CNS Lupus Flashcards
What is history of Lupus divided into?
- Classical
- Neoclassical
- Modern
What is Lupus described as?
Erosive facial lesions that were reminiscent of a wolf’s bite
What is the shape of Lupus?
Discoid lupus
What is Systemic Lupus Erythematosus?
A clinical syndrome, cause known, characterised by inflammation and multisystem involvement
Mainly a disease of women aged 15-50 (reproductive ears)
What is systemic Lupus Erythematosus a member of and give examples?
A member of the family of autoimmune rheumatic diseases:
- Rheumatoid’s syndrome
- Sherbone’s syndrome
- Polymyositis
- They coexist
What do 5% of Lupus patients have?
Erosive kind of arthritis
called Rufus
What do 15% of Lupus patients have?
Sherborne syndrome which cause profound dryness of the eyes and dryness of the mouth
What do 4% of Lupus patients have?
Muscle disease or myelitis
Where is Systemic Lupus Erythematosus common among?
Black (and probably Chinese) women than Caucasian women
What is matched by serological diversity?
Clinical diversity of Systemic Lupus Erythematosus
Why should SLE patients seen regularly?
This disease can affect any organ or system
What is the active and inactive disease of Lupus disease?
- Active disease: see every 1-3 months
2. Inactive disease: see 6-12 months
What is an example of drug that should be monitored carefully and what is it retreated by?
Hydroxychloroquine [treatment of malaria]
Retreated with non-steroidal, anti-inflammatory drugs
What does the drug Hydroxtchloroquine have?
Profound effect intracellularly
Affects the cellular PH
What is given to every Lupus patients?
Hydroxychloroquine
What is the consequence of taking too much of Hydroxychloroquine?
Take eye test as it causes balls-eye appearance at the back of ey e
What is given to treat more aggressive forms of Lupus?
Immunosuppressive drug
Steroids
How should Immunosuppressive drugs be monitored closely?
- Check their blood count
2. Their kidney and liver test
What is the number one test to do for the diagnosis of Lupus?
Anti-nuclear, antibody test (98%)
What does the nucleus house?
Nearly 2-3000 antigens
What is Ro/Lo?
- Combination of RNA and proteins
- Associated with photosensitivity
- Factor of 50
What can the antibodies of Ro/L0 do?
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
What are the 2 problems that Antiphospholipids are associated with?
- Clotting - Deep veins of the legs
2. Increasing Miscarriage
What is Increase in dsDNA associated with?
Renal disease
What are the co-morbidities for Lupus?
- Atherosclerosis
- Osteoporosis/ avascular necrosis
- Infection
- Cancer
What is strongly linked to the process of steroids?
Osteoporosis/avascular necrosis
What is Infection linked to?
Steroids and immunosuppressive drugs
What is decreased in Lupus patients?
Breast cancer
Endometrial cancer
Ovarian cancer
What is found in a 1/4 of the Lupus patients?
Hair loss
What are some examples of clinical characteristic in Lupus Clinic?
- Rash - 61%
- Photosensitivity - 35%
- Alopecia - 23%
- Oral ulcers - 26%
- Arthritis - 92%
- Serositis - 39%
- Renal - 30%
- CNS - 20%
In SLE, what are the common . Haematological abnormalities?
- Haemolytic anaemia [Hb <8g/dl)
- Leucopenia
- Lymphopenia
- Thrombocytopenia
What do a small significant of patients have?
Very low haemoglobin, it should be above 11
White cell reductions are quite common
What are the key measures of Lupus?
Antibodies to DNA and C3
What happens if the patients are flaring?
- DNA goes up
- C3 goes down [complement are deposited in the tissue]
- If the DNA are flat-lining and the C3 goes down
What is the normal amount for DNA antibodies?
50 units
What are more common in children?
Alopecia
oral ulcers
Thrombocytopaenia
Haemolytic anemia
What are the main cause of death?
- Infection
- Vascular
- Cancer
- Active disease including renal
What was neurological involvement in SLE first mentioned by?
Kaposi in 1875
In 1904, what did Baum relate?
Active delirium, aphasia and hemiparesis to ‘probable DLE’
What did Daly in 1945 correlate?
Clinical symptoms with abnormal CSF findings and with the presence of vasculitis
What did Dubois describe ?
