CNS Lupus Flashcards

1
Q

What is history of Lupus divided into?

A
  1. Classical
  2. Neoclassical
  3. Modern
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2
Q

What is Lupus described as?

A

Erosive facial lesions that were reminiscent of a wolf’s bite

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3
Q

What is the shape of Lupus?

A

Discoid lupus

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4
Q

What is Systemic Lupus Erythematosus?

A

A clinical syndrome, cause known, characterised by inflammation and multisystem involvement

Mainly a disease of women aged 15-50 (reproductive ears)

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5
Q

What is systemic Lupus Erythematosus a member of and give examples?

A

A member of the family of autoimmune rheumatic diseases:

  • Rheumatoid’s syndrome
  • Sherbone’s syndrome
  • Polymyositis
  • They coexist
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6
Q

What do 5% of Lupus patients have?

A

Erosive kind of arthritis

called Rufus

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7
Q

What do 15% of Lupus patients have?

A

Sherborne syndrome which cause profound dryness of the eyes and dryness of the mouth

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8
Q

What do 4% of Lupus patients have?

A

Muscle disease or myelitis

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9
Q

Where is Systemic Lupus Erythematosus common among?

A

Black (and probably Chinese) women than Caucasian women

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10
Q

What is matched by serological diversity?

A

Clinical diversity of Systemic Lupus Erythematosus

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11
Q

Why should SLE patients seen regularly?

A

This disease can affect any organ or system

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12
Q

What is the active and inactive disease of Lupus disease?

A
  1. Active disease: see every 1-3 months

2. Inactive disease: see 6-12 months

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13
Q

What is an example of drug that should be monitored carefully and what is it retreated by?

A

Hydroxychloroquine [treatment of malaria]

Retreated with non-steroidal, anti-inflammatory drugs

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14
Q

What does the drug Hydroxtchloroquine have?

A

Profound effect intracellularly

Affects the cellular PH

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15
Q

What is given to every Lupus patients?

A

Hydroxychloroquine

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16
Q

What is the consequence of taking too much of Hydroxychloroquine?

A

Take eye test as it causes balls-eye appearance at the back of ey e

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17
Q

What is given to treat more aggressive forms of Lupus?

A

Immunosuppressive drug

Steroids

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18
Q

How should Immunosuppressive drugs be monitored closely?

A
  1. Check their blood count

2. Their kidney and liver test

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19
Q

What is the number one test to do for the diagnosis of Lupus?

A

Anti-nuclear, antibody test (98%)

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20
Q

What does the nucleus house?

A

Nearly 2-3000 antigens

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21
Q

What is Ro/Lo?

A
  1. Combination of RNA and proteins
  2. Associated with photosensitivity
  3. Factor of 50
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22
Q

What can the antibodies of Ro/L0 do?

A

Cross the placenta and bind to the conducting tissue of heart
Heart beats in a disordered function [ heart block]
Heart block treated with a pacemaker

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23
Q

What are the 2 problems that Antiphospholipids are associated with?

A
  1. Clotting - Deep veins of the legs

2. Increasing Miscarriage

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24
Q

What is Increase in dsDNA associated with?

A

Renal disease

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25
Q

What are the co-morbidities for Lupus?

A
  1. Atherosclerosis
  2. Osteoporosis/ avascular necrosis
  3. Infection
  4. Cancer
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26
Q

What is strongly linked to the process of steroids?

A

Osteoporosis/avascular necrosis

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27
Q

What is Infection linked to?

A

Steroids and immunosuppressive drugs

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28
Q

What is decreased in Lupus patients?

A

Breast cancer
Endometrial cancer
Ovarian cancer

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29
Q

What is found in a 1/4 of the Lupus patients?

A

Hair loss

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30
Q

What are some examples of clinical characteristic in Lupus Clinic?

A
  1. Rash - 61%
  2. Photosensitivity - 35%
  3. Alopecia - 23%
  4. Oral ulcers - 26%
  5. Arthritis - 92%
  6. Serositis - 39%
  7. Renal - 30%
  8. CNS - 20%
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31
Q

In SLE, what are the common . Haematological abnormalities?

A
  1. Haemolytic anaemia [Hb <8g/dl)
  2. Leucopenia
  3. Lymphopenia
  4. Thrombocytopenia
32
Q

What do a small significant of patients have?

A

Very low haemoglobin, it should be above 11

White cell reductions are quite common

33
Q

What are the key measures of Lupus?

A

Antibodies to DNA and C3

34
Q

What happens if the patients are flaring?

A
  1. DNA goes up
  2. C3 goes down [complement are deposited in the tissue]
  3. If the DNA are flat-lining and the C3 goes down
35
Q

What is the normal amount for DNA antibodies?

A

50 units

36
Q

What are more common in children?

A

Alopecia
oral ulcers
Thrombocytopaenia
Haemolytic anemia

37
Q

What are the main cause of death?

A
  1. Infection
  2. Vascular
  3. Cancer
  4. Active disease including renal
38
Q

What was neurological involvement in SLE first mentioned by?

A

Kaposi in 1875

39
Q

In 1904, what did Baum relate?

A

Active delirium, aphasia and hemiparesis to ‘probable DLE’

40
Q

What did Daly in 1945 correlate?

A

Clinical symptoms with abnormal CSF findings and with the presence of vasculitis

41
Q

What did Dubois describe ?

