Intracranial Infection

Intracranial Infection

Objectives:

1. Intracranial Abscess
2. Encephalitis
3. Meningitis
4. Transmissible spongiform encephalopathies
   1. “Prions” – transmissible proteins – affect brain/nervous system

 

Infections of the CNS:

• CNS is very vulnerable (delicate control system)
• Relatively Impermeable
  • Inaccessible for immune system and drugs (antibiotics)
• Slow regeneration (nerve cells)
• Contained in hard solid (cranium / vertebral column)
  • Easy for pressure to build up (tumour presses on nearby structures)
  • Hard for external intervention (surgery)

 

Types of CNS Infections:

1. Meningitis (infection of Meninges)
2. Encephalitis (Acute inflammation of the brain tissue)
3. Intracranial Abscess (Collection of infected material)

 

Intracranial Abscesses

Location:

1. Epidural
2. Subdural
3. Meningeal
4. Intra-cerebral

 

Aetiology (spread from)

1. Entrance from paranasal sinuses, middle ear / mastoid
2. Metastatic infection (transported by blood vessel) – spread through bone structure
3. Post-meningitis (children <5 yrs)
4. Other sources eg. trauma, neurosurgery etc.

 

Microbiology

Source	Common Organisms
Sinuses/ Middle ear	streptococci (esp milleri), anaerobes, others: GNB, etc.
Trauma	S. aureus, Clostridium, GNB
Surgery	staphylococci, GNB
Haematogenous (blood)	depends on the source eg. staphviridans strep if endocarditis.

 

Clinical Features/Presentation

Influenced by size, location of abscess; virulence of pathogens, underlying disease

1. Headache
2. Fever (<50%) – uncommon as it is a local immune response, not systemic
3. Focal findings: hemiparesis, ataxia, aphasia (50%) – muscle weakeness
4. Raised ICP
   1. Altered mental status
   2. Papilloedema (optic disc swelling)
   3. Nausea

Signs in immunocompromised patients can be subtle – hard to detect

• Usually needs testing to tell CNS infection is present

 

Diagnostics

1. Lumbar Puncture

Risk:

Herniation of brain parenchyma

(removal of CSF removes pressure, and masses can force tissue “out”)

• Tentorial herniation
• Subfalcine herniation
• Tonsillar herniation (cerebellum)

 

2.  CT / MRI radiological test

• IV contrast – ring enhancing lesion
• Specimens obtained – microbiological test

 

Treatment

1. Antibiotics
2. Drainage of abscess (larger lesions)

 

Encephalitis

The inflammation of the CNS parenchyma (tissue)

Clinical Presentation

• Headache, Fever, Neck stiffness
• Focal Signs (muscle weakness), personality changes
• Seizure, Altered mental status, Raised ICP, Coma

 

Aetiology

Types	Common Organisms
Herpes Viruses	E.g. HSV 1
Arboviruses (mosquito-born)	West Nile, St. Louis, Eastern Equine, Japanese encephalitis virus, etc. “Zika-virus”
Enteroviruses	HIV, mumps, measles etc.
Non-Viral	Listeria, Lyme Disease, TB, Toxoplasma, etc.
Post-Infection	mumps, measles, rubella, influenza, VZV.

 

What is the organism that causes most concern in encephalitis?

• Herpes Simplex Virus 1

Do most patients have cold sores (blistering dry sores)?

• Not always (absence ≠ no HSV1)

How do you treat the infection?

• Antibiotics (acyclovir)
  • Higher dosage then normal or IV

Location:  generally at temporal lobe area (infection from ear canal)

Diagnosis:

• MRI eg. temporal lobe involvement in HSV encephalitis
• CSF analysis: cell count, glucose/protein levels, PCR, cell culture, etc.
• Check Viral aetiology: lymphocytic pleocytosis of 10-200/ml; ↑protein.

