the lining of the brain and spinal cord).
More specifically in relation to inflammation of the 2 inner layers called the leptomeninges.
Can be bacterial / viral / fungal.
Bacterial + viral -> acute meningitis.
Fungal -> chronic meningitis.
Name 3 organisms that can cause meningitis in adults.
- N.meningitidis (g-ve diplococci).
- S.pneumoniae (g+ve cocci chain).
- Listeria monocytogenes (g+ve bacilli).
- Haemophilus Influenza.
Name 3 organisms that can cause meningitis in children.
- E.coli (g-ve bacilli).
- Group B streptococci e.g. s.agalactiae.
- Listeria monocytogenes.
Name 5 organisms that commonly cause meningitis in immunocompromised populations.
- Cytomegalovirus (CMV)
- Cryptococcus neoformans (fungi)
- TB - Mycobacterium tuberculosis
- HIV
- Herpes simplex virus
Which organism can cause meningitis in pregnant women? What food are pregnant women advised to avoid due to this organism?
Listeria monocytogenes - found in cheese, why pregnant women told to AVOID
What is the most common cause of meningitis in neonates?
Group B Haemolytic streptococcus (group B strep - GBS)
e.g. Streptococcus Agalactiae
What is the most common cause of meningitis in adults?
Streptococcus Pneumoniae / Pneumococcus
N.meningitidis is a common cause of meningitis, especially in which populations?
Adults/students
H.influenzae is a cause of meningitis, most commonly affecting which population?
Children
Name 3 viral causes of meningitis.
- Herpes simplex virus (HSV)
- Enterovirus
- Varicella zoster virus (VZV)
What is the most common cause of viral meningitis?
Enterovirus.
Give 4 risk factors for meningitis.
- Intrathecal (into spinal canal) drug administration
- Immunocompromised
- Elderly
- Pregnant
- Bacterial endocarditis
- Crowding e.g. military base, university students
- Diabetes
- Malignancy
- IV drug abuse
Describe the pathophysiology of meningitis.
There are 2 routes of infection to the CSF and leptomeninges:
1. Direct spread
a. Pathogens gets inside skull or spinal column and then infiltrates the meninges
b. Has access to the CSF
c. Could enter through nose, skin break but most commonly due to anatomical defect such as spina bifida, fracture
- Haematogenous spread
a. Pathogen enters blood stream and moves through endothelial cells in blood vessels that make up BBB and then get into CSF.
b. Typically bind to surface receptors, or through areas of damage or by vulnerable spots e.g. choroid plexus.
- Once pathogen within CSF, it can start multiplying.
- The WBC within the CSF identify the pathogen and release cytokines to recruit additional immune cells.
- > 5 WBCs per microlitre of CSF = MENINGITIS
Explain the pathophysiology of acute bacterial meningitis.
- Typically sudden
- Neisseria meningitides is transmitted by droplet spread
- Can lead to meningococcal septicaemia:
- When bacteria invades into blood
- Presence of endotoxin in bacteria leads to a inflammatory cascade
- Petechial rash + signs of sepsis = meningococcal septicaemia
- The pia-arachnoid is congested with polymorphs
- A layer of pus forms which may organise to form adhesions causing cranial nerve palsies and hydrocephalus
Briefly describe the pathophysiology of chronic meningitis e.g. TB.
- Chronic infection e.g. TB:
- Brain is covered in a viscous grey-green exudate with numerous
meningeal tubercles.
Briefly describe the pathophysiology of viral meningitis.
Viral meningitis:
* Predominantly lymphocytic inflammatory CSF reaction WITHOUT PUS FORMATION
- Little of no cerebral oedema unless encephalitis develops
What is the classic triad of meningism?
- Fever
- Neck stiffness
- Headache / Altered mental state
Give 5 symptoms of meningitis.
Classic triad:
1. Fever
2. Neck stiffness
3. Headache
- Non-blanching petechial/purpuric rash, if meningoccoccal septicaemia.
- Papilloedema.
- Photophobia - discomfort with bright lights
- Phonophobia - discomfort with loud sounds
- Vomiting.
- Seizures.
- Altered consciousness.
Give 3 signs of meningitis.
- Kernigs sign
- Brudzinskis sign
- Non blanching purpuric rash, if meningoccoccal
How would you describe the rash that is characteristic of meningitis?
Non-blanching petechial rash.
Why is a rash associated with meningitis?
N.meningitidis is a common cause of meningitis.
Meningococcal sepsis = disseminated intravascular coagulation, the ‘rash’ is the red spots produced by the tiny clots.
What is Kernig’s sign?
Patient lying on back
Flex hip and straighten knee
= back pain
What is Brudzinski’s sign?
