Diagnosis and Management of Neuropsychiatric SLE

Amazing case presentation at Parkland Morning Report of neuropsychatric SLE presenting as severe depression. The diagnosis was made because of the remarkable clinical acumen of our residents! See below for a summary:

Nervous system involvement in systemic lupus erythematosus (SLE) can manifest as a range of neurological and psychiatric features, which are classified using the ACR case definitions for 19 neuropsychiatric syndromes. Approximately one-third of all neuropsychiatric syndromes in patients with SLE are primary manifestations of SLE-related autoimmunity, with seizure disorders, cerebrovascular disease, acute confusional state and neuropathy being the most common. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. Treatment involves the management of comorbidities contributing to the neuropsychiatric event, use of symptomatic therapies, and more specific interventions with either anticoagulation or immunosuppressive agents, depending upon the primary immunopathogenetic mechanism. Studies suggest a more favourable outcome for primary NPSLE manifestations.

Neuropsychiatric syndromes in SLE

  • Central nervous system
    • Aseptic meningitis
    • Cerebrovascular disease
    • Demyelinating syndrome
    • Headache
    • Movement disorder
    • Myelopathy
    • Seizure disorders
    • Acute confusional state
    • Anxiety disorder
    • Cognitive dysfunction
    • Mood disorder
    • Psychosis
  • Peripheral nervous system
    • Acute inflammatory demyelinating polyradiculoneuropathy (Guillain–Barré syndrome)
    • Autonomic neuropathy
    • Mononeuropathy
    • Myasthenia gravis
    • Cranial neuropathy
    • Plexopathy
    • Polyneuropathy

NPSLE Fig 1

Investigations in NPSLE

  • Measurement of autoantibodies (antineuronal, antiribosomal P and antiphospholipid antibodies)
  • CSF analysis to exclude infection and measure autoantibodies, inflammatory mediators, and degradation proteins
  • EEG assessment
  • Neuropsychological assessment
  • Neuroimaging: structure (CT, MRI, MTI, DWI, DTI) and function (PET, SPECT, MRA, MRS, fMRI)

NPSLE mediators

Management of neuropsychiatric events in patients with SLE

  • Establish diagnosis of neuropsychiatric SLE: Investigations might include CSF examination (primarily to exclude infection), autoantibody profiling, neuroimaging, and neuropsychological assessment.
  • Identify confounding factors: Comorbidities contributing to the neuropsychiatric event can include hypertension, infection and metabolic abnormalities.
  • Symptomatic therapy: The symptoms of some neuropsychiatric events might be eased by treatment with anticonvulsant, psychotropic and anxiolytic agents.
  • Immunosuppression: Immunosuppressive agents such as corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil and B‑lymphocyte depletion can be used to treat neuropsychiatric events arising primarily from inflammatory injury.
  • Anticoagulation: Neuropsychiatric manifestations arising primarily from a prothrombotic vascular injury should be treated with anticoagulants such as acetylsalicylic acid, heparin and warfarin.

Hanly, J. G. Nat. Rev. Rheumatol. 10, 338–347 (2014); published online 11 February 2014; doi:10.1038/nrrheum.2014.15