A

Clinical neurological subset in 1953 among 62 patients

42
Q

What did Lewis focus on?

A

First to focus on the importantce of EEG findings and psychometric testing in 1954

43
Q

What are the two major complications of Lupus?

A
  1. Psychosis

2. Depression

44
Q

Why is Depression in Lupus challenging to determine?

A
  1. Is it due to reactive depression to the circumstance?
  2. Is it due to fundamental problem within the brain?
  3. Vasculitis
  4. Thrombosis
45
Q

What does vasculitis respond to?

A

Steroids and immunosuppressive drugs

46
Q

When is warfarin required?

A

If it is clots

47
Q

What is associated with an increased risk of clotting?

A

Phospholipid antibodies

48
Q

What has a well established link with thrombosis and thromboemboli?

A

Anti-phospholipid antibodies

49
Q

What do anti-P antibodies bind to?

A

Cell surface membrane protein on a neuroblastoma cell line

50
Q

What do Intraventricular injection of IgG anti-P cause?

A

EEG and behavioural changes in rats

Bonfa et al

51
Q

Where is true vasculitis present in?

A

Only ~10% of CNS lupus

52
Q

What might the choroid plexus act as?

A

Non-specific trap for circulating immune complexes e.g. DNA/anti-DNA complexes

53
Q

What are neurone reactive antibodies ?

A

Lymphoctyotoxic antibodies (LCA) cross reactive with neuronal antigens

Directly targeted to neuronal antigens

54
Q

What does evidence suggest about LCA?

A

Have a specific role in the pathogenesis of cerebral Lupus, particularly cognitive dysfunction and visuospatial deficit

55
Q

What are potential antigenic targets in CNS-Lupus?

A
  1. Phospholipids +/- B2 glycoprotein 1
  2. Glycolipid
  3. Neurofilaments
  4. Ribosomal P
  5. 50-52 kDa (lymphatic, synaptic)
  6. 97 kDa (neuronal)
  7. GMP-140 (Endothelial)
  8. Limbic-system specigic antigen
56
Q

What are the major target for anti-ribosomal protein antibodies?

A

Ribosomal P proteins

  • P0
  • P1
  • P2
57
Q

Where are the ribosomal P proteins located?

A

On the larger 60 unit of eukaryotic ribsomes

At least 1 epitope is common to all 3 proteins

58
Q

What does the majority of patients with anti-ribsomal P antibodies do not have?

A

Psychosis

59
Q

What do a subset of anti-DNA antibodies react with?

A

A sequence within the glutamate/NMDA receptor subunit NR2

60
Q

What do X reactive antibodies recognise?

A

A common pentapaptide

Asp.Glu-Trp-Asp/Glu-Tyr Ser Se/Gly

61
Q

What are common in SLE?

A

Clinical anxiety

Depression

62
Q

What did depression show some link to?

A

Anti-Sm antibodies

63
Q

What is anxiety seem to b associated mainly with?

A

Appearance problems
Reduction in social contacts and interactions
Concern that mental/cognitive abilities are affected

64
Q

What are depression linked to?

A

Physical disability and anxiety

65
Q

What are common Neuropsychiatric events?

A
  1. Headache
  2. Anxiety
  3. Mild depression
  4. Mild cognitive impairment
  5. Polyneuropathy lacking confirmation
66
Q

What is Neuropsychiatriac events associated with?

A

Negative impact on HRQoL and increased mortality

67
Q

What are cytokines implicated in pathogenesis of NP-SLE?

A
  1. Interferon alpha
  2. IL-6
  3. IL-8
  4. APRIL
  5. BAFF
  6. CCL2
  7. RANTES
68
Q

What are the sources of intracranial cytokine production?

A
  1. Immune effector cell
  2. Glial
  3. Neuronal cells
69
Q

What is the stimulus for enhanced cytokine production?

A

Autoantibody mediated cell activation

70
Q

What are the treatment for CNS Lupus?

A
  1. Symptomatic e.g. anti-convulsants where epilepsy is a problem
  2. Immunosuppression
  3. No biologic drugs are yet approved
71
Q

Where is Lupus features more diverse?

A

CNS system
12 central
7 peripheral

72
Q

What is the immunopathology of CNS Lupus?

A

Equally diverse

73
Q

What does not help much in CNS disease?

A

The standard serological test for Lupus activity

74
Q

What are the investigations in SLE patients with NP events?

A
  1. Autoantibodies
  2. CSF
  3. Electophysiological assessment
  4. Electropsychological assessment
  5. Neuroimaging
75
Q

What are the management of NPSLE principles?

A
  1. Establish diagnosis of SLE
  2. Decide attribution of NP event
  3. Treat non-SLE factors
  4. Symptomatic therapy
  5. Focal NP-SLE
  6. Diffuse NP-SLE
76
Q

What are the potential outcome measures for CNS Lupus?

A
  1. Biomarkers
    - Tissue damage
    - BBB permeability
  2. Neuroimaging
    - Brain structure
    - Brain function
  3. Clinical outcome
    - Individual NP events
    - Multiple NP events
    - Brain function
77
Q

Key points - Treatment of CNS Lupus

A
Use immunosuppression (often steroids and azathioprine/iv cyclophosphamide/mycophenolate).
Use an appropriate drug e.g. an antipsychotic for a patient with delusions/psychosis or an anti convulsant for those with seizures.
Be patient!