Central Nervous System Infections - NICHOLAS Flashcards
1
Q
How can a microbe affect the CNS function?
A
- Direct
2. Indirect
2
Q
What is the direct version that affect CNS function?
A
- Invasion of parenchyma of brain
- Viral encephalitis
- Cerebral abscess
3
Q
What are the Invasion of supporting structures of brain
A
- VZV large vessel vasculopathy
- Damaging the blood vessels through an infarction e.g. chicken pox virus
- Complication of shingles
4
Q
What is shingles?
A
Recurrent manifestation of chicken pox virus
5
Q
What are examples of indirect CNS function?
A
- Immune mediated CNS damage
- Infection-triggered metabolic catastrophes
- Toxin-mediated disease (bacterial infections)
- Consequence of systemic sepsis
6
Q
What is Immune-mediated CNS damage?
A
- Acute disseminated encephalomyelitis [ADEM]
- ADAM - Preceding infection
- Causes immune system to lose self-tolerance and for the immune system to attack the brain
7
Q
What is Infection-triggered metabolic catastrophes?
A
- Reye’s syndrome
2. In kids, associated with concurrence of chicken pox and the use of aspirin
8
Q
What is Toxin-mediated diseases?
A
- Tetanus
2. Infection is local to the skin, but the problem is central
9
Q
What is consequence of systemic sepsis?
A
- Septic encephalopathy
- Severe fevere or severe systemic illness of sepsis
- Sickness behabiour
10
Q
What is more prominent in extreme of age?
A
Confusion in acute infection
11
Q
What makes patients very encephalopathic?
A
If patients have early Alzheimer’s or early neurodegenerative disease - Urinary tract infection
12
Q
What is the burden of neurological infection?
A
Rare complications of common infections
13
Q
What is the most feared complication of TB?
A
Tuberculosis causing meningitis
14
Q
What is Japenese encephalitis?
A
A condition that predominantly affects children
- Mosquito carrying form of encephalitis
15
Q
What is entirely preventable with vaccines?
A
Japenese encephalitis
16
Q
What is becoming common in resource rich part of world?
A
Measles
Lack of uptake of vaccine
17
Q
What is about 1 in 1000 cases of measles associated with?
A
Encaphalitis
18
Q
What affects the peripheral nervous system?
A
Leprosy
19
Q
What are the burden of neurological infection?
A
- Cerebral malaria
- Tuberculosis
- Japenese encephalitis
- Measles
- Rabies
- Tetanus
- Leprosy
20
Q
What are the classes of organisms causing CNS infections?
A
- Viruses
- Bacteria
- Fungi + Yeast
- Protozoa
5;. Helminths (worms)
21
Q
What is an example of viruses?
A
Multiple: DNA + RNA
22
Q
What is an example of Bacteria?
A
Aerobic and Anaerobic
23
Q
What is an example of Fungi and yeasts?
A
Cryptococcus neoformans
24
Q
What is an example of Protozoa?
A
Toxoplasma gondii
Naeglera spp
Trypanosomes & Malaria
25
What is an example of Helminths?
Taenia solium
| Echinococcus granulosus
26
How can bug be able to cause infections?
It has to be able to access the CNS
| This is called Neuroinvasiveness
27
How can bugs access the CNS through?
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
28
What is Haematogenous spread?
Spread through the bloodstream
| Typically occur at the grey-white matter junction e.g. enterovirus
29
What is Neurotropism?
A bug that requires intracellular infection
| Ability to infect neural cells
30
What can tropism be applied to?
Supporting cells of the CNS
31
What is Neurotropism applied to?
Neurone infections
32
What may explain variations in clinical phenotype?
Selective vulnerability of cell populations
33
What can cause terrible changes to the CNS of unborn child?
Rubella German
34
What is Neurovirulence?
The ability to cause disease
35
What are virulence factors?
Subtle changes in aa sequence that can take a bug that was relatively benign to lethal
36
What is the principle of Neuroimmunology?
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
Why are common infections rarely neurovirulent?
• Infectious dose/load of organisms
- Models of bacterial meningitis
• Host innate and adaptive immune response
• Neurovirulent features of organisms
38
What are some bugs capable of triggering?
Neuronal apoptosis or necrosis
39
How do CNS infections cause damage?
1. Vicious cycle
- Microbial invasion causes inflammatory response
- Raised ICP
- Direct neuronal injury
40
What are examples of microbial invasion that causes inflammatory response?
1. Blood brain barrier breakdown
2. Cytokine release
3. Endarteritis & microvascular thrombosis
41
What are examples of ICP?
1. Vasogenic
2. Interstitial
3. Cytotoxic cerebral oedema
42
What does direct neuronal injury result in?
Neuronal necrosis or apoptosis
43
What are examples of Neuroinfection syndromes?
1. Meningitis
2. Ventriculitis
3. Encephalitis
4. Myelitis
5. Radiculitis & Ganglionitis
44
What is meningitis?