Clinical neurological subset in 1953 among 62 patients
What did Lewis focus on?
First to focus on the importantce of EEG findings and psychometric testing in 1954
What are the two major complications of Lupus?
- Psychosis
2. Depression
Why is Depression in Lupus challenging to determine?
- Is it due to reactive depression to the circumstance?
- Is it due to fundamental problem within the brain?
- Vasculitis
- Thrombosis
What does vasculitis respond to?
Steroids and immunosuppressive drugs
When is warfarin required?
If it is clots
What is associated with an increased risk of clotting?
Phospholipid antibodies
What has a well established link with thrombosis and thromboemboli?
Anti-phospholipid antibodies
What do anti-P antibodies bind to?
Cell surface membrane protein on a neuroblastoma cell line
What do Intraventricular injection of IgG anti-P cause?
EEG and behavioural changes in rats
Bonfa et al
Where is true vasculitis present in?
Only ~10% of CNS lupus
What might the choroid plexus act as?
Non-specific trap for circulating immune complexes e.g. DNA/anti-DNA complexes
What are neurone reactive antibodies ?
Lymphoctyotoxic antibodies (LCA) cross reactive with neuronal antigens
Directly targeted to neuronal antigens
What does evidence suggest about LCA?
Have a specific role in the pathogenesis of cerebral Lupus, particularly cognitive dysfunction and visuospatial deficit
What are potential antigenic targets in CNS-Lupus?
- Phospholipids +/- B2 glycoprotein 1
- Glycolipid
- Neurofilaments
- Ribosomal P
- 50-52 kDa (lymphatic, synaptic)
- 97 kDa (neuronal)
- GMP-140 (Endothelial)
- Limbic-system specigic antigen
What are the major target for anti-ribosomal protein antibodies?
Ribosomal P proteins
- P0
- P1
- P2
Where are the ribosomal P proteins located?
On the larger 60 unit of eukaryotic ribsomes
At least 1 epitope is common to all 3 proteins
What does the majority of patients with anti-ribsomal P antibodies do not have?
Psychosis
What do a subset of anti-DNA antibodies react with?
A sequence within the glutamate/NMDA receptor subunit NR2
What do X reactive antibodies recognise?
A common pentapaptide
Asp.Glu-Trp-Asp/Glu-Tyr Ser Se/Gly
What are common in SLE?
Clinical anxiety
Depression
What did depression show some link to?
Anti-Sm antibodies
What is anxiety seem to b associated mainly with?
Appearance problems
Reduction in social contacts and interactions
Concern that mental/cognitive abilities are affected
What are depression linked to?
Physical disability and anxiety
What are common Neuropsychiatric events?
- Headache
- Anxiety
- Mild depression
- Mild cognitive impairment
- Polyneuropathy lacking confirmation
What is Neuropsychiatriac events associated with?
Negative impact on HRQoL and increased mortality
What are cytokines implicated in pathogenesis of NP-SLE?
- Interferon alpha
- IL-6
- IL-8
- APRIL
- BAFF
- CCL2
- RANTES
What are the sources of intracranial cytokine production?
- Immune effector cell
- Glial
- Neuronal cells
What is the stimulus for enhanced cytokine production?
Autoantibody mediated cell activation
What are the treatment for CNS Lupus?
- Symptomatic e.g. anti-convulsants where epilepsy is a problem
- Immunosuppression
- No biologic drugs are yet approved
Where is Lupus features more diverse?
CNS system
12 central
7 peripheral
What is the immunopathology of CNS Lupus?
Equally diverse
What does not help much in CNS disease?
The standard serological test for Lupus activity
What are the investigations in SLE patients with NP events?
- Autoantibodies
- CSF
- Electophysiological assessment
- Electropsychological assessment
- Neuroimaging
What are the management of NPSLE principles?
- Establish diagnosis of SLE
- Decide attribution of NP event
- Treat non-SLE factors
- Symptomatic therapy
- Focal NP-SLE
- Diffuse NP-SLE
What are the potential outcome measures for CNS Lupus?
- Biomarkers
- Tissue damage
- BBB permeability - Neuroimaging
- Brain structure
- Brain function - Clinical outcome
- Individual NP events
- Multiple NP events
- Brain function
Key points - Treatment of CNS Lupus
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!