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Meningitis
Meningitis

Meningitis

ðŸĶī Anatomy

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A quick recap of the anatomy of the meninges: the meninges are the membranous coverings of the brain and spinal cord. There are 3 layers of meninges:

  1. Dura mater - can be subdivided into the periosteal layer (lining the inner surface of the cranium) and the meningeal layer (continuous with the dura mater). Between the 2 layers we find the dural venous sinuses (which empty into the internal jugular vein). It receives its blood supply from the middle meningeal artery and is innervated by the trigeminal nerve.
  2. Arachnoid mater - an avascular layer in the middle. Underneath it lies the subarachnoid space in which we find the CSF. There are projections of arachnoid mater into the dura mater known as arachnoid granulations and these allow CSF to enter back into the circulation via the dural venous sinuses.
  3. Pia mater - thin adherent layer that is highly vascularised

They have 2 major functions: to provide a supportive framework and to protect the CNS from damage along with the CSF.

Meningitis is the inflammation of these meningeal layers. It may be considered infective or non-infective:

  • Infective meningitis - due to bacterial, viral, fungal causes.
  • Non-infective meningitis - due to cancer, injury, drugs, other diseases.

⚠ïļ Risk factors

  • Age - extremes of age.
  • Immunocompromised - especially patients with AIDS, diabetes, renal impairment etc.
  • Travel history
  • IV drug use

😷 Presentation

  • Headache
  • Photophobia - milder in viral meningitis than in bacterial meningitis.
  • Neck stiffness
  • Fever
  • Altered mental status
  • Nausea and vomiting
  • Focal neurological deficits
  • Seizures - suggestive on meningoencephalitis.
👞
Infants with bacterial meningitis often don’t have any of the typical clinical presentation.
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ðŸĐš
Clinical signs
  1. Kernig’s sign - inability to straighten the leg when the hip is flexed 90 degrees due to severe stiffness of the hamstrings.
  2. Brudzinski sign - severe neck stiffness causing a patient’s hips and knees to flex when the neck is flexed.
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VIRAL MENINGITIS

It is more common than bacterial meningitis. It is self-limiting and does not typically have serious complications associated with it.

ðŸĶ  Causative agents

  • ⭐ïļ Non-polio enteroviruses are the most common genus of viruses. Some specific causative agents within this genus are:
    • Coxsackievirus A & B
    • Echoviruses

      • They spread via the faecal-oral route. They replicate outside of the CNS and enter by penetrating the BBB after haematogenous spread.

  • HIV, measles, mumps often have manifestations of meningitis too.
  • Rabies virus (rabies lyssavirus) enters via the nAChRs found at the NMJ and enters the PNS before making its way to the CNS.
  • ⭐ïļ Herpes viruses are also common culprits:
    • HSV-2
    • HSV-1 although this is more associated with encephalitis as opposed to meningitis.
    • VZV
    • CMV
    • EBV
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BACTERIAL MENINGITIS

Bacterial meningitis is a lot more serious and needs urgent management. It is relatively less common as compared to aseptic meningitis (non-bacterial meningitis).

They most commonly are acquired through respiratory droplets and spread haematogenously into the subarachnoid space before leading meningeal inflammation which causes cerebral oedema and raised ICP.

ðŸĶ  Causative agents

⭐ïļ Common causative agents include:

  • Neisseria meningitidis - causing meningococcal meningitis. It is the most common cause of bacterial meningitis.
  • Strep. pneumoniae - causing pneumococcal meningitis. It is the most acute and most severe. It is a gram positive diplococci/chain
  • Haemophilus influenzae - causing Hib meningitis. It is a gram negative coccobacilli
  • Strep. agalactiae (GBS) - leading cause of neonatal meningitis.
  • Listeria monocytogenes - especially in the Immunocompromised, elderly and in neonates. It is a gram positive rod

Syphilitic meninigitis and tuberculous meningitis are also increasing due to HIV infections increasing susceptibility and severity.