Inflammation affecting the lining of the brain, the meninges
| - Enterovirus, mumps & HSV-2
45
What is ventriculitis?
Inflammation of the ventricles
| CMV in immunosuppressed
46
What is encephalitis?
Inflammation of the parenchyma of the brain
| including arboviral
47
What is myelitis?
Inflammation of the spinal cord
| -Poliomyelitis, JE, WNE, & Rabiies
48
What is Radiculitis & Ganglionitis?
Inflammation of the roots & DRG
| Shingles, Bell's palsy
49
What are examples of subacute and chronic?
1. Subacute sclerosing panencephalitis (measle)
2. Progressive multifocal leukoencephalopathy
3. HIV dementia
4. Tropical spastic paraparesis
50
What is progressive multifocal leukoencephalopathy?
DNA virus that affects oligodendrocytes leading to cell death
Infection of the immunosuprressed e.g. Human polyoma virus JC
51
What is HIV dementia?
HIV Neurocognitive disorders - HAND
52
What is tropical spastic paraparesis?
- 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
What is the diagnosis of Neurological infection?
1. Localise where the problem is in the CNS
2. Examination of the CSF
3. Lumbar puncture
54
What is the neurological formulation?
1. Anatomy
2. Pathogenic mechanism
3. Aetiology
55
What is the ID mantra?
1. Why did this person?
2. From this place?
3. At this time, get this disease?
56
What is investigation of suspected CNS infections?
1. Anatomy - Imaging techniques & EEG
2. Pathology & Aetiology - Anaysis of CSF
3. Contraindication to LP (without imaging)
57
What are the contraindications to LP?
1. Reduced level of consciousness
2. Focal neurological signs
3. Immunosuppression
4. Papilloedema
5. Anticoagulation/bleeding disorder
58
What is the CSF tests?
* 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
What are examples of CSF tests?
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
A 35-year-old man presents confused with high fever, seizures, auditory hallucinations and recent flu-like illness…
* 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
What is diagnosis of Acute Encephalitis: Bedside?
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
What does Entovirus cause?
Viral encephalitis but a severe viral meningitis
Most common in the summer monthj
63
What is most common in 22% of the population?
Herpes simplex
| Followed by acute disseminated encephalomyelitis
64
What is a rare cause?
Varicella zoster birus
65
What is the diagnosis of Acute Encephalitis: Lab & Imaging?
1. Imaging modalities
2. Electroencephalography
3. CSF analysis
66
Where does Entovirus cause most infection within?
Midbrain
| Also changes in the cortical spinal tract
67
What is the laboratory diagnosis of HSE?
1. PCR of CSF
2. CSF antibody studies
3. Brain biopsy - ''gold standard''
68
PCR of CSF
1. 95% sensitivity & specifity
2. Negative very early or late in disease
3. False negatives if blood stained CSF
69
What is CSF antibody studies?
1. Usually positive 7-10 days into illness
| 2. False positives
70
What is Treatment of HSE?
Intravenous aciclovir at 10mg/kg tds
71
What is a competitive inhibitor of viral DNA polymerase?
Aciclovir triphosphate
72
What does Aciclovir triphosphate do?
Acts as a chain terminator when incorporated into viral genome as lacks 3' hydroxyl group
It is an Virostatic agent
73
What is the outcome from HSE?
1. Mortality reduced from 70 to < 20%
2. Early treatment essential
3. Morbidity high
4. Relapse 5-10%
74
A 55-year old woman presents with fever, neck stiffness and photophobia illness…
Viral meningitis is more common than bacteria
75
What are the common aetiologies of acute infectious meningitis (viral)??
1. Enteroviruses
2. Herpes simplex virus type-2
3. Mumps
76
Acute Infectious Meningitis (viral)
1. Incidence: ~11/100,000/year
2. Predominently children and young adults
3. Usually benign and only requiring symptom relief
77
Acute Infectious Meningitis (bacterial)
1. Incidence 3-5/100,000/year
2. Different organisms in different age groups
3. High morbidity and mortality
78
What are the aetiologies accounting for 85% cases (bacterial)?
1. Neisseria meningitidis
2. Streptococcus pneumonaie
3. Haemophilus influenzae
4. Rarer causes include Listeria, E.coli, TB, Strept suis
79
What is Pneumoccoal meningitis?
Commonest cause of bacterial meningitis in USA & 2nd commonest in UK
80
What are the risk factors for Pneumoccocal meningitis?
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
What is the investiation of pneumoccoal meningitis?
1. Blood cultures
| 2. CSF
82
What is the treatment for Pneumoccocal meningitis?
1. High dose intravenous antibiotics
- Usually 3rd generation cephalosporin
- Add vancomycin if risk of resistance
- Antibiotics with bacteriocidal action
2. Steriods
83
What is the prognosis (without steroids) of pneumoccocal meningitis?
1. Mortality up to 30%
| 2. Morbidity 30-50% neurological sequelae
84
What is the definition of Emerging infections?
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
What are the emerging neuroviral infections?
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)
