Clinical validation of the watershed sign as a marker for neuropsychiatric systemic lupus erythematosus

Arthritis Rheum. 2008 Mar 15;59(3):332-7. doi: 10.1002/art.23308.


Objective: To study the relationship between single-photon-emission computed tomography (SPECT) brain imaging and neuropsychiatric signs/symptoms in a cohort of patients with systemic lupus erythematosus (SLE), analyzed using a stereotactic surface projection (SSP) technique.

Methods: Thirty-seven SLE patients were referred for 99mTc-ethyl cysteinate dimer SPECT brain imaging because of neuropsychiatric signs/symptoms. Nineteen normal controls were studied with the identical protocol. Reconstructed images were computed and Z scores were calculated using the SSP technique with the 2-sample t-tests comparing normal controls with SLE patients, and patients with mild cognitive dysfunction with those with severe cognitive dysfunction. The clinical characteristics of SLE patients were collected by retrospective chart review and categorized according to American College of Rheumatology case definitions for neuropsychiatric SLE. Cognitive dysfunction was rated by the treating physician on a scale of 0-3.

Results: Thirty of 37 SLE patients had abnormal SPECT results. SLE patients had reduced perfusion in the watershed areas of the frontal lobes bilaterally compared with controls. Additionally, SLE patients with severe cognitive dysfunction had more severe perfusion deficits than those with mild cognitive dysfunction. In some patients with severe cognitive dysfunction, the watershed areas had Z scores > or =4 SDs below controls.

Conclusion: A convenience sample of patients with SLE and neuropsychiatric signs/symptoms demonstrated reduced perfusion in the watershed areas of the frontal lobes on SPECT scanning analyzed by the SSP technique. The severity of findings correlated with severity of cognitive dysfunction. The area of the brain affected is one that is susceptible to ischemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cognition Disorders / diagnosis
  • Cognition Disorders / pathology*
  • Cysteine / analogs & derivatives
  • Female
  • Frontal Lobe / pathology*
  • Humans
  • Lupus Vasculitis, Central Nervous System / diagnosis*
  • Lupus Vasculitis, Central Nervous System / pathology*
  • Middle Aged
  • Organotechnetium Compounds
  • Tomography, Emission-Computed, Single-Photon*


  • Organotechnetium Compounds
  • technetium Tc 99m bicisate
  • Cysteine