Let’s look at their commonality based on age groups:

0-3 months

  1. Strep. agalactiae
  2. E. coli
  3. Listeria monocytogenes

3 months - 6 years

  1. N. meningitides
  2. S. pneumoniae
  3. H. influenzae

6 years - 60 years

  1. N. meningitides
  2. S. pneumoniae

>60 years

  1. S. pneumoniae
  2. N. meningitides
  3. Listeria monocytogenes

Immunosuppressed

Listeria monocytogenes

Mycobacterium tuberculosis

Treponema pallidum

These are not the most common in the Immunosuppressed but just are more common.

⚠ïļ Risk factors

  • Deficient immune system
  • Age >60
  • IV drug use
  • Crowds - increases risk of respiratory droplets/throat secretions.
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FUNGAL MENINGITIS

Fungal meningitis is much rarer than the aforementioned forms of meningitis. It usually occurs in hosts with compromised immunity.

ðŸĶ  Causative agents

  • ⭐ïļ Cryptococcus spp. - most notably cryptococcus neoformans causes primary pulmonary infection which is often asymptomatic but then disseminates to the brain to cause cryptococcal meningitis. Especially in HIV patients.
  • Histoplasma capsulatum
  • Coccidioses spp.
  • Candida albicans - acquired through skin/mucosal barriers are compromised.
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MENINGITIS

🔍 Investigations

💉
Lumbar puncture:

Is to be done within 1 hour of arrival at hospital if there are no signs of a raised ICP. 15mL of CSF is necessary for the investigations to be carried out.

We look at the CSF for a couple of factors:

  • MC&S
  • Glucose
  • Protein
  • Lactate
  • Cell count
  • PCR
    • Bacterial
    Tuberculous
    Viral
    CSF appearance
    Cloudy
    Slightly cloudy, fibrin web
    Clear/cloudy
    CSF glucose
    Low (<40% of plasma glucose)
    Low (<40% of plasma glucose)
    60-80% of plasma glucose Mumps and herpes encephalitis have a low CSF glucose, however.
    CSF protein
    High (>1g/L)
    High (>1g/L)
    Normal/raised
    CSF WCC
    10-5,000 polymorphs/mm3
    10-1,000 lymphocytes/mm3
    15-1,000 lymphocytes/mm3
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👀
Signs of a raised ICP:
  1. Papilloedema
  2. Focal neurological deficit
  3. Bulging fontanelles
  4. DIC
  5. Signs of cerebral herniation - such as CN3 palsy, reduced consciousness, decorticate/decerebrate positioning, blown pupil etc.
  6. Cushing’s triad

ðŸ’Ą Neuroimaging such as a CT scan is indicated if there are signs of a raised ICP.

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ðŸĐļ
Bloods
  • MC&S - bacterial causes will be positive for blood cultures.
  • VBG
    • Lactate may be elevated if the patient has sepsis. It may be elevated
  • LFTs - ⮆ïļ. Patients with severe bacterial meningitis have metabolic abnormalities.
  • Coagulation screen - coagulopathy is often seen due to DIC.
  • Serum HIV
  • FBC
    • Bacterial
      • WCC ⮆ïļ
      • RBC ⮇ïļ
      • Platelets ⮇ïļ
  • U&Es - may show:
    • Hypokalaemia
    • Hypocalcaemia
    • Hypomagnesaemia
  • Glucose - needed to compare CSF glucose levels.
  • Procalcitonin (PCT) - a serum PCT >0.74ng/mL has 95% sensitivity and 100% specificity for differentiating bacterial and viral meningitis.
    • If PCT is unavailable → CRP. Normal CRP excludes bacterial meningitis with almost 99% certainty.

🧰 Management

All patients with suspected meningitis require urgent transferral to hospital. If the patient is in a pre-hospital setting and IV antibiotics are not available then IM benzylpenicillin/cefotaxime/ceftriaxone may be given.