Treatment:

• specific: eg. aciclovir for HSV
• supportive / adjunctive Rx

 

 

Meningitis

Inflammation of the meninges

• global problem
• apart from epidemics, >1.2 million bacterial meningitis annually; >10% cases fatal;
• 10-15% long-term disabilities: loss of digit/limb, seizures, hearing loss, intellectual deficits, depression and chronic renal failure.

 

Types:

1. Viral Meningitis
2. Bacterial Meningitis
3. Fungal Meningitis

 

Viral Meningitis

(“culture-negative” meningitis)

• Enteroviruses: seasonal variation (late summer/early autumn)
• Clinical Presentation (less remarkable usually)
  • Headache, Neck stiffness etc.
  • Lymphocytes in CSF (neutrophils in early stages)

• Usually self-limiting: better prognosis

 

Bacterial Meningitis

General	Special groups
Neisseria meningitidis Streptococcus pneumoniae Haemophilus influenzae – rare(type B)	Escherichia coli Streptococcus agalactiae (GBS) Listeria monocytogenes Mycobacterium tuberculosis

Age groups	Common Pathogens
Neonates	group B strep, E. coli, Listeria
Infants	S.pneumoniae, N.meningitidis
Children/ young adults	N. meningitidis
Elderly	S. pneumoniae, Listeria

*Recap TB meningitis (tuberculosis)

Neisseria Meningitidis

(Gram-negative aerobic diplococci) Causes: Meningitis; sepsis/septic shock; Pneumonia (10%); septic arthritis, etc. Humans the natural reservoir; 5-10% adults are asymptomatic carriers (because of inadequate initial antibody response → colonisation) Peak carriage rates in 15-19 yrs age group (up to 25%) Response to carriage: development of bactericidal antibodies in majority; invasive infection in a small minority Basis of serogrouping: N.Meningitidis produces a polysaccharide capsule: 13 serogroups: A, B, C, W135,Y, etc. Vaccination is based on strain (local occurence) Epidemiology Ireland: prior to MenC vaccine in 2000: 99% meningococcal cases due to serogroups B and C Europe: (N. meningitidis : commonest bacterial pathogen) overall case fatality of 5-10% serogroup B: main cause of meningococcal cases in Ireland & UK serogroup C: marked decrease in incidence with the initiation of vaccination programme. African ‘meningitis belt’: Senegal to Ethiopia serogroup A & W135 recurrent causes of epidemics for >100 yrs. outbreaks every 5-12 yrs attack rates of 500-1000/100,000 population (control of disease hindered by poor economic conditions, paucity of infrastructure, inaccessibility of some regions etc.)

 

Fungal Meningitis

Cryptococcus neoformans

• immunocompromised eg. AIDS, steroid Rx, organ transplantation, DM, malignancy, etc.
• subacute (less) onset: a few days instead of hours
  • headache, lethargy,cranial nerve palsies, hydrocephalus etc.
  • Vague presentation

 

Meningococcal Infections Established meningitis (Local) vs Systemic features (rash) with few signs of meningitis Which has a better prognosis? Systemic features has poorer prognosis as onset of presentation is slower Or inadequate immune response (no external presentation) I.e. further spread of infection has already occured Invasion and establishment; Proliferation in the bloodstream → rash Infect other organs

 

Clinical Features (meningitis)

Classical Symptoms	high fever, headache, neck stiffness, vomiting, drowsiness
Others	photophobia, seizures, altered mental status, etc. Kernig’s sign: hip at 90* – extension of knee is painful
Rash	(indicative of bacteraemia) Non-blanching petechial/purpuric rash Glass test

 

Risk Factors

1. Young age eg. infants
2. Asplenia or hyposplenism (lack of spleen function – filtering of blood)
3. Complement or properdin deficiency eg. C5-8
   1. Prone to recurrent meningitis; serogroups W135,Y

 

1. Active/passive smoking
2. Concurrent viral URTI esp. influenza
3. Exposure risk: household contacts of index case (↑risk of 400-800X); living in closed quarters eg. military barracks, college halls, etc.