Patient lying on back
When you flex neck + bend head forward
= knees and hips with flex too
Describe the clinical presentation of meningitis in neonates + babies.
Neonates and babies can present with non-specific clinical features:
1. Hypotonia
2. Poor feeding
3. Lethargy
4. Hypothermia
5. A bulging fontanelle (an outward curving of an infant’s soft spot)
What investigations might you do in someone who you suspect has meningitis?
- Blood cultures BEFORE Lumbar puncture.
- Bloods: FBC, U+E, CRP, serum glucose, lactate.
- Lumbar puncture with CSF culture
- Send for microscopy and sensitivity. - CT head.
- To exclude lesions e.g. tumours - Throat swabs. (bacterial + viral).
- Pneumococcal and Meningococcal serum PCR.
What is the gold standard investigation for bacterial meningitis?
CSF culture from lumbar puncture
What investigations would you do on a CSF sample?
- Protein and glucose levels.
- MCS.
- Bacterial and viral PCR.
At what vertebral level would you do a lumbar puncture?
L4/5.
Give 4 potential adverse effects of doing a lumbar puncture.
- Headache.
- Damage to spinal cord.
- Paraesthesia.
- CSF leak.
Give 3 contraindications for lumbar puncture.
- Raised ICP
- Focal neurology
- Haemodynamically unstable e.g. bradycardia, hypotension
- Decreased GCS
What is the colour of the CSF in someone with bacterial infection?
Cloudy.
It is normally clear.
What is the CSF like in bacterial meningitis?
Cloudy/turbid colour
Neutrophils/granulocytes
High protein
Low glucose
What is the CSF like in viral meningitis?
Lymphocytes
High protein
Normal/low glucose
What is the CSF like in fungal meningitis?
Lymphocytes
High protein
Low glucose
If a CSF contains gram+ cocci, what is it most likely to be?
Strep pneumoniae
If a CSF contains gram+ bacilli, what is it likely to be?
H. influenzae
listeria
Explain a table of CSF results for meningitis.
Think:
Bacteria - stay in the CSF -> going to have lots of time to swim around + release proteins + use the glucose.
BUT:
Viruses -> not gonna use glucose -> if they do use protein, it’s only going to be a little.
Immune system:
- Sends neutrophils for bacteria
- Sends lymphocytes for viruses
Therefore CSF results:
For Bacteria: low glucose, high proteins, high WCC - neutrophils
For Viruses: high glucose, normal/mildly raised proteins, high WCC - lymphocytes
What would indicate doing a head CT scan before a lumbar puncture?
- Age > 60
- Immunocompromised
- History of CNS disease
- New onset/recent seizures
- Decreasing conscious levels (GCS < 14)
- Focal neurological signs
- Papilloedema
Treatment for bacterial meningitis.
- Start on empirical antibiotics based on age:
-> give 3rd generation Cephalosporin (e.g. cefotaxime or ceftriaxone)
1). < 3 months / > 50 YO / immunocompromised:
– IV cefotaxime + amoxicillin (covers listeria contracted during pregnancy)
2). > 3 months:
– IV ceftriaxone
3). For severe anaphylaxis with penicillins:
– IV Chloramphenicol
4) For foreign/return travellers:
– Additional IV Vancomycin for penicillin resistant pneumococcal infection
- Steroids - oral dexamethasone
-> to reduce cerebral oedema
What would you need to do, apart from treat them, if you were presented with a patient with meningitis?
Contact tracing for prophylaxis.
Inform local officer/PHE.
Describe the treatment for meningitis caused by listeria monocytogenes.
Cefotaxime and amoxicillin.
What is the treatment of meningitis?
Cefotaxime.
+ amoxicillin if L.monocytogenes infection.
+ steroids to reduce inflammation in S.pneumoniae infection.
What antibiotic is commonly given for the treatment of meningitis?
Cefotaxime.
What drug reduces the risk of developing complications after meningitis?
Dexamethasone
Treatment of meningococcal septicaemia.
- Immediate IM Benzylpenicillin in community
- IV Cefotaxime in hospital
Treatment of viral meningitis.
- Supportive treatment
- Self-liming in 4-40 days
- Acyclovir in herpes simplex virus or varisella zoster virus caused meningitis
Treatment of fungal meningitis.
- Cryptococcal meningitis - IV Amphoteracin B
When is a child vaccinated against meningitis B?
At 8 weeks and 16 weeks.
When is a child vaccinated against meningitis C?
At 12 weeks and 1 year.
When is a child vaccinated against meningitis ACWY?
At age 14.
What drugs would you give for meningitis prophylaxis for contacts?
Rifampicin or Ciprofloxacin.
