ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS
Systemic lupus erythematosus (SLE)
David Goldemund M.D.
Updated on 03/02/2024, published on 16/06/2023
- Systemic Lupus Erythematosus (SLE) is a systemic chronic autoimmune disease characterized by antibodies to nuclear and cytoplasmic antigens and multisystem inflammation (kidney, brain, heart, skin, and musculoskeletal system)
- more than 90% of cases of SLE occur in women, often starting in childbearing age
- SLE usually has a relapsing and remitting course, and presentation is highly variable (ranging from indolent to fulminant forms)
- neurologic symptoms in SLE occur in 60-70% of patients; however, but only a small proportion are caused by true vasculitis
- neuropsychiatric events may precede, accompany, or follow the diagnosis of SLE
- some events are caused by SLE itself; others are related to treatment complications or occur as a comorbidity
- CNS symptoms seem to identify patients with higher mortality
- the essential feature is an excessive overproduction of autoantibodies directed against intracellular antigens
Epidemiology
Epidemiology- prevalence in Europe 20-30/100 000, women: men = 10:1
- onset usually in reproductive age
- HLA-DR2 and -DR3 are frequently found in patients with SLE
Etiopathogenesis
- the exact cause of SLE is unknown, but it has been linked to environmental, genetic, and hormonal factors
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triggering mechanism ?? (EBV, CMV, retroviruses?)
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cytolysis of virus-infected cells
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DNA release
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immune reaction against DNA
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polyclonal activation of B-cells (hyperactivation)
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autoantibody-mediated tissue damage due to:
immune complex-induced inflammatory response antibody-mediated cellular dysfunction ↓
vasculitis/perivasculitis of small arteries and arterioles due to deposition of immune complexes (composed of DNA, anti-DNA, complement, and fibrin)
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Causes of CNS vascular involvement
- vasculitis – rare in SLE (~ 7%), more likely a cause of PNS involvement
- accelerated atherosclerosis [Stojan, 2013]
- thrombosis and thromboembolism
- infarcts are commonly located in the cortical regions, mainly due to non-inflammatory vasculopathy (endothelial cell proliferation, fibrosis, thrombosis) of small arteries
- thrombosis of veins, including the dural sinuses
- the CNS is very often affected by damage to other organs
- hypertensive encephalopathy, including PRES syndrome
- embolization from valvular vegetations
- hypercoagulation due to nephrotic syndrome
- metabolic encephalopathy (in uremia, hypoxia, electrolyte imbalance)
- meningitis or brain abscess
- CNS symptoms may also be related to the treatment
Clinical presentation
Neuropsychiatric SLE (NPSLE)
- no specific biomarkers or diagnostic tests allow us to confidently attribute neurologic symptoms to SLE
- other more likely causes must be ruled out
Non-focal symptoms (encephalopathy)
- delirium, cognitive impairment
- anxiety
- psychotic symptoms and depression (10%)
- epilepsy (15-30%)
- headache
Focal symptoms
- CNS involvement
- CNS involvement is relatively frequent in SLE (up to 50%) – most often, it is aseptic meningitis or vascular disease (stroke, ICH, dural sinus thrombosis)
- myelitis is rare (2-3%)
- many cases previously described as myelitis in SLE are actually SLE-associated NMO
- myelitis usually presents as LETM, often with subsequent development of optic neuritis
- AQP4-IgG antibodies are present in serum – screen all SLE patients who develop optic neuritis (ON) or myelitis
- peripheral nervous system (PNS) involvement
- cranial neuropathy
- mononeuropathy (single or multiplex), plexopathy, polyneuropathy, including Guilllain-Barré syndrome
- rarely myasthenia or Lambert-Eaton syndrome
- autonomic disorders
Other signs and symptoms
General symptoms
- intermittent fever
- fatigue, weight loss, lymphadenopathy
Muscle and joint disorders
- myalgia, arthralgia
Heart problems
- pericarditis, myocarditis
Libman-Sacks endocarditis
- Vasculitis of the coronary arteries
Respiratory system
- pleuritis
- acute lupus pneumonitis
- chronic diffuse interstitial pneumonitis
Skin changes
- butterfly (malar) rash
- discoid lupus
- photosensitivity (in about 1/2 of cases)
- oronasal ulcers
- secondary Raynaud’s syndrome
- scarring alopecia (hair loss caused by the destruction of your hair follicles)
Kidney
- glomerulonephritis (the most common and most severe organ manifestation)
- nephrotic syndrome
Hematologic manifestations
- anemia, leukopenia, thrombocytopenia
Articular manifestations
- arthralgia
- migratory polyarthritis
- pain spreads from one joint to another; the first joint may start to feel better before the pain starts in another joint
Diagnostic evaluation
- laboratory tests used to assess SLE activity are not sufficiently informative in case of CNS involvement
Blood tests
Inflammatory markers
- ↑ ESR, CRP, fibrinogen, α- and γ-globulins, CIK
- ↓ C3, C4, ceruloplasmin
Complete blood count (CBC)
- anemia
- leuko- and lymphopenia
- thrombocytopenia
Autoantibodies
CSF analysis
Cerebrospinal fluid (CSF) examination is important, but clear pathology is only found in approx. ½ of patients with neuropsychiatric SLE
- slight increase in total protein
- mild pleocytosis
- evidence of autoantibodies
- antibodies can be found in serum and CSF, where they probably enter via impaired BBB (due to vascular involvement), intrathecal production cannot be excluded – ANA, ds-DNA, ENA (antiSm, SS-A, SS-B), LA, ACLA
- increased immunoglobulin levels
- rarely, oligoclonal bands (these often disappear after successful steroid therapy)
Neuroimaging
- CT – nonspecific ischemic lesions or cerebral hemorrhage (possibly also SAH)
- MRI – multiple cortical lesions, often clinically silent
- PET and SPECT – metabolic and perfusion abnormalities
EEG, neuropsychiatric evaluation
Management
Stroke prevention
- primary prevention: ASA
- secondary prevention (and high-risk patients):
- warfarin with INR 2.5-3.5 [Ruis-Irastorza, 2005]
- robust data on DOACs are not available
Disease-modifying drugs
- biological treatment with DMARDs (disease-modifying antirheumatic drugs):
- rituximab
- belimumab
- IVIG
- nonbiologic DMARDs:
- cyclophosphamide (pulse therapy)
- methotrexate
- azathioprine
- mycophenolate
- cyclosporine
- nonsteroidal anti-inflammatory drugs (NSAIDs)
- ibuprofen, naproxen, diclofenac
- corticosteroids
- methylprednisolone – pulse therapy for acute exacerbations – 5g in 5 days
- prednisone – for long-term treatment, prevention of osteoporosis is necessary – e.g., Caltrate PLUS 1-0-1 or Kombi-Kalz 1000/880 1-0-0
- antimalarial drugs
- particularly useful in the treatment of inflammatory polyarthritis and skin conditions (Borden, 2001)
- hydroxychloroquine
Symptomatic therapy
- standard management of SLE symptoms and complications
Pregnancy
- women with systemic lupus can usually have a healthy baby
- pregnancy should be planned at a time when the patient is being treated with only a low dose of glucocorticoids and all medications that may cause fetal harm have been discontinued
- patients may experience spontaneous abortion, preterm delivery, or neonatal lupus in the baby
- IgG antibodies from the mother’s body can cross the placenta and then cause fetal cardiac arrhythmias
