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C2 Modules CLINICAL > Central Nervous System Infections - NICHOLAS > Flashcards

Central Nervous System Infections - NICHOLAS Flashcards

1
Q

How can a microbe affect the CNS function?

A
  1. Direct

2. Indirect

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2
Q

What is the direct version that affect CNS function?

A
  1. Invasion of parenchyma of brain
  2. Viral encephalitis
  3. Cerebral abscess
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3
Q

What are the Invasion of supporting structures of brain

A
  1. VZV large vessel vasculopathy
  2. Damaging the blood vessels through an infarction e.g. chicken pox virus
  3. Complication of shingles
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4
Q

What is shingles?

A

Recurrent manifestation of chicken pox virus

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5
Q

What are examples of indirect CNS function?

A
  1. Immune mediated CNS damage
  2. Infection-triggered metabolic catastrophes
  3. Toxin-mediated disease (bacterial infections)
  4. Consequence of systemic sepsis
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6
Q

What is Immune-mediated CNS damage?

A
  1. Acute disseminated encephalomyelitis [ADEM]
  2. ADAM - Preceding infection
  3. Causes immune system to lose self-tolerance and for the immune system to attack the brain
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7
Q

What is Infection-triggered metabolic catastrophes?

A
  1. Reye’s syndrome

2. In kids, associated with concurrence of chicken pox and the use of aspirin

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8
Q

What is Toxin-mediated diseases?

A
  1. Tetanus

2. Infection is local to the skin, but the problem is central

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9
Q

What is consequence of systemic sepsis?

A
  1. Septic encephalopathy
  2. Severe fevere or severe systemic illness of sepsis
  3. Sickness behabiour
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10
Q

What is more prominent in extreme of age?

A

Confusion in acute infection

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11
Q

What makes patients very encephalopathic?

A

If patients have early Alzheimer’s or early neurodegenerative disease - Urinary tract infection

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12
Q

What is the burden of neurological infection?

A

Rare complications of common infections

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13
Q

What is the most feared complication of TB?

A

Tuberculosis causing meningitis

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14
Q

What is Japenese encephalitis?

A

A condition that predominantly affects children

- Mosquito carrying form of encephalitis

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15
Q

What is entirely preventable with vaccines?

A

Japenese encephalitis

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16
Q

What is becoming common in resource rich part of world?

A

Measles

Lack of uptake of vaccine

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17
Q

What is about 1 in 1000 cases of measles associated with?

A

Encaphalitis

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18
Q

What affects the peripheral nervous system?

A

Leprosy

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19
Q

What are the burden of neurological infection?

A
  1. Cerebral malaria
  2. Tuberculosis
  3. Japenese encephalitis
  4. Measles
  5. Rabies
  6. Tetanus
  7. Leprosy
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20
Q

What are the classes of organisms causing CNS infections?

A
  1. Viruses
  2. Bacteria
  3. Fungi + Yeast
  4. Protozoa
    5;. Helminths (worms)
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21
Q

What is an example of viruses?

A

Multiple: DNA + RNA

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22
Q

What is an example of Bacteria?

A

Aerobic and Anaerobic

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23
Q

What is an example of Fungi and yeasts?

A

Cryptococcus neoformans

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24
Q

What is an example of Protozoa?

A

Toxoplasma gondii
Naeglera spp
Trypanosomes & Malaria

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25
Q

What is an example of Helminths?

A

Taenia solium

Echinococcus granulosus

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26
Q

How can bug be able to cause infections?

A

It has to be able to access the CNS

This is called Neuroinvasiveness

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27
Q

How can bugs access the CNS through?

A
  1. Neural route which is spread up a nerve into the CNS
    E.g. VZV (varicella zoster virus) or Rabies
  2. Olfactory route e.g. HSV-1 & Aerosol rabies
  3. Haematogenous spread
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28
Q

What is Haematogenous spread?

A

Spread through the bloodstream

Typically occur at the grey-white matter junction e.g. enterovirus

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29
Q

What is Neurotropism?

A

A bug that requires intracellular infection

Ability to infect neural cells

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30
Q

What can tropism be applied to?

A

Supporting cells of the CNS

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31
Q

What is Neurotropism applied to?

A

Neurone infections

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32
Q

What may explain variations in clinical phenotype?

A

Selective vulnerability of cell populations

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33
Q

What can cause terrible changes to the CNS of unborn child?

A

Rubella German

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34
Q

What is Neurovirulence?

A

The ability to cause disease

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35
Q

What are virulence factors?