 

Diagnosis (meningitis)

1. Clinical diagnosis (symptoms)
2. Cranial imaging (eg. CT) may be needed: to confirm or rule out space-occupying lesions or raised intracranial pressure, etc.

 

1. Lumbar puncture: to obtain CSF:
   1. Contraindications: (to not do lumbar puncture)
      1. evidence of ↑ICP
      2. evidence of abscess or other mass lesions
      3. severe septic shock

 

Laboratory Examination (of CSF)

• White Cell Count (Lymphocytes/Polymorphs)
• Protein & Glucose
• Gram Stain (type of bacteria/ -ve virus)
• Ziehl-Nielsen Stain (if relevant)
• Culture
• PCR

 

Meningitis type	WCC (per ml)	Cell Type	Protein (g/L)	Glucose
Normal	< 5	Lym	0.15-0.45 serum	>2/3
Bacterial	↑↑	PMN	↑↑	↓
Viral	↑	Lym	N/↑	N/↓
Crypt	↑	Lym	↑	↓
TB	↑	Lym	↑	↓

 

Others:

• Full blood count; U&E (urea and electrolyte); Coagulation
• Blood culture
• Blood for PCR

 

Treatment (management) of Bacterial Meningitis

When should you administer antibiotics? Would you wait for the laboratory results?

Which antibiotic would you give? What is the role of steroids?

• ASAP: Cefotaxime/ ceftriaxone
  • N. meningitidis and most strains of S. pneumoniae
  • & H. influenzae, although very rare nowadays
• Vancomycin (uncommon strains of S.pneumoniae non-susceptible to above)
• Ampicillin (L. monocytogenes, if indicated)

(management)

1. Prompt diagnosis (clinical suspicion)
2. Prompt relevant investigations (blood test and CT scans etc.)
3. Initial measures:
   1. Appropriate antibiotics
   2. Supportive measures – fluid resuscitation, ventilatory and circulatory support, etc.
   3. Role of steroids? – if indicated, usually given just before 1st dose of antibiotic (some recommended up to 24 hours after 1st dose antibiotic)
4. Tests are done: Patient is on appropriate antibiotics and supportive therapy.

 

1. What else would you need to do? Notify Public Health
2. Later – Targeted therapy based on pathogen and susceptibility results

 

Prevention of Meningitis

(prophylaxis treatment)

1. Chemoprophylaxis (for high risk exposure ppl):

• • close contacts of meningococcal index case ↑risk of infection by 400-1000X
  • eg. Household contacts, kissing contacts, creche/nursery
  • Healthcare workers?

• High-dose rifampicin x 2 days
• Alternative agents: ciprofloxacin, ceftriaxone

 

2. Meningococcal Immunisation

Polysaccharide vaccines poorly immunogenic

Conjugated vaccines are currently in use:

• Meningococcal C vaccine(MenC)
• Meningococcal ACWY vaccine (MenACWY)
• Meningococcal B vaccine (MenB)

 

MenC (Ireland): 3 doses at 4 mths, 13mths, 12-13 yrs MenACWY (Ireland): for at-risk groups: Asplenia/hyposplenism Complement deficiency Down syndrome Immunodeficiency (disease or Rx) Haemopoietic stem cell transplantation(HSCT) or solid organ transplantation (SOT) MenB vaccine (MenB capsule is poorly immunogenic) Outer membrane vesicles vaccines – short-term effect only Recombinant multicomponent vaccine Eg. Bexsero (Novartis) Licensed in Europe since 2013 4 proteins: factor H binding protein, Neisseria heparin binding antigen, Neisseria adhesion A protein, PorA P1.4 Part of routine childhood immunisation schedule At 2, 4, and 12 months of age Recommended for index cases, close contacts, at-risk groups, and possibly in clusters/outbreaks