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C2 Modules CLINICAL > HIV & Nervous System - Nicholas > Flashcards

HIV & Nervous System - Nicholas Flashcards

1
Q

What is HIV?

A

Retrovirus - RNA virus; posessing reverse transcriptase

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2
Q

What is HIV able to integrate?

A

Host genome, where it may appear dormant

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3
Q

What are the cell types that HIV infects?

A

CD4+ (T-helper cells)

Cells lacking CD4 receptor

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4
Q

What allows development of resistance?

A

Rapid replication with many errors with RNA transcription

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5
Q

What is HIV?

A

Virally encoded proteins associated with toxicity

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6
Q

What are the transmission of HIV?

A
  1. Vertically
  2. Sexually
  3. iv DU [Blood products that havent been screened for HIV]
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7
Q

What is the natural history of HIV infection untreated?

A

Following an infection, there is an initial fall in CD4 cell counts during acute seroconversion, levels recover to gradually fall off over time

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8
Q

What is the problem with HIV/AIDS?

A

There is long period of clinical latency where patients can be entirely fit and well but are very infectious towards other people

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9
Q

What happens when the CD4 count stops dropping below 300?

A

Immune system becomes compromised

-

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10
Q

What are the first symptoms of HIV?

A

Constitutional

  • Weight loss
  • Not feeling quite right
  • tired
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11
Q

When do patients suffer opportunistic diseases?

A

When the immune system becomes profoundly impaired

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12
Q

What are the natural history of HIV infection?

A
  1. Primary Infection
  2. Acute HIV syndrome - wide dissemination of virus seeding of lymphoid organs
  3. Clinical latency
  4. Constitutional symptoms
  5. Opportunistic diseases
  6. Death
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13
Q

Where is the burden of HIV situated in?

A

Sub-saharan Africa

  • Zimbabwe
  • South Africa
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14
Q

What is England HIV Data 2016?

A
  1. 89,400 estimated infected
  2. 11% thought to be unaware
  3. 5164 new diagnoses in 2016
  4. 42% at diagnosis have CD4 count < 350 cells; 25% < 200
  5. 95% sexual transmission; 45% heterosexual
  6. ~ 7,500 seek care at C&W
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15
Q

What is AIDS?

A

HIV infections where you are profoundly immunosuppressed and have a complication

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16
Q

What arrived in the mid 1990’s?

A

Anti-retroviral medicaitons

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17
Q

Where do different drugs act?

A

Different stages of the virus life cycle

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18
Q

What was the first range of drugs?

A

Drugs that specifically inhibited the reverse transciption

Enzyme that turn viral RNA to viral DNA

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19
Q

What was the second range of drugs?

A

Protease inhibitors that stopped the assembly of virally encoded proteins

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20
Q

What was the third range of drugs?

A

Integrase inhibitor which are drugs that stop reverse transcribed DNA being inserted into the human genome

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21
Q

What did the early drugs have?

A

Very significant toxicity causing peripheral nerve damage being really intolerable causing changes in metabolism, changes in fat distribution

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22
Q

What was estimated in the states 2015?

A

50% of the people living with HIV will be over the age of 50

23
Q

How can HIV affect the nervous system?

A
  1. Brain
  2. Spinal cord
  3. Peripheral nerves
  4. Muscle
  5. Meninges
  6. Cranial Neuropahties
24
Q

What are examples of the brain?

A
  1. Encephalitis
  2. Dementia
  3. Epilepsy
  4. Stroke
  5. Headache
25
Q

What are examples of spinal cord?

A
  1. Transverse myelitis

2. Vacuolar Myelopathy

26
Q

What are examples of peripheral nerves?

A
  1. DSPN
  2. GBS
  3. CIDP
  4. Vasculitic Neuropathy
  5. Polyradiculitis
  6. Autonomic Neuropathy
27
Q

What is an example of muscle?

28
Q

What is an example of meninges?

A

Meningitis

29
Q

What are the cranial nerves for cranial neuropathies?

A
  1. VII

2. VIII

30
Q

What are the principles of HIV Neurology?

A
  1. Time Locking
  2. Parallel Tracking
  3. Layering
  4. Unmasking
31
Q

What is Time Locking

A

Where in that natural history graph is the patient

  • Relationship to CD4 cell count
32
Q

What is Parallel Tracking?

A

Involvement of multiple parts of the nervous system

33
Q

What is layering?

A

Different pathologies superimposed

34
Q

What is unmasking?

A

Second pathology dominated by subacute first pathologies symptoms e.g. HIVE & Cryptococcus

35
Q

What happens when the CD4 count is less than 50?

A

Really serious trouble

36
Q

Immunosuppression

A

You need your immune system to not only prevent infections but to scan body and prevent you from developing cancer

37
Q

What are common in people that are immunosuppressed?

38
Q

What is the classical cancer with people living with HIV?

A

B-cell lymphoma

Driven by Epstein-Bar virus infection

39
Q

What is the definition of Immune Reconstitution Inflammatory Syndrome (IRIS)?

A

A paradoxical deterioration in clinical status attributable to the recovery of the immune system during HAART.

40
Q

What are other examples in neurological practice for IRIS?

A
  1. Reversal reactions in leprosy
  2. MS relapse following pregnancy
  3. Cessation of natalizumab in MS
  4. Tuberculoma development in treated- TBM
  5. Stroke in S pneumoniae meningitis
41
Q

What are the commonest form of IRIS associated with?

A
  1. CNS streptococcus infections

2. CNS Tuberculosis

42
Q

What are the commonest conditions causing IRIS in CNS?

A

JCV [causes PML]
CNS TB infections
Cryptococcus infections

43
Q

What are the clinical risk factors for IRIS?

A
  1. Profoundly Immunosuppressed
  2. Viral load falls very rapidly following antiretral viral therapy
  3. If you have an underlying opportunistic infections
44
Q

What was dementia caused by?

A

Viral CNS infections

45
Q

What is dementia called that is HIV related?

A

Subcortical dementia

46
Q

What are the triad of subcortical dementia?

A
  1. Cognition
  2. Motor function
  3. Behaviour
47
Q

Why are HIV dementia now only seen?

A
  1. Burnt out - damage sustained prior to cART
  2. Late presentation
  3. Non-adherence to ARVs
  4. Rarely in patients where CNS & systemic infection follow non-parallel course
48
Q

Patients with systemic control of HIV and high CD4 cell counts complaining of:

A
  1. Mild memory problems
  2. Slowness
  3. Difficulties in concentration
  4. Difficulties in planning
  5. Difficulties in multi-tasking
49
Q

What did the CHARTER study show?

A

High level of cognitive impairment in patients living with HIV who are on treatment

50
Q

What are the confounds for HIV cognitive Impairment?

A
  1. Current drug use
  2. Hepatitis C co-infection
  3. Depression
  4. '’Burnt-out’’ CNS disease
51
Q

What are the Imaging for HIV dementia?

A
  1. MRI

2. CSF

52
Q

What are the problems with CPE?

A 
Categorical not ordinal
Methodology not transparent:
Hard to independently validate
Weighting for each criterion?
ARV-ARV interactions not considered
No accounting for the effect of an impaired BBB
Anatomy: CSF not “a liquid brain biopsy”
Efficacy in brain cells not assessed specifically
Toxicity (CNS/CVS) not considered
53
Q

Small vessel Disease in HIV

A

Frequently found on post mortem and MRI; infarct defined as being < 20mm
More extensive subcortical WM hyperintensities seen in treated HIV than age-matched controls.*
May be important in pathogenesis of HAND (HIV-associated neurocognitive disorders)

C2 Modules CLINICAL (26 decks)

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