ðŸĪ”
Suspected meningitis:
  • Empirical IV antibiotics - 3rd generation cephalosporins are the go to as they are able to penetrate the BBB. Amoxicillin/ampicillin is used in <3 months and >50 years old when there is risk of listeria monocytogenes infection which is gram-positive and resistant to cephalosporins.
    • < 3 months - IV cefotaxime + amoxicillin/ampicillin
    • 3 months - 50 years - IV cefotaxime/ceftriaxone
    • >50 years - IV cefotaxime/ceftriaxone + amoxicillin/ampicillin
    • Vancomycin/rifampicin can be considered if patient is at risk of penicillin-resistant pneumococcal infection or have travelled within the last 6 months.
  • IV corticosteroids - IV dexamethasone reduces risk of neurological sequelae (ramifications).
    • Should be withheld if patient shows signs of shock, meningococcal septicaemia; is immunocompromised or has developed post-operative meningitis as well as children <3 months old.
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Confirmed viral meningitis:
  1. Supportive care
    1. Secure airway and provide oxygen.
    2. Analgesia and antipyretic
    3. Anti-emetics if the patient is vomiting
    4. IV fluids if needed
  2. Stop antibiotics
  3. Stop corticosteroids
ðŸ§Ŧ
Confirmed bacterial meningitis:
  1. IV antibiotics - as discussed below.
  2. IV corticosteroids
  3. Supportive therapy
Causative agent:
Choice of antibiotics:
Neisseria meningitidis
IV benzylpenicillin/cefotaxime/ceftriaxone
Streptococcus pneumoniae
IV cefotaxime/ceftriaxone
Haemophilus influenzae
IV cefotaxime/ceftriaxone
Listeria monocytogenes
IV amoxicillin/ampicillin + gentamicin (co-trimoxazole if allergic to penicillin)
🍄
Confirmed fungal meningitis:
  • Cryptococcal meningitis
    • Amphotericin
    • + Flucytosine

      • +

    • Fluconazole - for HIV patients especially. HIV patients also need to be on antiretroviral therapy (ART) as well.
  • Histoplasmal meningitis
    • Amphotericin
    • + Itraconazole
  • Coccidoidal meningitis
    • Fluconazole/itraconazole
  • Candidal meningitis
    • Amphotericin
    • + Flucytosine
  • Aspergillus meningitis
    • Voriconazole/Amphotericin
ðŸ”Ū
Prophylaxis:

For meningococcal meningitis, contacts of the patient may be given oral ciprofloxacin or rifampicin. Prophylaxis is given if the contact was made within 7 days of symptom onset. The Health Protection Agency (HPA) guidelines now state that whilst either may be used ciprofloxacin is the drug of choice as it is widely available and only requires one dose.

ðŸšĻ Complications

  • Hearing loss - sensorineural hearing loss is the most common complication in patients with meningitis.
  • Seizures
  • Focal neurological deficit
  • Sepsis
  • Intracerebral abscess
  • Brain herniation - as a result of the increased intracranial pressure
  • Hydrocephalus - due to cerebral oedema blocking CSF outflow
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MENINGOCOCCAL DISEASE

Meningococcal disease is any illness caused by neiserria meningitidis.

It is an acute, contagious and life-threatening illness and is a notifiable disease in the UK.

😷 Presentation

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  • Fever
  • Red/purple petechial/purpuric non-blanching rash - we can use the glass test to identify that it does not fade if you press the side of a clear glass firmly against the skin. It is a sign of meningococcal septicaemia.
  • Sepsis
  • Meningitis
ðŸ’Ķ
Waterhouse Friderichsen Syndrome:

Sepsis resulting from n. meningitidis may lead to DIC → rupture of adrenal glands → Addesonian crisis.

💉 Vaccination

The Bexsero MenB vaccine for meningococcal B (most common cause of bacterial meningitis in the UK) is given at 3 intervals in infants:

  1. 2 months
  2. 4 months
  3. 12-13 months