• 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


  • 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


  • the exact cause of SLE is unknown, but it has been linked to environmental, genetic, and hormonal factors
triggering mechanism ?? (EBV, CMV, retroviruses?)
cytolysis of virus-infected cells
DNA release
immune reaction against DNA
polyclonal activation of B-cells (hyperactivation)
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)

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

→ neuropsychiatric symptoms in SLE

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   Libman-sacks endocarditis
  • Vasculitis of the coronary arteries

Respiratory system

  • pleuritis
  • acute lupus pneumonitis
  • chronic diffuse interstitial pneumonitis

Skin changes

  • butterfly (malar) rash SLE - butterfly rush
  • discoid lupus SLE - 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) Scarring alopecia in SLE


  • 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

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)


  • 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

Classification criteria for SLE


Stroke prevention

  • primary prevention: ASA
  • secondary prevention (and high-risk patients):

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


  • 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

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Systemic lupus erythematosus (SLE)
link: https://www.stroke-manual.com/systemic-lupus-erythematosus-sle/