A

Subtle changes in aa sequence that can take a bug that was relatively benign to lethal

36
Q

What is the principle of Neuroimmunology?

A
  1. CNS is immunologically quiet
  2. There is a tight blood brain barrier
  3. Expression of Immunosuppressive substances
  4. Low expression of MHC moleucules
  5. Microglia
37
Q

Why are common infections rarely neurovirulent?

A

• Infectious dose/load of organisms
- Models of bacterial meningitis
• Host innate and adaptive immune response
• Neurovirulent features of organisms

38
Q

What are some bugs capable of triggering?

A

Neuronal apoptosis or necrosis

39
Q

How do CNS infections cause damage?

A
  1. Vicious cycle
    - Microbial invasion causes inflammatory response
    - Raised ICP
    - Direct neuronal injury
40
Q

What are examples of microbial invasion that causes inflammatory response?

A
  1. Blood brain barrier breakdown
  2. Cytokine release
  3. Endarteritis & microvascular thrombosis
41
Q

What are examples of ICP?

A
  1. Vasogenic
  2. Interstitial
  3. Cytotoxic cerebral oedema
42
Q

What does direct neuronal injury result in?

A

Neuronal necrosis or apoptosis

43
Q

What are examples of Neuroinfection syndromes?

A
  1. Meningitis
  2. Ventriculitis
  3. Encephalitis
  4. Myelitis
  5. Radiculitis & Ganglionitis
44
Q

What is meningitis?

A

Inflammation affecting the lining of the brain, the meninges

- Enterovirus, mumps & HSV-2

45
Q

What is ventriculitis?

A

Inflammation of the ventricles

CMV in immunosuppressed

46
Q

What is encephalitis?

A

Inflammation of the parenchyma of the brain

including arboviral

47
Q

What is myelitis?

A

Inflammation of the spinal cord

-Poliomyelitis, JE, WNE, & Rabiies

48
Q

What is Radiculitis & Ganglionitis?

A

Inflammation of the roots & DRG

Shingles, Bell’s palsy

49
Q

What are examples of subacute and chronic?

A
  1. Subacute sclerosing panencephalitis (measle)
  2. Progressive multifocal leukoencephalopathy
  3. HIV dementia
  4. Tropical spastic paraparesis
50
Q

What is progressive multifocal leukoencephalopathy?

A

DNA virus that affects oligodendrocytes leading to cell death

Infection of the immunosuprressed e.g. Human polyoma virus JC

51
Q

What is HIV dementia?

A

HIV Neurocognitive disorders - HAND

52
Q

What is tropical spastic paraparesis?

A
  • HTLV-1
  • Blood borne virus that is common in Caribbean and west Africa and Japan
  • 5% of people – chronic inflammatory process in the spinal cord resulting in difficulties walking
53
Q

What is the diagnosis of Neurological infection?

A
  1. Localise where the problem is in the CNS
  2. Examination of the CSF
  3. Lumbar puncture
54
Q

What is the neurological formulation?

A
  1. Anatomy
  2. Pathogenic mechanism
  3. Aetiology
55
Q

What is the ID mantra?

A
  1. Why did this person?
  2. From this place?
  3. At this time, get this disease?
56
Q

What is investigation of suspected CNS infections?

A
  1. Anatomy - Imaging techniques & EEG
  2. Pathology & Aetiology - Anaysis of CSF
  3. Contraindication to LP (without imaging)
57
Q

What are the contraindications to LP?

A
  1. Reduced level of consciousness
  2. Focal neurological signs
  3. Immunosuppression
  4. Papilloedema
  5. Anticoagulation/bleeding disorder
58
Q

What is the CSF tests?

A
  • Sample can be looked by technician under the microscope
  • The number of white blood cells can be counted, and their type assessed
  • Microbiologist can stain spinal fluid looking for bacterial organisms which in the context of bacterial meningitis before antibiotic is positive 60-90% of case
59
Q

What are examples of CSF tests?

A
  1. Cell count & cytology
  2. Gram stain
  3. Antigen detection
  4. Microbial culture
  5. CSF/plasma glucose or CSF lactate
  6. Nucleic acid detection
  7. CSF antibody tests
60
Q

A 35-year-old man presents confused with high fever, seizures, auditory hallucinations and recent flu-like illness…

A
  • Greatest incidence in young and old
  • Common sporadic form of viral encephalitis is herpes simplex encephalitis
  • Herpes simplex virus has a tropism towards limbic system
  • There are sporadic causes such as HSV and epidemic causes such as mosquito or insect borne form of viral encephalitis – happen during wet season
61
Q

What is diagnosis of Acute Encephalitis: Bedside?