- ORAL CIPROFLOXACIN STAT - for all ages and pregnancy
- Or can give ORAL RIFAMPICIN - for all ages but NOT PREGNANCY
For which bacteria is meningitis prophylaxis effective against?
N.meningitidis.
Give 3 potential complications of meningitis.
- Hearing loss
- Epilepsy
- Cognitive impairment
- Memory loss
- Focal neurological deficits
Give 3 differential diagnoses of meningitis.
- Encephalitis - altered mental state is the predominant symptom
- SAH - headache is MORE SUDDEN
- Sepsis
- Influenza or other viral illness
What is encephalitis?
Inflammation of the brain parenchyma
What is the most common cause of encephalitis?
HSV-1
In what group of people is encephalitis common?
The immunocompromised.
Name 3 viruses that can cause encephalitis.
- Herpes simplex virus.
- Varicella zoster virus.
- HIV.
- Coxsackie
- EBV
- Mumps
- CMV
- Measles
- Rabies
Give 2 non-viral causes of encephalitis.
- Bacteria: N.menigitidis, Tuberculosis (TB), Listeria, Klebsiella
- Parasites: Malaria
- Lyme disease
- Fungal: Cryptococcus
- Autoimmune: Acute disseminated encephalomyelitis, Anti-N-methyl-D-aspartate (NDMA) receptor encephalitis, T cell lymphoma
Give 3 risk factors for encephalitis.
- <1 years old or >65 years old (the extremes of age)
- Immunodeficiency -> the immunocompromised
- Viral infections
- Body fluid exposure
- Organ transplantation
- Animal or insect bites
Explain the pathophysiology of encephalitis.
- The pattern of brain involvement depends on the specific pathogen, immunological state of patient and range of environmental factors.
- In viral encephalitis: the virus initially gains entry and replicates in local or regional tissue such as: GI tract, skin, urogenital, or respiratory system.
- It can then disseminate to the CNS by haematogenous routes or via retrograde axonal transport.
(1). Haematogenous route: Enterovirus, Arbovirus, HSV, HIV, Mumps
(2). Retrograde axonal transport: herpes virus, rabies virus, or variant scrapie-isoform prion proteins.
- The process of brain parenchyma inflammation depends on interaction between neurotropic properties of virus and the host’s immune response.
Describe the clinical presentation of encephalitis.
Classic triad:
1. Fever
2. Headache
3. Altered mental status
Initially:
-> Fever, headaches, myalgia, fatigue and nausea
Progression to:
- Personality and behavioural changes - common early manifestation
Leading to Parenchymal involvement:
- Focal neurological deficit: aphasia, hemiparesis,
- Seizures
- Altered mental state: confusion, decreases consciousness, drowsiness
- Reduced GCSE -> coma
- Meningismus:
Some patients have evidence of meningeal inflammation with headache, photophobia, and neck stiffness- If absent this is an important negative
Investigations for encephalitis.
- MRI head
-> to see inflammation in inferior frontal + medial temporal areas in HSV - Electroencephalography (EEG)
-> showing diffuse abnormalities and help confirm diagnosis - Lumbar puncture
-> Raised lymphocyte count; diagnosis of specific cause - Bloods (FBC, CRP, U+Es), CSF serology and Blood cultures
-> bacterial pathogens - Throat swab
-> virus detection - Peripheral blood smear
-> detection of plasmodium falciparum
A lumbar puncture is done and a CSF sample is obtained from someone who is suspected to have encephalitis.
Describe what the lymphocyte, protein and glucose levels would be like in someone with encephalitis.
- Lymphocytosis (raised lymphocytes).
- Raised protein.
- Normal glucose.
What can the EEG show in encephalitis?
Periodic lateralised discharges at 2Hz (not specific)
What is the treatment for VIRAL encephalitis?
- Acylovir - FIRST LINE
- Every 8 hours for 10-21 days (usually 14)
- 21 days if immunocompromised
- If cytomegalovirus (CMV) encephalitis is suspected in an immunocompromised patient:
= ganciclovir + foscarnet are given with aciclovir - Could give ganicilovir → for HHV-6
- Anti-seizure medication e.g. PRIMIDONE
What is the first-line treatment for viral encephalitis?
IV acyclovir
Phenytoin/Primidone for seizures
Give 2 differential diagnoses for encephalitis.
- Meningitis
- Encephalopathy
- Status epilepticus
- CNS vasculitis
Give 3 complications for encephalitis.
- Seizures, ischaemic strokes, hydrocephalus
- Fatigue
- Aphasia
- Changes in cognition, personality, mood
- Headaches, chronic pain
- Movement, sensory disturbances
- Hormonal imbalances
