Table 3

EULAR recommendations for the management of NPSLE

StatementCategory of evidenceStrength of statementAgreement score
General NPSLE
 NPSLE
 Neuropsychiatric events may precede, coincide, or follow the diagnosis of SLE but commonly (50–60%) occur within the first year after SLE diagnosis, in the presence of generalised disease activity (40–50%)2B8.2
 Cumulative incidence
  Common (5–15% cumulative incidence) manifestations include CVD and seizures; Relatively uncommon (1–5%): severe cognitive dysfunction, major depression, ACS and peripheral nervous disorders; Rare (<1%) are psychosis, myelitis, chorea, cranial neuropathies and aseptic meningitis.2B8.4
 Risk factors
  Strong (fivefold increase) risk factors consistently associated with primary NPSLE are generalised SLE activity, previous severe NPSLE manifestations (especially for cognitive dysfunction and seizures), and antiphospholipid antibodies (especially for CVD, seizures, chorea)2B9.1
 Diagnostic work-up
  In SLE patients with new or unexplained symptoms or signs suggestive of neuropsychiatric disease, initial diagnostic work-up should be similar to that in non-SLE patients presenting with the same manifestations2D9.7
  Depending upon the type of neuropsychiatric manifestation, this may include lumbar puncture and CSF analysis (primarily to exclude CNS infection), EEG, neuropsychological assessment of cognitive function, NCS, and neuroimaging (MRI) to assess brain structure and function2D9.8
  The recommended MRI protocol (brain and spinal cord) includes conventional MRI sequences (T1/T2, FLAIR), DWI, and gadolinium-enhanced T1 sequences1A9.4
 Therapy
  Glucocorticoids and immunosuppressive therapy are indicated for neuropsychiatric manifestations felt to reflect an immune/inflammatory process (eg, ACS, aseptic meningitis, myelitis, cranial and peripheral neuropathies and psychosis) following exclusions of non-SLE-related causes1A9.1
  Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly in thrombotic CVD2B9.6
  The use of symptomatic therapies (eg, anticonvulsants, antidepressants) and the treatment of aggravating factors (eg, infection, hypertension and metabolic abnormalities) should also be considered3D9.8
  Antiplatelet agents may be considered for primary prevention in SLE patients with persistently positive, moderate or high, antiphospholipid antibody titres2D8.8
Specific NPSLE disorders
 CVD
  Atherosclerotic/thrombotic/embolic CVD is common, haemorrhagic stroke is rare, and stroke caused by vasculitis is very rare in SLE patients; accordingly, immunosuppressive therapy is rarely indicated2B9.1
  Long-term anticoagulation should be considered in patients with stroke who fulfil the classification criteria for antiphospholipid syndrome for secondary prevention of recurrent stroke which commonly occurs2C9.4
 Cognitive dysfunction
  Mild or moderate cognitive dysfunction is common in SLE but severe cognitive impairment resulting in functional compromise is relatively uncommon and should be confirmed by neuropsychological tests in collaboration with a clinical neuropsychologist when available2B9.3
  Management of both SLE and non-SLE-associated factors as well as psycho-educational support may prevent further deterioration of cognitive dysfunction; progressive cognitive decline develops only in a minority of patients2C9.2
 Seizure disorder
  Single seizures are common in SLE patients and have been related to disease activity. Chance of recurrence is comparable to that in the general population2B8.4
  The diagnostic work-up aims to exclude structural brain disease and inflammatory or metabolic conditions and includes MRI and EEG2D9.5
  In the absence of MRI lesions related to seizures and definite epileptic abnormalities on EEG following recovery from the seizure, withholding of AED after a single seizure should be considered. Long-term anti-epileptic therapy may be considered for recurrent seizures3D9.3
  For most patients without generalised disease activity, immunosuppressive therapy is not indicated for prevention of recurrences or control of refractory seizures3D9.0
  Anticoagulation may be considered in patients with antiphospholipid antibodies3D8.4
 Movement disorders (chorea)
  In addition to symptomatic therapy for persistent symptoms (dopamine antagonists), antiplatelet agents may be considered in SLE patients with antiphospholipid antibodies3D8.9
  Glucocorticoids/immunosuppressive and/or anticoagulation therapy may be considered in severe cases when generalised disease activity and/or thrombotic manifestations are present3D9.0
 ACS
  Lumbar puncture for CSF analysis and MRI should be considered to exclude non-SLE causes, especially infection3D9.6
  Glucocorticoids and immunosuppressive therapy may be considered in severe cases3D9.0
 Major depression and psychosis
  Major depression attributed to SLE alone is relatively uncommon while psychosis is rare; although steroid-induced psychosis may occur this is very rare2B9.1
  There is no strong evidence to support the diagnostic utility of serological markers or brain imaging in major depression2B8.7
  Glucocorticoids and immunosuppressive therapy may be considered in SLE-associated psychosis, especially in presence of generalised disease activity3D8.8
 Myelopathy
  The diagnostic work-up includes gadolinium-enhanced MRI and cerebrospinal fluid analysis2D9.5
  Timely (as soon as possible) induction therapy with high-dose glucocorticoids followed by intravenous cyclophosphamide should be institutedA9.4
  Maintenance therapy with less intensive immunosuppression to prevent recurrence may be considered3D9.3
 Optic neuritis is commonly bilateral in SLE
  The diagnostic work-up should include a complete ophthalmological evaluation (including funduscopy and fluoroangiography), MRI and visual evoked potentials3D9.5
  Optic neuritis needs to be distinguished from ischaemic optic neuropathy, which is usually unilateral, especially in patients with antiphospholipid antibodies3D9.3
  Glucocorticoids (intravenous methylprednisolone) alone or in combination with immunosuppressive agents should be considered, but failures are common1A9.1
 Peripheral neuropathy
  Peripheral neuropathy often co-exists with other neuropsychiatric manifestations and is diagnosed with electromyography and NCS3D9.1
  Combination therapy with glucocorticoids and immunosuppressive agents may be considered in severe cases1A8.8
  • ACS, acute confusional state; AED, anti-epilectic drug; CNS, central nervous system; CSF, cerebrospinal fluid; CVD, cerebrovascular disease; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuating inversion recovery sequence; NCS, nerve conduction studies; NPSLE, neuropsychiatric systemic lupus erythematosus; SLE, systemic lupus erythematosus.