L28: Fever and headache

Question 1

How does meningitis get into the brain?

Answer 1

• Infection gets in through the bloodstream or frontal sinus via cribriform plate
• CSF circulates in SA space
• Infection settles in the SA space which is sterile so there is no competition
• Innate immune system not overly active
• Inflammation of SA space extends onto surface of brain
  Meningitis = increase in WBCs in CSF within subarachnoid space (+cell debris, inflammatory proteins, bacteria)

Question 2

Causes of meningitis

Answer 2

1. Virus
2. Bacteria
3. Fungi
4. Protozoa
5. Others (common - drugs, trauma, neurosurgery, cancer)

Question 3

Viral meningitis

Answer 3

• Common, mostly benign
• Spontaneously improves
• Influenza (mainly A), enteroviruses, HSV2

Question 4

Bacterial meningitis

Answer 4

• Common, serious, medical emergency
• N. meningitidis, S. pneumoniae
• Rarer = Listeria monocytogenes (generally older patients), M. tuberculosis
• Illness preceded with nasopharyngeal colonisation
• 10-20% of young adults colonised with N. meningitidis
• Bacteria enter SA space via bloodstream or directly (e.g. sinus surgery) and propagate

Question 5

Fungal meningitis

Answer 5

• Rare
• Usually only in AIDS
• Cryptococcus neoformans

Question 6

Protozoal meningitis

Answer 6

• Angiostrongylus cantonensis (not in NZ)
• Rare, accidental ingestion of worms eggs or larvae
• No effective treatment, usually self-limiting

Question 7

Signs and symptoms of meningitis

Answer 7

Inflammation of meninges: headache, photophobia, neck stiffness, drowsiness

Systemic inflammatory response = fever, drowsiness, septic shock, rash (Neisserian meningitidis)

Question 8

Diagnosis of meningitis

Answer 8

• Clinical suspicion
• Symptoms vague early in illness, signs of meningitis appear late
• Kernigs sign (lift legs up - worsens headache/neck pain)
  Samples: CSF, blood culture, throat swab, blood to detect bacterial DNA by PCR

Question 9

Lumbar puncture

Answer 9

• Needle between L4/5 spinous processes (spinal cord ends at T12)
• Fluid drawn from subarachnoid space
• Main indication: predominantly neutrophils is bacterial meningitis, predominantly lymphocytes in viral meningitis

Question 10

CSF in meningitis

Answer 10

Bacterial:

• Decreased glucose
• Increased protein
• Increased white cells (mainly neutrophils)
• Gram stain +/- and culture ++/-

Viral:

• Normal glucose
• Increased or normal protein
• Increased white cells (mainly lymphocytes)
• No gram stain or culture

Question 11

PCR testing

Answer 11

• Tests for nucleic acid
• Primers with complimentary sequences on it (specific to pathogen)
• Amplifies it
• Does not require live bacteria
  Uses: in serious illness (e.g. meningitis) or when pathogens cannot be cultivated early
  (e.g. URTI viruses) or to improve diagnostic yield (e.g. urethritis - chlamydia or gonorrhoea)

Question 12

If there is no characteristic rash…

Answer 12

• All efforts to find aetiology especially to exclude meningococcal disease
  If CSF gram stain negative:
• Streptococcus pneumoniae antigen test CSF
• CSF PCR
• Blood PCR - meningococcus
• Throat swab (carriage of meningcoccus or pneumococcus)

Question 13

Meningococcal meningitis epidemiology

Answer 13

= Neisserian meningitidis

• Characteristic rash: petechial, non-blanching (sign of vasculitis)
• Cases most often in winter and overlap with rise and fall of influenza (often misdiagnosed)
• Most commonly very young Maori and Pacific children (household overcrowding)
• Mortality rate ~7%

Question 14

Pathogenic mechanisms of meningococcal meningitis

Answer 14

• Expert at avoiding complement cascade
• Gram negative cocci (thin peptidoglycan layer in cell wall)
• Terminal components of cascade form membrane attack complex (protein drill, enter cell wall, bacteria explode) = one of main defences against germs such as N. meningitidis
• Features that stop it being destroyed by complement e.g. pili, factor H
• Bacteria produces lipopolysaccharides to release in bloodstream (stimulates bloodstream causing shock, multi-organ failure), avoids complement fixation

Question 15

Neutrophil extracellular traps

Answer 15

• When bacterial load very high -> neutrophils commit suicide releasing their DNA into capillaries
• DNA form net in capillary, trapping circulating bacteria and immune cells
• In doing so, reduces blood flow to organs = shock

Question 16

Septic shock presentation

Answer 16

Reduced blood pressure, tachycardia, reduced perfusion of organs (skin grey/clammy, aches/pains, reduced urine output, breathing increased, drowsy, confused, fever)

Question 17

Management of bacterial meningitis

Answer 17

• IV antibiotics (penicillin)
• Resuscitate
• Take blood cultures when IV line inserted
• Transfer to hospital
• Investigations
• Pain relief, fluids, IV antibiotics
• Drop precautions (1-2 weeks)
• In meningococcus: prophylactic antibiotics to contacts

Question 18

Management of viral meningitis

Answer 18

Reassurance, analgesia, usually recover at home

Question 19

Management of shock

Answer 19

Maintain organ perfusion = IV fluids, oxygen
Resolve cause = antibiotics, surgery
High mortality so early recognition essential

Question 20

Role of cephalosporins

Answer 20

• Derived from mould acremonium
• Beta lactam ring same as penicillin
• Interferes with transpeptidase enzyme and cell wall loses structure
• Widely used, effective, well-tolerated
• Can use ceftriaxone to treat bacterial meningitis (broad spectrum)

Question 21

Generations of cephalosporins

Answer 21

1. Cefazolin, cephalexin - skin infections, pneumonia
2. Cefuroxime, cefaclor - surgery, gut infections
3. Ceftriaxone, ceftazidime - pneumonia, UTI, GI infection
4. Cefempime, cefpirome - febrile neutropenia, ICU
5. Ceftaroline - MRSA
   (1-3 have increased activity against gram neg bacilli but decreasing against gram pos)