A
  1. Cardinal symptoms and signs
    - Fever
    - Alterations in level of consciousness
    - Seizures
  2. Age
  3. Focal & lateralising neurology
  4. Sporadic vs epidemic
  5. Animals & vectors
  6. Immunocompetence
62
Q

What does Entovirus cause?

A

Viral encephalitis but a severe viral meningitis

Most common in the summer monthj

63
Q

What is most common in 22% of the population?

A

Herpes simplex

Followed by acute disseminated encephalomyelitis

64
Q

What is a rare cause?

A

Varicella zoster birus

65
Q

What is the diagnosis of Acute Encephalitis: Lab & Imaging?

A
  1. Imaging modalities
  2. Electroencephalography
  3. CSF analysis
66
Q

Where does Entovirus cause most infection within?

A

Midbrain

Also changes in the cortical spinal tract

67
Q

What is the laboratory diagnosis of HSE?

A
  1. PCR of CSF
  2. CSF antibody studies
  3. Brain biopsy - ‘‘gold standard’’
68
Q

PCR of CSF

A
  1. 95% sensitivity & specifity
  2. Negative very early or late in disease
  3. False negatives if blood stained CSF
69
Q

What is CSF antibody studies?

A
  1. Usually positive 7-10 days into illness

2. False positives

70
Q

What is Treatment of HSE?

A

Intravenous aciclovir at 10mg/kg tds

71
Q

What is a competitive inhibitor of viral DNA polymerase?

A

Aciclovir triphosphate

72
Q

What does Aciclovir triphosphate do?

A

Acts as a chain terminator when incorporated into viral genome as lacks 3’ hydroxyl group

It is an Virostatic agent

73
Q

What is the outcome from HSE?

A
  1. Mortality reduced from 70 to < 20%
  2. Early treatment essential
  3. Morbidity high
  4. Relapse 5-10%
74
Q

A 55-year old woman presents with fever, neck stiffness and photophobia illness…

A

Viral meningitis is more common than bacteria

75
Q

What are the common aetiologies of acute infectious meningitis (viral)??

A
  1. Enteroviruses
  2. Herpes simplex virus type-2
  3. Mumps
76
Q

Acute Infectious Meningitis (viral)

A
  1. Incidence: ~11/100,000/year
  2. Predominently children and young adults
  3. Usually benign and only requiring symptom relief
77
Q

Acute Infectious Meningitis (bacterial)

A
  1. Incidence 3-5/100,000/year
  2. Different organisms in different age groups
  3. High morbidity and mortality
78
Q

What are the aetiologies accounting for 85% cases (bacterial)?

A
  1. Neisseria meningitidis
  2. Streptococcus pneumonaie
  3. Haemophilus influenzae
  4. Rarer causes include Listeria, E.coli, TB, Strept suis
79
Q

What is Pneumoccoal meningitis?

A

Commonest cause of bacterial meningitis in USA & 2nd commonest in UK

80
Q

What are the risk factors for Pneumoccocal meningitis?

A
  1. Age - bimodal distribution
  2. Asplenic/hyposplenism
  3. Myeloma/ hypogammaglobulinaemia
  4. Alcoholism/malnutrition
  5. Chronic disease e.g. liver, kidney & diabetes mellitus
  6. Base of skull fracture
81
Q

What is the investiation of pneumoccoal meningitis?

A
  1. Blood cultures

2. CSF

82
Q

What is the treatment for Pneumoccocal meningitis?

A
  1. High dose intravenous antibiotics
    - Usually 3rd generation cephalosporin
    - Add vancomycin if risk of resistance
    - Antibiotics with bacteriocidal action
  2. Steriods
83
Q

What is the prognosis (without steroids) of pneumoccocal meningitis?

A
  1. Mortality up to 30%

2. Morbidity 30-50% neurological sequelae

84
Q

What is the definition of Emerging infections?

A

Infectious diseases that either have:

  • Not previously been recognised by medical science
  • Have jumped a species barrier
  • Have translocated to a discrete geographical area in which the disease was not previously found
85
Q

What are the emerging neuroviral infections?

A
  1. Newly evolved virus e.g. EV 71
  2. Environmental changes e.g. WNV in USA, TBE UK
  3. Virus crossing species barrier e.g. Nipah or bird flu (H5N1)

C2 Modules CLINICAL (26 decks)

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